The traditional diet of Greece and cancer. [Archive] - Page 2

R.B.

08-22-2008, 07:05 AM

http://www.universityofcalifornia.edu/news/article/7839

Omega-6 fats cause prostate tumors to grow twice as fast
Email this article
Date: 2006-02-01
Contact: Steve Tokar
Phone: (415) 221-4810
Email: steve.tokar@med.va.gov
Omega-6 fatty acids--such as those found in corn oil--caused human prostate tumors in cell culture to grow twice as quickly as tumors to which omega-6 fats had not been added, according to a study conducted at the San Francisco VA Medical Center.

An omega-6 fatty acid known as arachidonic acid turns on a gene signaling pathway that leads directly to tumor growth, according to principal investigator Millie Hughes-Fulford, PhD, director of the Laboratory of Cell Growth at SFVAMC and scientific advisor to the U.S. Under Secretary for Health for the Department of Veterans Affairs.

The results of the study are published in the February 1 issue of Cancer Research.

"After we added omega-6 fatty acids to the growth medium in the dish, and only omega-6, we observed that tumors grew twice as fast as those without omega-6," recounts Hughes-Fulford, who is also an adjunct professor of medicine at the University of California, San Francisco.

"Investigating the reasons for this rapid growth, we discovered that the omega-6 was turning on a dozen inflammatory genes that are known to be important in cancer. We then asked what was turning on those genes, and found that omega-6 fatty acids actually turn on a signal pathway called PI3-kinase that is known to be a key player in cancer," she adds.

Hughes-Fulford says the results are significant because of the high level of omega-6 fatty acids in the modern American diet, mostly in the form of vegetable seed oils such as corn oil-over 25 times the level of beneficial omega-3 fatty acids, which are found in canola oil, fish, and green vegetables. She notes that over the last 60 years, the rate of prostate cancer in the U.S. has increased steadily along with intake of omega-6, suggesting a possible link between diet and prostate cancer.

The study results build on earlier work in which Fulford and her research team found that arachidonic acid stimulated the production of an enzyme known as cPLA-2, which in turn caused a chain of biochemical reactions that led to tumor growth. In the current paper, the researchers have "followed that biochemical cascade upstream to its source," Hughes-Fulford says. "These fatty acids are initiating the signal pathway that begins the whole cascade."

Hughes-Fulford and her fellow researchers also found that if they added a non-steroidal antiflammatory or a PI3K inhibitor to the growth media, interrupting the signal pathway, the genes did not get turned on and increased tumor cell growth did not take place.

Currently, Hughes-Fulford is conducting a study in which research animals are fed diets with different levels of omega-3 and omega-6 fatty acids, "to see how the tumors grow in animals."

Hughes-Fulford says that her study results have directly influenced her own diet. "I'm not a physician, and do not tell people how to eat, but I can tell you what I do in my own home," she says. "I use only canola oil and olive oil. We do not eat deep-fried foods."

Co-authors of the study include Chai-Fei Li, BA, of the Northern California Institute for Research and Education, J.B. Boonyaratanakornkit, BS, of SFVAMC and UCSF, and Sina Sayyah, BA, of NCIRE.

The study was funded by grants from the Department of Veterans Affairs and a grant from NASA that was administered by NCIRE.

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in health care, and providing complex patient care.

R.B.

08-22-2008, 03:08 PM

This looks like a fascinating and informative paper. I have not paid to view it but part is available at the lower link.

Definitely worth at least a skim if you have the time.

It emphasises the importance of the Omega 3:6 ratio in breast cancer risk, and in one place suggests a need for a ration of around 1:1 or 1:2 Omega 3 :6.

http://www.ncbi.nlm.nih.gov/pubmed/16145262

http://books.google.co.uk/books?hl=en&lr=&id=_0PWAie_YIkC&oi=fnd&pg=PA133&dq=omega+6+crete&ots=flUu48dGKq&sig=0x7LZMe1CjR5mTvbx_eNx_kHJLU#PPA147,M1

R.B.

09-04-2008, 01:21 PM

The omega 3:6 balance, inflammation, COX 2 pathways and downstream products are factors in BC.

See also COX 2 posts.

http://www.ncbi.nlm.nih.gov/pubmed/17927497?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum

1: Nutr Cancer. 2007;59(1):14-20.Links
Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer.
Cerchietti LC, Navigante AH, Castro MA.

Translational Research Unit, Angel H Roffo Cancer Institute, Universidad de Buenos Aires, Buenos Aires, Argentina. lcerchie@aecom.yu.edu

Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others. Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states, but treatment's compliance is generally poor. Preferentially, Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids, although their role in SIMS is unknown. The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach, some of the symptoms of the SIMS could be controlled. We exclusively evaluated 12 patients for compliance. Patients were assigned 1 of the 4 treatment groups (15-, 12-, 9-, or 6-g dose, fractionated every 8 h). For patients assigned to 15 and 12 doses, the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose. The maximum tolerable dose was calculated to be around 2 capsules tid (6 g of fish oil per day). A second cohort of 22 patients with advanced lung cancer and SIMS were randomly assigned to receive either fish oil, 2 g tid, plus placebo capsules bid (n = 12) or fish oil, 2 g tid, plus celecoxib 200 mg bid (n = 10). All patients in both groups received oral food supplementation. After 6 wk of treatment, patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite, less fatigue, and lower C-reactive protein (C-RP) values than their respective baselines values (P < 0.02 for all the comparisons). Additionally, patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values (P < 0.02 for all the comparisons). Comparing both groups, patients receiving fish oil + celecoxib showed significantly lower C-RP levels (P = 0.005, t-test), higher muscle strength (P = 0.002, t-test) and body weight (P = 0.05, t-test) than patients receiving fish oil + placebo. The addition of celecoxib improved the control of the acute phase protein response, total body weight, and muscle strength. Additionally, the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and/or celecoxib. This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor, some of the signs and symptoms associated with a SIMS could be ameliorated.

TSund

09-09-2008, 08:54 AM

RB- what is celecoxib? A Cox2 inhibitor of some sort I assume?

And, do you think this would applicable to mom who suffers multiple immune system problems, probably stemming from her chronic leukemia, along with muscle wasting/fibromylagia.
Thanks

TRS

R.B.

09-11-2008, 02:25 PM

Hi T Sund

Here is a link for celecoxib.

http://en.wikipedia.org/wiki/Celebrex

I cannot in any way give advice on specific conditions in relation to individual circumstances. I have no training to do so. I can only draw your attention to the generality of relevant trials for your consideration.

Omega 3 and 6 do impact on the immune function through a number of mechanisms. IF there is dietary excess of Omega 6 and a lack of Omega 3 fats from plant sources (eg vegetable oils) AND a lack of long chain Omega 3s DHA and EPA or blocked conversion pathways there is significant evidence this can negatively impact on the immune function.

As posted already there is some evidence that increasing the intake of long chain omega 3s may help in some circumstances with fatigue etc.

These are listed as symptoms of CFS

http://www.spineuniverse.com/displayarticle.php/article155.html

Symptoms of Fibromyalgia include:

—Multiple tender points and muscle pain

—Disturbed sleep with morning fatigue and stiffness

—Aggravation of signs and symptoms by modulating factors (emotional stress, temperature changes)

—Subjective swelling and numbness

—Chronic headaches

—Irritable bowel syndrome

—Cold intolerance (Raynaud's Phenomenon)

—Dysmenorrhea - painful menstruation

—Exercise intolerance

—Weakness

A number of them have also been linked at some level with Omega 3:6 imbalances.

A search under leukemia or CFS and DHA or Omega 3 etc on Pubmed http://www.ncbi.nlm.nih.gov/ will produce some trials.

CFS
There are a few for CFS. This is an example suggesting CFS sufferers have a lack of Omega 3 and excess Omega 6

Neuro Endocrinol Lett. 2005 Dec;26(6):745-51.Links
In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation.
Maes M, Mihaylova I, Leunis JC.

M-Care4U Outpatient Clinics, and the Clinical Research Center for Mental Health, Antwerp, Belgium.

ABSTRACT

"There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things- --omega3 PUFAs, such as EPA and DHA."

http://www.ncbi.nlm.nih.gov/pubmed/16380690?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

So have a look at some more.

LEUKEMIA

There has been some work in the area of leukemia which seems to suggest possible benefits for EPA for example or usage as a treatment adjunct.

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=leukemia%20%20omega%203

GOOD CLINICAL BOOK ON ACUTE INFLAMMATION

This is expensive but an excellent book you could give to your doctor. It is rare in being clinically orientated It is a powerful book. It is not an easy read but your friend just needs to get the jist and give it to her doctor as a basis for dietary discussion.

Omega 3 Fatty Acids in Clinical Nutrition by Heller, Stehr and Koch.

AND FINALLY

Your friend must tell to her doctor before any significant change in diet. I would suggest doing some more reading on Omega 3 and 6 and CFS etc printing the information and taking it to the doctor at the time of visit.

R.B.

09-15-2008, 03:18 AM

Another mechanism by which Omega 6 linoleic acid induces tissue formation , migration and proliferation.

Oxidised Omega 6 linoleic acid induces rapid dose dependent upregulation of Syndecan-4

http://www.ncbi.nlm.nih.gov/pubmed/16636895

Breast Cancer Res Treat. 2006 Jul;98(1):91-8. Epub 2006 Apr 25.Click here to read Links
Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype.
Baba F, Swartz K, van Buren R, Eickhoff J, Zhang Y, Wolberg W, Friedl A.

Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA.

Members of the syndecan and glypican families of cell surface heparan sulfate proteoglycans (HSPGs) are modulators of growth factor signaling and cell adhesion. Both loss and gain in expression of syndecans and glypicans has been associated with malignant progression. The goal of this project was to investigate a possible relationship between expression of cell surface HSPGs (syndecan-1, syndecan-4 and glypican-1) and established prognostic factors or clinical outcome in breast carcinomas. Tissue arrays containing 207 human breast carcinoma samples in duplicate were immuno-labeled with antibodies to syndecan-1, syndecan-4, glypican-1, Ki67, E-cadherin, estrogen receptor (ER) and progesterone receptor (PR). Clinical follow-up information was available for up to 18.6 years (median follow-up 6.2 years). Syndecan-1 and syndecan-4 expression in carcinoma cells ranged from complete loss to high expression, but glypican-1 was detected only in a small subset of breast carcinomas. Expression of all three HSPGs was significantly associated with the Ki67 proliferation index (syndecan-1: p=0.0025; syndecan-4: p<0.0001; glypican-1 p=0.01). Syndecan-1 and syndecan-4 expression correlated with ER negativity, grade, and size of the primary tumors. Syndecan-1 expression (but not syndecan-4 nor glypican-1) predicted patient outcome (DFS: p=0.0054; OS: p=0.0086). However, multivariate analysis failed to identify syndecan-1 as an independent prognostic marker, which was due to its significant association with established prognostic factors. The strong association between cell surface HSPGs and the Ki67 proliferation marker would support a biologic role in carcinoma growth regulation. Furthermore, the close correlation between syndecan expression and negative ER status raises the possibility of hormonal regulation or more likely an association with an aggressive, ER-negative carcinoma phenotype.

http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=2&abstractID=202291

Specific Induction of Syndecan-4 in Vascular Endothelial Cells of Breast Cancer - Implications for FGF-2-Induced Angiogenesis.
Sub-category:

Proc Am Soc Clin Oncol 19: 2000 (abstr 2603)
Author(s):

Christoph Mundhenke, Sally Drew, Zhen Chang, Aung Choon, Andreas Friedl
Abstract:

Introduction: Fibroblast growth factor-2 (FGF-2) is a potent angiogenic stimulator. Binding of FGF-2 to its receptor tyrosine kinases (RTKs) and cellular signaling are modulated by heparan sulfate proteoglycans (HSPGs) via their heparin-like heparan sulfate (HS) side chains. HS can be specific positive or negative regulators of FGF signaling depending on their ability to bind to both FGF ligand and RTK. Aim: The goal of this study was to localize different cell surface HSPGs in breast cancer and normal breast tissue and to examine their roles in FGF signaling. Materials and Methods: HSPGs were detected immunohistochemically in paraffin embedded tissues using antibodies directed against the HSPG core proteins of glypican-1, syndecan-1 and syndecan-4. The ability of HSPGs to promote FGF-2 signaling complex assembly was tested by using FGF-2 ligand and soluble RTK fusion protein (FR1-AP) as binding probes (Chang et al. FASEB J., in press). Results: HSPGs are induced in the stroma of infiltrating carcinomas in a striking tissue compartment and cell type-specific fashion. Syndecan-4 is dramatically induced in activated endothelial cells within infiltrating carcinoma tissue, while endothelial cells in normal breast gland are syndecan-4 negative. Syndecan-1 is strongly up-regulated in fibroblasts within the desmoplastic stroma surrounding infiltrating cancer cells. Glypican-1 is found in stromal fibroblasts in the immediate vicinity of cancer cells. FGF-2 binds to HSPGs in all stromal compartments. FR1-AP binds to FGF-2 immobilized on stromal fibroblast and endothelial cell HSPGs, suggesting, that syndecan-1 on fibroblasts and syndecan-4 on endothelial cells promote FGF-2 signaling complex assembly. Summary: Syndecan-4 is induced in tumor vessel endothelial cells of infiltrating carcinomas of the breast, facilitating FGF-2 signaling and thereby likely promoting angiogenesis.

http://ajpcell.physiology.org/cgi/content/full/288/2/C458
ABSTRACT

Syndecan-4, a heparan sulfate proteoglycan that is widely expressed in the vascular wall and as a cell surface receptor, modulates events relevant to acute tissue repair, including cell migration and proliferation, cell-substrate interactions, and matrix remodeling. While syndecan-4 expression is regulated in response to acute vascular wall injury, its regulation under chronic proatherogenic conditions such as those characterized by prolonged exposure to oxidized lipids has not been defined. In this investigation, arterial smooth muscle cells were treated with 13-hydroperoxy-9,11-octadecadienoic acid (HPODE) and 13-hydroperoxy-10,12-octadecadienoic acid, oxidized products of linoleic acid, which is the major oxidizable fatty acid in LDL. Both oxidized fatty acids induced a dose-dependent, rapid upregulation of syndecan-4 mRNA expression that was not attenuated by cycloheximide. This response was inhibited by pretreatment with N-acetylcysteine, catalase, or MEK1/2 inhibitors, but not by curcumin or lactacystin, known inhibitors of NF-{kappa}B. These data suggest that oxidized linoleic acid induces syndecan-4 mRNA expression through the initial generation of intracellular hydrogen peroxide with subsequent activation of the extracellular signal-regulated kinase signaling pathway via MEK1/2. Notably, the HPODE-induced enhancement of syndecan-4 mRNA was accompanied by accelerated shedding of syndecan-4. In principle, alterations in both the cell surface expression and shedding of syndecan-4 may augment a variety of proatherogenic events that occur in response to oxidized lip

R.B.

09-15-2008, 04:23 AM

PPAR gamma has made a previous appearance as having a link with BC. The trial below suggest that the products of oxidation of Omega 6 linoleic acid promote PPAR gamma which is suggested to be a tumour promoter in BC.

http://genesdev.cshlp.org/cgi/content/abstract/18/5/528

ABSTRACT

"These results suggest that once an initiating event has taken place, increased PPAR{gamma} signaling serves as a tumor promoter in the mammary gland."

http://carcin.oxfordjournals.org/cgi/content/abstract/24/11/1717

ABSTRACT

Activation of PPAR {gamma} in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR {gamma}

Arthur W. Bull1,4, Knut R. Steffensen2, JÃ¶rg Leers2 and Joseph J. Rafter3

1 Oakland University, Department of Chemistry, Rochester MI 48309-4477, USA, 2 Center for Biotechnology, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden and 3 Department of Medical Nutrition, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden

The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) {gamma} plays an important role in the differentiation of intestinal cells and other tissues. Real-time PCR examination of PPAR mRNA for {gamma}1, {gamma}2 and {gamma}3, in Caco-2 and HCT-116 colon cell lines showed that {gamma}3 is the most abundant message in both lines. Treatment of Caco-2 cells with sodium butyrate, which induces cell differentiation, also leads to an increase in all three PPAR mRNAs. In contrast, treatment of HCT-116 cells with sodium butyrate, which does not lead to differentiation of these cells, causes a decrease in the amount of all three PPAR mRNAs. Furthermore, the amount of PPAR mRNA is greater in Caco-2 cells than in HCT-116 cells at all times examined. As several oxidative metabolites of linoleic acid, including 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic acid (13-OXO) have been shown to bind PPAR, and there is a strong positive correlation between enzymes for metabolism of linoleate oxidation products, intestinal cell differentiation and the distribution of PPAR, we also performed a detailed investigation of the activation of PPAR {gamma} by 13-HODE and 13-OXO. For these experiments, Caco-2 and HCT-116 cells were transfected with constructs containing PPAR {gamma}1 or {gamma}2 then a PPRE-luc reporter construct. Exposure of transfected cells to micromolar concentrations of 13-HODE or 13-OXO produced concentration-dependent increases in luciferase activity. In addition, the two linoleate metabolites activate endogenous PPAR in these cell lines transfected with only PPRE-luc. The data substantiate the contention that oxidation products of linoleic acid are metabolically produced endogenous ligands for PPAR {gamma} and that PPAR {gamma} plays an important role in the differentiation of intestinal cells.

R.B.

09-30-2008, 04:30 AM

Linoleic Acid-Induced VCAM-1 Expression in Human Microvascular Endothelial Cells Is Mediated by the NF-κβ-Dependent Pathway
Authors: Hyen Joo Park; Yong Woo Lee; Bernhard Hennig; Michal Toborek
DOI: 10.1207/S15327914NC41-1&2_18
Publication Frequency: 6 issues per year
Published in: journal Nutrition and Cancer, Volume 41, Issue 1 & 2 September 2001 , pages 126 - 134

Abstract
Vascular cell adhesion molecule-1 (VCAM-1) has been reported to play an important role in cancer metastasis via the adhesive interaction between tumor cells and endothelial cells. In this study, we examined the effects of linoleic acid on VCAM-1 expression and its transcriptional regulatory mechanism in human microvascular endothelial cells (HMEC-1). Time- and dose-dependent increases of VCAM-1 mRNA levels were observed in linoleic acid-treated HMEC-1 as detected by reverse transcriptase-polymerase chain reaction. Flow cytometry analysis showed a significant and dose-dependent upregulation of VCAM-1 expression in HMEC-1 stimulated with linoleic acid compared with controls. To clarify the transcriptional regulatory pathway, we investigated the role of nuclear factor-κβ (NF-κβ) in the expression of VCAM-1 by linoleic acid in HMEC-1. Nuclear extracts from HMEC-1 stimulated with linoleic acid showed a dose-dependent increase in binding activity to the NF-kB consensus sequences. These effects were preventable by cotreatment with inhibitors of NF-κβ activity, such as sodium salicylate, aspirin, or pyrrolidine dithiocarbamate. In addition, pretreatment with NF-κβ inhibitors markedly suppressed the ability of linoleic acid to induce VCAM-1 gene expression. The role of NF-κβ in linoleic acid-induced VCAM-1 expression was confirmed by functional promoter studies in HMEC-1 transfected with reporter constructs of the VCAM-1 promoter with or without mutated NF-κβ binding site. These results indicate that linoleic acid upregulates VCAM-1 expression in HMEC-1 through the NF-κβ-dependent pathway.

R.B.

10-17-2008, 04:01 PM

Fat -1 is a gene in worms that converts omega 6 to omega 3. Animals and humans do not have that ability.

They have done trial where they insert the gene into pigs and mice and they make Omega 6 into Omega 3 and tend to balance the two.

Here they are seeing what happens to cancer cells if the fat gene is inserted into cancer cells and the cells put into mice.

The fat gene inhibited cell proliferation in prostate cancer.

In essence once again a balance of Omega 3s and 6s / lower Omega 6s may help inhibit cancer.

RB

Expression of the fat-1 gene diminishes prostate cancer growth in vivo through enhancing apoptosis and inhibiting GSK-3{beta} phosphorylation.
Lu Y, Nie D, Witt WT, Chen Q, Shen M, Xie H, Lai L, Dai Y, Zhang J.

Department of Medicine, University of Pittsburgh, VA Pittsburgh Healthcare Systems, Room 2E146, University Drive, Pittsburgh, PA 15240. zhangj2@upmc.edu.

Epidemiologic studies inclusively indicate that "unhealthy" dietary fat intake is one of the potential risk factors for cancer. In dietary fat, there are two types of polyunsaturated fatty acids (PUFA), omega-3 (n-3) and omega-6 (n-6). Numerous studies support that the ratio of n-6/n-3 affects tumorigenesis. It was reported that adenoviral transfer of the fat-1 gene, which converts n-6 to n-3, into breast and lung cancer cells had an antitumor effect in vitro. However, the effects of the fat-1 gene expression on tumor growth in vivo have not been studied and the mechanisms remain unclear. Accordingly, prostate cancer DU145 and PC3 cells were transfected with either the fat-1 gene or a control vector. The cells that expressed the fat-1 gene had a lower n-6/n-3 PUFA ratio compared with the cells that expressed the control vector. The fat-1 gene expression significantly inhibited prostate cancer cell proliferation and invasion in vitro. The fat-1 and control vector-transfected prostate cancer cells were s.c. implanted into severe combined immunodeficient mice for 6 weeks. The fat-1 gene expression significantly diminished tumor growth in vivo, but the control vector had no effect. Finally, we evaluated signaling pathways that may be important for fat-1 gene function. Administration of n-3 PUFA induced caspase-3-mediated prostate cancer cell apoptosis in vitro. The fat-1 gene expression inhibited prostate cancer cell proliferation via reduction of GSK-3beta phosphorylation and subsequent down-regulation of both beta-catenin and cyclin D1. These results suggest that fat-1 gene transfer directly into tumor cells could be used as a novel therapeutic approach. [Mol Cancer Ther 2008;7(10):3203-11].

R.B.

10-26-2008, 01:54 PM

Arachidonic acid is the long chain Omega 6 and raw material of the Omega 6 chemicals. COX 2 is one of the enzymes that converts arachidonic acid to its down stream products.

This is another confirmation of a link between oestrogen production and Omega 6.

The vegetable based Omega 6 increases COX 2 expression.

The only place you can get Omega 6 is in the diet you cannot make it.

Long chain Omega 3 has a blocking effect on COX2 Omega 6 products by a variety of mechanisms.

RB

Cyclooxygenase-2 mRNA expression correlates with aromatase expression in human breast cancer.
Salhab M, Singh-Ranger G, Mokbel R, Jouhra F, Jiang WG, Mokbel K.

St. George's University of London, Tooting, London, United Kingdom.

INTRODUCTION: The cyclooxygenase-2 (COX-2), responsible for the conversion of arachidonic acid into prostaglandin (PG) E2, is known to increase intracellular cAMP and estrogen production in malignant breast tissue. The aromatase enzyme complex is responsible for local production of estrogens in breast cancer. Increasing evidence supports a role for COX-2 in upregulation of aromatase activity. The aim of this study was to examine the relationship between COX-2 and aromatase mRNA expression in human breast cancer. METHODS: A total of 160 breast samples (127 tumor tissues and 33 normal tissues) were analyzed. Levels of transcription were determined using real-time quantitative PCR. COX-2 and aromatase mRNA expression were normalized against CK19. Levels of expression of COX-2 were correlated with those of aromatase using Pearson's correlation method. RESULTS: Levels of expression of COX-2/CK19 of both benign and malignant tissues were positively correlated with aromatase/CK19 transcript levels (correlation coefficient = +0.536, P < 0.0001). When we compared levels of expression of both genes in malignant samples only, there was a highly significant positive correlation (r = +0.611, P < 0.00001). CONCLUSION: This study demonstrates a strong positive relationship between COX-2 and aromatase mRNA expression, and lends further support to the hypothesis that COX-2 is an upregulator of aromatase in breast tissue.

R.B.

11-21-2008, 02:57 PM

1: Breast Cancer Res Treat. 2007 Jan;101(1):7-16. Epub 2006 Jul 6.Click here to read Links
Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells.
Hammamieh R, Chakraborty N, Miller SA, Waddy E, Barmada M, Das R, Peel SA, Day AA, Jett M.

Division of Pathology, Walter Reed Army Institute of Research, 503 Robert Grant Road, Silver Spring, MD 20910, USA.

Essential fatty acids have long been identified as possible oncogenic factors. Existing reports suggest omega-6 (omega-6) essential fatty acids (EFA) as pro-oncogenic and omega-3 (omega-3) EFA as anti-oncogenic factors. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells while the omega-6 fatty acids induces growth of these cells in animal models and cell lines. In order to explore likely mechanisms for the modulation of breast cancer cell growth by omega-3 and omega-6 fatty acids, we examined the effects of arachidonic acid (AA), linoleic acid (LA), EPA and DHA on human breast cancer cell lines using cDNA microarrays and quantitative polymerase chain reaction. MDA-MB-231, MDA-MB-435s, MCF-7 and HCC2218 cell lines were treated with the selected fatty acids for 6 and 24 h. Microarray analysis of gene expression profiles in the breast cancer cells treated with both classes of fatty acids discerned essential differences among the two classes at the earlier time point. The differential effects of omega-3 and omega-6 fatty acids on the breast cancer cells were lessened at the late time point. Data mining and statistical analyses identified genes that were differentially expressed between breast cancer cells treated with omega-3 and omega-6 fatty acids. Ontological investigations have associated those genes to a broad spectrum of biological functions, including cellular nutrition, cell division, cell proliferation, metastasis and transcription factors etc., and thus presented an important pool of biomarkers for the differential effect of omega-3 and omega-6EFAs.

R.B.

12-03-2008, 04:35 AM

Changing your Omega 3 6 intake shows up quite quickly in breast tissue (3 months).

It take about 680 day to change half of your adipose fat.

Fats in blood change quite quickly but still reflect stored Omega 6.

The body heavily stores Omega 6 (Omega 6 is 3-30% of body fat dependent on the amount in the diet) but stores very little Omega 3 (Omega 3 is usually under 1% of body fat and in the West often a fraction of a percent).

Omega 6 increases the risk of cancer and Omega 3s reduce the risk of cancer.

Does concentration of Omega 6 in the breast where the diet is high in Omega 6 could explain why breasts are more susceptible to cancer than part of the body that are less reliant on Omega 3 and 6..

These patients were given 1.8 gram EPA and 1.2 grams DHA a day. The full trial is free.

http://jnci.oxfordjournals.org/cgi/reprint/89/15/1123

Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer.
Bagga D, Capone S, Wang HJ, Heber D, Lill M, Chap L, Glaspy JA.

Department of Medicine, School of Medicine, University of California at Los Angeles, 90095-6956, USA.

BACKGROUND: Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found in corn and safflower oils, can act as precursors for intermediates involved in the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these effects. The effects of dietary intervention on the ratios of these fatty acids in breast and other adipose tissues have not previously been prospectively studied. PURPOSE: The present investigation was conducted to study the impact on the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in adipose tissue of the breast and buttocks when women with breast cancer consume a low-fat diet and fish oil supplements. METHODS: Twenty-five women with high-risk localized breast cancer were enrolled in a dietary intervention program that required them to eat a low-fat diet and take a daily fish oil supplement throughout a 3-month period. Breast and gluteal fat biopsy specimens were obtained from each woman before and after dietary intervention. The fatty acid compositions of specimens of plasma, breast fat, and gluteal fat were determined by gas-liquid chromatography. Statistical analysis involved use of a two-sided paired t test. RESULTS: After dietary intervention, a reduction in the level of total omega-6 polyunsaturated fatty acids in the plasma was observed (P<.0003); moreover, total omega-3 polyunsaturated fatty acids increased approximately three-fold (P<.0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41; P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast adipose tissue was observed following dietary intervention (P = .04); the omega-3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to 0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was observed in gluteal adipose tissue following the intervention (P = .05); however, the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of 0.036-0.045; P = .06) was unchanged. CONCLUSION: Short-term dietary intervention can lead to statistically significant increases in omega-3/omega-6 polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast adipose tissue changed more rapidly than gluteal adipose tissue in response to the dietary modification tested in this study. Therefore, gluteal adipose tissue may not be a useful surrogate to study the effect of diet on breast adipose tissue.

R.B.

12-09-2008, 04:05 PM

This is technical and relates to pancreatic cancer and not BC (although it mentions it) and posted for specialists who keep an eye on this thread if any.

But the pathways under discussion are so basic there is undoubtedly some communality, as in the impact of COX blockers like aspirin in BC.

Linoleic acid is the plant based Omega 6.

A way of reducing Omega 6 COX and LOX activity is not to eat excess Omega 6 in the first place, and Omega 3 DHA has been shown to be a natural COX blocker.

The article gives an idea as to how widespread the effects of the products of Omega 6 are.

Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer
Xian-Zhong Ding,1 Rene Hennig,1 and Thomas E Adriancorresponding author1
1Department of Surgery and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Tarry 4-711, Chicago, IL 60611, U.S.A

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=149414

"COX and LOX metabolism of linoleic and arachidonic acids leads to the formation of a variety of metabolically active products with different roles in carcinogenesis. Our understanding of these roles is steadily increasing. This new information is providing a theoretical basis for development of new cancer chemoprevention approaches targeted to COX and LOX activity."

R.B.

12-22-2008, 05:09 PM

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China.
Shannon J, King IB, Lampe JW, Gao DL, Ray RM, Lin MG, Stalsberg H, Thomas DB.

Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR.

BACKGROUND: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes. OBJECTIVES: The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. DESIGN: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. RESULTS: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons. CONCLUSION: Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

R.B.

01-09-2009, 07:15 AM

ALA is the plant based Omega 3.

Nuts are high in Omega 6, as are many processed foods.

Processed foods may also contain oxidised fats, and be low on antioxidants.

Fruit and veg contain antioxidants.

Again the trial generally underlines the importance of diet.

RB

1: Int J Cancer. 2009 Feb 15;124(4):924-31.Click here to read Links
Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer.
ThiÃ©baut AC, ChajÃ¨s V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, Riboli E, BÃ©nichou J, Clavel-Chapelon F.

INSERM, ERI-20, Institut Gustave Roussy, Villejuif Cedex, France.

Experimental studies suggest detrimental effects of omega-6 polyunsaturated fatty acids (PUFA), and beneficial effects of omega-3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow-up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with alpha-linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between omega-6 and long-chain omega-3 PUFAs, with breast cancer risk inversely related to long-chain omega-3 PUFAs in women belonging to the highest quintile of omega-6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk.

R.B.

01-23-2009, 04:26 PM

Role of fatty acids in malignancy and visual impairment: epidemiological evidence and experimental studies.
Tsubura A, Yuri T, Yoshizawa K, Uehara N, Takada H.

Department of Pathology II, Kansai Medical University, Takii Hospital, Moriguchi, Osaka, Japan. tsubura@takii.kmu.ac.jp

International variation in breast and colon cancer incidence is positively related to total fat intake. However, total fat consists of different fatty acid families, e.g., saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-3 and n-6 polyunsaturated fatty acids (PUFAs). Epidemiological evidence and experimental studies suggest that these fatty acid families have different effects on breast and colon carcinogenesis. Therefore the action of each fatty acid on carcinogenesis should be evaluated separately. Although it is difficult to establish firm conclusions on the effect of each fatty acid in human epidemiological studies, experimental studies on animals and cultured cells suggest that n-6 PUFAs (linoleic acid and arachidonic acid) may have a tumor promoting effect, while n-3 PUFAs (eicosapentaenoic acid, docosahexaenoic acid and alpha-linolenic acid) and conjugated fatty acids (CFAs; a mixture of positional and geometric isomers of PUFAs with conjugated double bonds) exert an inhibitory effect on tumor growth. SFAs such as palmitic acid and stearic acid show little or no tumor promoting effect, and the action of oleic acid, a MUFA, is inconclusive. In addition to regulation of abnormal cell growth seen in cancers, fatty acids also control cell loss seen in degenerative eye diseases, such as degeneration of lens material in cataract and degeneration of photoreceptor cells in retinitis pigmentosa. Experiments suggest that n-6 PUFAs cause deleterious effects, while n-3 PUFAs result in beneficial effects on the lens and retina. In particular, docosahexaenoic acid is known to be effective in rescuing photoreceptor cells from damage. Thus, understanding the function of each fatty acid is likely to be important for making progress in treating these and other diseases.

R.B.

01-28-2009, 03:40 PM

To correlate breast cancer outcomes with Omega 3: tissue status you arguably need to look at breast fat at the time of biopsy.

This trial suggests central adipose tissue is not a good marker. Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer. (below)

Adipose buttock tissue saves fats differently again and tends to accumulate more Omega 3 and 6, and significant changes are seen in 3 months. http://www.ncbi.nlm.nih.gov/pubmed/11489728

Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer.

For me this throws into question Omega 3:6 trials on breast cancer looking a buttock fat after the event. http://jnci.oxfordjournals.org/cgi/reprint/85/10/785

Fatty Acid Composition of the Subcutaneous
Adipose Tissue and Risk of Proliferative
Benign Breast Disease and Breast Cancer

Breasts are designed to make milk so probably have fat accumulation and conversion rules all of their own, which might make them more susceptible to fat imbalances (more reading required when I have time).

http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=81227

Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer.

BACKGROUND: Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found in corn and safflower oils, can act as precursors for intermediates involved in the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these effects. The effects of dietary intervention on the ratios of these fatty acids in breast and other adipose tissues have not previously been prospectively studied. PURPOSE: The present investigation was conducted to study the impact on the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in adipose tissue of the breast and buttocks when women with breast cancer consume a low-fat diet and fish oil supplements. METHODS: Twenty-five women with high-risk localized breast cancer were enrolled in a dietary intervention program that required them to eat a low-fat diet and take a daily fish oil supplement throughout a 3-month period. Breast and gluteal fat biopsy specimens were obtained from each woman before and after dietary intervention. The fatty acid compositions of specimens of plasma, breast fat, and gluteal fat were determined by gas-liquid chromatography. Statistical analysis involved use of a two-sided paired t test. RESULTS: After dietary intervention, a reduction in the level of total omega-6 polyunsaturated fatty acids in the plasma was observed (P less than .0003); moreover, total omega-3 polyunsaturated fatty acids increased approximately three-fold (P less than .0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41; P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast adipose tissue was observed following dietary intervention (P = .04); the omega-3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to 0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was observed in gluteal adipose tissue following the intervention (P = .05); however, the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of 0.036-0.045; P = .06) was unchanged. CONCLUSION: Short-term dietary intervention can lead to statistically significant increases in omega-3/omega-6 polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast adipose tissue changed more rapidly than gluteal adipose tissue in response to the dietary modification tested in this study. Therefore, gluteal adipose tissue may not be a useful surrogate to study the effect of diet on breast adipose tissue.

R.B.

01-28-2009, 03:48 PM

Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer.
Bagga D, Anders KH, Wang HJ, Glaspy JA.

Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095, USA.

Animal studies suggest that dietary polyunsaturated fatty acids (PUFAs) of the n-6 class, found in corn and safflower oils, may be precursors of intermediates involved in the development of mammary tumors, whereas long-chain (LC) n-3 PUFAs, found in fish oil, can inhibit these effects. This case-control study was designed to examine the relationship between the PUFA composition of breast adipose tissue and the risk of breast cancer. Using fatty acid levels in breast adipose tissue as a biomarker of past qualitative dietary intake of fatty acids, we examined the hypothesis that breast cancer risk is negatively associated with specific LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) and positively associated with n-6 PUFAs (linoleic acid and arachidonic acid). Breast adipose tissue was collected from 73 breast cancer patients and 74 controls with macromastia. The fatty acid levels were determined by gas-liquid chromatography. A logistic regression model was used to obtain odds ratio estimates while adjusting for age. The age-adjusted n-6 PUFA (linoleic acid and arachidonic acid) content was significantly higher in cases than in controls (P = 0.02). There was a trend in the age-adjusted data suggesting that, at a given level of n-6 PUFA, LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) may have a protective effect (P = 0.06). A similar inverse relationship was observed with LC n-3-to-n-6 ratio when the data were adjusted for age (P = 0.09). We conclude that total n-6 PUFAs may be contributing to the high risk of breast cancer in the United States and that LC n-3 PUFAs, derived from fish oils, may have a protective effect.

R.B.

01-28-2009, 03:49 PM

N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France.
Maillard V, Bougnoux P, Ferrari P, Jourdan ML, Pinault M, LavillonniÃ¨re F, Body G, Le Floch O, ChajÃ¨s V.

Laboratoire de Biologie des Tumeurs, Clinique d'Oncologie-RadiothÃ©rapie, Service de GynÃ©cologie-ObstÃ©trique, E.A. 2103, UnitÃ© de Recherche AssociÃ©e UniversitÃ©-INRA, CHU, Tours, France.

Experimental studies have indicated that n-3 fatty acids, including alpha-linolenic acid (18:3 n-3) and long-chain n-3 polyunsaturated fatty acids inhibit mammary tumor growth and metastasis. Earlier epidemiological studies have given inconclusive results about a potential protective effect of dietary n-3 polyunsaturated fatty acids on breast cancer risk, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis that n-3 fatty acids protect against breast cancer, we examined the fatty acid composition in adipose tissue from 241 patients with invasive, nonmetastatic breast carcinoma and from 88 patients with benign breast disease, in a case-control study in Tours, central France. Fatty acid composition in breast adipose tissue was used as a qualitative biomarker of past dietary intake of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Unconditional logistic regression modeling was used to obtain odds ratio estimates while adjusting for age, height, menopausal status and body mass index. We found inverse associations between breast cancer-risk and n-3 fatty acid levels in breast adipose tissue. Women in the highest tertile of alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39 (95% confidence intervals [CI] = 0.19-0.78) compared to women in the lowest tertile (trend p = 0.01). In a similar way, women in the highest tertile of docosahexaenoic acid (22:6 n-3) had an odds ratio of 0.31 (95% CI = 0.13-0.75) compared to women in the lowest tertile (trend p = 0.016). Women in the highest tertile of the long-chain n-3/total n-6 ratio had an odds ratio of 0.33 (95% confidence interval = 0.17-0.66) compared to women in the lowest tertile (trend p = 0.0002). In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n-3 fatty acids on breast cancer risk and support the hypothesis that the balance between n-3 and n-6 fatty acids plays a role in breast cancer. Copyright 2001 Wiley-Liss, Inc.

R.B.

01-28-2009, 04:00 PM

Not as certain as looking at breast tissue but interesting none the less.

A prospective study of association of monounsaturated fat and other types of fat with risk of breast cancer.
Wolk A, BergstrÃ¶m R, Hunter D, Willett W, Ljung H, Holmberg L, Bergkvist L, Bruce A, Adami HO.

Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.

BACKGROUND: Animal studies suggest that monounsaturated and polyunsaturated fat may have opposite effects on the risk of breast cancer. METHODS: We performed a population-based prospective cohort study, including 61,471 women aged 40 to 76 years from 2 counties in central Sweden who did not have any previous diagnosis of cancer; 674 cases of invasive breast cancer occurred during an average follow-up of 4.2 years. All subjects answered a validated 67-item food frequency questionnaire at baseline. Cox proportional hazards models were used to obtain adjusted rate ratio (RR) estimates with 95% confidence intervals (CIs). RESULTS: After mutual adjustment of different types of fat, an inverse association with monounsaturated fat and a positive association with polyunsaturated fat were found. The RR for each 10-g increment in daily intake of monounsaturated fat was 0.45 (95% CI, 0.22-0.95), whereas the RR for a 5-g increment of polyunsaturated fat was 1.69 (95% CI, 1.02-2.78); the increments correspond to approximately 2 SDs of intake in the population. Comparing the highest quartile of intake with the lowest, we found an RR of 0.8 (95% CI, 0.5-1.2) for monounsaturated fat and 1.2 (95% CI, 0.9-1.6) for polyunsaturated fat. Saturated fat was not associated with the risk of breast cancer. CONCLUSIONS: Our results indicate that various types of fat may have specific opposite effects on the risk of breast cancer that closely resemble the corresponding effects in experimental animals. Research investigations and health policy considerations should take into account the emerging evidence that monounsaturated fat might be protective for risk of breast cancer.

R.B.

01-28-2009, 04:04 PM

Off the track of Omega 3s and 6s but interesting that increased protein decreased risk significantly. It would be interesting to see the whole paper to get a better idea what was going on in their diet, what sort of protein, how it related to fats carbs Omega 3 and 6s etc.

Dietary factors and survival from breast cancer.
Author: Rohan, T E : Hiller, J E : McMichael, A J
Citation: Nutr-Cancer. 1993; 20(2): 167-77

The association between self-reported intake of various dietary factors at diagnosis and survival from breast cancer was studied in a population-based cohort of breast cancer patients in Adelaide, South Australia. These patients had been recruited between 1982 and 1984 into a case-control study of diet and incident breast cancer. Of the 451 patients recruited originally, 412 were followed for a median interval of 5.5 years. There were decreases in the risk of death from breast cancer ranging from 25 to 40% at all levels of energy and protein intake above the baseline, whereas for fat intake there was a 40% increase in risk at the uppermost quintile level. There was also some reduction in risk at the upper levels of intake of beta-carotene and vitamin C. However, there were no dose-dependent variations in risk of death by level of intake for any of the dietary factors studied, and most of the variation in risk that was observed was relatively insubstantial.

R.B.

02-27-2009, 04:44 PM

Melatonin is an very powerful antioxidant and is an Omega 6 inflammatory chemical blocker.

Found as usual whilst looking for something else.(-:

Melatonin production in general terms falls post menopause. Obesity and poor sleep are associated with lower melatonin.

Application of melatonin improved mood and reduced depression in post menopausal women.

Depressed melatonin has been noted in some cancers.

Melatonin
By S. R. Pandi-Perumal, Daniel P. Cardinali
http://books.google.com/books?id=m_6okSRjzloC&printsec=frontcover&dq=Melatonin++By+S.+R.+Pandi-Perumal,+Daniel+P.+Cardinali&ei=hXyoSaSaEZbCyQT3obHbDg&client=firefox-a#PPR7,M1

RB

http://cancerres.aacrjournals.org/cgi/content/abstract/65/23/11174

Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats

The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Exposure of rats bearing rat hepatomas or human breast cancer xenografts to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 ÂµW/cm2) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 ÂµW/cm2 (i.e., 2,800 lx). Compared with tumors perfused with daytime-collected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers.

David E. Blask1, George C. Brainard2, Robert T. Dauchy1, John P. Hanifin2, Leslie K. Davidson1, Jean A. Krause1, Leonard A. Sauer1, Moises A. Rivera-Bermudez3, Margarita L. Dubocovich3, Samar A. Jasser2, Darin T. Lynch1, Mark D. Rollag4 and Frederick Zalatan1

1 Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, New York; 2 Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania; 3 Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and 4 Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland

Requests for reprints: David E. Blask, Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, NY 13326. Phone: 607-547-3677;

R.B.

02-28-2009, 06:00 AM

Oops accidentally deleted.

Sorry

RB

R.B.

04-01-2009, 12:29 PM

Fatty acid facts, part II: Role in the prevention of carcinogenesis, or, more fish on the dish?
Pauwels EK, Kairemo K.

Pisa University Medical School, Pisa, Italy. ernestpauwels@gmail.com.

Many laboratory studies suggest that n-3 fatty acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antitumor effects. The mechanisms involved in their anticarcinogenic action include the suppression of the biosynthesis of proinflammatory molecules, the influence on transcription factor activity and gene expression, the influence on signal transduction, the alteration of hormone-stimulated cell growth and the suppression of the production of free radicals and reactive oxygen species. In general, n-6 fatty acids and their derivatives promote the production of proinflammatory eicosanoids, whereas n-3 fatty acids suppress this action. The encouraging preclinical results are only scarcely confirmed in reviews and meta-analysis of epidemiological data roughly published before 2005. However, around 2005, the first reports on epidemiological studies based on the assessment of the concentration of EPA and DHA in the erythrocyte cell membrane in individual study participants started to appear. Without exception, these publications demonstrate that higher EPA (and possibly DHA) concentrations in the cell membrane, a validated measure for plasma fatty acids, is associated with lower cancer risk. These intriguing results are confirmed by the recently published huge European Prospective Investigation into cancer and nutrition (N = 478,040 men and women) and U.S.-based Physicians Health Study (N = 22,071 men). These studies have unequivocally confirmed that fish intake has a favorable effect on cancer risk . This review aims to elucidate the various mechanisms by which n-3 fatty acids may affect the process of carcinogenesis. For this summary of knowledge, we focus on the effects of n-3 intake on the risk of breast cancer, prostate cancer and colorectal cancer. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

julierene

04-02-2009, 07:16 AM

This all talks about cancer risk. But what about actually killing cancer cells?

R.B.

04-03-2009, 03:25 AM

***** Five star in terms of being a thought provoking trial - and it was in 1985 !!

Interestingly in rats the risk of developing a mammary tumour were proportionally related to the level of Omega 6 LA intake between 0.5% and 4.4% and after that the risk did not increase.

In the rats the lower the intake of Omega six the lower the risk of tumours developing. Once the level of Omega six reached about 4 1/2% the extra Omega six had little additional effect. Whilst you cannot translate this directly as being applicable in humans there is evidence that tribes on non-western diets are very healthy and relatively free of western conditions on Omega six intakes of under 1%.

The diets in the rats in the trial were very low in Omega 3. This trial adds to the suggestion that our Omega 6 intake requirement is low and that Omega 6 intake in the absence of Omega 3 at low levels is implicated in the increased risk of cancer. There are other trials that suggest that it is essential to balance the Omega three and six plant-based fats even if the intake of Omega six is very low.

At low intake levels there were even difficulties in inducing cancer, and it was necessary to apply a second dose of a cancer producing agent.The trial is called “Requirement of Essential Fatty Acid for Mammary Tumorigenesis in the Rat” and can be found on FREE the web http://www.ncbi.nlm.nih.gov/pubmed/3921234.

I have to thank Stephan of the Whole Health blog for finding it.

http://wholehealthsource.blogspot.com/search/label/cancer

I highly recommend his excellent and thought provoking dietary blogs.

ABSTRACT

Requirement of essential fatty acid for mammary tumorigenesis in the rat.
Ip C, Carter CA, Ip MM.

In an attempt to determine the requirement of essential fatty acid for dimethylbenz(a)anthracene-induced mammary tumorigenesis, rats were fed diets containing different levels of linoleate: 0.5, 1.1, 1.7, 2.2, 3.5, 4.4, 8.5, or 11.5%. Each diet contained 20% of fat by weight, with varying amounts of coconut oil and corn oil added to achieve the desired levels of linoleate. Mammary tumorigenesis was very sensitive to linoleate intake and increased proportionately in the range of 0.5 to 4.4% of dietary linoleate. Regression analysis indicated that a breakpoint occurred at 4.4%, beyond which there was a very poor linear relationship, suggesting the possibility of a plateau. From the intersection of the regression lines in both the upper and lower ranges, the level of linoleate required to elicit the maximal tumorigenic response was estimated to be around 4%. The differences in tumor yield could not be correlated with changes in prostaglandin E concentration in the mammary fat pads of normal animals maintained on similar diets, suggesting that linoleate may act by some other mechanism to stimulate mammary tumorigenesis.

Unregistered

04-03-2009, 07:41 AM

So how do you suggest we get our Omega 6 level to 4.4%?

R.B.

04-03-2009, 01:50 PM

Hi unregistered,

This is a trial on rats and not people. however there's evidence in humans that the ideal Omega six intake is somewhere between a 1/2 and 2%. It is however a subject of considerable debate amongst the experts, some suggest 1% some suggest 3%.

The primary source of plant-based 18 carbon Omega six are the vegetable oils that are commonly used in processed foods, like the sunflower, soy, safflower, grape seed, corn etc. They are found almost everywhere in the manufactured food chain.

We also feed our livestock with grain. This distorts their Omega 3:6 profile. the more the grain they eat the worse the impact. So chickens and industrial eggs have surprisingly high levels of Omega Six. Grass fed animals have better profiles. True free range farmyard eggs are good if you can find them.

A diet of fish and shellfish and vegetables as a core would be a good start. Shellfish are an excellent source of minerals. If that is not possible use meat that has been grass grazed, lamb for example, or range grazed cattle. Dried seaweed is a good source of a wide range of minerals. Use only small amounts of low Omega six oils e.g. olive or macadamia. Use butter rather than vegetable-based spreads. Choose nuts that are low in Omega six. If you use soy products check the label to see if they contain Omega sixes. Always check the label on processed and packaged foods, which generally means they go back on the shelf. (-:. Ensure that you get a supply of the plant-based 18 carbon Omega three by including a small amount of flax oil or flaxseed. Eat lots of dark green vegetables, a moderate intake of nutrient dense fruits, bone broths, organ meats, etc.

Omega three EPA and DHA will help offset the inflammatory and other effects of excess Omega six. The cheapest way to do that is through a good quality bottled fish oil.

I am just finishing a revised copy of my book that looks at how as well as why. The Ultimate Omega-3 Diet by Evelyn Tribole is quite helpful on the how.

R.B.

04-15-2009, 09:03 AM

Interesting links between melatonin and plant based Omega 6 linoleic acid.

Melatonin is a COX blocker by various mechanisms.

COX blockers have also been shown to reduce risks of BC

Rich also has a melatonin thread.
http://her2support.org/vbulletin/showthread.php?t=31403

In my book I propose a theory that Melatonin brings sleep about by closing down the Omega 6 pathways and opening the Omega 3 pathways. The consequence is that if you have Omega 3:6 imbalances and lack long chain Omega 3 you will sleep less well.

These trial confirm a link between melatonin and Omega 6.

Melatonin uptake and growth prevention in rat hepatoma 7288CTC in response to dietary melatonin: melatonin receptor-mediated inhibition of tumor linoleic acid metabolism to the growth signaling molecule 13-hydroxyoctadecadienoic acid and the potential role of phytomelatonin*

David E. Blask1, Robert T. Dauchy, Leonard A. Sauer and Jean A. Krause

Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, One Atwell Road, Cooperstown, NY 13326, USA

Both physiological and pharmacological levels of the pineal hormone melatonin exhibit substantial anticancer activity in tissue-isolated rat hepatoma 7288CTC via melatonin receptor-mediated blockade of tumor uptake of linoleic acid (LA) and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin is also present in significant amounts in edible plants and is supplied in nutritional supplements. We confirmed the presence of significant quantities of melatonin in 20 varieties of edible plants. In pinealectomized tumor-free rats, 3 weeks of ingestion of either 5 or 50 Âµg/day of melatonin contained in a semi-purified diet resulted in a dose-dependent elevation in steady-state plasma melatonin levels within the nocturnal physiological range. In pineal-intact tumor-bearing rats, the daily intake of 5 Âµg/day of melatonin for 3 weeks resulted in an enhanced amplitude and duration of the nocturnal melatonin levels within physiological circulating limits. The nocturnal melatonin amplitude in rats ingesting 500 ng of melatonin/day remained within the physiological range. A dose-related increase in tumor concentrations of melatonin occurred in animals ingesting melatonin from the diet. Perfusion of tumors in situ with physiological, nocturnal blood levels of melatonin resulted in a mean 31% uptake and retention of the melatonin. Chronic ingestion of 50 ng, 500 ng or 5 Âµg of melatonin/day supplied in a semi-purified 5% corn oil diet led to a significant dose-dependent reduction in the rates of tumor total fatty acid uptake, LA uptake, 13-HODE production and tumor growth. The co-ingestion of melatonin receptor antagonist S20928 completely blocked the effects and prevented the intra-tumoral accumulation of melatonin. Melatonin receptor-mediated suppression of tumor growth, LA uptake and metabolism, and stimulation of tumor melatonin uptake and retention in response to the dietary intake of phytomelatonin from edible plants or melatonin from nutritional supplements, could play an important role in cancer growth prevention.

Effect of Melatonin and Linolenic Acid on Mammary Cancer in Transgenic Mice with c-neu Breast Cancer Oncogene

Ghanta N. Rao, Elizabeth Ney and Ronald A. Herbert

Abstract Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of a MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000) and some retinoid analogues have been shown to significantly delay the development of mammary cancer in the TG.NK model. Four-week-old hemizygous TG.NK female mice with MMTV/c-neu oncogene fed NTP-2000 diet were gavaged with 0.05â€“0.2thinspml of flaxseed oil as the source of ohgr-3 rich PUFA, or melatonin at 50â€“200thinspmg/kg or a combination of 0.10thinspml flaxseed oil and 50thinspmg/kg melatonin in a gavage volume of 0.2thinspml per mouse with corn oil as the vehicle for 30 weeks. The time course of the mammary tumor incidence pattern was advanced by flaxseed oil compared to the control. At the high dose (0.2thinspml) of flaxseed oil, when the ohgr-6: ohgr-3 PUFA ratio was closer to 1, there was some delay in the growth of mammary tumors. Melatonin delayed the appearance of palpable tumors and the growth of the tumors with a dose-related statistically significant negative trend for the incidence of tumors. The combination of flaxseed oil and melatonin caused a significant decrease in the number of tumors and tumor weight per mouse compared to the control and to flaxseed oil but not to melatonin alone. Flaxseed oil may delay the growth of mammary tumors if the ohgr-6:ohgr-3 PUFA ratio of fat consumed is closer to 1. Melatonin has the potential to markedly delay the appearance of palpable mammary tumors. Studies are in progress with the TG.NK mouse model to understand the histological and molecular changes associated with the dose-response pattern of mammary tumor incidence and growth after treatment with a broad range of doses of melatonin.

New Actions of Melatonin on Tumor Metabolism and Growth
DavidE. Blask, LeonardA. Sauer, RobertT. Dauchy, EugeneW. Holowachuk, MaryS. Ruhoff

Bassett Research Institute, Mary Imogene Bassett Hospital, Cooperstown, N.Y., USA

Melatonin is an important inhibitor of cancer growth promotion while the essential polyunsaturated fatty acid, linoleic acid is an important promoter of cancer progression. Following its rapid uptake by tumor tissue, linoleic acid is oxidized via a lipoxygenase to the growth-signaling molecule, 13-hydroxyoctadecadienoic acid (13-HODE) which stimulates epidermal growth factor (EGF)-dependent mitogenesis. The uptake of plasma linoleic acid and its metabolism to 13-HODE by rat hepatoma 7288CTC, which expresses both fatty acid transport protein and melatonin receptors, is inhibited by melatonin in a circadian-dependent manner. This inhibitory effect of melatonin is reversible with either pertussis toxin, forskolin or cAMP. While melatonin inhibits tumor linoleic acid uptake, metabolism and growth, pinealectomy or constant light exposure stimulates these processes. Thus, melatonin and linoleic acid represent two important environmental signals that interact in a unique manner to regulate tumor progression and ultimately the host-cancer balance.

R.B.

04-21-2009, 07:37 AM

Full paper available free.

http://www.ajcn.org/cgi/reprint/79/6/935

Dietary long-chain n3 fatty acids for the prevention of cancer:
a review of potential mechanisms1–3
Susanna C Larsson, Maria Kumlin, Magnus Ingelman-Sundberg, and Alicja Wolk
ABSTRACT
Increasing evidence from animal and in vitro studies indicates that n3 fatty acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, present in fatty fish and fish oils inhibit carcinogenesis. The epidemiologic data on the association between fish consumption, as a surrogate marker for n3 fatty acid intake, and cancer risk are, however, somewhat less consistent. This review highlights current knowledge of the potential mechanisms of the anticarcinogenic actions of n3 fatty acids.Moreover, a possible explanation of why some epidemiologic studies failed to find an association between n3 fatty acid intake and cancer risk is provided. Several molecular mechanisms whereby n3 fatty acids may modify the carcinogenic process have been proposed. These include suppression of arachidonic acid– derived eicosanoid biosynthesis; influences on transcription factor activity, gene expression, and signal transduction pathways; alteration of estrogen metabolism; increased or decreased production of free radicals and reactive oxygen species; and mechanisms involving insulin sensitivity and membrane fluidity. Further studies are needed to evaluate and verify these mechanisms in humans to gain more understanding of the effects of n3 fatty acid intake on cancer
risk. Am J Clin Nutr 2004;79:935– 45.

R.B.

04-21-2009, 07:43 AM

http://aje.oxfordjournals.org/cgi/reprint/147/4/342

Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer.
Simonsen N, van't Veer P, Strain JJ, Martin-Moreno JM, Huttunen JK, Navajas JF, Martin BC, Thamm M, Kardinaal AF, Kok FJ, Kohlmeier L.

University of North Carolina, Chapel Hill 27599, USA.

The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992) was used to explore the hypothesis that fatty acids of the omega-3 family inhibit breast cancer and that the degree of inhibition depends on background levels of omega-6 polyunsaturates. Considered in isolation, the level of omega-3 or omega-6 fat in adipose tissue displayed little consistent association with breast cancer across study centers. The ratio of long-chain omega-3 fatty acids to total omega-6 fat showed an inverse association with breast cancer in four of five centers. In Malaga, Spain, the odds ratio for the highest tertile relative to the lowest reached 0.32 (95% confidence interval 0.13-0.82). In this center, total omega-6 fatty acid was strongly associated with breast cancer. With all centers pooled, the odds ratio for long-chain omega-3 to total omega-6 reached 0.80 for the second tertile and 0.65 for the third tertile, a downward trend bordering on statistical significance (p for trend = 0.055). While not definitive, these results provide evidence for the hypothesis that the balance between omega-3 and omega-6 fat may play a role in breast cancer.

R.B.

05-12-2009, 07:19 AM

1: J Nutr Biochem. 2009 Apr 13. [Epub ahead of print]Click here to read Links
Docosahexaenoic acid induces proteasome-dependent degradation of estrogen receptor alpha and inhibits the downstream signaling target in MCF-7 breast cancer cells.
Lu IF, Hasio AC, Hu MC, Yang FM, Su HM.

Department of Physiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.

About two thirds of breast cancers in women are hormone-dependent and require estrogen for growth, its effects being mainly mediated through estrogen receptor alpha (ERalpha). Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) have opposite effects on carcinogenesis, with DHA suppressing and AA promoting tumor growth both in vitro and in vivo. However, the mechanism is not clear. Here, we examined whether the effect is mediated through changes in ERalpha distribution. MCF-7 cells, an ERalpha-positive human breast cancer cell line, was cultured in estrogen-free medium containing 0, 10 or 60 muM DHA or AA, then were stimulated with estradiol. DHA supplementation resulted in down-regulation of ERalpha expression (particularly in the extranuclear fraction), a reduction in phosphorylated MAPK, a decrease in cyclin D1 levels and an inhibition in cell viability. In contrast, AA had no such effects. The DHA-induced decrease in ERalpha expression resulted from proteasome-dependent degradation and not from decreased ERalpha mRNA expression. We propose that breast cancer cell proliferation is inhibited by DHA through proteasome-dependent degradation of ERalpha, reduced cyclin D1 expression and inhibition of MAPK signaling.

Andrea Barnett Budin

05-12-2009, 10:19 AM

HELLO RB! I think of you so often. Truly. I hope you are well.

I just received your most recent post re Omega 3's anti-inflammatory and anti-proliferative benefits. I take my Omega 3's faithfully every day.

I believe the fact that I am 64 and have been blessed with joint muscle or joint pain, no arthritis or rhumitoid ailments is attributable to my Omega intake. Of course I try to eat as much salmon (fresh caught, not farm raised) as I can.

Perhaps you could refresh our minds as to the foods that are rich in Omega 3s. IT IS ALL THE RAGE THESE DAYS. EXPERTS GALORE TOUTING IT. YOUR BOOK IS A WONDERFUL ADDITION TO OUR WORLD OF UNDERSTANDING THE MULTIPLE AND IMPERATIVE BENEFITS DERIVED FROM OMEGA 3. (They even have it advertised on dog foods. Those of us who love our pets are anxious for them know the wondrous effects of this recent discovery.)

BTW, PLEASE REMIND US ALL OF THE NAME OF YOUR BOOK, AND WHERE WE CAN PURCHASE IT.

And, if you have any info to share re the anti-inflammatory properties that might explain my pain-free muscles/joints, etc. -- please enlighten us!

I saw my endocrinologist the other day. She is young and fabulously brilliant and she was wearing a brace on her wrist. It's a carpal tunnel thing she explained when I asked. I whispered -- TAKE OMEGA 3! She has spoken of this, along w/the need for us to check out our magnesium bld counts and our Vitamin D bld counts.

Many on this board suffer from pain in muscles and joints. Have carpal tunnel issues. Many are aware of the need to take magnesium, selenium, and loads of Vitamin D.

I know you are in charge of keeping us up on the essential taking and eating of Omega 3s.

Stay well, my Friend! You are such a great addition to this board. A fund of information that is so very valuable. I pray your book will be as well received by us lay people as the experts have. You deserve the highest of kudos!

R.B.

05-13-2009, 03:07 PM

Hi Andi,

Very many thanks for your generous spirit and encouragement it is much appreciated.

I have been working on a new version for a year now, and I hope it will be finished in the next few months. The new version includes much more information on how to and is hopefully easier reading than the first book.

The subject is a passion. The book looks at Omega six which is the sibling of Omega three. It is excess Omega six that is responsible for the damage, and Omega three is the brake. A lack of Omega three compounds the excess Omega six.

These two fats alter the way the body works at the most fundamental cellular levels. They each produce families of highly influential chemicals. They are part of the cell membranes structure.

The imbalance of these fats arguably is a factor behind the increased risks of many Western conditions and cancers.

The chemical products of Omega six are highly inflammatory, and those of Omega three are largely anti-inflammatory. The long chain Omega three found in fish oil (DHA) is actually more effective as a inflammation blocker than many drugs NSAIDS, and without the side-effects.

I will of course let you all know when the new version is ready.

This is the Amazon.com link http://www.amazon.com/Omega-Six-Devils-Message-Dietary/dp/0955707404/ref=sr_1_1?ie=UTF8&s=books&qid=1242251624&sr=1-1

This is the Amazon.co.uk http://www.amazon.co.uk/Omega-Six-Devils-Fat-infertility/dp/0955707404/ref=sr_1_1?ie=UTF8&s=books&qid=1242251888&sr=1-1

It can also be ordered through book shops.

And this is the resource page of my WEB site. http://www.omegasixthedevilsfat.com/resources.aspx

R.B.

05-23-2009, 02:09 PM

Another article outlining why Omega 3 reduces the risk of BC and other cancers.

Please note the action on the Omega 6 COX2 pathways, which is what COX blocking drugs interrupt. Eating less Omega 6 and more long chain Omega 3 will reduce COX 2 activity.

Anticancer actions of omega-3 fatty acids--current state and future perspectives.
Wendel M, Heller AR.

Department of Physiology, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Germany. MartinaWendel@gmx.de

Omega-3 fatty acids (omega3-FA) were shown to attenuate growth and induce apoptosis in a variety of human cancer cell lines derived from colonic, pancreatic, prostate, and breast cancer. In addition, recent findings indicate that omega3-FA act synergistically with chemotherapeutic agents and may also be used to enhance tumour radiosensitivity. The mechanisms underlying the anti-tumour effects of omega3-FA are complex. Incorporation of omega3-FA in biological membranes alters the profile of lipid mediators generated during inflammatory reactions. Furthermore, omega3-FA act as ligands of nuclear peroxisome proliferator-activated receptors that attenuate transcription of NF-kappaB-dependent genes. Thereby, the cyclooxygenase-2/prostaglandin E(2)-dependent production of pro-angiogenic vascular endothelial growth factor and levels of anti-apoptotic bcl-2 and bcl-X(L) are decreased. Eicosanoid-independent pro-apoptotic pathways include enhanced lipid peroxidation, modulation of mitochondrial calcium homeostasis and enhanced production of reactive oxygen species as well as activation of p53. This review article will give a comprehensive overview over the pleiotropic actions of omega3-FA and will discuss the potential of omega3-FA and derivatives like conjugated eicosapentaenoic acid as important nutritional adjuvant therapeutics in the management of various human cancer diseases and the impact of nutritional omega-3 FA on cancer prevention.

R.B.

05-23-2009, 02:25 PM

I have long asked if Omega 6 has a role in HER2, and if herceptin somehow influences related pathways.

This trial proves Omega 6 product PGE2 has a role in HER2 by increasing HER" expression. It is saying a reduction on PGE2 expression = a reduction in HER2 expression.

PGE 2 is made from Omega 6. IF you do not have an excess of Omega 6 in your system you will not make so much PGE2.

DHA is a more effective COX2 (PGE2) blocker than many drugs.

This is an excellent blog and Stephan is currently looking at Omega 6 and heart disease, and you might find the background helpful. http://wholehealthsource.blogspot.com/

RB

Free Access
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19399184

AND within the paper

"As positive control for COX2 downregulation, cells were treated with the COX2-specific inhibitor CelecoxibÂ® at 20 and 40 ÂµM for 48 hours. 40 ÂµM CelecoxibÂ® significantly inhibited PGE2 production by more than 80% (p<0.001). Consistent with a prior report that PGE2 influences HER2 expression [29], we found that reduction of HER2 correlated to a reduction in PGE2 synthesis (Figure 3B)."

t10c12 conjugated linoleic acid suppresses HER2 protein and enhances apoptosis in SKBr3 breast cancer cells: possible role of COX2.
Flowers M, Thompson PA.

Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA. mflowers@email.arizona.edu

BACKGROUND: HER2-targeted therapy with the monoclonal antibody trastuzumab (Herceptin) has improved disease-free survival for women diagnosed with HER2-positive breast cancers; however, treatment resistance and disease progression are not uncommon. Current data suggest that resistance to treatment in HER2 cancers may be a consequence of NF-kappaB overexpression and increased COX2-derived prostaglandin E2 (PGE(2)). Conjugated linoleic acid (CLA) has been shown to have anti-tumor properties and to inhibit NF-kappaB activity and COX2. METHODS: In this study, HER2-overexpressing SKBr3 breast cancer cells were treated with t10c12 CLA. Protein expression of the HER2 receptor, nuclear NF-kappaB p65, and total and phosphorylated IkappaB were examined by western blot and immunofluorescence. PGE(2) levels were determined by ELISA. Proliferation was measured by metabolism of 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and apoptosis was measured by FITC-conjugated Annexin V staining and flow cytometry. RESULTS/CONCLUSIONS: We observed a significant decrease in HER2 protein expression on western blot following treatment with 40 and 80 microM t10c12 CLA (p<0.01 and 0.001, respectively) and loss of HER2 protein in cells using immunoflourescence that was most pronounced at 80 microM. Protein levels of nuclear NF-kappaB p65 were also significantly reduced at the 80 microM dose. This was accompanied by a significant decrease in PGE(2) levels (p = 0.05). Pretreatment with t10c12 CLA significantly enhanced TNFalpha-induced apoptosis and the anti-proliferative action of trastuzumab (p = 0.05 and 0.001, respectively). These data add to previous reports of an anti-tumor effect of t10c12 CLA and suggest an effect on the HER2 oncogene that may be through CLA mediated downregulation of COX2-derived PGE(2).

R.B.

06-09-2009, 01:43 PM

R.B.

06-28-2009, 08:06 AM

More of the same. (-:

Profound is a word I like (-:

PGE 2 is a direct downstream product of Omega 6, and as above, increases HER2 expression.

PGE 2 is also connected with inflammation and the growth of new cells and blood vessels. If you eat less Omega 6, and reduce your intake below 4%, balance the plant based Omega 3 and 6 fats and get a gram or two of long chain Omega 3 DHA and EPA you will reduce your cancer risk profile.

Nobody makes any money out of telling you to eat LESS Omega 6, in fact the drugs companies would make a lot less, the food producers would have to reformulate most processed foods, margarine producers would be out of a job, and farmers would have to switch to other crops.

You cannot generally sell a negative diet recommendation that has no product attached. It is human nature industry will not be out there marketing eat less Omega 6, because it does not attract advertising budgets, or column inches in a world that takes comfort from being part of the pack. Those with the biggest financial interests would in the short term be shooting themselves in the foot.

In the long term they would be helping to create a healthier happier world and a more secure future for the species, but hey where does that appear on the big company corporate balance sheet, or in the way we value each other.

http://www.ncbi.nlm.nih.gov/pubmed/19493674?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential.
Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A.

Department of HPB and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, United Kingdom.

Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. This review explores the evidence and the mechanisms by which omega-3 FA may act as angiogenesis inhibitors and identifies opportunities for original research trialling omega-3 FAs as anti-cancer agents in humans. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases and beta-catenin.

Andrea Barnett Budin

06-28-2009, 10:59 AM

HELLO R.B... I take my Omega 3 EPA (2400) & DHA (1200) daily. Without fail. I watch my Omega 6 intake and try to supplement my supplements w/the right foods (rich in Omega 3). I totally get how out of proportion most diets are and the great benefits of doing all of the above.

In glancing through your book OMEGA SIX THE DEVIL'S FAT I read about many more good reasons to follow this course w/Omega 3's. Obviously on this site we are most concerned with the anti-cancer qualities in Omega 3.

But many of us suffer from muscle pain, arthritis and such. I do believe Omega 3 has anti-inflammatory characteristics that contribute to helping in this area as well as a host of others.

I would love if you would provide us with some info/studies on these, especially the common joint and muscle pain we experience (as side effects of our tx and as we age).

Thanks or keeping us AWARE, R.B.!!

Andi

Ellie F

06-28-2009, 11:51 AM

Hi all
Good to see some research from the UK on this important issue.
I have followed this thread with great interest.When I was diagnosed I, like most of us searched for an answer to the 'why me'question.The two things I came up with was a diet loaded with omega 6 processed foods, little omega 3 and a huge amount of stress in the two years before diagnosis.
I wonder if there is any evidence that the chemicals released under stress reduce the amount of omega 3 in the body??
Any views or research?
Ellie

chrisy

06-28-2009, 12:02 PM

[try to supplement my supplements w/the right foods]

Andi, I've always thought you were supposed to eat the right foods and supplement with supplements! Now I find out I've been doing it wrong all the time!!!

Unfortunately, the food tastes better than the supplements so that's gonna be hard to change!

Thanks for the smile:)

Andrea Barnett Budin

06-28-2009, 12:53 PM

Okay then Chrisy, Glad to make you smile! I laughed myself as I typed supplement my supplements. Laughter and humor are most essential to good health!

But, seriously, ever since Taxotere my stomach has never been the same. There are soooo many foods I simply cannot eat or I suffer the consequences (doubled over w/cramping and tummy somersaults, not to mention hrs of bathroom drama).

So just about every fruit, beans, corn, nuts, squash, slaw and on and on -- are DO NOT INGEST/Verboden to me. I am thrilled to be able to add the benefits of these vividly colored foods to my body through supplements. I truly am an excellent candidate for supplements. The good old fashioned way just doesn't work for me. My gullet doesn't love all the swallowing of pills, but my belly sure does.

I am a fresh caught salmon addict (this works). But I love my vitamins, however I can get them. I would much rather have a peach or a plum or a pear. Not so sure about pomegranate. But they are all included in my supplements, w/an array of berries, blah, blah.

ELLIE -- I have read of several studies that show that stress depletes us of T cells, which are immune system boosters. This leaves us unable to fight off a host of ailments and dysfunctions. It all begins with stress I think.

And since we cannot avoid stress (though some amazingly seem to thrive on it) I find deep breathing, meditation and guided imagery to be great tools to allow me to feel joyful and One With The Universe, even midst all my unwanted realities, which clearly suck... http://cdn-cf.aol.com/se/clip_art/gstres/thghts/smile

Andi

Ellie F

06-28-2009, 01:34 PM

Hi Andi
I was interested about the T cell issue especially as a lot of research is currently focusing on modifying patients own T cells then reintroducing them to fight bc.
It also seems reasonable to assume that as we age our immune system may not be as robust as before,so extra stress may tip it over the edge.
Ellie

R.B.

06-29-2009, 02:43 PM

Thanks Andi and Ellie for your support it is appreciated.

Andi said "But many of us suffer from muscle pain, arthritis and such."

(They know oestrogen allows people to make more DHA and testosterone reduces the ability to make DHA from looking at the effect of hormones on transsexuals.)

BASIC FACT. Omega 3 and Omega 6 must ultimately be got from food. The body can make all other fats from carbohydrates including Omega 9.

Long chain Omega 3 EPA and DHA are needed to balance the Omega 6s, as is very evident if you have read the previous posts. This is fundamental to the way the body functions and not just BC.

These are some mix and match excerpts from the revised version of my book which I am working on at the moment. I will post the refs separately.

"Women have a very special need for Omega 3 DHA, and can make much more of it from the plant based Omega 3 ALA than men.

Higher DHA in women gives them a different brain structure. DHA is a big factor in the control of their hormone levels, makes their skin and hair softer, affects their metabolism, improves their sensory perception, and makes women think and behave differently.

This all happens because oestrogen allows women to convert 10-20 times more of the plant fat Omega 3 ALA to DHA than men. Oestrogen increases production of DHA. Women make 10 - 20 times as much DHA as men. DHA defines women behaviourally, structurally, and hormonally. Women have a very fundamental relationship with the Omega 3s, and particularly EPA and DHA.

A consequence of oestrogen blockers or ovarian removal, will likely be that the increased levels of conversion of Omega 3 ALA to DHA, due to higher oestrogen in women, will not occur. IF conversion is already poor, this may further increase DHA deficiency in women on oestrogen blocking strategies. Also there is evidence that low DHA /Omega 3s and high Omega 6 increases the risk breast cancer and other cancers, so a low level of DHA may increase the risk of breast cancer recurrence"

This is why it is so important for those who have had BC and been on oestrogen blockers to supplement with long chain Omega 3s. Women need more long chain Omega 3 to make their bodies work. More DHA is part of being female. If you can no longer make so much you must get it in your diet.

On arthritis

"Omega 6 AA reduces the pain threshold, and so increase the sensitivity to pain. PGE2 is a direct product of Omega 6 AA. In knee operations the postoperative level of PGE2 in fluid from knees related directly to the amount of pain experienced; the higher the PGE2 the higher the pain.

If the Omega 6 intake is reduced below the 4% of calories threshold, and or balanced with Omega 3s PGE2 production and so pain will be reduced.
Omega 3 DHA and EPA reduce pain by blocking the inflammatory effects of the PGE2 pathway by competing for the COX2 enzyme used to make PGE2.
DHA is a more effective COX2 blocker than a number of NSAIDS. (Drugs used to block the inflammatory pathways.) DHA and EPA do not come with a long list of potential side effects. Inflammatory cytokines such as TNF alpha, and IL1, are also downgraded by fish oil. As discussed elsewhere the products of the Omega 3s DHA and EPA are also anti-inflammtory.

NSAIDS alleviate pain and symptoms but do not stop progression.In contrast to DHA NSAIDS increase TNF-alpha synthesis. TNF- alpha and IL1 are reported as being involved in cartilage degradation. Omega 3 DHA reduces cartilage degradation. DHA and EPA also reduce bone loss. Fish oil may alleviate symptoms of rheumatoid arthritis.

A paper by Philip Calder in 2009 looking at trials on rheumatoid arthritis, with doses of long chain Omega 3s between 1.6 and 7.1, with an average of 3.5 grams a day, said “Almost all these trials have shown some benefit of fish oil… Such benefits include reduced duration of morning stiffness, reduced number of tender or swollen joints, reduced joint pain, reduced time to fatigue, increased grip strength and decreased use of non-steroidal anti-inflammatory drugs”"

R.B.

06-29-2009, 03:07 PM

Ellie said

"I wonder if there is any evidence that the chemicals released under stress reduce the amount of omega 3 in the body??"

In essence Omega 6 increases stress and aggression and Omega 3 reduces it. There are a significant number of trials on animals, students, prison inmates that support this.

How?

There are a number of mechanisms. They include that Omega 6 ultimately controls the hormones and steroids including testosterone. Omega 6 also reduces serotonin and dopamine the happy hormones. Omega 6 increase noradrenaline the stress hormone.

Stress and Omega 6 are connected with higher levels of oxidation. Oxidation ultimately damages cells and DNA which may be a factor increasing the risk cancer is triggered.

IF you have not done so please check out the videos on the first post.

Please also make sure you get adequate minerals and fat soluble vitamins.

In Australia in 2005 a large proportion of the population were mild to moderate iodine deficient.

In the USA the number who are vitamin D deficient is rising.

Minerals are essential to the production of the internal antioxidants. Vitamin D is a more powerful antioxidant than vitamin E.

There is the beginning of a recognition thanks to some far sighted individuals that iodine may an important antioxidant as well as its roles in the thyroid.

Please discuss diet with you medical advisor.

R.B.

07-09-2009, 04:43 PM

Fatty fish and fish omega-3 fatty acid intakes decrease the breast cancer risk: a case-control study.
Kim J, Lim SY, Shin A, Sung MK, Ro J, Kang HS, Lee KS, Kim SW, Lee ES.

ABSTRACT: BACKGROUND: Although it is believed that fish omega-3 fatty acids may decrease breast cancer risk, epidemiological evidence has been inconclusive. This study examined the association between fish and fish omega-3 fatty acids intake with the risk of breast cancer in a case-control study of Korean women. METHODS: We recruited 358 incident breast cancer patients and 360 controls with no history of malignant neoplasm from the National Cancer Center Hospital between July 2007 and April 2008. The study participants were given a 103-item food intake frequency questionnaire to determine their dietary consumption of fish (fatty and lean fish) and omega-3 fatty acids derived from fish (eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)). RESULTS: Using a multivariate logistic regression model, high intake of fatty fish was associated with a reduced risk for breast cancer in both pre- and postmenopausal women (OR [95% CI] for highest vs. lowest intake quartiles, p for trend: 0.19 [0.08 to 0.45], p < 0.001 for premenopausal women, 0.27 [0.11 to 0.66], p = 0.005 for postmenopausal women). Similarly, reductions in breast cancer risk were observed among postmenopausal subjects who consumed more than 0.101 g of EPA (OR [95% CI]: 0.38 [0.15 to 0.96]) and 0.213 g of DHA (OR [95% CI]: 0.32 [0.13 to 0.82]) from fish per day compared to the reference group who consumed less than 0.014 g of EPA and 0.037 g of DHA per day. Among premenopausal women, there was a significant reduction in breast cancer risk for the highest intake quartiles of omega-3 fatty acids (ORs [95% CI]: 0.46 [0.22 to 0.96]), compared to the reference group who consumed the lowest quartile of intake. CONCLUSIONS: These results suggest that high consumption of fatty fish is associated with a reduced risk for breast cancer, and that the intake of omega-3 fatty acids from fish is inversely associated with postmenopausal breast cancer risk.

R.B.

07-09-2009, 04:53 PM

angiogenesis = new blood vessel growth

The wikipedia page is helpful (MMP = matrix metalloproteinases) http://en.wikipedia.org/wiki/Angiogenesis

PGE2 is a direct product of Omega 6.

The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential.
Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A.

Department of HPB and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, United Kingdom.

Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. This review explores the evidence and the mechanisms by which omega-3 FA may act as angiogenesis inhibitors and identifies opportunities for original research trialling omega-3 FAs as anti-cancer agents in humans. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases and beta-catenin.

R.B.

07-09-2009, 05:03 PM

This suggest that women with certain genes may be at greater risk of breast cancer if they eat a lot of Omega 6 as well.

This is increased risk over the basic risks created by too much Omega 6 in the diet.

n-6 polyunsaturated fat = Omega 6

5-lipoxygenase = a downstream chemical family made from Omega 6

1: Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2748-54.Click here to read Links
5-lipoxygenase and 5-lipoxygenase-activating protein gene polymorphisms, dietary linoleic acid, and risk for breast cancer.
Wang J, John EM, Ingles SA.

Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. jwang1@tuftsmedicalcenter.org

The n-6 polyunsaturated fatty acid 5-lipoxygenase pathway has been shown to play a role in the carcinogenesis of breast cancer. We conducted a population-based case-control study among Latina, African-American, and White women from the San Francisco Bay area to examine the association of the 5-lipoxygenase gene (ALOX5) and 5-lipoxygenase-activating protein gene (ALOX5AP) with breast cancer risk. Three ALOX5AP polymorphisms [poly(A) microsatellite, -4900 A>G (rs4076128), and -3472 A>G (rs4073259)] and three ALOX5 polymorphisms [Sp1-binding site (-GGGCGG-) variable number of tandem repeat polymorphism, -1279 G>T (rs6593482), and 760 G>A (rs2228065)] were genotyped in 802 cases and 888 controls. We did not find significant main effects of ALOX5 and ALOX5AP genotypes on breast cancer risk that were consistent across race or ethnicity; however, there was a significant interaction between the ALOX5AP -4900 A>G polymorphism and dietary linoleic acid intake (P=0.03). Among women consuming a diet high in linoleic acid (top quartile of intake, >17.4 g/d), carrying the AA genotype was associated with higher breast cancer risk (age- and race-adjusted odds ratio, 1.8; 95% confidence interval, 1.2-2.9) compared with carrying genotypes AG or GG. Among women consuming <or=17.4 g/d of linoleic acid, ALOX5AP -4900 genotype was not associated with breast cancer risk (age- and race-adjusted odds ratio, 0.9; 95% confidence interval, 0.7-1.2). [COLOR="Red"][/COLThese results support a role for n-6 polyunsaturated fatty acids in breast carcinogenesis and suggest that epidemiologic studies on dietary fat and breast cancer should take into account genetic predisposition related to n-6 polyunsaturated fatty acid OR]

R.B.

07-09-2009, 05:06 PM

Anticancer actions of omega-3 fatty acids--current state and future perspectives.
Wendel M, Heller AR.

Department of Physiology, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Germany. MartinaWendel@gmx.de

Omega-3 fatty acids (omega3-FA) were shown to attenuate growth and induce apoptosis in a variety of human cancer cell lines derived from colonic, pancreatic, prostate, and breast cancer. In addition, recent findings indicate that omega3-FA act synergistically with chemotherapeutic agents and may also be used to enhance tumour radiosensitivity. The mechanisms underlying the anti-tumour effects of omega3-FA are complex. Incorporation of omega3-FA in biological membranes alters the profile of lipid mediators generated during inflammatory reactions. Furthermore, omega3-FA act as ligands of nuclear peroxisome proliferator-activated receptors that attenuate transcription of NF-kappaB-dependent genes. Thereby, the cyclooxygenase-2/prostaglandin E(2)-dependent production of pro-angiogenic vascular endothelial growth factor and levels of anti-apoptotic bcl-2 and bcl-X(L) are decreased. Eicosanoid-independent pro-apoptotic pathways include enhanced lipid peroxidation, modulation of mitochondrial calcium homeostasis and enhanced production of reactive oxygen species as well as activation of p53. This review article will give a comprehensive overview over the pleiotropic actions of omega3-FA and will discuss the potential of omega3-FA and derivatives like conjugated eicosapentaenoic acid as important nutritional adjuvant therapeutics in the management of various human cancer diseases and the impact of nutritional omega-3 FA on cancer prevention.

R.B.

07-09-2009, 05:08 PM

1: Nutr Cancer. 2009;61(3):287-301.Links
Antineoplastic effects of n-3 polyunsaturated fatty acids in combination with drugs and radiotherapy: preventive and therapeutic strategies.
Calviello G, Serini S, Piccioni E, Pessina G.

Institute of General Pathology, Catholic University, L.go F. Vito, 1, Rome 00168, Italy. g.calviello@rm.unicatt.it

Many data support the beneficial effect of n-3 polyunsaturated fatty acids (PUFAs) as chemopreventive and chemotherapeutic agents in the treatment of several chronic pathologies including cancer. Different molecular mechanisms have been proposed to explain their effects, including alterations in arachidonic acid oxidative metabolism and metabolic conversion of n-3 PUFAs to novel discovered bioactive derivatives; modification of oxidative stress; changes in cell membrane fluidity and structure and altered metabolism and function of membrane proteins. Considerable knowledge has been recently gathered on the possible beneficial effects of n-3 PUFAs administered in combination with different antineoplastic drugs and radiotherapy against melanoma, leukemia, neuroblastoma, and colon, breast, prostate, and lung cancer. The efficacy of these combinations has been demonstrated both in vivo and in vitro, and clinical trials have also been conducted. The aim of this review is to analyze all the n-3 PUFA combinations investigated so far, their efficacy, and the possible molecular mechanisms involved. It would be highly auspicable that the detailed analysis of the literature in this field could further support the common use of n-3 PUFAs in combination with other chemopreventive agents and warrant more clinical investigations designed to test the effectiveness of n-3 PUFA treatments coupled with conventional antineoplastic therapies.

Cal-Gal

07-12-2009, 06:41 PM

R.B.
Thanks so much for all this information--it is fabulous but at the same time a bit overwhelming and a bit confusing to me....

I researched the 'mercury issue' and found the brand I take to be the best--- I just started taking "Nordic Naturals" Brand--bottled-
"Complete-Omega 3*6*9" the recommended dosage is 1 teaspoon daily--

How does that fit within your vast knowledge noted here??

Thanks so much!!!!

R.B.

07-13-2009, 03:03 PM

Thanks so much for all this information--it is fabulous but at the same time a bit overwhelming and a bit confusing to me....

Thanks for the kind thought.

Most of the information you need is contained in the first post. The problem is if I say just;

1. Significantly cut down on your plant-based Omega six intake
2. Balance your Omega three and six plant based intake
3. Ensure you get an adequate supply of long chain Omega three DHA and EPA
4. Make sure you have enough minerals iodine and vitamin D

because this will reduce your risk of breast cancer, nobody is going to take any notice.

I post the trials to make the point that there is a significant amount of evidence that Omega six increases and Omega three reduces the risk of breast cancer.

Nordic naturals is a very good brand but you really need fish oil and not a 3 6 9 oil. Nordic sell fish oils by the bottle too. http://www.nordicnaturals.com/en/Products/Product_Details/98/?ProdID=1425

The body makes Omega 9s. Omega sixes are everywhere in the food chain. Most vegetable oils with the exception of olive and macadamia are very high in Omega 6, and the problem for most of us is avoiding Omega six rather than taking more of it.

All good quality refined fish oils are going to be mercury free. For those on a budget fish oil in the bottle is a cheaper option. Modern quality refined oils DO NOT "REPEAT".

Fish has to be the first choice because it contains minerals and other valuable nutrients. Fish and shellfish is the best source of minerals. Most short lived fish from the marine environment do not contain very much mercury. Seaweed is also a good source of minerals, and contains significant amounts of iodine which can be an issue for those with thyroid problems. The Japanese eat a lot of seaweed and are generally quite healthy.

This is a list from the USFDA. Avoid tuna and stick to the fish on the low mercury part of the list and you can eat almost as much as you want without doing any harm. http://www.fda.gov/Food/FoodSafety/Product-SpecificInformation/Seafood/FoodbornePathogensContaminants/Methylmercury/ucm115644.htm

Trials have suggested that even for pregnant women the benefits of the Omega threes and minerals from the sensibly chosen fish far outweighed the negative effects of the pollution they contain.

Most people with high Omega six intake need 1 to 2 g a day of Omega three EPA and DHA combined, which is 2 to 4 teaspoons of a quality refined fish oil. If you are on blood thinning medication or heart medication you should discuss taking Omega threes with your doctor. Please advise your doctors prior to surgery that you are taking fish oil.

You also need to check the label for the amount of vitamin A and vitamin D contained in the fish oil. In most products they take the vitamin A and vitamin D out and replace it with lower levels, so it is not an issue, but check anyway.

You also need to get some plant-based Omega three. Flax oil is a good source of plant-based Omega three, and you're looking at maybe a teaspoon of day.

Finally you need to get your Omega six intake down to about 2% of calories which is not easy, and most do not manage it. Most common vegetables are very high in Omega six, so you need to keep an eye out for vegetable oils in all processed foods.

Olive oil only contains about 10% Omega six, but contains useful plant products, and has been associated with lowering the risk of breast cancer. This may be in part because people are replacing Omega six in other oils with Omega nines from olive oil.

Nutrition data.com is a useful site that allows you to look up the Omega 3:6 content of foods.

Seeks nuts and grains are high in Omega sixes generally so try and pick the ones that are lower in Omega six, and eat them in moderation.

I hope this helps.

Cal-Gal

07-13-2009, 04:28 PM

Thanks so much R.B for taking the time to educate and inform us and to clarify this for me---

R.B.

07-24-2009, 03:15 PM

P13K is a pathway that comes up regularly as a factor in BC trials.

The trial below suggests increased Omega 3 and reduced Omega 6 intake may reduce output of some P13k pathways.

http://www.dana-farber.org/res/research/dana-farber-scientists-home-in-on-key-cancer-signal.html

"For more than 20 years, Dana-Farber scientists have been looking for the best way to attack a complex cell-signaling pathway known as PI3K that often goes awry in breast, colon, and other cancers. . ."

http://www.hhmi.org/news/vogelstein20071214.html

"In the study, Amzel, Gabelli, Vogelstein and their colleagues focused on the enzyme complex called PI3K-alpha, which influences how biochemical signals are interpreted by cells. The enzyme complex is made up of two proteins, known as p110 alpha and p85. The complex, Vogelstein explained, normally responds to events that occur on the surface of the cell, such as growth factor stimulation. It responds to those external events by signaling to other proteins inside the cell. “It's kind of the intermediary in the signal transduction pathway,” he said."

Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans*
Kelly L. Weaver{ddagger}Â§, Priscilla IvesterÂ§1, Michael Seeds{ddagger}, L. Douglas CaseÂ¶, Jonathan P. Arm||, and Floyd H. ChiltonÂ§

From the From the {ddagger}Department of Internal Medicine, Section on Molecular Medicine, and , Departments of Â§Physiology and Pharmacology and , Â¶Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 and the , ||Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

ABSTRACT

Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 ({omega}6) to {omega}3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased {omega}6/{omega}3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the {omega}6/{omega}3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B4 production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NF{kappa}B, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain {omega}3 PUFA concomitant with a reduction in the {omega}6/{omega}3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B4 was decreased by 31%. Expression of PI3K{alpha} and PI3K{gamma} and the quantity of PI3K{alpha} protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.

R.B.

08-13-2009, 04:12 PM

This is about colorectal cancer not BC but the messages and probably many of the mechanisms are the same. Thanks Martie for sending me the link http://www.radiomartie.com/

"Their findings suggested that “the dietary total omega-6 to omega-3 PUFA ratio was strongly associated with colorectal cancer risk”. Indeed, increasing ratios of omega-6 to omega-3 were associated with increased risks of colorectal cancer. Compared to women with the lowest ratio, women with the highest ratio of omega-6 to -3 had a relative risk 95 per cent higher."

http://www.nutraingredients-usa.com/content/view/print/256189

Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2283-91.Click here to read Links
A prospective study of dietary polyunsaturated fatty acids and colorectal cancer risk in Chinese women.
Murff HJ, Shu XO, Li H, Dai Q, Kallianpur A, Yang G, Cai H, Wen W, Gao YT, Zheng W.

Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37203-1738, USA. Harvey.j.murff@vanderbilt.edu

In animal models of colon cancer, n-3 polyunsaturated fatty acids (PUFA) have antineoplastic properties, whereas n-6 PUFAs may promote carcinogenesis. Prior epidemiologic studies have been inconsistent regarding the association of PUFAs and colorectal cancer. We prospectively evaluated the association between PUFA intake and colorectal cancer in a cohort of 73,242 Chinese women who were interviewed in person at the baseline survey for the Shanghai Women's Health Study. Dietary fatty acid consumption was derived using data collected from two food frequency questionnaires administered at baseline and 2 to 3 years later. The dietary total n-6 to n-3 PUFA ratio was strongly associated with colorectal cancer risk. Compared with women in the lowest quintile group, elevated relative risks (RR) were observed for the second [RR, 1.52; 95% confidence intervals (CI), 1.00-2.32], third (RR, 2.20; 95% CI, 1.41-3.45), fourth (RR, 1.65; 95% CI, 0.99-2.75), and fifth (RR, 1.95; 95% CI, 1.07-3.54) quintile groups. Arachidonic acid was associated with colorectal cancer risk with elevated RRs of 1.20(Q2-Q1) (95% CI, 0.87-1.64), 1.44(Q3-Q1) (95% CI, 1.05-1.98), 1.61(Q4-Q1) (95% CI, 1.17-2.23), and 1.39(Q5-Q1) (95% CI, 0.97-1.99; P(trend) = 0.03) with increasing dietary quintile. In a subset of 150 cancer cases and 150 controls, we found a statistically significant trend between an increasing n-6 to n-3 PUFA ratio and increasing production of prostaglandin E(2) (PGE(2)) as measured by urinary PGE(2) metabolites (P = 0.03). These results suggest that dietary PUFA and the ratio of n-6 to n-3 PUFA intake may be positively associated with colorectal cancer risk, and this association may be mediated in part through PGE(2) production.

R.B.

09-17-2009, 01:51 PM

http://en.wikipedia.org/wiki/Plasminogen_activator_inhibitor-1
http://en.wikipedia.org/wiki/Plasmin

I have not seen this mechanism before and know nothing about it, but in general terms it appears to be another mechanism by which Omega 6 increases the risk of BC.

PAI-1 apparently is a poor prognostic factor for BC and is induced by Omega 6 in the cell line examined.

http://serpins.med.unc.edu/~fcc/ResearchPicts2006/CancerBiology.html (re article in general terms Omega 6 is a much stronger promoter of PPAR gamma than Omega 3 is. OMega 3 is more strongly associated with PPAR alpha)

http://breastcancer.about.com/od/diagnosis/f/upa_pai1.htm

Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4.
Byon CH, Hardy RW, Ren C, Ponnazhagan S, Welch DR, McDonald JM, Chen Y.

Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL, USA.

Obesity is a risk factor for breast cancer and is associated with increased plasma concentrations of free fatty acids (FFAs). We and others have demonstrated that FFA induces plasminogen activator inhibitor-1 (PAI-1) expression in a variety of cells. Emerging evidence supports elevation of PAI-1 as a prognostic marker for breast cancer. Therefore, we hypothesized that FFAs might increase expression of PAI-1 in breast cancer cells and facilitate breast cancer progression. Secreted PAI-1 was higher in invasive and metastatic MDA-MB-231 cells compared with less invasive and non-metastatic Hs578T cells. Utilizing FFAs with different saturation and chain lengths, we demonstrated that linoleic acid induced expression of PAI-1 in MDA-MB-231 cells. Linoleic acid also induced in vitro migration of MDA-MB-231. By contrast, other FFAs tested had little or no effect on PAI-1 expression or migration. Linoleic acid-induced breast cancer cell migration was completely inhibited by virally expressed antisense PAI-1 RNA. Furthermore, increased expression of PAI-1 by FFAs was not detected in the SMAD4-deficient MDA-MB-468 breast carcinoma cells. Electrophoretic mobility-shift assay confirmed that linoleic acid-induced expression of PAI-1 was mediated, at least in part, by SMAD4 in MDA-MB-231 cells. That linoleic acid induces PAI-1 expression in breast cancer cells through SMAD4 provides a novel insight into understanding the relationships between two migration-associated molecules, FFAs, and PAI-1.Laboratory Investigation advance online publication, 14 September 2009; doi:10.1038/labinvest.2009.97.

R.B.

10-17-2009, 03:15 AM

MMP9 has been shown in previous posts to be a risk factor in BC.

RB

Omega-3 fatty acid supplementation decreases matrix metalloproteinase-9 production in relapsing-remitting multiple sclerosis.
Prostaglandins Leukot Essent Fatty Acids 80(2-3):131-6 (2009)
L Shinto, G Marracci, S Baldauf-Wagner, A Strehlow, V Yadav, L Stuber and D Bourdette
Department of Neurology, Oregon Health & Science University (OHSU), 3181 SW Sam Jackson Park Road, CR120 Portland, OR 97239, USA. shintol@ohsu.edu
OBJECTIVES: The primary objective was to evaluate the effect of omega-3 fatty acids (omega-3 FA) on matrix metalloproteinase-9 (MMP-9) production by immune cells in multiple sclerosis (MS). Quality of life, fatty acid levels, and safety were also evaluated. MATERIALS AND METHODS: Ten participants with relapsing-remitting MS (RRMS) received omega-3 FA supplementation (9.6g/day fish oil) in an open-label study. Participants were evaluated at four time points, baseline, after 1 month of omega-3 FA supplementation, after 3 months of omega-3 FA supplementation, and after a 3-month wash out. RESULTS: Immune cell secretion of MMP-9 decreased by 58% after 3 months of omega-3 FA supplementation when compared with baseline levels (p<0.01). This effect was coupled with a significant increase in omega-3 FA levels in red blood cell membranes. CONCLUSIONS: Omega-3 FA significantly decreased MMP-9 levels in RRMS and may act as an immune-modulator that has potential therapeutic benefit in MS patients. | PMID: 19171471 | DOI: 10.1016/j.plefa.2008.12.001

R.B.

10-27-2009, 05:07 PM

This is for prostate cancer and not BC but it might get your husbands interested in the subject of Omega 6 and 3 in our diet.

Male food executives please listen up. (-:

Neoplasia. 2009 Jul;11(7):692-9.
Prostate tumor growth can be modulated by dietarily targeting the 15-lipoxygenase-1 and cyclooxygenase-2 enzymes.

Kelavkar UP, Hutzley J, McHugh K, Allen KG, Parwani A.

Division of Hematology/Oncology and Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA. kelavkarup@upmc.edu

The main objectives of our study were to determine the bioavailability of omega-3 (omega-3) to the tumor, to understand its mechanisms, and to determine the feasibility of targeting the omega-6 polyunsaturated fatty acids (PUFAs) metabolizing 15-lipoxygenase-1 (15-LO-1) and cyclooxygenase-2 (COX-2) pathways. Nude mice injected subcutaneously with LAPC-4 prostate cancer cells were randomly divided into three different isocaloric (and same percent [%] of total fat) diet groups: high omega-6 linoleic acid (LA), high omega-3 stearidonic acid (SDA) PUFAs, and normal (control) diets. Tumor growth and apoptosis were examined as end points after administration of short-term (5 weeks) omega-3 and omega-6 fatty acid diets. Tumor tissue membranes were examined for growth, lipids, enzyme activities, apoptosis, and proliferation. Tumors from the LA diet-fed mice exhibited the most rapid growth compared with tumors from the control and SDA diet-fed mice. Moreover, a diet switch from LA to SDA caused a dramatic decrease in the growth of tumors in 5 weeks, whereas tumors grew more aggressively when mice were switched from an SDA to an LA diet. Evaluating tumor proliferation (Ki-67) and apoptosis (caspase-3) in mice fed the LA and SDA diets suggested increased percentage proliferation index from the omega-6 diet-fed mice compared with the tumors from the omega-3 SDA-fed mice. Further, increased apoptosis was observed in tumors from omega-3 SDA diet-fed mice versus tumors from omega-6 diet-fed mice. Levels of membrane phospholipids of red blood cells reflected dietary changes and correlated with the levels observed in tumors. Linoleic or arachidonic acid and metabolites (eicosanoid/prostaglandins) were analyzed for 15-LO-1 and COX-2 activities by high-performance liquid chromatography. We also examined the percent unsaturated or saturated fatty acids in the total phospholipids, PUFA omega-6/omega-3 ratios, and other major enzymes (elongase, Delta [Delta]-5-desaturase, and Delta-6-desaturase) of omega-6 catabolic pathways from the tumors. We observed a 2.7-fold increase in the omega-6/omega-3 ratio in tumors from LA diet-fed mice and a 4.2-fold decrease in the ratio in tumors from the SDA diet-fed mice. There was an increased Delta-6-desaturase and Delta-9 desaturase enzyme activities and reduced estimated Delta-5-desaturase activity in tumors from mice fed the SDA diet. Opposite effects were observed in tumors from mice fed the LA diet. Together, these observations provide mechanistic roles of omega-3 fatty acids in slowing prostate cancer growth by altering omega-6/omega-3 ratios through diet and by promoting apoptosis and inhibiting proliferation in tumors by directly competing with omega-6 fatty acids for 15-LO-1 and COX-2 activities.

R.B.

11-09-2009, 04:47 PM

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711973/?tool=pubmed

"After adjusting for confounding variables in the multivariate logistic regression models, postmenopausal subjects consuming more than 0.101 g of EPA and 0.213 g of DHA from fish per day showed a 62% and 68% decreased breast cancer risk compared to the reference group (who consumed less than 0.014 g of EPA and 0.037 g of DHA per day), respectively."

BMC Cancer. 2009 Jun 30;9:216.
Fatty fish and fish omega-3 fatty acid intakes decrease the breast cancer risk: a case-control study.

Kim J, Lim SY, Shin A, Sung MK, Ro J, Kang HS, Lee KS, Kim SW, Lee ES.

Cancer Epidemiology Branch, Division of Cancer Epidemiology and Management, Research Institute, National Cancer Center, Gyeonggi, South Korea. jskim@ncc.re.kr

BACKGROUND: Although it is believed that fish omega-3 fatty acids may decrease breast cancer risk, epidemiological evidence has been inconclusive. This study examined the association between fish and fish omega-3 fatty acids intake with the risk of breast cancer in a case-control study of Korean women. METHODS: We recruited 358 incident breast cancer patients and 360 controls with no history of malignant neoplasm from the National Cancer Center Hospital between July 2007 and April 2008. The study participants were given a 103-item food intake frequency questionnaire to determine their dietary consumption of fish (fatty and lean fish) and omega-3 fatty acids derived from fish (eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)). RESULTS: Using a multivariate logistic regression model, high intake of fatty fish was associated with a reduced risk for breast cancer in both pre- and postmenopausal women (OR [95% CI] for highest vs. lowest intake quartiles, p for trend: 0.19 [0.08 to 0.45], p < 0.001 for premenopausal women, 0.27 [0.11 to 0.66], p = 0.005 for postmenopausal women). Similarly, reductions in breast cancer risk were observed among postmenopausal subjects who consumed more than 0.101 g of EPA (OR [95% CI]: 0.38 [0.15 to 0.96]) and 0.213 g of DHA (OR [95% CI]: 0.32 [0.13 to 0.82]) from fish per day compared to the reference group who consumed less than 0.014 g of EPA and 0.037 g of DHA per day. Among premenopausal women, there was a significant reduction in breast cancer risk for the highest intake quartiles of omega-3 fatty acids (ORs [95% CI]: 0.46 [0.22 to 0.96]), compared to the reference group who consumed the lowest quartile of intake. CONCLUSION: These results suggest that high consumption of fatty fish is associated with a reduced risk for breast cancer, and that the intake of omega-3 fatty acids from fish is inversely associated with postmenopausal breast cancer risk.

R.B.

12-05-2009, 04:28 AM

The whole paper is on the web for free.

It is well worth a skim just looking for Omega 3 and 6 comments, even if you have difficulty with some of the rest.

FIG 5 clearly cleverly and simply visually explains the Omega 3:6 imbalance

"The results of animal studies have demonstrated that the
consumption of omega-3 fatty acids can slow the growth of
cancer xenografts, increase the efficacy of chemotherapy and
reduce the side effects of the chemotherapy or of the cancer"

http://jn.nutrition.org/cgi/reprint/132/11/3508S.pdf

Omega-3 Fatty Acids to Augment Cancer Therapy1
W. Elaine Hardman2
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808

R.B.

12-10-2009, 08:13 AM

The whole paper is free on the Web

Dietary fatty acids regulate the activation status of Her-2/neu (c-erbB-2) oncogene in breast cancer cells

http://annonc.oxfordjournals.org/cgi/content/full/15/11/1719

Summary
"This report shows, to the best of our knowledge for the first time, that dietary FAs previously characterized for either their breast cancer protective effect (ALA, EPA, DHA and OA) or its tumoricidal actions (GLA) significantly downregulate Her-2/neu ECD concentration and, consequently, the activation status of Her-2/neu in SK-Br3 and BT-474 human breast cancer cell lines, which contain Her-2/neu oncogene amplification. Remarkably, LA, a {omega}-6 FA with a strong tumorigenesis stimulating effect, significantly increased Her-2/neu ECD concentration. Our current results using human breast cancer cell lines are in concordance with our previous findings demonstrating that dietary lipids influence DMBA-induced experimental mammary tumorigenesis in female rats though modulation of Her-2/neu expression [11Go]. Although much remains to be learned about the ultimate molecular mechanisms of FAs in relation to Her-2/neu, the recent characterization of a molecular link between Her-2/neu and the proinflammatory prostaglandin biosynthesis catalyzed by the enzyme cyclooxigenase-2 (COX-2) suggest an original working model in which dietary FAs would regulate either the expression and/or the activation status of Her-2/neu oncogene via COX-2 [12Go–15Go]. Nonetheless, it is reasonable to suggest that some types of dietary FAs not only represent promising therapies for prevention and/or management of Her-2/neu-overexpressing breast carcinomas, but also may be even more beneficial when given in combination with novel therapies directed against Her-2/neu. We are currently investigating whether these findings will be helpful in the design of novel approaches to delay or prevent trastuzumab (HerceptinTM) resistance."

Ellie F

12-10-2009, 09:13 AM

Thanks for posting this article.Surely very soon we will have some definitive answers.For my own part I believe I had massive amounts of omega 6 and 9 in my diet for years prior to diagnosis and very little omega 3. i believe a period of extreme prolonged stress and the release of related hormones lit the touch paper.

Ellie

R.B.

01-19-2010, 04:09 PM

Evidence Omega 3 DHA may improve the outcome of some chemotherapies

Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial
P Bougnoux,1,2* N Hajjaji,1,2 M N Ferrasson,1,2 B Giraudeau,3 C Couet,1,4 and O Le Floch1,2

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779856/?tool=pubmed

"Several research groups, including ours, have shown that docosahexaenoic acid (DHA), a lipid of marine algal origin mainly provided by diet, has, experimentally, the ability to increase the efficacy of anti-cancer agents."

"As DHA incorporates into cell membranes, this differential handling of ROS may account for the selectivity of DHA-induced tissue sensitisation by anti-cancer agents in tumour tissues compared with non-tumour tissues. Along this line, the lack of additional toxicity in non-tumour tissues has been consistently documented under conditions in which tumour tissue DHA was sensitised to chemotherapy (Hardman et al, 1999; Kato et al, 2002; Germain et al, 2003; Xue et al, 2007) or radiation therapy (Wen et al, 2003) in rodents.
On the basis of these results, we conducted a pilot phase II clinical trial in metastatic breast cancer patients to investigate the efficacy and safety of adding DHA to an ROS-generating chemotherapy regimen, that is an anthracycline-based regimen (FEC). We found that the combination was safe while retaining significant anti-tumour activity in the sub-population of patients with high plasma DHA incorporation, suggesting that DHA has a potential to specifically chemosensitise tumours."

jhandley

01-23-2010, 01:27 AM

Researchers at the University of California, San Francisco reveal in the January 20, 2010 issue of the Journal of the American Medical Association (http://jama.ama-assn.org/) (JAMA) that heart disease patients who have higher levels of omega-3 fatty acids experience a lower rate of reduction in telomere length over time. Telomeres, which are protective DNA sequences at the ends of chromosomes, shorten with the age of the cell, and their length is a marker of biological aging.
In their introduction to the article, Ramin Farzaneh-Far, MD and colleagues note that "Multiple epidemiologic studies, including several large randomized controlled trials, have demonstrated higher survival rates among individuals with high dietary intake of marine omega-3 fatty acids and established cardiovascular disease. On this basis, the American Heart Association recommends increased oily fish intake and the use of omega-3 fatty acid supplements for the primary and secondary prevention of coronary heart disease. The mechanisms underlying this protective effect are poorly understood but are thought to include anti-inflammatory, antiplatelet, antihypertensive, antiarrhythmic, and triglyceride-lowering effects."

weety

07-16-2010, 11:36 PM

Wow! This is a fascinating thread. I read lots of it. . . and now, I'm set on improving my omega 3 uptake! Which nuts & seeds are high in omega-6 and which are higher in omega-3? I'm also confused about olive oil. Does it have omega-3?

R.B.

07-21-2010, 02:07 PM

Hi Weety

Thanks for the kind thoughts.

Olive oil has a plant based 3:6 ratio of 1:10. and is about 10% Omega 6, and mainly Omega 9. We can make Omega 9 in the body. The useful parts of olive oil are the antioxidant compounds they contain, so virgin cold pressed is best. Commercial oils may be adulterated with cheaper high six oils - money again - bulking oils to obtain farm subsidies.

You will find info on seeds and nuts here. Nuts are a useful source of minerals.
http://nutritiondata.self.com/

Please do check out the vitamin D and iodine videos. Many are deficient in both.

Many of us are also mineral deficient due to depletion of minerals in the soil and refining of food, so lots of nutrient dense foods, bone broths, offal etc.

If you eat a lot of grain, fresh ground is better. Stephan regularly blogs on the best way to prepare grains to minimise the substances they contain that inhibit mineral uptake. http://wholehealthsource.blogspot.com/

R.B.

07-21-2010, 02:24 PM

In essence Omega 3 and 6 fats alter the activation and activity of genes in breast cancer cells

Estrogen receptor-dependent genomic expression profiles in breast cancer cells in response to fatty acids

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844056/?tool=pubmed

"A case-case study that evaluated the association of dietary fat intake of selected fatty acids found that high intakes of linoleic acid in premenopausal breast cancer patients were associated with a threefold higher risk of ER− than ER+ tumors.[5]"

"A study of the dietary intake of fatty acids in premenopausal breast cancer patients found an association between linoleic acid intake and a higher risk of ER− than ER+ breast tumors.[5] The omega-3 fatty acids, EPA and DHA, are shown to inhibit the growth of ER− and ER+ breast cancer cells in vitro.[15,16]"

R.B.

10-26-2010, 10:55 AM

http://www.ncbi.nlm.nih.gov/pubmed/20878979

Int J Cancer. 2010 Sep 28. [Epub ahead of print]
Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: A prospective cohort study.

Murff HJ, Shu XO, Li H, Yang G, Wu X, Cai H, Wen W, Gao YT, Zheng W.

Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Abstract

Breast cancer is the most common cancer in women. Controversy exists regarding the role of dietary fat in breast cancer etiology. We investigated the association of dietary polyunsaturated fatty acids (PUFA) and the ratio of n-6 PUFAs to marine-derived n-3 PUFAs with breast cancer risk in the Shanghai Women's Health Study, a prospective cohort study including 72,571 cancer-free participants at baseline. Dietary fatty acid intake was determined using food frequency questionnaires. We used Cox proportional hazards analysis to estimate the relative risks (RR) and 95% confidence intervals (CI) for the association of breast cancer risk with dietary fatty acids consumption. In 583,998 person-years of follow-up, we identified 712 breast cancer cases. We found no association of breast cancer risk to dietary intake of linoleic acid, arachidonic acid, α-linolenic acid, or marine-derived n-3 PUFA. We found a statistically significant interaction between n-6 PUFA intake, marine-derived n-3 PUFA intake and breast cancer risk (p = 0.008). Women with lower intake (the lowest tertile) of marine-derived n-3 PUFA and higher intake (the highest tertile) of n-6 PUFA had an increase risk for breast cancer (RR=2.06; 95% CI=1.27-3.34) compared to women with higher intake (the highest tertile) of marine-derived n-3 PUFAs and lower intake (the lowest tertile) of n-6 PUFAs after adjusting for potential confounders. The relative amounts of n-6 PUFA to marine-derived n-3 PUFAs may be more important for breast cancer risk than individual dietary amounts of these fatty acids. Â© 2010 UICC.

Unregistered

10-26-2010, 12:10 PM

Could you interpret this study please? WHat is PUFA?

THanks

R.B.

10-26-2010, 01:28 PM

Sorry over familiarity with the terms on my part (-:

PUFA = polyunsaturated fatty acid

n3 = Omega 3

n6 = Omega 6

Marine 'PUFA' are likely to be mainly Omega 3 EPA and DHA

RR = relative risk

It looks like they split the groups into 3, and are saying that the group with the most Omega 6 and the least Omega 3 in the diet had approximately twice the risk of breast cancer of the group with the highest Omega 3 and lowest Omega 6.

They are saying at the most basic level that the results suggest risk of BC is more about the Omega 3:6 balance rather than the absolute amounts of Omega 3 or 6 in the diet.

I have not seen the whole paper, and Chinese dietary Omega 3 : 6 ratios historically would have been better that those in the west, so I just post this as another twig in the Omega 3 : 6 debate.

This is part of the pattern seen in this thread.

There is a French paper posted here somewhere looking at the risk that excised breast lumps were cancerous. They looked at the amount of long chain Omega 3 in the breast tissue v the number of lumps that were cancerous. They split the group into four. The women with the highest amounts of long chain Omega 3 had a 70% lower risk that the lumps were cancerous than the women with the lowest amounts of long chain Omega 3.

Thought provoking stuff (-:

R.B.

11-04-2010, 04:39 AM

The plant based Omega 3 (as found in flax oil) may reduce the invasive potential of cancer cells a 1994 paper suggests. This is particularly interesting as it looks a breast fat tissue. ( found whilst looking for something unrelated as usual)

Alpha-Linolenic acid content of adipose breast tissue: a host determinant of
the risk of early metastasis in breast cancer
P. Bougnoux"2, S. Koscielny3, V. Chajes', P. Descamps4, C. Couet5 & G. Calais'
'Laboratoire de Biologie des Tuneurs and 2Clinique d'Oncologie et Radiotherapie, JE 313, Faculte de Medecine, 37032 Tours,
France; 3Departement de Statistique Medicale, Institut Gustave-Roussy, 94805 Vilejuif, France; 'Clinique Gvnecologique et
Obstetricale, CHU, 37044 Tours, France; 5Laboratoire de Nutrition, JE 313, Faculte de Medecine, 37032 Tours, France.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033520/pdf/brjcancer00054-0150.pdf

"Summuary: The association between the levels of various fatty acids in adipose breast tissue and the emergence of visceral metastases was prospectively studied in a cohort of 121 patients with an initia!ly localised breast cancer. Adipose breast tissue was obtained at the time of initial surgery, and its fatty acid content analysed by capillary gas chromatography. A low level of a-linolenic acid (18:3f,3) in adipose breast tissue was associated with positive axillary lymph node status and with the presence of vascular invasion, but not with tumour size or mitotic index. After an average 31 months of follow-up, 21 patients developed metastases. Large tumour size, high mitotic index, presence of vascular invasion and low level of 18:3,, were single factors significantly associated with an increased risk of metastasis."

"The main cause of death in breast cancer patients is the development of distant metastases. Since a reduced 18:3,3 content of breast adipose tissue appears to be the first determinant of their occurrence in our series of patients, dietary supplementation of breast cancer patients in conditions
leading to a replenishment of adipose stores of 18:3,3 might delay or even prevent their clinical appearance."

pibikay

11-05-2010, 01:27 AM

Can someone knowledgable spell out what fors partof traditional Greek diest
Best of luck to all

R.B.

11-25-2010, 03:43 PM

^Hi Pibikay I will try and respond soon. Time has been a little short lately.

The work below was in mice but fascinating none the less.

Fish oil prevents breast cancer cell metastasis to bone.

Biochem Biophys Res Commun. 2010 Oct 28. [Epub ahead of print]

Mandal CC, Ghosh-Choudhury T, Yoneda T, Choudhury GG, Ghosh-Choudhury N.

Department of Pathology, University of Texas Health Science Center at San Antonio, Texas, United States.
Abstract

The data derived from epidemiological and animal models confirm a beneficial effect of fish oil (rich in ω-3 polyunsaturated fatty acids) in the amelioration of tumor growth and progression, including breast cancer. The breast cancer patients often develop bone metastasis evidenced by osteolytic lesions, leading to severe pain and bone fracture. Using a mouse model of MDA-MB-231 human breast cancer cell metastasis to bone, here we show that fish oil diet enriched in DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) prevents the formation of osteolytic lesions in bone, indicating suppression of cancer cell metastasis to bone. These results are supported by our data showing both DHA and EPA significantly attenuate the migration/invasion of MDA-MB-231 breast cancer cells in culture. The mechanism that limits breast cancer cells to selective metastasis to bone remains hitherto unexplored. Aberrant increased expression of CD44 is associated with generation of cancer stem cells, which contribute to metastasis of breast cancer cells. We demonstrate that DHA and EPA significantly inhibit the expression of CD44 protein and mRNA by a transcriptional mechanism. Furthermore, we show markedly reduced levels of CD44 mRNA and protein in the tumors of mice, which were fed fish oil diet than those in control diet. Our data provide the first evidence for a salutary effect of fish oil on breast cancer metastasis to bone. Our results identify a novel function of the fish oil active components, DHA and EPA, which target the cell-intrinsic pro-metastatic molecule CD44 to inhibit migration/invasion.

R.B.

12-15-2010, 04:29 PM

More of the same (-:

Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):237-41. Epub 2010 Apr 2.
Fatty acids and breast cancer: the role of stem cells.

Erickson KL, Hubbard NE.

Department of Cell Biology and Human Anatomy, University of California, School of Medicine, Davis, CA 95616-8643, USA. klerickson@ucdavis.edu
Abstract

Studies with animal models in vivo as well as with animal and human tumor cells in vitro suggest that specific fatty acids could reduce breast tumorigenesis. The most striking dietary fatty acid studies in animal models that show promise for reduction of breast cancer risk in humans are with conjugated linoleic acids (CLA) and n-3 fatty acids.Although a number of mechanisms have been proposed, the specific target of those fatty acids is not yet known. We sought to determine whether the effects of those fatty acids on terminally differentiated tumor cell seen could be due to alteration of breast cancer stem cells. The isomers, cis9, trans11-CLA and trans10, cis12-CLA, and the n-3 fatty acids, docosahexaenoic and eicosapentaenoic, reduced the proliferation of, and had increased toxicity towards, mammary tumor initiating cells. One mechanism involved in the effect of n-3 fatty acids may be due to alteration of the profile of prostaglandins. These results indicate that select fatty acids may be useful for preventing or reducing the risk of breast cancer as they may target the tumor initiating cell.

R.B.

01-18-2011, 12:23 PM

And More (-:

J Nutr. 2010 Dec 22. [Epub ahead of print]
Marine Fatty Acid Intake Is Associated with Breast Cancer Prognosis.

Patterson RE, Flatt SW, Newman VA, Natarajan L, Rock CL, Thomson CA, Caan BJ, Parker BA, Pierce JP.

Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Abstract

EPA and DHA, long-chain (n-3) PUFA largely obtained from fish, inhibit the proliferation of breast cancer cells in vitro and reduce the initiation and progression of breast tumors in laboratory animals. Our purpose in this analysis was to examine whether intake of these marine fatty acids (EPA and DHA) were associated with prognosis in a cohort of women who had been diagnosed and treated for early stage breast cancer (n = 3,081). Median follow-up was 7.3 y. Dietary intake was assessed using 24-h recalls (~4 recalls per dietary assessment obtained at 7 time points over 6 y). Survival models with time-dependent covariates were used to examine the association of repeated measures of dietary intake of EPA and DHA from food (i.e., marine sources) and supplements with disease-free survival and overall survival. Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events [tertile 2: HR = 0.74 (95% CI = 0.58-0.94); tertile 3: HR = 0.72 (95% CI = 0.57-0.90)] compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality [tertile 2: HR = 0.75 (95% CI = 0.55-1.04); tertile 3: HR = 0.59 (95% CI = 0.43-0.82)]. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality.

R.B.

02-04-2011, 03:03 AM

I found this whilst looking for something else.

It provides another reason to keep and eye on Omega 3 intake.

Am J Clin Nutr. 2008 Jul;88(1):216-23.
Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction.

Sun Q, Ma J, Campos H, Rexrode KM, Albert CM, Mozaffarian D, Hu FB.

Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Abstract

BACKGROUND: Whereas dietary intake of long-chain n-3 fatty acids has been associated with risk of nonfatal myocardial infarction (MI), few studies have examined the relation for blood concentrations.

OBJECTIVE: We aimed to investigate the effect of long-chain n-3 fatty acids in blood on the risk of nonfatal MI.

DESIGN: Baseline blood samples were collected from 32 826 participants of the Nurses' Health Study in 1989-1990, among whom 146 incident cases of nonfatal MI were ascertained during 6 y of follow-up and matched with 288 controls.

RESULTS: After multivariate adjustment, the relative risks (95% CI) comparing the highest with the lowest quartiles in plasma were 0.23 (0.09, 0.55; P for trend = 0.001) for eicosapentaenoic acid (EPA), 0.40 (0.20, 0.82; P for trend = 0.004) for docosapentaenoic acid (DPA), and 0.46 (0.18, 1.16; P for trend = 0.07) for docosahexaenoic acid (DHA). The associations for these fatty acids in erythrocytes were generally weaker and nonsignificant. In contrast to EPA and DHA, blood concentrations of DPA were not correlated with dietary consumption of n-3 fatty acids. Higher plasma concentrations of EPA, DPA, and DHA were associated with higher plasma concentrations of HDL cholesterol and lower concentrations of triacylglycerol and inflammatory markers.

CONCLUSIONS: Higher plasma concentrations of EPA and DPA are associated with a lower risk of nonfatal MI among women. These findings may partly reflect dietary consumption but, particularly for DPA, may indicate important risk differences based on metabolism of long-chain n-3 fatty acids.

R.B.

02-20-2011, 07:29 AM

Interesting that benefits were associated with fish rather than fish oil. I have only seen the extract of the paper so cannot comment.

J Nutr. 2011 Feb;141(2):201-6. Epub 2010 Dec 22.
Marine fatty acid intake is associated with breast cancer prognosis.

Patterson RE, Flatt SW, Newman VA, Natarajan L, Rock CL, Thomson CA, Caan BJ, Parker BA, Pierce JP.

Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. repatterson@ucsd.edu
Abstract

EPA and DHA, long-chain (n-3) PUFA largely obtained from fish, inhibit the proliferation of breast cancer cells in vitro and reduce the initiation and progression of breast tumors in laboratory animals. Our purpose in this analysis was to examine whether intake of these marine fatty acids (EPA and DHA) were associated with prognosis in a cohort of women who had been diagnosed and treated for early stage breast cancer (n = 3,081). Median follow-up was 7.3 y. Dietary intake was assessed using 24-h recalls (~4 recalls per dietary assessment obtained at 7 time points over 6 y). Survival models with time-dependent covariates were used to examine the association of repeated measures of dietary intake of EPA and DHA from food (i.e., marine sources) and supplements with disease-free survival and overall survival. Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events [tertile 2: HR = 0.74 (95% CI = 0.58-0.94); tertile 3: HR = 0.72 (95% CI = 0.57-0.90)] compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality [tertile 2: HR = 0.75 (95% CI = 0.55-1.04); tertile 3: HR = 0.59 (95% CI = 0.43-0.82)]. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality.

PMID: 21178081 [PubMed - in process]PMCID: PMC3021439 [Available on 2012/2/1]

Unregistered

02-26-2011, 02:54 PM

Does anyone take DHA and EPA separately... if so how much?
Thanks

R.B.

02-28-2011, 09:38 AM

Med Princ Pract. 2011;20(2):103-11. Epub 2011 Jan 20.
The protective effect of the Mediterranean diet: focus on cancer and cardiovascular risk.

Pauwels EK.

University of Pisa Medical School, Pisa, Italy. ernestpauwels @ gmail.com
Abstract

The lower occurrence of cancer and cardiovascular disease in the population around the Mediterranean basin has been linked to the dietary habits of the region. Indeed, this so-called Mediterranean diet is essentially different from the diets consumed in Western and Northern European countries and is rich in nuts, fruits, vegetables, legumes, whole-wheat bread, fish, and olive oil, with moderate amounts of red wine, which is mainly consumed during meals. Although a variety of cultural and religious traditions exist among the peoples of the Mediterranean area, olive oil, fish, and red wine hold a traditional and central position in the culinary routines of the region. The components of the diet contain an ample source of molecules with antioxidant and anti-inflammatory actions, among which omega-3 fatty acids, oleic acid, and phenolic compounds hold a prominent place. This review will summarize the results of important epidemiological studies that have investigated the protective effect of fish and olive oil on the risk of breast, prostate, and colorectal cancer and of wine on the risk of cardiovascular disease. The present review also aims to elucidate the various mechanisms by which various dietary components exhibit their beneficial action. In this respect, emphasis will be placed on the properties of omega-3 fatty acids from fish, oleic acid from olive oil, and phenolic compounds from olive oil and red wine.

R.B.

02-28-2011, 09:42 AM

Synergistic effects of garlic and Omega 3 EPA

eicosapentaenoic acid = EPA
linoleic acid = common plant based Omega 6

Anticancer Agents Med Chem. 2011 Jan 26. [Epub ahead of print]
Anticancer Effects of Garlic and Garlic-derived Compounds for Breast Cancer Control.

Tsubura A, Lai YC, Kuwata M, Uehara N, Yoshizawa K.

Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan. tsubura@takii.kmu.ac.jp.
Abstract

Garlic and garlic-derived compounds reduce the development of mammary cancer in animals and suppress the growth of human breast cancer cells in culture. Oil-soluble compounds derived from garlic, such as diallyl disulfide (DADS), are more effective than water-soluble compounds in suppressing breast cancer. Mechanisms of action include the activation of metabolizing enzymes that detoxify carcinogens, the suppression of DNA adduct formation, the inhibition of the production of reactive oxygen species, the regulation of cell-cycle arrest and the induction of apoptosis. Selenium-enriched garlic or organoselenium compounds provide more potent protection against mammary carcinogenesis in rats and greater inhibition of breast cancer cells in culture than natural garlic or the respective organosulfur analogues. DADS synergizes the effect of eicosapentaenoic acid, a breast cancer suppressor, and antagonizes the effect of linoleic acid, a breast cancer enhancer. Moreover, garlic extract reduces the side effects caused by anti-cancer agents. Thus, garlic and garlic-derived compounds are promising candidates for breast cancer control.

R.B.

03-15-2011, 03:55 PM

FADS 1 and 2 play a role in the creation of long chain polyunsaturated fats. There are genetic variants of FADS that make our ability to convert plant fats to long chain fats more or less efficient.

Those with less efficient conversion may have a greater need for food like fish which supply the long chain fats like DHA and EPA ready made.

Our ability to make EPA and DHA has a wide range of health and functional impacts, including the amount of EPA and DHA in breast milk.

Exp Biol Med (Maywood). 2010 Jul;235(7):785-95.
Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk.

Simopoulos AP.

The Center for Genetics, Nutrition and Health, 2001 S Street NW, Washington, DC 20009, USA. cgnh@bellatlantic.net
Abstract

The tissue composition of polyunsaturated fatty acids is important to health and depends on both dietary intake and metabolism controlled by genetic polymorphisms that should be taken into consideration in the determination of nutritional requirements. Therefore at the same dietary intake of linoleic acid (LA) and alpha-linolenic acid (ALA), their respective health effects may differ due to genetic differences in metabolism. Delta-5 and delta-6 desaturases, FADS1 and FADS2, respectively, influence the serum, plasma and membrane phospholipid levels of LA, ALA and long-chain polyunsaturated fatty acids during pregnancy, lactation, and may influence an infant's IQ, atopy and coronary heart disease (CHD) risk. At low intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), polymorphisms at the 5-lipoxygenase (5-LO) level increase the risk for CHD whereas polymorphisms at cyclooxgenase-2 increase the risk for prostate cancer. At high intakes of LA the risk for breast cancer increases. EPA and DHA influence gene expression. In future, intervention studies on the biological effects of LA, ALA and LC-PUFAs, and the effects of genetic variants in FADS1 and FADS2, 5-LO and cyclooxygenase-2 should be taken into consideration both in the determination of nutritional requirements and chronic disease risk. Furthermore, genome-wide association studies need to include environmental exposures and include diet in the interaction between genetic variation and disease association.

SoCalGal

03-15-2011, 10:36 PM

Great update! Hello and thanks :)
Flori

pibikay

03-25-2011, 12:15 AM

Interesting. What does FADS stand for?

Jackie07

03-25-2011, 01:24 AM

Am J Clin Nutr. (javascript:AL_get(this, 'jour', 'Am J Clin Nutr.');) 2010 May;91(5):1368-76. Epub 2010 Mar 24.
FADS1 FADS2 gene variants modify the association between fish intake and the docosahexaenoic acid proportions in human milk.

MoltÃ³-PuigmartÃ* C (http://her2support.org/pubmed?term=%22Molt%C3%B3-Puigmart%C3%AD%20C%22%5BAuthor%5D), Plat J (http://her2support.org/pubmed?term=%22Plat%20J%22%5BAuthor%5D), Mensink RP (http://her2support.org/pubmed?term=%22Mensink%20RP%22%5BAuthor%5D), MÃ¼ller A (http://her2support.org/pubmed?term=%22M%C3%BCller%20A%22%5BAuthor%5D), Jansen E (http://her2support.org/pubmed?term=%22Jansen%20E%22%5BAuthor%5D), Zeegers MP (http://her2support.org/pubmed?term=%22Zeegers%20MP%22%5BAuthor%5D), Thijs C (http://her2support.org/pubmed?term=%22Thijs%20C%22%5BAuthor%5D).
Department of Nutrition and Food Science, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
Abstract

BACKGROUND: The genes encoding Delta(5)- and Delta(6)-desaturases (FADS1 FADS2 gene cluster) were reported to be associated with n-3 (omega-3) and n-6 (omega-6) fatty acid proportions in human plasma, tissues, and milk. Docosahexaenoic acid (DHA) can be supplied especially by dietary fish or fish oil and synthesized from alpha-linolenic acid through a pathway involving these desaturases.
OBJECTIVE: We evaluated whether FADS gene variants modify the effect of maternal fish and fish-oil intake on plasma and milk DHA proportions.
DESIGN: FADS1 rs174561, FADS2 rs174575, and intergenic rs3834458 single nucleotide polymorphisms were genotyped in 309 women from the KOALA Birth Cohort Study in The Netherlands. Plasma was collected at 36 wk of pregnancy, and milk was collected at 1 mo postpartum. Fish and fish-oil intake was assessed by using a food-frequency questionnaire at 34 wk of pregnancy and updated for the week of milk collection. Gene-diet interactions were tested by linear regression analysis.
RESULTS: DHA proportions were lower in women homozygous for the minor allele than in women who were homozygous for the major allele (DHA proportions in plasma phospholipids: P < 0.01; DHA proportions in milk: P < 0.05). Fish intake ranged from 0 to 2.5 portions of fatty fish/wk, and 12 women took fish-oil supplements during pregnancy. DHA proportions in plasma phospholipids increased with increasing fish and fish-oil intake, irrespective of the genotype. DHA proportions in milk increased only with fish and fish-oil intake in the major-allele carriers.
CONCLUSION: Lower proportions of DHA in milk from women who were homozygous for the minor allele could not be compensated for by increasing fish and fish-oil intake, possibly because of limited incorporation into milk.

R.B.

03-25-2011, 05:33 PM

pibikay

^ This may help

FADS = Fatty acid desaturase

http://en.wikipedia.org/wiki/Fatty_acid_desaturase

Jackie 07

Could the failure of dietary DHA to raise DHA in breast milk be because even with additional intake the women were still not making enough to meet the needs of the foetus / their own needs and that higher intakes than used may have raised levels in breast milk. Other papers seem to suggest that in general supplementation raises DHA in breast milk

The effects of fish oil supplementation in pregnancy on breast milk fatty acid composition over the course of lactation: a randomized controlled trial.

Dunstan JA, Mitoulas LR, Dixon G, Doherty DA, Hartmann PE, Simmer K, Prescott SL.

School of Paediatrics and Child Health, The University of Western Australia, Crawley WA 6009.
Abstract

This study evaluated the longitudinal effect of fish oil in pregnancy on breast milk fatty acid composition and infant outcomes. In a randomized, controlled trial, 98 women received 2.2 g docosahexaenoic acid (DHA) and 1.1 g eicosapentaenoic acid (EPA) or olive oil from 20 wk of gestation until delivery. Fatty acid composition in breast milk (at 3 d, 6 wk, and 6 mo) and infant erythrocyte membranes (at 1 y) were determined by gas liquid chromatography. Breast milk fatty acids were examined in relationship to growth and development. Compared with control group, breast milk from women who received fish oil had proportionally higher DHA and EPA levels at 3 d and 6 wk after delivery, but this difference was no longer apparent by 6 mo. Infant DHA status at 1 y of age was directly related to DHA levels at 3 d, 6 wk, and 6 mo postpartum (but not to antenatal supplementation). Both EPA and DHA in breast milk were positively correlated with Griffith's developmental scores including hand and eye coordination. Thus, supplementation in pregnancy was associated with increased n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in breast milk, particularly in early lactation, and this was positively associated with infant DHA status at 1 y.

Thanks for posting that link I will bear the contents in mind.

R.B.

04-26-2011, 03:16 PM

More emphasis as to the importance of fats in cancer.

Cancer Biol Ther. 2011 Apr 15;11(8):724-31. Epub 2011 Apr 15.
Fatty acids as potential adjunctive colorectal chemotherapeutic agents.
Fauser JK, Prisciandaro LD, Cummins AG, Howarth GS.
Source

University of Adelaide, Adelaide, Australia; The Queen Elizabeth Hospital, Woodville, South Australia, Australia.
Abstract

Fatty acids (FA) are bioactive molecules which have potential as adjunctive chemotherapeutic agents. FA are classified as short-, medium; or long-chain on the basis of the number of carbon atoms in the aliphatic chain and have been reported to induce apoptosis in vitro in a range of cancer cell types, including breast, tongue, cervix and colorectal. However, to date the chain length exerting optimal anti-neoplastic properties remains undefined. Short chain fatty acids, such as butyrate (C4:0), have induced high rates of in vitro apoptosis, presumably related to epigenetic modification, cell cycle arrest and activation of pro-apoptotic genes. Medium chain fatty acids have demonstrated in vivo and in vitro cytotoxic and anti-microbial properties; however, scant evidence currently exists on their anti-neoplastic potential. Longer unsaturated fatty acids (C16-24: ω3-9), including conjugated linoleic acid and eicosapentaenoic acid, also exhibit in vitro anti-proliferative actions, including induction of oxidative stress and modification of intracellular signalling pathways. Although incorporation of FA into CRC chemotherapy regimens is in its infancy, evidence is accumulating to allow identification of the FA chain length capable of exerting the most effective anti-neoplastic activity.

PMID:
21430438
[PubMed - in process]

R.B.

05-15-2011, 03:58 PM

In essence the fat composition of the breast tissue is diet sensitive.

A trial looking at the impact of dietary EPA + DHA suggests that in terms of tissue composition there was not any significant benefit in more that 2.52 grams a day.

Full Free Text

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854898/?tool=pmcentrez

ω-3 Fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition1,2,3
Lisa D Yee,corresponding author Joanne L Lester, Rachel M Cole, Julia R Richardson, Jason C Hsu, Yan Li, Amy Lehman, Martha A Belury, and Steven K Clinton

Background: Preclinical evidence of the preventive benefits of ω-3 (nâ€“3) polyunsaturated fatty acids (PUFAs) in breast cancer continues to fuel interest in the potential role of dietary fat content in reducing breast cancer risk. The dose of fish-oil/ω-3 PUFAs needed to achieve maximal target tissue effects for breast cancer prevention remains undefined.
Objective: To determine the dose effects of ω-3 fatty acids on breast adipose tissue fatty acid profiles, we conducted a study of 4 doses of ω-3 PUFAs in women at high risk of breast cancer.
Design: In this 6-mo randomized open-label study, 48 women with increased breast cancer risk received 1, 3, 6, or 9 capsules/d of an ω-3 PUFA supplement that provided 0.84, 2.52, 5.04, and 7.56 g docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) daily, respectively. Subjects made monthly visits, at which time pill counts were made and fasting blood samples were collected to determine fatty acid profiles; anthropometric measurements were made, breast adipose tissue samples were collected, and laboratory tests of toxicity (alanine aminotransferase, LDL cholesterol, and platelet function) were made at baseline and at 3 and 6 mo.
Results: All doses led to increased serum and breast adipose tissue EPA and DHA concentrations, but the response to 0.84 g DHA+EPA/d was less than the maximum possible response with ≥2.52 g/d. Body mass index attenuated the dose response for serum tissue DHA and EPA (P = 0.015 and 0.027, respectively) and breast adipose tissue DHA (P = 0.0022) in all of the treatment groups. The incremental increase in DHA and EPA correlated inversely with baseline fat and serum values. Compliance over 6 mo was 92.9 Â± 9.2% and was unaffected by treatment arm. No severe or serious toxicities were reported.

Conclusions: Daily doses up to 7.56 g DHA+EPA were well tolerated with excellent compliance in this cohort at high risk of breast cancer. Body mass index and baseline fatty acid concentrations modulated the dose-response effects of ω-3 PUFA supplements on serum EPA and DHA and breast adipose tissue DHA.

pibikay

05-16-2011, 07:02 AM

Thanks All.We have been away for a week at Kangra Valley in Himachal.Hence my late reply

R.B.

06-10-2011, 03:21 PM

http://www.ncbi.nlm.nih.gov/pubmed/21569413

Lipids Health Dis. 2011 May 12;10(1):73. [Epub ahead of print]
Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane.
Corsetto PA, Montorfano G, Zava S, Jovenitti IE, Cremona A, Berra B, Rizzo AM.
Abstract

ABSTRACT:
BACKGROUND:

PUFAs are important molecules for membrane order and function; they can modify inflammation-inducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. PUFAs could alter cancer growth influencing cell replication, cell cycle, and cell death. The question that remains to be answered is how n-3 PUFAs can affect so many physiological processes. We hypothesize that n-3 PUFAs alter membrane stability, modifying cellular signalling in breast cancer cells.
METHODS:

Two lines of human breast cancer cells characterized by different expression of ER and EGFR receptors were treated with AA, EPA or DHA. We have used the MTT viability test and expression of apoptotic markers to evaluate the effect of PUFAs on cancer growth. Phospholipids were analysed by HPLC/GC, to assess n-3 incorporation into the cell membrane.
RESULTS:

We have observed that EPA and DHA induce cell apoptosis, a reduction of cell viability and a decrease of Bcl2 and procaspase-8 expression. Moreover, DHA slightly reduces the concentration of EGFR but EPA has no effect. Both EPA and DHA reduce the activation of EGFR. N-3 fatty acids are partially metabolized in both cell lines; AA is integrated without being further metabolized. We have analysed the fatty acid pattern in membrane phospholipids where they are incorporated with different degrees of specificity. N-3 PUFAs influence the n-6 content and vice versa.
CONCLUSIONS:

Our results indicate that n-3 PUFA feeding might induce modifications of breast cancer membrane structure that increases the degree of fatty acid unsaturation. This paper underlines the importance of nutritional factors on health maintenance and on disease prevention.

R.B.

08-12-2011, 02:43 PM

Int J Cancer. 2011 Mar 15;128(6):1434-41. doi: 10.1002/ijc.25703. Epub 2010 Nov 23.
Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: a prospective cohort study.
Murff HJ, Shu XO, Li H, Yang G, Wu X, Cai H, Wen W, Gao YT, Zheng W.
Source

Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203-1738, USA. harvey.j.murff@vanderbilt.edu
Abstract

Breast cancer is the most common cancer in women. Controversy exists regarding the role of dietary fat in breast cancer etiology. We investigated the association of dietary polyunsaturated fatty acids (PUFAs) and the ratio of n-6 PUFAs to marine-derived n-3 PUFAs with breast cancer risk in the Shanghai Women's Health Study, a prospective cohort study including 72,571 cancer-free participants at baseline. Dietary fatty acid intake was determined using food frequency questionnaires. We used Cox proportional hazards analysis to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for the association of breast cancer risk with dietary fatty acids consumption. In 583,998 person-years of follow-up, we identified 712 breast cancer cases. We found no association of breast cancer risk to dietary intake of linoleic acid, arachidonic acid, α-linolenic acid or marine-derived n-3 PUFA. We found a statistically significant interaction between n-6 PUFA intake, marine-derived n-3 PUFA intake and breast cancer risk (p = 0.008). Women with lower intake (the lowest tertile) of marine-derived n-3 PUFA and higher intake (the highest tertile) of n-6 PUFA had an increase risk for breast cancer (RR = 2.06; 95% CI = 1.27-3.34) compared to women with higher intake (the highest tertile) of marine-derived n-3 PUFAs and lower intake (the lowest tertile) of n-6 PUFAs after adjusting for potential confounders. The relative amounts of n-6 PUFA to marine-derived n-3 PUFAs may be more important for breast cancer risk than individual dietary amounts of these fatty acids.

R.B.

09-26-2011, 02:52 PM

Expert Review of Anticancer Therapy
August 2011, Vol. 11, No. 8, Pages 1151-1153 , DOI 10.1586/era.11.106
(doi:10.1586/era.11.106)

Omega-3 fatty acids: a potential booster for tamoxifen therapy?
Lucas Tadeu Bidinotto, Ricardo LÃ³pez de Cicco & Jose Russoâ€*

http://www.expert-reviews.com/doi/full/10.1586/era.11.106

Quote from paper

"In summary, there are several pathways by which omega-3 fatty acids can act in an anticancer response. The downregulation of the CDK1-cyclin B1 complex, resulting in prolongation of the G2-phase, and the downregulation of the MAPK pathway may be responsible for slowed breast cancer growth. Increased lipid peroxidation along with the accumulation of ROS and downregulation of Akt may be responsible for an increased apoptotic index. The improvement of the immune response against tumors and the lack of inflammatory cytokines in the tumors of animals fed omega-3-rich diets and treated with tamoxifen contribute to the impairment of tumor growth. The improvement of wasting syndrome in patients with advanced cancer may contribute to their overall health. Finally, the increased membrane fluidity may improve the internalization of chemotherapeutic drugs. Therefore, the combination of these mechanisms represents a potential boost to tamoxifen therapy."

R.B.

10-02-2011, 03:33 PM

Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane
Paola A Corsetto,1 Gigliola Montorfano,1 Stefania Zava,1 Ilaria E Jovenitti,1 Andrea Cremona,1 Bruno Berra,1 and Angela M Rizzocorresponding author1
1Dipartimento di Scienze Molecolari Applicate ai Biosistemi, UniversitÃ* degli Studi di Milano, Italy

(Full Free Text)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127786/?tool=pmcentrez

Background
PUFAs are important molecules for membrane order and function; they can modify inflammation-inducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. N-3 PUFAs could alter cancer growth influencing cell replication, cell cycle, and cell death. The question that remains to be answered is how n-3 PUFAs can affect so many physiological processes. We hypothesize that n-3 PUFAs alter membrane stability, modifying cellular signalling in breast cancer cells.

Methods
Two lines of human breast cancer cells characterized by different expression of ER and EGFR receptors were treated with AA, EPA or DHA. We have used the MTT viability test and expression of apoptotic markers to evaluate the effect of PUFAs on cancer growth. Phospholipids were analysed by HPLC/GC, to assess n-3 incorporation into the cell membrane.
Results
We have observed that EPA and DHA induce cell apoptosis, a reduction of cell viability and the expression of Bcl2 and procaspase-8. Moreover, DHA slightly reduces the concentration of EGFR but EPA has no effect. Both EPA and DHA reduce the activation of EGFR.
N-3 fatty acids are partially metabolized in both cell lines; AA is integrated without being further metabolized. We have analysed the fatty acid pattern in membrane phospholipids where they are incorporated with different degrees of specificity. N-3 PUFAs influence the n-6 content and vice versa.

Conclusions
Our results indicate that n-3 PUFA feeding might induce modifications of breast cancer membrane structure that increases the degree of fatty acid unsaturation. This paper underlines the importance of nutritional factors on health maintenance and on disease prevention.

R.B.

10-07-2011, 03:26 PM

Hi All

Apologies I managed to duplicate a reference above.

The ongoing saga of dental infection continues, and my suspicion that dental infections can fog the brain remains. My childhood hockey accident broken root filled and refilled and apisectomied tooth [twice] appears to have been reinfecting the bone through escape of bacteria living in the space where the post sits - the tooth and a neighbouring tooth have now been removed - not a good look (-: - but hopefully the recurring infection in the bone in the area and likely higher in the face which has been going on to greater and lesser extent for several years, now may clear up.

This is a fascinating summary adding to the evidence excess linoleic acid (plant based 18 carbon Omega Six which makes up 50 - 70 % of the fat in many vegetable oils, and arguably which many of us get too much of) is a factor in BC.

Int J Biochem Cell Biol. 2011 Sep 16. [Epub ahead of print]
Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A.
Espinosa-Neira R, Mejia-Rangel J, Cortes-Reynosa P, Salazar EP.
Source

Departamento de Biologia Celular, Cinvestav-IPN, Av. IPN # 2508, San Pedro Zacatenco, Mexico, DF 07360, Mexico.
Abstract

Epidemiological studies and animal models suggest an association between high levels of dietary fat intake and an increased risk of developing breast cancer. Epithelial-mesenchymal-transition (EMT) is a process, by which epithelial cells are transdifferentiated to a mesenchymal state, and it has been implicated in cancer progression, including invasion and metastasis. Linoleic acid (LA) induces proliferation and invasion in breast cancer cells. However, the role of LA on the EMT process in human mammary epithelial cells remains to be studied. In the present study, we demonstrate that LA induces a transient down-regulation of E-cadherin expression, accompanied with an increase of Snail1, Snail2, Twist1, Twist2 and Sip1 expressions. Furthermore, LA induces FAK and NFκB activation, MMP-2 and -9 secretions, migration and invasion. In summary, our findings demonstrate, for the first time, that LA promotes an EMT-like process in MCF10A human mammary epithelial cells.

Copyright Â© 2011 Elsevier Ltd. All rights reserved.

PMID:
21945809
[PubMed - as supplied by publisher]

R.B.

10-19-2011, 02:40 PM

More Omega 3 and 6 mechanisms which affect cancer cell function (-:

Omega 6 derivatives are the main natural activators of pathways in which cannabis derivatives are also active, which has a host of implications, including in controlling mood, food intake, weight gain etc. As well as influencing brain function these Omega 6 compounds are also active in many cells, including the reproductive system. This paper suggests they affect proliferation in cancer cells.

It looks as if Omega 3 derivatives have different roles in these pathways to Omega 6 derivatives and once again the balance between the two appears to affect cell function. ( FYI anandamide and 2-arachidonoylglycerol are omega 6 based products - see below)

The involvement of cannabis receptors begs the question does cannabis affect cancer (increase or decrease) by inhibiting the access of other compounds to these pathways - scientists are looking a the effects of cannabis derivatives on cancer - and that in turn would depend on the balance of natural activators produced in the body, including through the Omega 3 and 6 pathways but the wider implications ??? These receptors are found widely in the body including in the brain, and I value the function of mine.

Prostaglandins Leukot Essent Fatty Acids. 2011 Oct 11. [Epub ahead of print]
Omega-3 N-acylethanolamines are endogenously synthesised from omega-3 fatty acids in different human prostate and breast cancer cell lines.
Brown I, Wahle KW, Cascio MG, Smoum-Jaouni R, Mechoulam R, Pertwee RG, Heys SD.
Source

Translational Medical Sciences, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
Abstract

Omega-3 (n-3) fatty acids inhibit breast and prostate cancer cell growth. We previously showed that N-acylethanolamine derivatives of n-3 (n-3-NAE) are endocannabinoids, which regulate cancer cell proliferation. These n-3-NAE are synthesised in certain cells/tissues, after supplementing with fatty acids, however, no one has assessed whether and to what extent this occurs in cancer cells. We determined levels of endogenous n-3-NAEs in hormone sensitive and insensitive prostate and breast cancer cells and subsequent effects on other endocannabinoids (anandamide and 2-arachidonoylglycerol), before and after supplementing with DHA and EPA fatty acids, using HPLC tandem mass spectrometry. This is the first study reporting that n-3-NAEs are synthesised from their parent n-3 fatty acids in cancer cells, regardless of tumour type, hormone status or the presence of fatty acid amide hydrolase. This could have important implications for the use of n-3 fatty acids as therapeutic agents in breast and prostate cancers expressing cannabinoid receptors.

Copyright Â© 2011 Elsevier Ltd. All rights reserved.

PMID:
21995886
[PubMed - as supplied by publisher]

R.B.

10-25-2011, 04:09 PM

This is neat because it relates the Omega 3:6 profile of strictly controlled diet to what is happening in prostate cancer cells in living humans. The diet was tested in the time frame whilst patients were awaiting surgical removal of cancerous tissue, which tissue was then available for examination as to the effect of the different diets on cancer cell fat composition, structure, cell division rate, etc. The trial is small but has prompted a bigger trial

http://www.newswise.com/articles/you-are-what-you-eat-low-fat-diet-with-fish-oil-slowed-growth-of-human-prostate-cancer-cells

You are What You Eat: Low-Fat Diet with Fish Oil Slowed Growth of Human Prostate Cancer Cells
Released: 10/25/2011 7:00 AM EDT
Source: University of California, Los Angeles (UCLA), Health Sciences

"Newswise — A low-fat diet with fish oil supplements eaten for four to six weeks prior to prostate removal slowed down the growth of prostate cancer cells – the number of rapidly dividing cells – in human prostate cancer tissue compared to a traditional, high-fat Western diet.

Done by researchers at UCLA’s Jonsson Comprehensive Cancer Center, the short-term study also found that the men on the low-fat, fish oil supplement diet were able to change the composition of their cell membranes in both the healthy cells and the cancer cells in the prostate. They had increased levels of omega-3 fatty acids from fish oil and decreased levels of omega-6 fatty acids from corn oil in the cell membranes, which may directly affect the biology of the cells, though further studies are needed, said Dr. William Aronson, the study’s first author and a researcher with UCLA’s Jonsson Comprehensive Cancer Center.

The study also found that blood obtained from patients after the low-fat, fish oil diet program slowed the growth of prostate cancer cells in a test tube as compared to blood from men on the Western diet, which did not slow cancer growth.

“The finding that the low-fat, fish oil diet reduced the number of rapidly dividing cells in the prostate cancer tissue is important because the rate at which the cells are dividing can be predictive of future cancer progression,” Aronson said. “The lower the rate of proliferation, the lesser the chances that the cancer will spread outside the prostate, where it is much harder to treat.” . . .

"- the “treatment” was indeed reaching the targeted organ because of the changes in the prostate cell membrane’s fatty acid composition." . . .

"Diet studies often are difficult to evaluate because getting patients to comply with dietary changes can be challenging. However, the food eaten by men in both arms of this study was precisely controlled, Aronson said. The meals were prepared by chefs in the UCLA Clinical Translational Research Center and delivered in bulk to study participants several times a week. Participants also met with a dietician, kept food diaries and were required to return uneaten food."

"
The study appeared Oct. 25, 2011 in Cancer Prevention Research, a peer-reviewed journal of the American Association for Cancer Research."

Andrea Barnett Budin

10-26-2011, 01:10 PM

For goodness sakes -- IS THERE NO END TO THE MANY WAYS IN WHICH OMEGA 3 BENEFITS US ALL...???

Hi, RB! Can you list some of the diseases and ailments Omega 3 can alter our lives? Just in a neat little package. (I've read your book, and am ever impressed with it's messages.)

I know people in their 40s, 50s, 60s, 70s, and 80s who are on to this life-saver!

I take 2 a day. Every day...

R.B.

11-03-2011, 03:10 PM

Hi Andrea

Great to your positive posts. Thanks for the kind words. The book is not very well written, but the science in it is generally fine, and I am well received at specialist conferences on lipids on the strength of it. It raises important issues, is thought provoking, but is a bit disjointed and best read in small sections - it leaves lots of questions and that is because this is a developing area of science and much is still simply not known - if the book gets you to realise that excess Omega 6 (and not enough Omega 3) in our diet is an important issue it is a positive step - I stand by some of the more sweeping claims - excess Omega 6 will be seen in the future to be a very serious health issue - I have largely rewritten an expanded book, which is much fuller and more confidently written, and ties in other areas, but I need to find some serious time to finish it - the researchers that are doing all the fine work that made the book and rewrite possible are way ahead of their time.

One of the pieces of good news is that the US military are beginning to take the subject seriously, and they really do have the power to influence food production and composition.

Excess Omega 6 is strongly connected with the ability to reproduce and all of the processes that entails. Excess omega 6 is a factor in many western conditions, and particularly those that are inflammation related. I will try and find time over the weekend to add a list.

(For anyone who has read the biography at the back the issue is still ongoing, and it was disclosed at a recent Freedom of Information Tribunal seeking disclosure of a secret practice direction dealing with the closure of Royal wills that the document related to a secret illegitimate royal child; so the claim may not be as batty as it sounds.)

R.B.

11-13-2011, 03:42 PM

Some of you may also have seen the vitamin D threads in the nutrition section that suggest those with 'higher' levels of vitamin D on average have a lower risk of BC / recurrence.

The body is enormously complicated and interlinked as is evidenced by the paper below. The study suggests there may be links between the vitamin D pathways and Omega 6 pathways. PGE2 (a prostaglandin) is an oxidised downstream product of the 20 carbon fat called arachidonic acid (a member of the Omega 6 family, its name is explained by the fact it was first isolated from a spider). PGE2 features in lots of body functions, including inflammation, and hormone production.

The paper suggests links between a combination of increased Omega 6 PGE2 and lower Vitamin D (calcitriol) in breast cancer patients - double trouble.

Another paper on vitamin D and cancer below suggests a mechanism. Vitamin D is suggested to regulate enzymes that produce and dispose of prostaglandins including one called COX2, which is the enzyme that allows PGE2 to be made.

As a very broad generalisation Omega 3 competes for the same enzymes as Omega 6, and those with lower Omega 6 tend to have lower levels of Omega 6 products including PGE2 in their systems. In this way increased Omega 3 and lower Omega 6 may reduce the risk of a number of conditions including an array of cancers including BC and prostate cancer

A significant number of non-steroidal drugs commonly block the production or action of PGE2, which may explain why they and asprin may be associated with a reduction in the risk of cancer - but have other side effects

"Prostaglandin Metabolising Enzymes and PGE2 are Inversely Correlated with Vitamin D Receptor and 25(OH)2D3 in Breast Cancer

http://ar.iiarjournals.org/content/30/5/1673.abstract

Abstract

Background: Breast cancer is associated with inflammatory processes based on an up-regulation of cyclooxygenase-2 (COX-2) expression. The antiproliferative effects of calcitriol (1,25(OH)2D3) mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. First data suggest a correlation between vitamin D and prostaglandin metabolism. Materials and Methods: We determined the expression of VDR, COX-2, 15-PGDH and the prostaglandin receptors EP2/EP4 in normal and malignant breast tissue by real-time PCR and Western blot analysis, as well as 25(OH)2D3 and PGE2 plasma levels from healthy and breast cancer patients. Results: Significantly higher COX-2, lower VDR and lower EP2 and EP4 receptor protein levels in the malignant tissue and a significantly lower 15-PGDH protein level in normal breast tissue were detected. Breast cancer patients older than 45 years, diagnosed and sampled in the wintertime had significantly lower 25(OH)2D3 and higher PGE2 serum levels. Conclusion: The inverse correlation between VDR and both COX-2 and 15-PGDH, as well as between PGE2 and 25(OH)2D3 levels, suggests a possible link between VDR-associated target genes and prostaglandin metabolism."

Vitamin D and cancer: current dilemmas and future research needs1,2,3
Cindy D Davis
1 From the Nutritional Sciences Research Group, National Cancer Institute, Rockville, MD

2 Presented at the National Institutes of Health conference "Vitamin D and Health in the 21st Century: an Update," held in Bethesda, MD, September 5–6, 2007.

(the paper includes the following quote)

"Vitamin D regulates many genes involved in prostaglandin metabolism. 1,25(OH)2D inhibits COX-2 expression and activity, inhibits expression of prostaglandin receptors, and increases prostaglandin catabolism by increasing expression of 15-prostaglandin dehydrogenase (25). In combination, these 3 mechanisms reduce prostaglandin levels and signaling, thereby attenuating the growth-stimulatory effects of prostaglandins in prostate cancer (25). Furthermore, 1,25(OH)2D and naproxen (a nonsteroidal antiinflammatory drug) act synergistically in vitro and inhibit prostate cancer cell growth more effectively than either alone in patients on the basis of a slowing of the prostate-specific antigen doubling time (25). Thus, by understanding the molecular targets for vitamin D, researchers can develop more effective strategies for cancer prevention and treatment. "

R.B.

11-25-2011, 11:31 AM

A cautionary tale for those with troublesome root fillings.

For those of you who may have noted my observations starting in 2007 as to an ongoing infection in the jaw I finally went to see a top London Maxi-facial Consultant with the support of an excellent new dentist.

The Noted Consultant confirmed what I have always suspected that the bone at the corner of the nose was / had been infected. I have unsuccessfully spent 5 years and more, based on my analysis of the symptoms (sometime symptoms including pain, red eye lid, tender bones round eye, swollen gland at the back of the skull, skin reddening and flaking, swelling, acid night-time discharges, blocked lacrimal duct, bad tastes /breath from affected nostril, fluid discharge / sensitivity from the nose during exercise, abbesses in that segment of the jaw, eye glued shut etc) trying to convince a wider range of dentists, my doctor, the hospital et al that I had a wider jaw / skull infection, and had had an MRI, 2 CTs, OPGs etc etc etc.

It took the Noted Consultant about 10 seconds (almost instant with no hesitation) of looking at the copy of the disc of a year old CT scan before he pointed to the damaged bone, which he then showed me on a 3D image of the skull. You could not miss it - a black space surrounded by grey about the size of my thumbnail at the base of the entrance to the nose - exactly where all this time I have been pointing,with my finger half stuck up my nose, pleading plaintiffully "the problem is here". I have no idea if he had better software, or why it was so easy for him, using an existing CT to almost instantly come to that conclusion that there was damaged / infected bone, when after many x-rays etc the fact had eluded others for several years .

The upshot is that hopefully the infection should clear now the incisor, root filled as a child following a hockey accident, and subsequently apisectomied twice etc etc. the likely source of infection, had recently been removed, (when the tooth was extracted the putrid smell confirmed that area round the crown post was evidently a bacterial Hilton, and bacterial safehaven from antibiotics etc - 4 root filled teeth all in the same segment have now been the source of bone infection - including one more that died following an adjacent apisectomy, and including the offending incisor which resulted in infection to the bone around the entrance to the nose - I have not needed any other dental work for 15 years so this is not due to poor maintenance, and gums appeared healthy etc.) I now have to wait six months to find out if the bone has healed. It looks like the song "All I want for Christmas is my two front teeth" will resonate for a while yet. It is still an intermittent source of pain at a low level, and the occasional source of bad tastes / smells in the affected nostril but is much improving, as hopefully is my brain fuzz / anxiety.

On the positive side I suspect if my diet was not as good as it is (always room for improvement) that there is a chance it could have spread. Also I now know what it is, that my analysis was right, and I can no longer be treated with a certain amount of disdain by some medical / dental professionals who made it pretty clear that they viewed my symptoms as being in my imagination.

Andrea Barnett Budin

11-25-2011, 03:59 PM

I always say, Listen to your Inner Voice. You may call it your gut. By any name, it is your Spirit talking to you. And it can be counted on for excellent guidance.

By the same token, if you are with a doc who is very nice but... Look elsewhere for answers. Don't waste time with those that think your pain is a manifestation of your imagination. Nor stay with a doc who responds to your questions as you try to get your brain around something -- You don't have to understand, let me do the worrying. WRONG.

If a doc shows disdain for your mention of 2nd opinions, know that any really good doc welcomes more input. Is that comfortable in his or her own skin.

If the problem persists, go bigger. It may be inconvenient, but you may have to travel to an expert who can tell in a heartbeat what's happening to you. These are pearls.

I had 4 oncs at one time. Each was brilliant, each had a slightly different take on my situation. One was a stem cell guy (1 of an additional 2 who specialized in this, as I was considering such a transplant and was gathering information) -- this one was an hour away from my then home in NY, and at first in a dark, dank basement office. Finally he moved to a grand institute. Either way, there were always longgggg lines waiting to get to him. Even if you had the first appointment.

I was mid chemo and feeling really rotten. But both my husband and I loved this genius and felt we'd make an exception for his inconvenient location(s) and the 2 hour waits. In general, we refuse to go to anyone who leaves you hanging for hrs. But this guy was worth the wait.

Hope you're feeling way better, RB!

That doc, BTW, was one of 2 oncs who said, next time bring me your CT scans so I can have "my" radiologist read them. And so we did. And both, independent and unaware of one another, disagreed w/my regular radiologist's report. It was those 2, back in '99, who each said, I don't believe what I am looking at are tumors (splattered throughout my liver). They appear to be the dead remains of tumors. Cyst-like. Filled w/fluid.

What does this mean, we asked my wonderful and inconvenient onc?! It means, he paused and beamed his familiar smile, and sang out -- You are... in... cautious... remission!

And so it was! And has remained so since '99.

Listen to your Inner Voice and follow wherever it guides you. Your Spirit loves you more than any human being on this earth.

Sending healing energy to you all,

Andi

Jackie07

11-25-2011, 09:29 PM

Almost missed the very important messages posted by R.B. and Andrea. No, their conversation today was not about diet, but somehing that's cruicial to our survival.

Everyone, please read the previous two postings by these two ladies. They are both long-time survivors and full of wisdom.

R.B.

11-26-2011, 02:34 PM

HI Jackie07,

Many thanks for your very kind words. I have been posting on this board for quite a few years now, and am honoured that you thought I was female, but am a man with a particular interest in this devastating cancer.

Hi Andrea,

I had no idea you had gone through a misdiagnosis, your thoughts are always inspirational.

Doctors do their very best but the body is very complex, and sometimes as you say, we just have to go with our gut analysis and try and answer our concerns

Jackie07

11-26-2011, 04:21 PM

O - sorry; I thought R. B. stood for 'Roseanne Barr'. :)

Andrea Barnett Budin

12-13-2011, 12:45 PM

ABB here. Hi RB. Jackie, you rock!

Just hoping to bump this up -- for an array of reasons.

The whole link, of course, and -- the last 3 posts. I agree, some valuable info here "NOT ABOUT DIET BUT CRUCIAL TO OUR SURVVAL!

R.B.

01-04-2012, 11:40 AM

The formation of blood vessels to supply a tumour, called 'angiogenisis', is a key part of cancer.

Some Omega 6 products increase of VGEF which promotes blood vessel formation.

This article recognises the role of Omega 3 but does not look in any depth at Omega 6.

Tumor Angiogenesis as a Target for Dietary Cancer Prevention

http://downloads.hindawi.com/journals/jo/2012/879623.pdf

HER2 is listed as a promoter of angiogenisis

This is a fascinating article on the topic which can be read free.

The article looks at how many of us carry cancerous cells and very small cancers saying

"Microscopic cancer cells are commonly present in the healthy adult, the result of errors during replication of 60–90 trillion cells."

It looks a evidence that many foods may play a part in controlling new blood vessel production.

Some suggest that those with hormone sensitive cancer should be careful about taking Resveratrol.

R.B.

01-26-2012, 12:02 PM

More evidence that Omega 6 linoleic acid has a potential role in the development and spread of breast and logically other cancers.

An explanation for 'Epithelial-mesenchymal-transition' can be found at this wiki link
http://en.wikipedia.org/wiki/Epithelial-mesenchymal_transition

Cadherins are proteins a bit like living velcro that help keep cells anchored to each other. Vitamin D reportedly increases adhesion between cells. In contrast this paper suggests Omega 6 linoleic acid weakens them, which would tie in with other reading

Int J Biochem Cell Biol. 2011 Dec;43(12):1782-91. Epub 2011 Sep 16.
Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A.
Espinosa-Neira R, Mejia-Rangel J, Cortes-Reynosa P, Salazar EP.
Source

Departamento de Biologia Celular, Cinvestav-IPN, Av. IPN # 2508, San Pedro Zacatenco, Mexico, DF 07360, Mexico.
Abstract

Epidemiological studies and animal models suggest an association between high levels of dietary fat intake and an increased risk of developing breast cancer. Epithelial-mesenchymal-transition (EMT) is a process, by which epithelial cells are transdifferentiated to a mesenchymal state, and it has been implicated in cancer progression, including invasion and metastasis. Linoleic acid (LA) induces proliferation and invasion in breast cancer cells. However, the role of LA on the EMT process in human mammary epithelial cells remains to be studied. In the present study, we demonstrate that LA induces a transient down-regulation of E-cadherin expression, accompanied with an increase of Snail1, Snail2, Twist1, Twist2 and Sip1 expressions. Furthermore, LA induces FAK and NFκB activation, MMP-2 and -9 secretions, migration and invasion. In summary, our findings demonstrate, for the first time, that LA promotes an EMT-like process in MCF10A human mammary epithelial cells.

Ellie F

01-26-2012, 12:49 PM

Thanks RB for the interesting article from hindawi.
Ellie

R.B.

02-05-2012, 04:48 PM

Clearly fish has to be a better option than fish oils as fish contain minerals, vitamin D, iodine etc, but there are lots of reasons for taking a couple of grams total combined of EPA plus DHA in the form of fish oil.

The paper in arriving at its conclusion of no benefits with fish oil as against whole fish, caveats "However, use of fish oil supplements in this cohort of breast cancer survivors was low (generally <5%) and therefore we were not well powered to examine this exposure."

Full free article on line

Marine Fatty Acid Intake Is Associated with Breast Cancer Prognosis1,2

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021439/?tool=pubmed

EPA and DHA, long-chain (n-3) PUFA largely obtained from fish, inhibit the proliferation of breast cancer cells in vitro and reduce the initiation and progression of breast tumors in laboratory animals. Our purpose in this analysis was to examine whether intake of these marine fatty acids (EPA and DHA) were associated with prognosis in a cohort of women who had been diagnosed and treated for early stage breast cancer (n = 3,081). Median follow-up was 7.3 y. Dietary intake was assessed using 24-h recalls (~4 recalls per dietary assessment obtained at 7 time points over 6 y). Survival models with time-dependent covariates were used to examine the association of repeated measures of dietary intake of EPA and DHA from food (i.e., marine sources) and supplements with disease-free survival and overall survival. Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events [tertile 2: HR = 0.74 (95% CI = 0.58–0.94); tertile 3: HR = 0.72 (95% CI = 0.57–0.90)] compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality [tertile 2: HR = 0.75 (95% CI = 0.55–1.04); tertile 3: HR = 0.59 (95% CI = 0.43–0.82)]. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality.

karen z

02-10-2012, 06:31 PM

o.k., RB,
I am feeling a bit tired and would like to go to the punch line on this important thread. Could you (or someone) give me the short and sweet version (from any source) of a classic mediterranean diet? Perhaps a yes/no list (recipes along with that list would be great) but mostly the punchline. Sorry to be lazy!!!

karen z

02-10-2012, 07:39 PM

Can anyone help with my request?
THANKS.

Mtngrl

02-12-2012, 07:04 PM

Karen--

I'll take a stab at it, though R.B. is the expert. He even wrote a book on it.

In an early post it says: "The diet of our ancestors was less dense in calories, being higher in fiber, rich in fruits, vegetables, lean meat, and fish. As a result, the diet was lower in total fat and saturated fat, but contained equal amounts of n-6 and n-3 essential fatty acids. Linoleic acid (LA) is the major n-6 fatty acid, and alpha-linolenic acid (ALA) is the major n-3 fatty acid. In the body, LA is metabolized to arachidonic acid (AA), and ALA is metabolized to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)."

Translation: Nowadays, our diet has a much higher ratio of Omega 6 to Omega 3 than the diet we evolved on, both because we directly eat a lot of vegetable oils that are high in Omega 6 and because the animal foods that we consume (meat, eggs, milk, butter) have the same imbalance, because the animals were fed a high Omega 6 diet (i.e. grains and soy.)

The practical application is this: Eat a predominately plant-based diet of whole, unprocessed foods: whole grains, lots and lots of vegetables, and fruit. Eat wild, cold-water fish a few times a week. If you can get it, eat "pastured" (grass fed) meat, eggs, butter and milk. Milk from grass fed cows is higher in Omega 3 fatty acids than conventional milk, and it has conjugated linoleic acid, which is good for you, and which conventional milk does not have. If you can't get red meat, chicken, eggs and dairy foods from grass fed animals, consider skipping them or severely limiting them. (Nonfat dairy foods should be alright--no fat means no imbalance of fats, I should think.) Don't eat anything fried. Use just a little olive oil on your salads. Avoid all trans fats (hydrogenated fats). Avoid or limit added sugar. Don't use artificial sweeteners.

You might want to take fish oil supplements--one or two grams a day. If you are a vegetarian, flax seed is high in Omega-3, but it is a kind that your body has to convert to be useful. Some people's bodies do this better than others'.

For breast cancer, the question of drinking red wine, which is another component of the "Mediterranean Diet," is controversial. At least one researcher thinks it's fine to have one glass a day with a meal of the "right" foods. The consensus, however, seems to be to the contrary.

One "flat belly" diet program based on the Mediterranean diet says to eat monounsaturated fatty acids with each meal. Sources include olives, dark chocolate, olive oil, avocado, cashew, sesame, and other nuts. But fats are very nutrient dense, and as the opening sentence stated, we evolved on a less dense, lower-fat diet than we typically eat now.

karen z

02-12-2012, 08:32 PM

Amy,
Thanks so much for your summary of main points for me. I know this wasn't easy to do and that you are busy. I greatly appreciate your help.
Grazie ! !
Karen Z

R.B.

02-14-2012, 05:16 PM

Hi Karen and thanks for your help Mtngrl,

Whilst I have been nerding for several years on the subject of Omega 3 and 6 and wider diet, and have completed a not well written but general scientifically sound and hopefully thought provoking book on Omega 3 and 6, and their impact on western disease, I am not an expert in the traditional sense of the word in that I have no formal qualifications. I have been working for several years on a follow up that puts Omega 3 and 6 into a wider dietary context through the common thread of oxidative stress and its role in western disease.

Whilst the thread was titled the Greek Diet, the traditional Mediterranean diet lifestyle is in a sense a ghost, so it is not adequate just to refer to a particular diet plan, because even unprocessed food it not what it was a generation or two ago. Traditional Island foods were locally grown on highly mineralized often volcanic based soils. Goats and chicken got to wander and select their own foods. Islanders got sun and exercise etc.

The Mediterranean diet is not the only protective one. Reports by doctors working with a mix of European and native populations in locations around the world in the 1920s to 1940s clearly showed tribes on a wide variety of native diets rarely got western conditions - so it is as much about food quality and mix as type of diet.

Today in contrast western diseases are common in the same population groups that have moved to the west.

Our diets are not what they were. Most of us are deficient in one or more minerals (RDA) because the crops we and animals feed on no longer contain the mineral content they did. We abstract minerals in crops and do not replace them. A British paper records drops over the last 50 years of the amounts of various minerals in a basket of foods foods of between 20-70%. This is partly due to soil depletion and partly to breeding for carbohydrate quantity / size rather than mineral density etc. These mineral deficits obviously work up the food chain to us, and are a factor in all sorts of ailments, in both humans and animals (e.g. sheep often need to be routinely given minerals because the farmers know otherwise they are not sufficiently healthy to reproduce - but ironically we often do not ensure women with fertility issue are mineral sufficient)

Most of us are vitamin D deficient because we no longer go in the sun / wear sun cream / wash with soap before or after going in the sun.

Many of us are iodine deficient.

A good proportion of us are deficient in one or more B vitamins

Many of us are vitamin K deficient.

We eat way to much Omega 6 and not enough Omega 3

To add to these woes we refine food, and try to increase its shelf life. We treat crops / foods with all sorts of things like ammonia and bleach to prevent bacteria formation. As well as killing the bacteria these processes arguably can damage important sensitive nutrients. Many of the processes used in refining, damage the food (oxidation in various forms), as well as removing minerals.

Precooked stored meals etc probably add to the problem.

Vegetable water, the juices from meat etc and the nutrients they contain go down the sink. . .

Digestive disturbances can impair digestion - eg H Pylori affects absorption, of iron, vitamin c, and folate. Many of us have impaired digestion for a variety of reasons.

Grains contain anti nutrients, including phytate. Fermentation reduces phytate, but under the commercial imperative we have found ways of making bread rise quickly without fermenting it so saving several hours, and ironically sometimes even add phytate to bread, leading to blocking of mineral uptake. Most traditional cultures fermented their grains prior to eating them.

The lists just go on . . .

Trying to mimic a long gone Mediterranean diet of one sort or another is a hugely positive step compared to eating high levels of processed foods, but there is no ideal modern equivalent diet based on historic diets, because we have so badly distorted the quality and variety of food, and depleted it of nutrients. Even if you notionally ate the same food as your grandparents it will not contain as many nutrients, and will have been damaged by some of the industrial processes used in its storage and preparation.

Sunshine, a wide range of home grown foods on mineral rich volcanic soils, marine foods, chickens and goats that wandered round the mountains, and exercise, kept Mediterranean people healthy until they started working indoors and eating processed foods . . . better start saving for your own Island if you want a true Greek Island diet

So even with a whole (unprocessed) food diet most of us urban dwellers will be nutrient deficient. Appropriate supplementation, however imperfect and difficult to optimise, has to be a better option than deficiencies in essential very basic nutrients, particularly iodine, Vit D, minerals, K, etc. In very general terms at sensible recommended supplementation levels, for most healthy people but not necessarily those with specialist conditions, the negatives from deficiency far outweigh the risks of toxicity. Just to be clear I am not a fan of supplementation in general terms for iodine, Vit D, minerals, K, etc. as they are much better obtained in food (sunshine is the primary source in the case of Vit D) - the problem is they are not in general in foods in sufficient quantities any more. How much we get is a lottery as different soils contain different mixes and amounts.

There is a great deal we do not understand as to how the body absorbs minerals etc, but cows lick iron gateposts to get at the iron they contain, wild animals seek out mineral licks, and farmers give them mineral supplements so they reproduce, and they do. So clearly supplementation may not be optimal but has a place, and particularly so if you do not want to go to work with a gatepost for lunch - they are quite heavy and do not fit well into pockets.

However as stated. pragmatically supplementation however imperfect is a much better option than deficiency. For many of us, what we have done to the food chain / modern lifestyle, leaves us with little option but to supplement. Welcome to the nutritional lottery / risk reward guesstimate game.

Supplementation is of course an add on to doing the best we can do to pick the most nutritious foods available to us and should be undertaken only in consultation with your medical advisors.

I hope this helps. The above is a hint of what I have been nerding away at, and am currently preparing what I hope is a final restructure of the new book I have occasionally mentioned over the years, which has taken rather longer than expected, there is always just one more thing to check . . . In the meanwhile there is a book I would recommend with which I share much common ground albeit from a different perspective, which I will link to hopefully at the weekend (sorry for the delay), along with some blogs links that may be of interest

karen z

02-14-2012, 08:20 PM

Hi R.B.,
Thanks again. This is very enlightening and, I can see, quite complex. I have had problems with D for some time (seems to be good now) and just found out from a holistic/integrative center I started going to that I am very low in B and have some definite digestive problems- so being supplemented with both with the help of a compounding pharmacy (also, again taking the correct omegas hopefully). Also, starting to take melatonin and magnesium at night for sleep. Will look forward to links and,hey, my first acupuncture treatment went very well (thought I'd throw that into the mix).
Best,
Karen

SoCalGal

02-15-2012, 08:23 PM

Hi RB. Just wanted to say hello and thanks for all the awesome info. Been a bit lax in my vitamin taking and this thread has encouraged me to be more diligent. All the best! Flori

R.B.

02-20-2012, 03:59 AM

I meant to do this at the weekend and got distracted, mostly usefully (-: but not always )-:

I have hesitated to post information that does not come directly out of trials, but I would recommend this book by impassioned scientists written from the knowledge gained in trying to sort out their own health issues. There are lots of good health books, but for me this flags some core health issues, some of which I have already raised on this site. I suspect the book is probably more accessible because it is written by people with a passion born of their own experience coming fresh to the subject. My totally revised and expanded book which I am trying to complete at the moment covers a lot of common ground with theirs, albeit from a different perspective. Trying to answer Karen z's post made me think I should highlight the book

http://perfecthealthdiet.com/?page_id=781
http://www.amazon.com/Perfect-Health...9178399&sr=8-1

I have had no contact with them but I do get a 'hat tip' in the notes - I suspect for my posts on this site.

This is their blog -http://perfecthealthdiet.com/

I do not agree with everything in it, but do agree with much of the general direction. I have found their book very useful, and though provoking.

I very much agree with the general direction of travel. The issue of what is the ideal mix of fats v carbs is more complex than they portray, which they acknowledge post book on their blog. They try to work out an ideal ratio and give their reasons for that, but nature throws exceptions, which exceptions beg questions.

For example Eskimos on a high marine (largely), often raw, meat / fish diet did not have western conditions, and neither did Indonesians who lived on a 97% carb diet eating mainly varieties of sweet potatoes. They each had their issues as a result of their diets - late development and small stature in the Indonesians - higher risk of cerebral hemorrhage in Eskimos - but both and all other tribes on traditional diets - no matter what the diet - had very low western diseases including BC - so the problem is not whole food but what we have done with it.

The Hunza who had very long lives ate grain -reportedly they lived well into their 100s - which suggests that grains are not inherently bad - but we have depleted soils, altered varieties, treat grains in storage, industrially process the result, . . . and now increasing numbers of people seem to have problems with grains . . .

I do think that wheat/ grains generally should be avoided unless fresh ground from organic sources, as industrial processing treatment in storage may (and based on small studies certain processes probably do) be leading to oxidative damage of the fats and proteins they contain. Grains also contain anti-nutrients which fermenting removes to a degree - our ancestors used to ferment grains - perversely we have worked out way of proving bread artificially in much shorter times because of economics. I think their argument that there are 'safer' carbs may have some basis, but in the negative some of these carbs may not be very nutrient rich.

I agree their arguments for keeping glucose levels under control, on the basis excess glucose leads to oxidation products, and glucose is arguably is a good fuel for cancer cells.

They also 'broadly' encapsulate the Omega 3:6 argument although they are not aware that plant based Omega 3 has important roles, as does plant based Omega 6, which is why an imbalance is so damaging, etc.

There is also lots of useful information on commonly deficient essential nutrients; Iodine, Vitamin D, minerals, vitamin K, some B vitamins etc.

They also raise the issue of the effect of different diets and fasting on the immune function, which lead me to start reading more on this very complex and fascinating issue.

This is a highly thought provoking and useful book that tries to explain why rather than just telling you to take things. So I return the compliment and hats off to Paul and Shou-Ching Jaminet. http://perfecthealthdiet.com/?page_id=2

Tests that accurately disclose the status of many nutrients are simply not available. Even where they are available they are often only looking at one area eg blood. For example mineral levels in the blood will not tell you much about your bone mineral status.

As posted above, trying to get the dietary nutrients that meet our basic needs by using supplements to try and address the damage we have done to our foods is a bit of a guessing game. Even whole organic foods may well not contain the same levels of minerals as those eaten 50 years ago - which by then were already often depleted compared with foods from earlier in the century. . .

As ever it is important not to lose sight that the body is enormously complex, much is not know, we are all subtly different, so please discuss dietary changes etc with you medical and or dietary advisors.

R.B.

03-22-2012, 03:34 PM

http://www.ncbi.nlm.nih.gov/pubmed/22412148

J Clin Oncol. 2012 Mar 12. [Epub ahead of print]
Fatigue, Inflammation, and ω-3 and ω-6 Fatty Acid Intake Among Breast Cancer Survivors.
Alfano CM, Imayama I, Neuhouser ML, Kiecolt-Glaser JK, Wilder Smith A, Meeske K, McTiernan A, Bernstein L, Baumgartner KB, Ulrich CM, Ballard-Barbash R.
Source

Catherine M. Alfano, Ashley Wilder Smith, and Rachel Ballard-Barbash, National Cancer Institute, National Institutes of Health, Bethesda, MD; Ikuyo Imayama, Marian L. Neuhouser, Anne McTiernan, and Cornelia M. Ulrich, Fred Hutchinson Cancer Research Center; Anne McTiernan, University of Washington, Seattle, WA; Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine, Columbus, OH; Kathleen Meeske, University of Southern California, Los Angeles; Leslie Bernstein, City of Hope National Medical Center, Duarte, CA; Kathy B. Baumgartner, University of Louisville, Louisville, KY; and Cornelia M. Ulrich, German Cancer Research Center, Heidelberg, Germany.
Abstract

PURPOSEEvidence suggests that inflammation may drive fatigue in cancer survivors. Research in healthy populations has shown reduced inflammation with higher dietary intake of ω-3 polyunsaturated fatty acids (PUFAs), which could potentially reduce fatigue. This study investigated fatigue, inflammation, and intake of ω-3 and ω-6 PUFAs among breast cancer survivors. METHODSSix hundred thirty-three survivors (mean age, 56 years; stage I to IIIA) participating in the Health, Eating, Activity, and Lifestyle Study completed a food frequency/dietary supplement questionnaire and provided a blood sample assayed for C-reactive protein (CRP) and serum amyloid A (30 months after diagnosis) and completed the Piper Fatigue Scale and Short Form-36 (SF-36) vitality scale (39 months after diagnosis). Analysis of covariance and logistic regression models tested relationships between inflammation and fatigue, inflammation and ω-3 and ω-6 PUFA intake, and PUFA intake and fatigue, controlling for three incremental levels of confounders. Fatigue was analyzed continuously (Piper scales) and dichotomously (SF-36 vitality ≤ 50).ResultsBehavioral (P = .003) and sensory (P = .001) fatigue scale scores were higher by increasing CRP tertile; relationships were attenuated after adjustment for medication use and comorbidity. Survivors with high CRP had 1.8 times greater odds of fatigue after full adjustment (P < .05). Higher intake of ω-6 relative to ω-3 PUFAs was associated with greater CRP (P = .01 after full adjustment) and greater odds of fatigue (odds ratio, 2.6 for the highest v lowest intake; P < .05). CONCLUSION Results link higher intake of ω-3 PUFAs, decreased inflammation, and decreased physical aspects of fatigue. Future studies should test whether ω-3 supplementation may reduce fatigue among significantly fatigued breast cancer survivors.

R.B.

03-22-2012, 03:43 PM

Low vitamin D is a huge issue for lots of reasons. This information comes from this thread
http://her2support.org/vbulletin/showthread.php?t=43711
in case you have not seen it.

Two telling excepts from scientific papers

"More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population."
http://jcem.endojournals.org/cgi/con...ract/90/6/3215

"These findings show that free-living elderly Europeans, regardless of geographical location, are at substantial risk of inadequate vitamin D status during winter and that dietary enrichment or supplementation with vitamin D should be seriously considered during this season."
http://grande.nal.usda.gov/ibids/ind...&therow=110910

(-: Some Must Watch University of California TV videos (-:

Pass them on please (-:

This is a passionate understandable very punchy slightly acerbic lecture to doctors by Dr Holick, a man ahead of his time, an expert in the vitamin D field, and someone who bravely stuck to his science through the dark days despite wide opposition and ridicule, and now thanks to his grit and the determined work of others Vitamin D is on the agenda.

Dr Holick - D-Lightful Vitamin D: Bone & Muscle Health and Prevention of Autoimmune and Chronic Diseases
http://www.uctv.tv/search-details.aspx?showID=15773

Other fascinating UCLA lectures

Vitamin D Prevents Cancer: Is It True?
http://www.uctv.tv/search-details.aspx?showID=16940

Skin Cancer/Sunscreen - the Dilemma
http://www.uctv.tv/search-details.aspx?showID=15770

Dose-Response of Vitamin D and a Mechanism for Cancer Prevention
http://www.uctv.tv/search-details.aspx?showID=15767

Vitamin D & Cardiovascular Disease- New Frontiers for Prevention
http://www.uctv.tv/search-details.aspx?showID=15772

R.B.

04-07-2012, 03:38 PM

Iodine is another potential major dietary issue.

It is hard to believe in a modern world with so many resources and so much technology that many people are iodine deficient, but that is exactly what the evidence and science points to.

Iodine is truly fundamental to the function of the body. Only 20% of the stored iodine in the body is in the thyroid, the other 80% is used in other cells all over the body, in a variety of very important ways. Iodine has very particular chemical properties and may well have been fundamental in the development of life as outlined by Professor Venturi, a leading and arguably under-recognised researcher in the field.

"Environmental iodine deficiency: A challenge to the evolution of terrestrial life?

Venturi S, Donati FM, Venturi A, Venturi M.
Thyroid. 2000 Aug;10(8):727-9.

http://iodine4health.com/special/evolution/venturi_evolution.htm

“In conclusion, we believe that environmental iodine deficiency might be an important evolutionary factor of terrestrial life of vertebrates. ”"

Many people are arguably iodine insufficient due to a combination of low intake, iodine blocking foods, higher iodine utilisation, iodine blocking chemicals, and the inclusion in the diet of 'large' amounts of bromine and fluorine products which compete with iodine.

Western recommended intakes are much lower than recorded Japanese intakes. Current Japanese intake was reported to be about 1mg a day, and their parents ate more. Historically the Japanese had lower levels of many western conditions.

Iodine in the soil is deficient in many parts of the world, so you cannot count on getting it in your diet. Some Governments have recognised falling iodine intake is a serious health issue, for example in Australia they have restarted to iodise bread.

Iodine intakes have fallen significantly over the last 30 years, for a number of reasons. For example the intake / iodination of foods has fallen and iodine is no longer used to disinfect cattle milking systems / teats.

There are many factors in the modern lifestyle and diet that increase the requirement for iodine. Things that block iodine uptake and usage by the body are everywhere, for example fire retardants, and form an increasing part of our lives. Many of the healthy green vegetables such as brassica are goitregenic (iodine blocking). Industrial production and some rock based fertilizers introduce perchlorate into the food chain. Perchlorate is a strong iodine blocker.

Other chemicals of the same family as iodine, the halides, such as fluoride and bromide compete with iodine and block iodine usage and uptake. Our intakes of bromine and fluorine have significantly increased.

For example bromide is added to flour in some countries, and included in drinks. It is also used a a flame retardant. Bromide is found in sea food but with iodine.

Fluoride is added to water and toothpaste, and there is evidence it may protect young teeth, but does not seem to have much effect on adult teeth - but possibly at the cost of reducing the structural 'hardness' of the bone in teeth - does that include other bones I have no idea, but logically it might.

Most foods contain very little iodine. The primary source of iodine is marine foods. Seaweeds often contain from significant to very large amounts of iodine.

Iodine is concentrated by the breast and dairy foods are an important dietary iodine source, but many now avoid dairy products. The amount of iodine in the milk will reflect the amount in the pasture / and or feed - so cattle fed on deficient pastures will produce milk low in iodine.

Some fresh water plants provide a source of iodine and some cultures would burn them and eat the ash.

We are probably able to survive on relatively low iodine intakes on a 'natural' diet in an unpolluted world, and many peoples who had relatively limited access to iodine lived long health lives. These people may have relied on particular food sources to provide the minimum of iodine needed. People of the Andes carried and traded fish eggs far inland. Mountain people like the Georgians and Hunza ate dairy products. People in Africa are reported to have collected burnt and ate fresh water plants. In contrast some populations are seriously iodine deficient with very serious health and developmental consequences.

Many western populations are also seriously iodine deficient. The problem today is a combination of changing diets that increase iodine need, dietary goitregens, chemical goitregens, and declining intake.

Iodine has many roles in the body and deficiency results in a wide range of health issues.

Everything in the body interlinks, for example selenium has particular importance in the metabolism of iodine, and in considering iodine intakes it is important not to loose sight of the whole picture. Omega 3 and 6 which also interact with iodine, which is where my interest started, and lead to me reading round the subject.

This passionate excellent and highly thought provoking video by a respected Doctor who has been working with iodine for a number of years deals with some of the items mentioned above in more detail, as well as setting out his clinical experience in using iodine to treat his patients. The video is iodine centric, and needs to be considered in a wider dietary context.

You may wish to start the video at 1 hour 24 minutes 20 seconds where Dr Brownstein talks about iodine and breast cancer.

Sadly research into iodine is limited presumably because it cannot be patented - one of the flaws of a purely financially driven economic model.

I have started an iodine thread on the nutrition page which includes this post, included further information, and tries to bring together historic posts by others.
http://her2support.org/vbulletin/showthread.php?t=53928

As usual please discuss dietary change with your doctor.

Must watch video. You may want to start at the breast cancer / fibrosis section at just after 1 hour 24 minutes in.

Iodine The Misunderstood Nutrient David Brownstein

http://www.youtube.com/watch?v=Kd34EJ5E3bI

R.B.

06-04-2012, 03:50 PM

The risk associated with saturated fats may be because of how we process it, and what is defined as saturated fat e.g. lard, which in fact contains significant amounts of Omega 6 etc, and or saturated fats in processed foods that are derived from 'artificial' saturated fats such as trans and interestified fats.

For me it is clear that excess Omega 6 increases the risk of a number of diseases, as does a lack of Omega 3.

I think the story on saturated fats is more complex, and as we learn more it will become recognized that natural dietary unprocessed saturated fats have a place as part of a healthy diet. This comment comes with a lot of caveats which are too complex for this post, including calorie intake, the type of saturated fats, exercise, industrial processing, the source, what we are feeding our animals on, the wider diet etc.

New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids

http://www.biomedcentral.com/content/pdf/1741-7015-10-50.pdf

Michel DE Lorgeril and Patricia Salen

Cardiovascular diseases and cancers are leading causes of morbidity and mortality. Reducing dietary saturated fat and replacing it with polyunsaturated fat is still the main dietary strategy to prevent cardiovascular diseases, although major flaws have been reported in the analyses supporting this approach. Recent studies introducing the concept of myocardial preconditioning have opened new avenues to understand the complex interplay between the various lipids and the risk of cardiovascular diseases. The optimal dietary fat profile includes a low intake of both saturated and omega-6 fatty acids and a moderate intake of omega-3 fatty acids. This profile is quite similar to the Mediterranean diet. On the other hand, recent studies have found a positive association between omega-6 and breast cancer risk. In contrast, omega-3 fatty acids do have anticancer properties. It has been shown that certain (Mediterranean) polyphenols significantly increase the endogenous synthesis of omega-3 whereas high intake of omega-6 decreases it. Finally, epidemiological studies suggest that a high omega-3/omega-6 ratio may be the optimal strategy to decrease breast cancer risk. Thus, the present high intake of omega-6 in many countries is definitely not the optimal strategy to prevent CVD and cancers. A moderate intake of plant and marine omega-3 in the context of the traditional Mediterranean diet (low in saturated and omega-6, but high in plant monounsaturated fat) appears to be the best approach to reduce the risk of both cardiovascular diseases and cancers, in particular breast cancer.

Ellie F

06-05-2012, 08:39 AM

Thanks for the reminders!! Having recently been diagnosed with osteoporosis I am trying very hard to get the balance right so as to get as much calcium from diet but also to ensure I get enough vit d and magnesium.AS I hardly eat dairy it is much more of a struggle.
Ellie

R.B.

06-25-2012, 02:31 AM

The ratios and amounts of the fats you eat ultimately alters the structure of the membranes of the cells. Changes in the the structure of the cell membrane alters their function. Polyunsaturated fats make cell membranes more flexible.

For example skin is made of cells, and cells are enclosed by membranes. Women make more long chain Omega 3 DHA than men and this may be part of the explanation for softer skin etc

Cell membranes have different composition in different parts, in a sense in the same way as our skin, our membrane with the outside world, differs in composition according to its functions. Lipid rafts are areas with a different composition within the main membrane.

The body also uses the cell membrane as a 'larder' for fats, and draws down on them when they are needed as ingredients to make chemical messengers.

The the type and amount of Omega 3 and 6 you eat really does matter, in that it has significant effect on the function of cells and so the body.

Cell Biochem Biophys. 2012 May 24. [Epub ahead of print]
Chemical-Physical Changes in Cell Membrane Microdomains of Breast Cancer Cells After Omega-3 PUFA Incorporation.
Corsetto PA, Cremona A, Montorfano G, Jovenitti IE, Orsini F, Arosio P, Rizzo AM.
Source

Dipartimento di Scienze Farmacologiche e Biomolecolari, UniversitÃ* degli Studi di Milano, Via D. Trentacoste 2, 20134, Milan, Italy, paola.corsetto@unimi.it.
Abstract

Epidemiologic and experimental studies suggest that dietary fatty acids influence the development and progression of breast cancer. However, no clear data are present in literature that could demonstrate how n - 3 PUFA can interfere with breast cancer growth. It is suggested that these fatty acids might change the structure of cell membrane, especially of lipid rafts. During this study we treated MCF-7 and MDA-MB-231 cells with AA, EPA, and DHA to assess if they are incorporated in lipid raft phospholipids and are able to change chemical and physical properties of these structures. Our data demonstrate that PUFA and their metabolites are inserted with different yield in cell membrane microdomains and are able to alter fatty acid composition without decreasing the total percentage of saturated fatty acids that characterize these structures. In particular in MDA-MB-231 cells, that displays the highest content of Chol and saturated fatty acids, we observed the lowest incorporation of DHA, probably for sterical reasons; nevertheless DHA was able to decrease Chol and SM content. Moreover, PUFA are incorporated in breast cancer lipid rafts with different specificity for the phospholipid moiety, in particular PUFA are incorporated in PI, PS, and PC phospholipids that may be relevant to the formation of PUFA metabolites (prostaglandins, prostacyclins, leukotrienes, resolvines, and protectines) of phospholipids deriving second messengers and signal transduction activation. The bio-physical changes after n - 3 PUFA incubation have also been highlighted by atomic force microscopy. In particular, for both cell lines the DHA treatment produced a decrease of the lipid rafts in the order of about 20-30 %. It is worth noticing that after DHA incorporation lipid rafts exhibit two different height ranges. In fact, some lipid rafts have a higher height of 6-6.5 nm. In conclusion n - 3 PUFA are able to modify lipid raft biochemical and biophysical features leading to decrease of breast cancer cell proliferation probably through different mechanisms related to acyl chain length and unsaturation. While EPA may contribute to cell apoptosis mainly through decrease of AA concentration in lipid raft phospholipids, DHA may change the biophysical properties of lipid rafts decreasing the content of cholesterol and probably the distribution of key proteins.

R.B.

08-01-2012, 01:21 PM

More about the importance of lipid rafts ^ (see previous post) and the possibility they have a very special role in HER2

This explains the active HER2 receptors (Docking stations built into the cells outer wall (membrane) into which the HER2 protein fits like a key) are only found in a particular areas of the double skin fat/protein/cholesterol bubbles that form the outer layer of cells (think bubble). The particular areas in which active HER2 receptors are apparently exclusively found are called lipid rafts (Special functional areas within the surface of the bubble that contain greater amounts of close packed fats)

It also explains that the docking locks come in three types, on activated by one HER2 protein (monomer), another type by a pair of HER2s (homodimer) and a third by an HER2 combined with another, probably specific, substance (heterodimer).

The results also suggest that there may be a connection between an increased number of HER2 docking locks and more numerous areas of lipid rafts in the cell membrane.

The HER2 protein may look something like this
http://en.wikipedia.org/wiki/File:Trastuzumab_Fab-HER2_complex_1N8Z.png see Wikipedia http://en.wikipedia.org/wiki/HER2/neu

The paper explains DHA may alter the structure of the rafts so possibly disrupting the docking locks which ultimately may lead to higher cell death rates in cells expressing more HER2 receptors.

ABSTRACT

http://www.ncbi.nlm.nih.gov/pubmed/22749134

J Nutr Biochem. 2012 Jun 27. [Epub ahead of print]
Lipid raft disruption by docosahexaenoic acid induces apoptosis in transformed human mammary luminal epithelial cells harboring HER-2 overexpression.
Ravacci GR, Brentani MM, Tortelli T Jr, Torrinhas RS, Saldanha T, Torres EA, Waitzberg DL.
Source

Department of Oncology Medical School, University of SÃ£o Paulo, 01246-903 SÃ£o Paulo, Brazil; Department of Gastroenterology Medical School, University of SÃ£o Paulo-LIM 35, 01246-903 SÃ£o Paulo, Brazil.
Abstract

In HER-2-overexpressing breast cells, HER-2 receptors exist on the cell surface as monomers, homodimers and heterodimers. For signal activation and transduction to occur, HER-2 must be localized to lipid rafts. Therefore, we hypothesized that the amount of lipid rafts on the cell membrane would be a factor in HER-2 signaling. To test this, we used HB4a (an untransformed human mammary epithelial cell line) and HB4aC5.2 cells. HB4aC5.2 cells are HB4a derivatives that have been transfected with five copies of pJ5E.c-ErbB-2 and express approximately 900 times more HER-2 than HB4a cells. In these cells, HER-2 overexpression was accompanied by increased lipid rafts in cell membranes, a hyperactivation of downstream Akt and ERK1/2 proteins, and an increased rate of cell growth compared to HB4a. In addition, HER-2 overexpression was associated with an increased activation of FASN, a key enzyme involved in cellular lipogenesis. Its final product, palmitate, is frequently used to synthesize lipid rafts. We further hypothesized that treatment with docosahexaenoic acid (DHA), an omega-3 fatty acid, would disrupt the lipid rafts and lead to a growth arrest. In HB4aC5.2 cells, but not HB4a cells, we found that DHA treatment disrupted lipid raft; inhibited HER-2 signaling by decreasing activation of Akt, ERK1/2 and FASN proteins; and induced apoptosis.Although little is known about lipid rafts, our data support the idea that disturbances in these microdomains induced by DHA may represent a useful tool for controlling the signaling initiated by HER-2 receptors and its therapeutic potential in the treatment of HER-2 positive breast cancer.

R.B.

09-18-2012, 11:20 AM

BMC Cancer. 2012 Aug 15;12(1):355. [Epub ahead of print]
Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial.
Ghoreishi Z, Esfahani A, Djazayeri A, Djalali M, Golestan B, Ayromlou H, Hashemzade S, Asghari Jafarabadi M, Montazeri V, Keshavarz SA.
Abstract

ABSTRACT:
BACKGROUND:

Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy.
METHODS:

This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score".
RESULTS:

Twenty one patients (70 %) of the group taking omega-3 fatty acid supplement (n = 30) did not develop PN while it was 40.7 %( 11 patients) in the placebo group(n = 27). A significant difference was seen in PN incidence (OR = 0.3, .95 % CI = (0.10-0.88), p = 0.029). There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95 % CI = ([MINUS SIGN]2.06 -0.02), p = 0.054).
CONCLUSIONS:

Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients' quality of life.Trial registrationThis trial was registered at ClinicalTrials.gov (NCT01049295).

rhondalea

09-18-2012, 11:42 AM

Thanks for that study.

During chemo, I took 4.252 grams of fish oil daily, for a total of 800mg DHA and 1600mg EPA. I thought it was ALCAR that prevented me from experiencing any neuropathy, but it now appears that the high dose fish oil may have played a role.

R.B.

10-03-2012, 04:25 PM

BMC Med. 2012 May 21;10:50.
New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids.
de Lorgeril M, Salen P.
Source

Laboratoire Cœur & Nutrition, TIMC-IMAG, UniversitÃ© Joseph Fourier-CNRS, FacultÃ© de MÃ©decine, Grenoble, France. michel.delorgeril@ujf-grenoble.fr
Abstract

Cardiovascular diseases and cancers are leading causes of morbidity and mortality. Reducing dietary saturated fat and replacing it with polyunsaturated fat is still the main dietary strategy to prevent cardiovascular diseases, although major flaws have been reported in the analyses supporting this approach. Recent studies introducing the concept of myocardial preconditioning have opened new avenues to understand the complex interplay between the various lipids and the risk of cardiovascular diseases. The optimal dietary fat profile includes a low intake of both saturated and omega-6 fatty acids and a moderate intake of omega-3 fatty acids. This profile is quite similar to the Mediterranean diet. On the other hand, recent studies have found a positive association between omega-6 and breast cancer risk. In contrast, omega-3 fatty acids do have anticancer properties. It has been shown that certain (Mediterranean) polyphenols significantly increase the endogenous synthesis of omega-3 whereas high intake of omega-6 decreases it. Finally, epidemiological studies suggest that a high omega-3 to omega-6 ratio may be the optimal strategy to decrease breast cancer risk. Thus, the present high intake of omega-6 in many countries is definitely not the optimal strategy to prevent cardiovascular disease and cancers. A moderate intake of plant and marine omega-3 in the context of the traditional Mediterranean diet (low in saturated and omega-6 fatty acids but high in plant monounsaturated fat) appears to be the best approach to reduce the risk of both cardiovascular diseases and cancers, in particular breast cancer.

PMID:
22613931
[PubMed - in process]
PMCID:
PMC3394202

Free PMC Article here http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394202/

R.B.

10-03-2012, 04:42 PM

Lani kindly posted this comment / paper summary which identifies COX1 and COX2 related genes as possible targets in HER2 related cancer. Interestingly COX 1 and COX 2 are key enzymes in the Omega 6 pathways in that they convert Omega 6 fats to active derivatives. NSAIDS intervene in these pathways in different ways and prevent formation of these products. . . In very simplistic terms reducing the amount of plant based Omega 6 in the diet to under 4% of calories and increasing Omega 3 which competes for space in the cell membrane will also reduce the amount of Omega 6 COX products made by the body.

The full free version of the paper referred to in the above post includes the following comment. "In animal studies, omega-6 PUFAs have a strong mammary tumor-enhancing effect [21,22]. In order to exert their carcinogenic effects, they must first undergo an oxidative metabolization, mainly through the lipoxygenase and cyclooxygenase pathways [23,24]. " COX is the short form for cyclooxygenase, the same COX 1 and COX 2 family as Lani is talking about above. COX enzymes prefer Omega 6s. So give COX enzymes a ready supply of Omega 6 and the right conditions and they will get busy. Incidentally LOX enzymes prefer Omega 3s, but will also use Omega 6s particularly when Omega 3s are in short supply . . .

http://her2support.org/vbulletin/showthread.php?t=56001

"I have railed for years on the need to divide her2+ bc into subtypes in order to discover the best targets/ combination treatment for each subtype

I have also railed for years to encourage bone marrow sampling to discover if the disseminated tumor cells there could tell which patients needed systemic therapy as well as local treatment (surgery and/or radiation therapy) and to discover whether the initial therapy was successful or whether additional therapy against other targets is needed

I have not hidden that I believe in the cancer stem cell "theory" of breast cancer

Here scientists have found (in mice, but results corroborated when evaluating a cohort of human breast cancer patients accumulated by vantViver) that an 8 gene signature derived from cancer stem cells of her2+ breast cancer (in mice)
can stratify her2+ breast cancer patients prognoses and serve as targets for therapy.

Two of the genes can be affected by over the counter NSAIDs (cox1 and cox2) and an already FDA approved drug in use for many years -an iron chelator used for iron poisoning and inherited iron deposition diseases is available as well.

I am hopeful studies in this direction will help stratify her2+ breast cancer into groups (even though every patients tumor is unique) which can be treated similarly ie similar targets, turning her2+ breast cancer into an annoying chronic disease or even curing it.

I hope this approach can be used against other forms of cancer as well

Proteomics. 2012 Sep 19. doi: 10.1002/pmic.201200103. [Epub ahead of print]
Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu transgenic mice.
Kanojia D, Zhou W, Zhang J, Jie C, Lo PK, Wang Q, Chen H.
Source
Department of Biological Science, Centre for colon cancer, University of South Carolina, Columbia, SC 29208, USA.
Abstract
HER2 overexpression leads to mammary tumorigenesis and its elevated levels leads to increase in cancer stem cells (CSCs), invasion and metastasis. CSCs are resistant to radiation/chemotherapeutic drugs and are believed to be responsible for recurrence/relapse of cancer. CSCs are isolated using flow cytometry based sorting, although reliable, this technology hinders the convenient identification of molecular targets of CSCs. Therefore to understand the molecular players of increased CSC through HER2 overexpression and to develop meaningful targets for combination therapy, we isolated and characterized breast CSCs through convenient tumorsphere culture. We identified the altered protein expression in CSC as compared to non-CSC using LC-MS/MS and confirmed those results using qRT-PCR and western blotting. Ferittin Heavy Chain 1 was identified as a candidate gene which is involved in iron metabolism and iron depletion significantly decreased the self-renewal of CSCs. We further performed in silico analysis of altered genes in tumorsphere and identified a set of genes (PTMA, S100A4, S100A6, TNXRD1, COX-1, COX-2, KRT14 and FTH1), representing possible molecular targets, which in combination showed a promise to be used as prognostic markers for breast cancer.
Â© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PMID: 22997041"

KDR

10-03-2012, 05:25 PM

Could this be summarized, i.e., what is a good ratio of O3 to O6 by example. Thank you.
Karen

R.B.

04-26-2013, 02:47 PM

(In Progress - I will revisit this over the next few days and amend it - if I put it in a word folder I will be less motivated to get it finished (-:)

Hi KDR

I simply cannot believe it is over a year that I have been meaning to respond to your question !!!

The reason I did not respond straight away is that the answer is not simple, biology it seems rarely is.

I will try and summarize a few thoughts that may help identify key issues.

1. Omega 3 and 6 fats are families made from a basic Omega 3 and a basic Omega 6 building block, which cannot be made by mammals but which can be made by plants. The fact that these fat must be got in the diet, and are hugely influential in body function is of immeasurable functional significance. Each member of each family has different functions. In general terms Omega 6 products promote inflammation, blood vessel formation, cell migrations and related activities. Omega 3s tend to be counter inflammatory, reduce blood vessel formation etc. It is complex, and these are generalizations.

2. With the help of our cells, and or the bacteria in our guts, we can make almost all other fats. Bacteria make short fats. We can make a 16 carbon saturated fat palmitic acid, which can be elongated and double bonds added to make other fats including oleic acid; the fat found in olive oil. We also have mechanisms to break fats down to shorter units

3. The plant based Omega 6 is an 18 carbon chain, with 2 double bonds.

4. The plant based Omega 3 is an 18 carbon chain with 3 double bonds.

5 The plant based Omega 3 and 6 can be elongated and double bonds added to make longer fats. DHA and EPA are longer fats of the Omega 3 family. GLA has one more double bond, and arachidonic acid is a longer fat and has more double bonds; both are from the Omega 6 family.

6. Plant based Omega 3 and 6 is very common because it is found in all 'green' plant based material, but in relatively small amounts; parts per thousand. Plant based Omega 6 is only found in quantity in plant reproductive material, seeds nuts and grains. Plant based Omega 3 is occasionally found in quantity in seeds, nuts and grains but not very often.

7. So in a wild diet we would have got slightly more plant based Omega 3 than 6 for most of the year with a boost of mainly Omega 6 in the fruiting and seeding seasons. In the wild seeds and nuts were not that plentiful, and very much weather dependent. On a year round basis we are maybe looking at an average intake of about 2% of calories, maybe a bit more or less depending on the particular diet. Modern intake of the Omega 6 plant based fat is maybe 10% and up to 25%, so a vast increase over our pre agricultural ancestors. The main source by far is vegetable oils.

8 Our cells can convert the plant based fats using two enzymes to the longer fats in the family. Conversion becomes increasingly difficult as the fats get longer. Conversion is much more efficient at lower intake levels. Imbalances heavily disrupt conversion. Some people are genetically less efficient converters, maybe up to 40% less efficient, and more often include celtic types/ maybe descendents of people who dwelled near the oceans ( the ocean dweller bit is postulation).

9. Importantly and probably because of estrogen ( and progesterone?) women convert plant based fats to long chain fats eg plant based Omega 3 to DHA about 10 times more efficiently than men do. This is arguably of huge importance and helps define some of the gender differences. It also magnifies the effect of Omega 3 and 6 dietary imbalances and deficiencies. These fats are fundamental to the reproductive processes and pathways including the hormonal pathways. Breast tissue concentrates these fats in breast milk to supply them to the infant, so they have a particularly important role in the breast in general terms.

10. A small amount of long chain fat Omega 3 and 6 can be got through the diet taking advantage of conversion by other animals. Long chain Omega 3s are primarily found in marine animals. Wild animals (pastured herbivores, fowl, etc) have higher Omega 3 levels than grain fed animals.

11. Omega 3 and 6 are rival siblings. The amount of each in the cell membranes reflects the amount in the diet. Both compete for the elongation conversion enzymes. An excess of either will create imbalances. Too much Omega 6 will magnify the effects of Omega 6, and too much Omega 3 will magnify the Omega 3 pathways at the expense of Omega 6 activity, which is why a balance is so important. It is not just the amount of Omega 3 and 6 that go out of balance but all their downstream products and effects. including inflammation, blood vessel formation, cell migration, cell structure, cell function at a host of levels etc etc.

In summary

You are aiming to balance plant based Omega 3 and 6, and get adequate long chain Omega 3s. Long chain Omega 6s are more readily available than 3s due to our modern food chain and higher plant based Omega 6 intake / body fat stores. Most but by no means not all will have adequate long chain Omega 6; for example breast feeding women are often lowish in long chain Omega 6.

As a vast generalization most vegetable oils are best avoided partially because they contain lots of Omega 6 and partly because of what processing does to them. Some have other useful properties - eg cold pressed olive is rich in antioxidants, so it is best to look them up, http://nutritiondata.self.com/ but the majority are high or very high in Omega 6, and often contain almost no Omega 3. They are starting to try and breed plants which are higher in Omega 9 or have a better 3:6 balance, but there is still the issue of processing and onward treatment in food preparation.

Most of us are short of Omega 3s so adding an Omega 3 rich source eg a little flax seed or oil - there are others - is logically a good idea.

Avoid industrial chicken which is very high in Omega 6, because they are fed almost exclusively on grains.

Many processed foods products will contain vegetable oils so are best avoided, and particularly so crisps cooked in vegetable oils; it is not just the vegetable oils per se but what treatment temperature cooking etc does to them which is arguably such an issue.

Try and get some oily marine foods / marine foods generally, and or supplement with fish oil in modest amounts. Omega 3 in fish muscle are in a different form to those in fish fats, and are metabolized differently, so marine foods provide a wider range of Omega 3 related products than fish oil, and marine foods contain lots of other useful nutrients.

Nuts are rich in minerals and other nutrients, and so I am ambivalent about them in larger quantities, and for them in smaller quantities.

Most have a historic excess of Omega 6, which the body likes to store in the body fats. Our omega 6 in body fat has increased from maybe 4% in the 1950s to up to 25% today. It can take a significant amount to time to re-balance the body fat content - years - but interestingly breast tissue changes much faster. So it is going to take a while to re-balance the body tissues.

There is some evidence that the benefits of fish oil e.g. EPA and DHA tail off around 2.5 to 3 grams (EPA plus DHA combined total) a day.

The optimal amount of plant based Omega 3 e.g. flax oil is less clear - the issues are very complex. Johana Budwig interestingly reported good results with flax oil and cottage cheese in the diet, and was robustly supported by her patients. The explanations were based in the knowledge of the day and lack clarity, but make some sense in a very fuzzy intuitive way - these fats are central to plant function; and plants derive their energy from light; Omega 3 it is suggested may have an important role in photosynthesis; Omega 6 is central to plant reproduction - so they may also have important roles in humans and have proved to do so. We do not really know as much about the metabolism of plant based Omega 3 as we should. Interestingly her suggestions also include sun (vitamin D), 'fermented foods' good for gut function / source of short chain fats, no refined foods etc - so lots that is familiar. Unfortunately there does not appear to be any references to her clinical notes etc, which information would provide a much clearer view of what her protocol was and how effective it was, so I post information about her with a cautionary caveat, and particularly as to some of the claims that are made by sites promoting 'her' protocol, which sites also often promote some pretty quirky treatments which good or bad should not be confused with my simple premis that Omega 3s and in this case plant based Omega 3 has highly influential roles in cellular metabolism.

I do think and the trial based evidence on this site supports a general premis that excess Omega 6 and lack of Omega 3 may increase the risk of cancer, and that the Omega 3 and 6 families and their downstream products have their own individual roles, some of which have received more research attention than others.

Getting adequate plant based and long chain Omega 3s and reducing excessive intake of plant based Omega 6s, as part of a healthy diet may well reduce the risk of cancer. Work by Budwig, anecdotal evidence etc raises the question if taking larger amounts of plant based Omega 3 and longer chain Omega 3s than would be found in the natural diet as a initial strategy to try and rebalance body fats, and cellular function at many levels, is a useful strategy in the prevention / slowing / reduction of recurrence etc.

The importance of wider diet, adequate vitamin D and related fat soluble vitamins, iodine, and a host of other nutrients, cannot be stressed enough. The Omega 3;6 balance may prove to be a highly significant factor in the risk of cancer, but it is only one of many.

R.B.

04-26-2013, 02:55 PM

D6D is short hand for one of the two enzymes that convert the plant based Omega 3 and 6 to the long fats.

LA is the plant based Omega 6 linoleic acid

AA arachidonic acid is an important elongated fat made form the plant based Omega 6.

PGE2 is a downstream product of Omega 6

Excessive Omega 6 tends to overwhelm the D6D enzyme creating an excess of downstream product. Omega 3 if present would help counterbalance that effect.

Also see following post

Cancer Sci. 2013 Feb 18. doi: 10.1111/cas.12129. [Epub ahead of print]
Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue.
Pender-Cudlip MC, Krag KJ, Martini D, Yu J, Guidi A, Skinner SS, Zhang Y, Qu X, He C, Xu Y, Qian SY, Kang JX.
Source

Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract

Omega-6 (n-6) arachidonic acid (AA) and its pro-inflammatory metabolites, including prostaglandin E2 (PGE2 ), are known to promote tumorigenesis. Delta-6 desaturase (D6D) is the rate-limiting enzyme for converting n-6 linoleic acid (LA) to AA. Our objective was to determine if AA synthesis, specifically D6D activity, and PGE2 levels are increased in cancerous breast tissue, and whether these variables differ between estrogen receptor positive (ER+) and negative (ER-) breast cancers. Gas chromatography was performed on surgical breast tissue samples collected from 69 women with breast cancer. Fifty-four had ER+ breast cancer, and 15 had ER- breast cancer. Liquid chromatography-mass spectrometry was used to determine PGE2 levels. Lipid analysis revealed higher levels of LA metabolites (C18:3 n-6, C20:3 n-6, and AA) in cancerous tissue than in adjacent noncancerous tissue (P < 0.01). The ratio of LA metabolites to LA, a measure of D6D activity, was increased in cancerous tissue, suggesting greater conversion of LA to AA (P < 0.001), and was higher in ER- than in ER+ patients, indicating genotype-related trends. Similarly, PGE2 levels were increased in cancerous tissue, particularly in ER- patients. The results showed that the endogenous AA synthetic pathway, D6D activity, and PGE2 levels are increased in breast tumors, particularly those of the ER- genotype. These findings suggest that the AA synthetic pathway and the D6D enzyme in particular may be involved in the pathogenesis of breast cancer. The development of drugs and nutritional interventions to alter this pathway may provide new strategies for breast cancer prevention and treatment.

Â© 2013 Japanese Cancer Association.

R.B.

04-26-2013, 03:01 PM

As a follow on from the above the D6D conversion enzyme activity has been shown to have an important role in cancer promotion and blocking it has been shown to significantly reduce tumor growth.

They suggest blocking this pathway and increasing Omega 3 intake of both plant and long chain fats may be an interesting potential treatment strategy.

Increasing Omega 3 intake and reducing Omega 6 intake will help rebalance these pathways.

Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice
Chengwei He,1,4 Xiying Qu,1 Jianbo Wan,1 Rong Rong,1 Lili Huang,1 Chun Cai,2 Keyuan Zhou,2 Yan Gu,3 Steven Y. Qian,3 and Jing X. Kang1,2,*
Wolf-Hagen Schunck, Editor

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480421/

The whole article is available on the link above

"Arachidonic acid (AA), an omega-6 (n−6) polyunsaturated fatty acid, is converted through three major pathwaysâ€“ the cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 epoxygenase pathwaysâ€“into bioactive lipid mediator eicosanoids, including prostaglandins (PGs), leukotrienes (LTs), and epoxyeicosatrienoids (EETs), respectively [5], [6] (Figure S1). These metabolites have crucial roles in chronic inflammation and cancer [5]â€“[7]. Increased AA metabolism and eicosanoid formation is a common feature of various types of cancer cells [8], [9]. AA-derived pro-inflammatory eicosanoids, particularly PGE2 and LTB4 which are produced by tumor cells and their surrounding stromal cells, are key mediators in their crosstalk and can accelerate tumor growth and metastasis through several mechanisms [5], including: 1) directly activating their receptors on tumor cells to induce cell proliferation, survival, migration, and invasion through multiple signaling pathways in both autocrine and paracrine manners, 2) directly inducing cancer cells to secrete growth factors, pro-inflammatory mediators and angiogenic factors that turn a normal microenvironment into one that supports tumor growth and spread, and 3) directly binding receptors on stromal cells to promote a tumor-supportive microenvironment by inducing angiogenesis and evading attack by the immune system"

Andrea Barnett Budin

05-03-2013, 08:16 AM

Should I be taking Krill Oil vs my Omega 3's?

I don't need a symposium answer, just a simple explanation for a simple girl, please.

RB, you are the go-to guy on this topic and you've always been sooo great to all of us, your Sisters. Thanks for remembering us.

Andi

R.B.

05-10-2013, 12:53 PM

Hi Andi

I love your positive outlook and smiley posts.

Both fish oils and krill oils are high in Omega 3. The amount of long chain Omega 3 also called EPA and DHA per 1gram (1000mg) of oil depends on the marine source of the oil, as well as the extraction and refining process used in the particular oil product, and varies hugely; so check the label when considering which brand to purchase.

The primary difference between fish and krill oil are the structures to which Omega 3 is attached, which affects the way and location in which it is mainly used in the body. To understand this you need to know a little about how fats are organised in different tissues.

Fat is most commonly attached to another substance most commonly in either pairs or sets of three; image toast in toast racks, the toast is the fat and the rack the binding substance. In cell membranes fats are generally found in pairs, two slices of 'toast' to a 'rack' (phospholipids). Fat in fat cells is always found in threes, three slices of toast to a rack (triglycerides).

The toast racks used in cell membranes and fat storage are different designs; and to make things more complicated whilst there is only one design of rack for fat storage there are several models used in cell membranes.

Fish oil are extracted from fish, and crustaceans like Krill, by a combination of pressure and solvents. The ratio of storage fat to membrane fat in the krill or fish body will determine the ratio of phospholipids to triglycerides.

Krill do not contain much body storage fat compared to oily fish, and so krill oil contains mainly membrane fats (phospholipids). Oily fish contain lots of storage fat so fish oil contains mainly triglycerides.

Cell membrane fat is less resistant to oxidation than storage fat, so when they process oily fish they generally remove the cell membrane fat from fish oil products because it is easier to produce a stable product with a good shelf life; so even though membranes fats were present in the fish they do not make it into fish oil.

Krill are processed into other food products, such as protein etc, which involves removing the oil, so they started at looking at ways to process and conserve the oil rich in cell membrane fats as an Omega 3 rich product, and found ways to do so. They were helped because the krill contained a powerful antioxidant that helped protect these membrane fats from oxidation. The result is Krill oil, which contains omega 3 and other fats, and is mainly in the form of fats found in the cell membrane rather than storage fats.

Once they are in the body, the fats in cell membrane form can be directly used in the structure of cell membranes. In contrast storage fats would first have to be broken down and remade into cell membrane fats. Omega 3 rich membrane based fats are important to the function of many tissues, (and particularly the brain) which is why Krill oil may have some advantages over fish oil in so far as cell membrane function goes.

Omega 3 rich storage fats have important roles in the body too. The body will also use the Omega 3 fish oil storage based fats, but in different ways, and some of the storage fats will be converted to membrane fats for use in the cell membranes.

There are still more layers to this; not all the oil you eat ends up in the same form once it has been digested. When storage fats and cell membrane fats are digested, they are stripped down to the toast rack structure with just one fat attached, and either one or two free fats. A proportion of what is digested then gets put back together again in the original structure, but a proportion is also used as building blocks for other products including storage fats. So after digestion only a proportion of the Omega 3 rich cell membrane fats from the Krill oil eaten will be available directly for use in cell membranes in the body, while in comparison storage fats that remain in the same form after digestion would need to be reprocessed and adapted before they could be used in the cell membranes.

So krill oil is a very useful supplement along with fish oil; both provide much needed Omega 3s albeit in different forms. But they are generally both ‘solvent’ extracted so may not contain the full spectrum of fats and structures that would be found in whole food. It is also important to be cautious about miracle claims for one or other, and the advantages for krill over fish oil; they are going to do slightly different things, benefits of one over the other are not as clear cut as reports would suggest, as results depend on tissues examined, dosages, form of Omega 3s, exactly what you are looking at etc. Krill oil tends to be more expensive too, but does usefully provide the fats largely in Omega 3 rich membrane form, which you will not get in fish oil (because of the way it is processed) but will get to varying extents in fish and other marine products.

So if you are going to supplement some of both would seem a reasonable strategy, and as previously identified do not loose sight of the importance of the humble plant based Omega 3 rich foods such as flax.

Natural foods have to be the best source. Some oily fish and interestingly offal etc are good sources of membranes fats; but because we feed our livestock on grain they do not have the Omega 3 levels they should, as well as potentially containing too much Omega 6; and in reality we do not tend to eat offal any more. Brain was a traditional source of membrane Omega 3s but that is off the menu on a precautionary basis due to potential uncertainties as to the origin of neurological conditions in cattle that occurred some while ago (certainly in the UK).

The best options are the marine foods themselves, which raises the issue of the sustainability of supply. . .

I hope that helps. Thank you for your kind words they are appreciated.

P.S. Look for the phospholipid and Omega 3 content on Krill oil labels because it varies a lot between products - hopefully with both a decent phospholipid and Omega 3 content a good proportion of the phospholipids will be high in Omega 3.

P.P.S. For those unable to afford Krill a good quality fish oil is still an excellent way to get Omega 3s - but as ever fish and marine products contain a much wider range of important nutrients; but not everybody has access to or can afford fish and fish oil is a much better option than a significant Omega 3 / 6 imbalance.

P.P.P.S The amount of Omega 3 that people may want to take at the outset of a dietary change to rebalance these fats in the body might sensibly be higher, but taking large quantities for years is probably not a good idea for a wide range of reasons.

P.P.P.P.S Very very very importantly it is in significant part ultimately about balance between Omega 3 and 6. It is equally important to reduce the Omega 6 intake; the amount of omega 3 needed rises with rising Omega 6. Ultimately it is simply not possible to compensate for an excess of Omega 6 even by taking excessive amounts of Omega 3.

Andrea Barnett Budin

05-12-2013, 11:14 AM

Thanks RB. So thorough and complex. Will process. Appreciate you sharing. A little Omega 3 and a little Krill is what I think I'm seeing. So interesting. So essential to everyone's life!!!! My nephew takes this and he's healthy and in his 40s. My husband has consented to take it. I am working on my dghtrs.

Plus co-enzyme Q10, plus Carnitine, plus Alpha Lipoic Acid, plus D, plus B's (especially 12 for energy!!!!!), calcium, C. Basic to wellness...

So kind of you to take the time to respond, RB...

AlaskaAngel

05-23-2013, 01:45 PM

RB, thank you for taking the time to give us a better description and mental picture of how it all works. I understand it a bit better for that.

A.A.

Becky

05-24-2013, 04:30 AM

Never told you guys this but I think I have told you I am a sales rep. However, in more detail, I am a sales rep for a major chemical company. I sell for many divisions of the company but only to our distributors who then sell to small and medium sized end users who can't meet our minimum orders (hence they buy from our distributors). Last year our Human Nutrition group decided to put their products into distribution and I have the one National distributor that does this. Hence - training. I just got back from a big training seminar (2 days) on Omega 3 (we are a huge producer). So, I asked the question on how to sell our products more effectively over Krill. The big answer is don't. They are different products and you do need to take both. As RB stated, there is virtually no way to get the phospholipids that Krill provides. Phospholipids are also important. Also, if you are not sure of the Fish Oil source you are buying from, buy the higher strength softgels (usually named "Triple Strength" etc). These softgels use the highest purity fish oil. They are highly refined (with membrane separation not chemical separation) and are heavy metal free. Do not buy salmon fish oil as they use salmon (duh) which is a large fatty fish and could have heavy metal contaminates. Most fish oil (if not all) use anchovy or sardines fished off the Peruvian coast. These are small fish hence far, far less natural heavy metal contamination.

On the flip side, I also sell sodium nitrate for hot dogs:(

karen z

05-24-2013, 05:04 AM

RB
Can you recommend name brands/dosages for those folks who want to get seriously started on taking both Krill and Omega 3?

NEDenise

05-25-2013, 07:32 AM

Becky,
I've found that if I spread the fish oil on the hotdogs...I get a nice anti-oxidant buzz going! :)
Denise
PS - India relish is also good!

Andrea Barnett Budin

05-25-2013, 12:18 PM

Denise -- you spread the Fish Oil on hot dogs??? Huh?

Sounds weird but if you say so, I'm thinking...

How about on the zucchini pancakes I have for dinner?

You actually cut open the capsule? I am lost here. Please explain ...

NEDenise

05-25-2013, 12:40 PM

Joking! Hello! Remember who you're talking to my friend! :)

Wouldn't crack open that capsule on a bet!
Denise

Andrea Barnett Budin

05-25-2013, 05:17 PM

I think you had me with THE ANTI-OXIDANT BUZZ GOING...

Thanks for clearing that up. (I'm sooo literal... Silly...)

Andi

NEDenise

05-26-2013, 05:13 AM

You crack me up!

How about dishin' up the recipe for those zucchini pancakes though. I LOVE zucchini anything! :)
Denise
I'm not planning to put fish oil on them! :)

Andrea Barnett Budin

05-26-2013, 01:36 PM

Ok, Denise (and all interested in zucchini pancakes)...!

First -- you go to Costco.

Buy GABELIA'S ZUCCHINI PANCAKES from freezer section.

I am laughing. But this is the recipe.

Keep in freezer till ready to cook. Put extra virgin olive oil (of course) in pan. Saute 2 minutes on each side. Serve. Eat.

My family like raspberry jam w/these. But they are excellent with nothing. They are 120 calories each. I had 1 last night -- without spreading any omega 3 on it. LOL... My husband had 1 and 1/2 (which he split w/my son-in-law who'd already eaten his 1). My dghtr ate 1. I could have eaten 2 for sure.

Really yummy delicious!! **** 4 stars!!!!

(Aside: I swallowed my Omega 3 and alllllllll my other supplements with a gallon of filtered water an hour before and ate a banana.)

This is how I "cook"...

Much love,
Andi

NEDenise

05-26-2013, 06:07 PM

Yay Costco! I love that place!
This recipe is VERY do-able!
You got me! Now we're even!

Don't know how I've never been there on a day these were 'sampled'...but your recommendation is good enough for me! Now what will they be topped with? chopped tomatoes? butter? cheese? krill oil? :)

Denise

R.B.

06-08-2013, 03:33 PM

Hi Karen Z

I will respond to your question re products brands etc in the next day or so.

This is a great interview by Martie Whittekin a passionate health radio show host of many years standing, of one of the leading research lights in the Omega 3:6 field Artemis Simopolous, whose name you will see on some of the papers cited.

Martie is a charming knowledgeable passionate and very active proponent of the importance of diet to health, who also promotes health conferences and events.

The interview is about Omega 3 and 6 generally.

http://www.radiomartie.com/archives/2013.shtml

3rd item down in Martie's archive (-:

http://www.hbnarchive.com/2013/052513.mp3

karen z

06-09-2013, 08:28 PM

R.B.
Thanks. I look forward to receiving the information.
Best wishes,
Karen z

R.B.

08-01-2013, 03:33 AM

AndiBB emailed me about the report that Omega 3 increases prostate cancer risk and particularly high grade cancer, which seems to have caused considerable concern.

Karen z sorry about the delay - I have started but not yet finished a response - things have been a bit hectic.

This was the paper, http://jnci.oxfordjournals.org/content/early/2013/07/09/jnci.djt174.abstract
which I consider in more depth below. The title of the press release of the nested Select trial was:

“Study confirms link between high blood levels of omega-3 fatty acids and increased risk of aggressive prostate cancer - Consumption of fatty fish and fish-oil supplements linked to 71 percent higher risk ”

This was the press release
http://www.fhcrc.org/en/news/releases/2013/07/omega-three-fatty-acids-risk-prostate-cancer.html

Sadly publicity is often important to research organisations; the media respond to ‘results’ that people will talk about and are clear cut or appear as such; human nature dictates in consequence media departments; self evidently non-specialists, are at risk of over egging results, and the result is public ends up getting very confused by potentially misleading messages.

Apart form a few basic truths about the need for essential nutrients for life, the reality is things in cell biology are very rarely simple.

There is a lot of work that suggests that Omega 3 intake is associated with lower rates of prostate cancer. There are a number of biological mechanisms that would explain why Omega 3 may reduce prostate http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676993/ and some other cancer risks, and a number of observations suggest this is the case. In contrast some papers do not support this generality as is the case in this paper and its predecessor, but closer reading of the Select paper raises a host of questions as to the conclusion, some of which I raise below.

My first thought based on wider reading of reports from the mid 1900s, was that cancers were low in historic populations on non-western diets, which prompted the thought do people like Inuit who eat loads of Omega 3s have higher prostate cancer rates; the answer is no; they actually appear to have very low rates of prostate cancer. http://cebp.aacrjournals.org/content/12/9/926.long In the summary this paper includes the following statement “the prevalence of latent carcinoma is extremely low among Inuits compared with other populations”. The introduction includes the following comment "In Greenland, the age-standardized incidence rate for the 1969–1988 period was 1.7/100 000, and only four cases were diagnosed." Intriguingly the one prostate cancer case they found in the study was in a man with an unusually (for Inuit) poor Omega 3:6 ratio.

Historically population groups on non-western diets who ate significant amounts of fish also had relatively low rates of prostate cancer, and this paper, although having limitations, looking at 6272 Swedish men over 30 years found men that ate no fish had a two to three times greater risk of prostate cancer . http://www.sciencedirect.com/science/article/pii/S0140673600048893 http://ajcn.nutrition.org/content/77/3/532.full

There is also a genetically created mouse called fat1, that unlike normal mammals can convert Omega 6 to Omega 3, and even if fed Omega 6 tends to make enough Omega 3 to balance the Omega 6 in it's diet. Prostate cancer invasion and proliferation was significantly inhibited in fat1 mice. https://www.google.co.uk/search?q=fat1+mice+prostate+cancer&ie=utf-8&oe=utf-8&rls=org.mozilla:en-US:official&client=firefox-a&channel=fflb&gws_rd=cr Ok this is in rather special mice but the generality of the result goes against the suggestion that Omega 3s increase prostate cancer risk.

The fact traditional fish eaters appear to have very low or low incidence of prostate cancer suggests that whatever the Select trial was picking up, it is not as simple as dietary Omega 3s increases the risk of prostate cancer.

What might the above Select paper and its predecessor actually have detected? Unfortunately that is a pretty big question; the studies did not look at participants diet they just assumed that changed levels of long chain Omega 3 EPA and DHA in the blood must be the result of dietary intake of fish or fish oil, but these two fats are also made in the body from the plant based Omega 3 linolenic acid. As discussed below men do this pretty poorly but a host of things could alter conversion rates including hormonal changes. So the results could be down to a host of reasons excluding dietary intake, or may be due to dietary intake, as we have no idea what these people ate we simply do not know. Let us look at things in a bit more detail.

The latest Select trial was a subset of the original Select Trial which looked at the question did a particular form and dosage of Vitamin E (synthetic all rac-α-tocopheryl acetate), and or a particular form of selenium reduce prostate cancer http://jama.jamanetwork.com/article.aspx?articleid=183163 . The result was that no real change was seen for the type of selenium selected, and those that took the form of vitamin E chosen had higher rates of aggressive prostate cancer.

The particular form is important because different forms may be differently absorbed and act in different ways in the cells. Other papers have shown other forms of Vitamin E and Selenium to reduce the risk of prostate cancer. http://jnci.oxfordjournals.org/content/92/24/2018.short The dosage may also be an important factor as positive results have been seen with lower doses of some forms of vitamin E.

In the Select trial they selected those with high grade prostate cancer from all participants, including those taking selenium and vitamin E. They did not breakdown those with high Omega 3 in the blood high and high grade prostate cancer by treatment group, so we do not know if most or conversely few of the them were taking vitamin E, but we do know from the main trial that vitamin E was found to increase the risk of high grade prostate cancer, and the majority of the participants were taking vitamin E. We also know that there were more people with high BMIs in the high grade cancer group, and a greater number were taking asprin. We also know that vitamin E can block http://cancerres.aacrjournals.org/content/57/12/2410 http://www.sciencedirect.com/science/article/pii/S0271531799001554 or sometimes increase the process of apoptosis (cell death) depending on what type it is and what the dosage is.

Some forms of vitamin E at high dosages may reduce cell death because they protect polyunsaturated fats from oxidation; the oxidation of polyunsaturated fats have important roles in process of cell death, so reducing oxidation may reduce cell death, which may be great in some circumstances, but not so good if you are wanting to kill damaged or cancerous cells.

The conclusion to the Select paper should maybe have been vitamin E in the synthetic all rac-α-tocopheryl acetate form at the dosage selected, increases high grade prostate cancer, and the increase in high grade cancer was also linked with high levels of Omega 3 in the blood, but the groups were not separated out to determine if the effect of high Omega 3 was dependent on the presence of either Vitamin E or selenium in the forms selected – which would not have grabbed much media attention ! The trial is telling us something but exactly what is not clear. It is clear the press release headline should not have been the bald simplistic press statement that dietary Omega 3 increases the risk of high grade prostate cancer.

The predecessor trial looking at Omega 3s http://en.wikipedia.org/wiki/Finasteride and its original primary purpose was to look at the use of a product called finasteride http://en.wikipedia.org/wiki/Finasteride to reduce prostate cancer. The result was that finasteride may reduce prostate cancer but also may ? increase the risk of high grade cancers. Again the researchers used the same study population group including those who took the finasteride and looked at their Omega 3 status; again they found a link between Omega 3s and high grade cancers, but consideration of the effect of Omega 3 on prostate cancer risk is tainted by the fact at least part of the selected group was taking finasteride which may? increase the risk of high grade prostate cancer; did Omega 3 add to the finasteride risk; maybe, but we do not know from the information available; we cannot separate out and quantify from the information the effects of finasteride and long chain Omega 3s (be that from the diet or improved conversion) so the observed result cannot justify a conclusion that Omega 3 on its own increases the risk of high grade prostate cancer, or even that or that higher amounts of long chain Omega 3s in the plasma originated in the diet rather than by increased conversion.

As neither trial actually asked people what they were eating let alone if their Omega 3 came from fish or fish oil, we cannot even begin to differentiate the effects of fish intake or supplementation in the form of fish or krill oil on prostate cancer risk, or indeed determine if the higher levels of long chain Omega 3 in the blood was due to dietary intake, or some metabolic differences in the rate of conversion of plant based Omega 3 to long chain Omega 3. Interestingly one of the factors that affect the rates of conversion of the plant based to the longer chain Omega 3s and 6s is hormonal status; women convert much better than men, with oestrogen primarily with help from progesterone arguably increasing, and conversely testosterone arguably decreasing, conversion rates. So we do not actually know why these men had higher long chain Omega 3 in the blood; higher EPA and DHA could even for example be a marker of hormonal changes such as falling testosterone or rising oestrogen due to treatment protocols or changes in metabolism with onset of prostate cancer, or it might be what they ate, or a combination of both.

In conclusion there is no doubt the Select and Finasteride papers are telling us something; maybe long chain Omega 3 plus vitamin E, higher BMI, and aspirin use together, increase the risk of prostate cancer, or finasteride and Omega 3 further increase the risk of prostate cancer in those taking finasteride, or hormone levels change in aggressive cancers, or treatments affect hormones, so impacting on Omega 3 and 6 plant based fat conversion to long chain fats; but I suggest the basis of the trial and consequent results simply do not justify the bald title of the press release namely “Study confirms link between high blood levels of omega-3 fatty acids and increased risk of aggressive prostate cancer - Consumption of fatty fish and fish-oil supplements linked to 71 percent higher risk” which in the circumstances is not a conclusion which can in anyway be definitely drawn from the study.

It is important not to forget that Omega 3 and 6 along with many other nutrients are fundamental to cell function, and in nature are more of less in balance in the diet. Many men are very poor converters, and some population groups are genetically less efficient converters. If you are not very good at making long chain Omega 3 from plant based Omega3 you have to get it from food or supplements.

Our massive intake of Omega 6 fats increases the requirements for Omega 3s; reducing Omega 6 intake is a better strategy that taking lots of Omega 3 to compensate. Taking higher amounts of Omega 3s in the short term may be a good way to initially try and help rebalance the bodies Omega 3 / 6 status, so reducing inflammatory, replenishing tissue, displacing Omega 6s etc, but as ever the body is complex and ultimately there are down as well as upsides to all supplementation, and particularly so large amounts in the longer term.

In summary looking at the biology of the body you cannot escape the fact Omega 3 is essential to cellular function, nervous system and brain function, vision, and indeed arguably life; on which basis there is no question that in the absence of adequate dietary supply, supplementation will be of benefit. Based on a raft of reasons I recommend marine whole food sources over fish oil; but many do not eat fish, and pressure on fish populations is a fast increasing issue. Ultimately there is no question that marine oil supplementation has a place; taking fish oil is better than being Omega 3 deficient due to dietary deficiencies, and or genetic or other common dietary factors leading to poor conversion of plant based to long chain fats. Many do not get adequate dietary plant based Omega 3, even if they could efficiently convert it, and I repeat men are generally very poor converters.

In conclusion long chain Omega supplementation definitely for some has a place, because it is a healthier option than being deficient; but not as good as getting adequate long chain Omega 3s from whole foods ( and this really means quite a lot of marine foods as the way we grow our animals means they too are often low in Omega 3s eg eggs, and we no longer eat the Omega 3 rich parts like brain)

PS Martie Whittekin, impassioned health journalist, and talk show host, includes some excellent links on the Omega 3 prostate issue in the second section of her weekly diary

http://www.radiomartie.com/newsletter/2013/072513.htm

(One of the papers suggests an increased risk of prostate cancer with fried fish, which on the balance of probabilities may actually contain little Omega 3 and a lot of Omega 6 if fried in vegetable oil, and more if in batter. Fried foods absorbs considerable amounts of frying oils)

Andrea Barnett Budin

08-01-2013, 03:46 PM

RB, You're the best! Important info ladies -- for the man in your life.

The CNN report caught many of us offguard. It was alarming news. So I went to the source on Omegas.

I suppose many studies are flawed, unfortunately. And we need to investigate further.

Remember when they warned us about carcinogens in our lipstick? I have really dry lips. Chapsticks don't quite do it for me. That was decades ago. And, I'm still here...

Thanks, RB.

NEDenise

08-02-2013, 06:16 AM

Oh! How I cherish the man in my life!
Fortunately, I already have him on Omega 3s and CoQ10 for heart health.

The idea of him having to deal with cancer from the patient side of the fence is revolting! Horrifying! More than a just God would allow!

So...I hope the supplements do the trick! :)
Denise

Andrea Barnett Budin

08-05-2013, 01:12 PM

A doctor friend of my my husband's said he thinks that omega study and prostate cancer was based on the same science as -- if you play basketball, you'll grow taller...

Paul is on omega, co-enzyme, carnitine, alpha lipoic acid, b12. let me see, did I leave something out?

ANDI

Jackie07

08-05-2013, 02:24 PM

http://www.ncbi.nlm.nih.gov/pubmed/23872953

R.B.

08-07-2013, 02:59 PM

Whilst this thread is primarily about Omega 3 and 6, many are also vitamin D deficient, iodine insufficient, and lacking in one or more minerals, and may have other deficiencies in other essential nutrients, and these deficiencies ultimately inevitably must impact on cell function and most likely in a negative way.

I would strongly recommend the videos on the vitamin D thread, and in particular those by Dr Holick and Dr JoEllen Welsh.

http://her2support.org/vbulletin/showthread.php?t=43711

There is also a fascinating talk by Dr Flechas on iodine on this thread

http://her2support.org/vbulletin/showthread.php?t=53928

R.B.

09-26-2013, 03:27 PM

More evidence that Omega 3s -:) and Omega 6s (in excess -:( ) have a role in breast cancer risk reduction.

(Ooops just noted that Lani is quicker off the mark than me - thanks Lani -:) http://her2support.org/vbulletin/showthread.php?t=59076 )

FAT1 is a mouse with a gene from a worm inserted that allows them to convert Omega 6 to Omega 3; normally mammals including humans cannot convert Omega 6 to Omega 3, and we must get it from our diet, which is why getting Omega 3 in the diet is so important. Fat1 mice tend to change enough Omega 6 into Omega 3 to create an equal balance of the two in their body.

They compared how implanted HER2 cells grew in FAT1 and normal wild type (WT) mice.

Both mice were fed the same diet which contained lots of Omega 6 and very little Omega 3 (Safflower oil), but FAT1 mice (-: unlike the WT mice )-: could make their own Omega 3.

The implanted HER2 tumors initially grew in both normal (WT) and FAT1 mice, and continued to grow in the normal WT mice -:(, but in contrast shrunk and eventually disappeared -:) in the FAT1 mice.

The tumors in the FAT1 mice contained much more EPA and DHA and a much better Omega 3:6 ratio -:).

Clearly we are not FAT1 mice, but nonetheless the results are intriguing.

(15-HEPE, 17-HDHA and PGE3 are downstream Omega 3 products produced in the body
https://www.caymanchem.com/app/template/Product.vm/catalog/14990

WT is the normal mouse (Wild Type)

http://www.ncbi.nlm.nih.gov/pubmed/24052576

J Lipid Res. 2013 Sep 19. [Epub ahead of print]
Inhibition of the HER2 pathway by n-3 polyunsaturated fatty acids prevents breast cancer in fat-1 transgenic mice.
Zou Z, Bellenger S, Massey KA, Nicolaou A, Geissler A, Bidu C, Bonnotte B, Pierre AS, Minville-Walz M, Rialland M, Seubert J, Kang JX, Lagrost L, Narce M, Bellenger J.
Source

Universite de Bourgogne, France;
Abstract

Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25% to 30% of invasive breast cancer (BC) with poor patient prognosis. Due to confounding factors, inconsistencies still remain regarding protective effects of n-3 polyunsaturated fatty acids (PUFA) on BC. We therefore evaluated whether fat-1 transgenic mice, endogenously synthesizing n-3 PUFA from n-6 PUFA, were protected against BC development and we then aimed to study in vivo a mechanism potentially involved in such protection. E0771 BC cells were implanted into fat-1 and wild-type (WT) mice. After tumorigenesis examination, we analyzed the expression of proteins involved in HER2 signaling pathway and lipidomic analyses were performed in tumor tissues and plasma. Our results showed that tumors totally disappeared by day 15 in fat-1 mice when they continued to grow up in the WT. This prevention can be related in part to significant repression of the HER2/beta-catenin signaling pathway and formation of significant levels of n-3 PUFAs derived bioactive mediators (particularly 15-HEPE, 17-HDHA and PGE3) in the tumor of fat-1 mice compared to WT. All together these data demonstrate an anti-BC effect of n-3 PUFAs through, at least in part, HER2 signaling pathway downregulation, and highlight the importance of gene-diet interactions in BC.

The full paper can be read free here (-: http://www.jlr.org/content/early/2013/09/19/jlr.M042754.long and includes the comment below

"To test the hypothesis that balanced ratio of n-6/n-3 fatty acid is able to decrease the risk of
BC, we implanted E0771 mouse BC cells into the fat-1 and WT mice and examined the
tumorigenicity of inoculated tumor cells. As shown in Fig.1, there was a dramatic difference
in the tumor volume between fat-1 transgenic (n=10) and WT mice (n=6). Over an
observation period of 25 days, all mice initially developed a palpable tumor by day 7 but,
importantly, all the tumors in fat-1 mice never grew up more and all palpable tumors
disappeared at day 18. By contrast, all the tumors in wild-type mice continued to grow up
until host sacrifice. These findings clearly show that expression of fat-1 inhibits the growth of
BC cells in vivo and results in mammary tumor regression.
Inhibition"

"Tumor n-3 fatty acid enrichment and formation of PUFA-derived mediators
As shown in Fig. 3A, fatty acid composition of tumor total lipids revealed higher levels of
10
EPA (20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) in fat-1 transgenic mice compared
with WT animals, whereas AA (20:4n-6) was decreased by 70%. Interestingly, the n-6/n-3
PUFA ratio (Figure 3B) was significantly reduced in tumors from fat-1 mice (8.92Â±2.63)
compared to WT animals (30.51Â±6.99) despite the animals were fed the same diet. These
results indicate expression of fat-1 enriches the transgenic animals in n-3 PUFA at the
expense of n-6, giving a lower n-6/n-3 ratio."

The pictures of the dead mice and their tumors or lack of them are not pretty but exceptionally powerfully make the point of this important trial; and yes I do 'feel' for the mice. (page 27)

The graph of the relative tumor sizes is equally very powerful. (page 27)

All of which takes us back to a French paper in which it was noted that women with higher levels of DHA in breast tissue had a 70% lower risk of their excised breast tissue 'lumps' being cancerous

R.B.

09-27-2013, 03:19 PM

This trial was mentioned in the paper above and is specifically relevant to HER2. I do not recall posting it before.

Essentially more of the same . . .

LA = linoleic acid the omega 6 found in quantity in most vegetable oils

Dietary fatty acids regulate the activation status of Her-2/neu (c-erbB-2) oncogene in breast cancer cells

http://annonc.oxfordjournals.org/content/15/11/1719.long

"This report shows, to the best of our knowledge for the first time, that dietary FAs previously characterized for either their breast cancer protective effect (ALA, EPA, DHA and OA) or its tumoricidal actions (GLA) significantly downregulate Her-2/neu ECD concentration and, consequently, the activation status of Her-2/neu in SK-Br3 and BT-474 human breast cancer cell lines, which contain Her-2/neu oncogene amplification. Remarkably, LA, a ω-6 FA with a strong tumorigenesis stimulating effect, significantly increased Her-2/neu ECD concentration. "

"Nonetheless, it is reasonable to suggest that some types of dietary FAs not only represent promising therapies for prevention and/or management of Her-2/neu-overexpressing breast carcinomas, but also may be even more beneficial when given in combination with novel therapies directed against Her-2/neu. We are currently investigating whether these findings will be helpful in the design of novel approaches to delay or prevent trastuzumab (Herceptin™) resistance. "

R.B.

10-12-2013, 10:53 AM

Number of views 44,444 :)

I just visited and saw this and it made me smile; I like patters in numbers, looking forward to 55,555 :)

Thank you very much for your interest and support everybody :)

I have learned a lot in the process :)

Andrea Barnett Budin

10-14-2013, 09:49 AM

Hi RB,

It's always good to feel appreciated for all your hard work and well-intentioned efforts! And that you are.

Plus, you're right, as we give we learn, and grow and that is the marvelous part of giving of yourself. It's a WIN WIN situation!!

Love,
Andi

R.B.

11-18-2013, 02:36 PM

A bit complicated but yet more evidence of the involvement of Omega 6 in breast cancers.

D6D is one of the enzymes that convert plant based Omega 6 (LA) and plant based Omega 3 to the longer fats of the same respective families. The amount of Omega 3 or 6 stored in cell membranes ready for conversion by these enzymes is proportional to the dietary intake.

AA is a longer chain Omega 6.

PGE2 is an oxidized from of AA.

So it is possible to change the processes that take place in these pathways though the choice of dietary intakes of fats.

As often discussed in general on a population wide basis we eat far to much plant based Omega 6 (50% to 70% of many vegetable oils), and too little Omega 3 both plant based and long chain including EPA and DHA, which are not found in many food in quantity. etc etc.

Cancer Sci. 2013 Jun;104(6):760-4. doi: 10.1111/cas.12129. Epub 2013 Mar 19.
Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue.
Pender-Cudlip MC, Krag KJ, Martini D, Yu J, Guidi A, Skinner SS, Zhang Y, Qu X, He C, Xu Y, Qian SY, Kang JX.
Source

Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Abstract

Omega-6 (n-6) arachidonic acid (AA) and its pro-inflammatory metabolites, including prostaglandin E2 (PGE(2)), are known to promote tumorigenesis. Delta-6 desaturase (D6D) is the rate-limiting enzyme for converting n-6 linoleic acid (LA) to AA. Our objective was to determine if AA synthesis, specifically D6D activity, and PGE(2) levels are increased in cancerous breast tissue, and whether these variables differ between estrogen receptor positive (ER+) and negative (ER-) breast cancers. Gas chromatography was performed on surgical breast tissue samples collected from 69 women with breast cancer. Fifty-four had ER+ breast cancer, and 15 had ER- breast cancer. Liquid chromatography-mass spectrometry was used to determine PGE(2) levels. Lipid analysis revealed higher levels of LA metabolites (C18:3 n-6, C20:3 n-6, and AA) in cancerous tissue than in adjacent noncancerous tissue (P < 0.01). The ratio of LA metabolites to LA, a measure of D6D activity, was increased in cancerous tissue, suggesting greater conversion of LA to AA (P < 0.001), and was higher in ER- than in ER+ patients, indicating genotype-related trends. Similarly, PGE(2) levels were increased in cancerous tissue, particularly in ER- patients. The results showed that the endogenous AA synthetic pathway, D6D activity, and PGE(2) levels are increased in breast tumors, particularly those of the ER- genotype. These findings suggest that the AA synthetic pathway and the D6D enzyme in particular may be involved in the pathogenesis of breast cancer. The development of drugs and nutritional interventions to alter this pathway may provide new strategies for breast cancer prevention and treatment.

OR eat much less Omega 6 and more Omega 3, a whole food diet that has not been de-mineralised and oxidised in storage and processing etc . . . but to give this advice would not be very helpful if your future career depended on securing future funding for drugs research. . . there has to be a better way of looking at health provision, a market that is more aware that we all share a very small precious planet, and will need to be at our best to have any hope of keeping it that way, that allows researchers to both secure research funding to expand important knowledge and give optimal health advice !

R.B.

11-18-2013, 02:54 PM

Thing are rarely simple, and still much is unknown; the mysteries of estrogen !

N-3 Poly-Unsaturated Fatty Acids Shift Estrogen Signaling to Inhibit Human Breast Cancer Cell Growth

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0052838

WenQing Cao, ZhiFan Ma, Mark M. Rasenick, ShuYan Yeh, JiangZhou Yu

"These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment."

"Introduction

Fish oil dietary supplements have become increasingly popular. They are consumed for a variety of ailments as well as for promotion of general health. Population and preclinical studies have suggested that n-3 PUFAs inhibit BCa growth and improve treatment outcomes [1]. Accumulating evidence states that n-3 PUFAs may exert an antitumor action by altering lipid composition of the plasma membrane, which may affect the physical and chemical properties of lipid rafts, consequently, affecting localization of and interactions among signaling components in the microdomains of cell membrane [2]–[4]. Recent studies in breast cancer cells also found that, n-3 PUFA could incorporate different components of the cell membrane to remodel membrane architecture [5], [6]. These suggested a potential mechanism underlying n-3 PUFA anti-cancer effect. N-3 PUFA treatment decreases EGFR signaling [7], and down-regulates CXCR4 signaling in MDA-MB-231 cells [8], which might play the important roles in the anti-BCa effect of n-3 PUFAs. While E2 signaling is crucial for BCa tumorigenesis and progression, fewer studies have addressed how n-3 PUFAs affect E2 signaling and biologic function in BCa cells. It is noteworthy that in the animal studies on chemo-preventive properties of n-3 PUFAs, estrogen does not override the inhibitory effect of high n-3 PUFA diet on BCa growth [9], implying that n-3 PUFAs might abrogate/reduce/reverse the pro-proliferative effect of estrogen.

Estrogen, a mitogen, stimulates cell proliferation and prevents cell death in many different cell types, and is an important risk factor for BCa development [10]. Anti-estrogen therapies have been widely employed to treat hormone dependent BCa. However, laboratory studies have suggested that estrogen stimulates the apoptosis in long-term estrogen deprivation of MCF-7 BCa cells, and switches from being a mitogenic agent to inhibiting growth and inducing apoptosis [11]–[13]. Two potential mechanisms underlying this paradoxical effect of estrogen have been suggested in the studies that can be triggered either through the extrinsic death receptor pathway [12] or via the intrinsic pathway of mitochondrial disruption and release of cytochrome C [11]. Nevertheless, it is not clear how estrogen might promote BCa cell apoptosis.

Based on the above scientific findings, we propose that n-3 PUFAs alter estrogen signaling cascades in BCa cells, and initiate/augment the inhibitory effect of E2 (or compounds binding to membrane E2 receptors) on breast cancer. In this study, we first found that n-3 PUFA treatment initiated the inhibitory effect of E2 on MCF-7 and T47D BCa cell growth, and increased cell apoptosis. While these effects of estrogen were independent of the classical estrogen receptors, ERα or ERβ, they required the presence of the estrogen-sensitive G protein coupled receptor (GPCR), GPER1. Data from this study could lead to novel insights into the usefulness of n-3 PUFAs in the treatment of BCa."

R.B.

11-18-2013, 03:25 PM

And just in case you missed this on the iodine thread on the nutrition page . . .

"And for all you reggae fans; something to listen to http://tonyvendryes.com/ whilst reading this thread (-:

(It takes a few seconds for the music to start once you the page opens, worth the wait :) )

Bear with the spoken intro (-:

Love the lyrics (-:

I have not looked at the site content, but love this Doctor's approach."

http://tonyvendryes.com/

"Prevention is better than cure you often have been told make wellness your number one goal for health is better than gold"

Andrea Barnett Budin

11-18-2013, 04:59 PM

Love the music, the accent AND THE MESSAGE!

We are each a healer. We just have to awaken that part of ourselves.

Thanks, R.B.

R.B.

01-03-2014, 03:20 PM

Both Omega 3 and calorie restriction have been suggested to have a role inhibiting cancers.

Here mice that over-express HER2 were allowed to eat as much as they wanted (AL), or calorie restricted. Some were fed with an omega 6 rich oil (soy oil which contains some plant based Omega 3 unlike many other vegetable oils) as their main fat and others with the Omega 3 EPA as their main fat.

The eat all you like high Omega 6 mice :( had an 87% tumor incidence, and the intermittently calorie restricted with a high Omega 3 EPA intake had a 15% tumor incidence, which is thought provoking :) as well as supporting the general contention of this thread.

It is interesting that intermittent calorie restriction was more effective than chronic restriction, which raises a lot of questions.

It would be interesting to know the original dietary content of the mice and their fat tissue compositions prior to the experiment; I have not seen the full paper.

As previously discussed on the separate but related topic of ketogenic diets for cancer, it is also likely that outcomes will depend on the type of fat consumed.

control (Con) ad libitum (AL),
intermittent calorie-restricted (ICR)
chronic calorie-restricted (CCR)

Cancer Prev Res (Phila). 2013 Jun;6(6):540-7. doi: 10.1158/1940-6207.CAPR-13-0033. Epub 2013 Apr 2.
Combination of intermittent calorie restriction and eicosapentaenoic acid for inhibition of mammary tumors.
Mizuno NK, Rogozina OP, Seppanen CM, Liao DJ, Cleary MP, Grossmann ME.
Author information
Abstract

There are a number of dietary interventions capable of inhibiting mammary tumorigenesis; however, the effectiveness of dietary combinations is largely unexplored. Here, we combined 2 interventions previously shown individually to inhibit mammary tumor development. The first was the use of the omega-3 fatty acid, eicosapentaenoic acid (EPA), and the second was the implementation of calorie restriction. MMTV-Her2/neu mice were used as a model for human breast cancers, which overexpress Her2/neu. Six groups of mice were enrolled. Half were fed a control (Con) diet with 10.1% fat calories from soy oil, whereas the other half consumed a diet with 72% fat calories from EPA. Within each diet, mice were further divided into ad libitum (AL), chronic calorie-restricted (CCR), or intermittent calorie-restricted (ICR) groups. Mammary tumor incidence was lowest in ICR-EPA (15%) and highest in AL-Con mice (87%), whereas AL-EPA, CCR-Con, CCR-EPA, and ICR-Con groups had mammary tumor incidence rates of 63%, 47%, 40%, and 59%, respectively. Survival was effected similarly by the interventions. Consumption of EPA dramatically reduced serum leptin (P < 0.02) and increased serum adiponectin in the AL-EPA mice compared with AL-Con mice (P < 0.001). Both CCR and ICR decreased serum leptin and insulin-like growth factor I (IGF-I) compared with AL mice but not compared with each other. These results illustrate that mammary tumor inhibition is significantly increased when ICR and EPA are combined as compared with either intervention alone. This response may be related to alterations in the balance of serum growth factors and adipokines.

R.B.

01-26-2014, 01:00 PM

Nutr Cancer. 2014 Jan;66(1):68-76. doi: 10.1080/01635581.2014.847964. Epub 2013 Nov 25.
High-dose eicosapentaenoic Acid and docosahexaenoic Acid supplementation reduces bone resorption in postmenopausal breast cancer survivors on aromatase inhibitors: a pilot study.
Hutchins-Wiese HL, Picho K, Watkins BA, Li Y, Tannenbaum S, Claffey K, Kenny AM.
Author information
Abstract

Postmenopausal breast cancer survivors are living longer; however, a common class of drugs, aromatase inhibitors (AI), depletes estrogen levels, promotes bone loss, and heightens fracture risk. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may offset AI effects to bone because of the known effects on cellular processes of bone turnover. Therefore, we hypothesized that 4 g of EPA and DHA daily for 3 mo would decrease bone turnover in postmenopausal breast cancer survivors on AI therapy in a randomized, double-blind, placebo controlled pilot study that included 38 women. At baseline and 3 mo, serum fatty acids, bone turnover, and inflammatory markers were analyzed. Serum EPA and DHA, total and long-chain (LC) omega (n)-3 polyunsaturated fatty acids (PUFA) increased, whereas arachidonic acid, total and LC n-6 PUFA, and the LC n-6:n-3 PUFA ratio decreased compared to placebo (all P < .05). Bone resorption was inhibited in the fish oil responders compared to placebo (P < .05). Inflammatory markers were not altered. This short-term, high-dose fish oil supplementation study's findings demonstrate that fish oil can reduce bone resorption; however, longer-term studies are needed to assess bone density preservation and to explore mechanistic pathways in this population at high risk for bone loss.

R.B.

06-14-2014, 06:01 AM

More general advice on the importance of the Omega 3:6 ratio

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3987049/

Helping women to good health: breast cancer, omega-3/omega-6 lipids, and related lifestyle factors
Michel de Lorgerilcorresponding author1 and Patricia Salen1
Author information ► Article notes ► Copyright and License information ►
Go to:
Abstract

In addition to genetic predisposition and sex hormone exposure, physical activity and a healthy diet play important roles in breast cancer (BC). Increased intake of omega-3 fatty acids (n-3) associated with decreased omega-6 (n-6), resulting in a higher n-3/n-6 ratio compared with the western diet, are inversely associated with BC risk, as shown by Yang et al. in their meta-analysis in BMC Cancer. High consumption of polyphenols and organic foods increase the n-3/n-6 ratio, and in turn may decrease BC risk. Intake of high fiber foods and foods with low glycemic index decreases insulin resistance and diabetes risk, and in turn may decrease BC risk. The modernized Mediterranean diet is an effective strategy for combining these recommendations, and this dietary pattern reduces overall cancer risk and specifically BC risk. High-risk women should also eliminate environmental endocrine disruptors, including those from foods. Drugs that decrease the n-3/n-6 ratio or that are suspected of increasing BC or diabetes risk should be used with great caution by high-risk women and women wishing to decrease their BC risk.

Please see related article: http://www.biomedcentral.com/1471-2407/14/105/abstract.

R.B.

06-14-2014, 06:05 AM

And from the same authors the following heads up. I have not looked into statins in any detail so cannot meaningfully comment. There are suggestions that statins both increase and reduce cancer risk

http://www.ncbi.nlm.nih.gov/pubmed/24903828

BMC Med. 2014 Jun 5;12(1):94. doi: 10.1186/1741-7015-12-94.
Do statins increase and Mediterranean diet decrease the risk of breast cancer?
de Lorgeril M1, Salen P.
Author information
Abstract
BACKGROUND:

Physical exercise and healthy dietary habits are recommended to prevent breast cancer.
DISCUSSION:

Increased intake of omega-3 fatty acids associated with decreased omega-6 - resulting in higher omega-3 to omega-6 ratio compared with Western-type diet - is inversely associated with breast cancer risk. The modernized Mediterranean diet with high omega-3 to omega-6 ratio, high fiber and polyphenol intake, and consumption of low-glycemic index foods reduces overall cancer risk and specifically breast cancer risk. It has been suggested that consuming no more than one alcoholic drink per day, preferably wine, is preferable. Eliminating environmental contaminants, including endocrine disruptors, and favoring organic foods to increase polyphenol intake and the omega-3 to omega-6 ratios were also shown to be beneficial. Cholesterol-lowering statins may decrease antitumor defenses; are toxic for the mitochondria; decrease the omega-3 to omega-6 ratio; increase body mass index, insulin resistance and diabetic risk; and have been associated with an increased breast cancer risk.
SUMMARY:

Therefore, as well as making lifestyle changes to decrease breast cancer risk, we argue that physicians should carefully consider (and often avoid) therapies that may increase breast cancer or diabetes risk in high-risk women and women who wish to decrease their breast cancer risk

SoCalGal

06-14-2014, 03:17 PM

Hi RB,
great info as always. one of my best docs has been talking about this for 7 years. It's why I'm gluten and dairy free and work hard to balance the omegas. He's also very down on statins as they are so widely prescribed. Luckily not an issue for me.
Thanks for the info - gonna copy and re-post on my Facebook feed!

R.B.

10-03-2014, 06:05 AM

If anybody is in the UK and interested I am speaking at a Royal Society of Medicine food section conference on hidden nutritional deficiencies in my new role as recently appointed Chair of the McCarrison Society, which is a venerable society with its own widely recognized Journal 'Nutrition and Health'.

I will be looking in whistle-stop fashion at deficiencies in nutrients particularly Iodine, Vitamin D, minerals, and imbalances in Omega 3 and 6 set within the context of the shoreline diet which arguably provided the conditions for out existence.

The Society has a long illustrious history, but is in need of a bit of revamping including a new web site.

I am hoping to make it a forum to bring together the Food Agricultural and Health sectors to the same table, which they never are, to try and bring focus on deficiencies such as Vitamin D, Iodine and secure the implementation of strategies to address them.

This is the link to the conference.

http://www.rsm.ac.uk/events/fhf01

R.B.

10-20-2014, 11:35 AM

GREAT to see the forum back :) :) :) :) :)

FREE STUDENT PLACES (UK accredited conference at the Royal Society of Medicine - food section)

There are a small number of free student (medical nutrition related) places at the above, but the offer closes tomorrow apparently. If interested please Pmail me

Availability depends on demand but I will be delighted to pass the application on.

The spaces have now gone - sorry about the previous typos - did not see them at the time

R.B.

01-19-2015, 06:38 AM

18:3n3 is linolenic acid the plant based 18 carbon found for example in flaxseed oil

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033520/

FREE FULL TEXT available

Br J Cancer. 1994 Aug;70(2):330-4.
alpha-Linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer.
Bougnoux P1, Koscielny S, ChajÃ¨s V, Descamps P, Couet C, Calais G.
Author information
Abstract

The association between the levels of various fatty acids in adipose breast tissue and the emergence of visceral metastases was prospectively studied in a cohort of 121 patients with an initially localised breast cancer. Adipose breast tissue was obtained at the time of initial surgery, and its fatty acid content analysed by capillary gas chromatography. A low level of alpha-linolenic acid (18:3n-3) in adipose breast tissue was associated with positive axillary lymph node status and with the presence of vascular invasion, but not with tumour size or mitotic index. After an average 31 months of follow-up, 21 patients developed metastases. Large tumour size, high mitotic index, presence of vascular invasion and low level of 18:3n-3 were single factors significantly associated with an increased risk of metastasis. A Cox proportional hazard regression model was used to identify prognostic factors. Low 18:3n-3 level and large tumour size were the two factors predictive of metastases. These results suggest that host alpha-linolenic acid has a specific role in the metastatic process in vivo. Further understanding of the biology of this essential fatty acid of the n-3 series is needed in breast carcinoma.

R.B.

01-19-2015, 06:47 AM

Eur J Cancer. 2000 Feb;36(3):335-40.
Low alpha-linolenic acid content of adipose breast tissue is associated with an increased risk of breast cancer.
Klein V1, ChajÃ¨s V, Germain E, Schulgen G, Pinault M, Malvy D, Lefrancq T, Fignon A, Le Floch O, Lhuillery C, Bougnoux P.
Author information
Abstract

Data derived from experimental studies suggest that alpha-linolenic acid may have a protective effect in breast cancer. Observations obtained from epidemiological studies have not allowed conclusions to be drawn about a potential protective effect of dietary alpha-linolenic acid on breast cancer, possibly because of methodological issues. This case-control study conducted in an homogeneous population from a central area in France was designed to explore the hypothesis that alpha-linolenic acid inhibits breast cancer, using fatty acid levels in adipose breast tissue as a biomarker of past qualitative dietary intake of fatty acids. Biopsies of adipose breast tissue at the time of diagnosis were obtained from 123 women with invasive non-metastatic breast carcinoma. 59 women with benign breast disease served as controls. Individual fatty acids were analysed by capillary gas chromatography. An unconditional logistic regression model was used to obtain odds ratio estimates whilst adjusting for age, menopausal status and body mass index (BMI). No association was found between fatty acids (saturates, monounsaturates, long-chain polyunsaturates n-6 or n-3) and the disease, except for alpha-linolenic acid which showed an inverse association with the risk of breast cancer. The relative risk of breast cancer for women in the highest quartile of adipose breast tissue alpha-linolenic acid level was 0.36 (95% confidence interval=0.12-1.02) compared with those in the lowest quartile (P trend=0.026), suggesting a protective effect of alpha-linolenic acid in the risk of breast cancer. The effects of dietary alpha-linolenic on the risk of breast cancer warrant further study.

R.B.

08-22-2015, 02:30 AM

Hi All :)

Role of dietary fatty acids in mammary gland development and breast cancer

Definitely worth a quick skin or full read if you have the time.

Some general and understandable background into the role of Omega 6 and 3 on the risk of breast cancer set in the context of long term intakes.

I am sorry there have not been as many posts lately I have been really busy on related issues.

Hopefully you to will get full free access.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096965/

Breast Cancer Res. 2010; 12(5): 211.
Published online 2010 Oct 26. doi: 10.1186/bcr2646
PMCID: PMC3096965
Role of dietary fatty acids in mammary gland development and breast cancer
Mira MacLennan and David WL Ma

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096965/

R.B.

01-01-2016, 03:02 PM

"Sugar in western diets increases risk for breast cancer tumors and metastasis"

"The high amounts of dietary sugar in the typical Western diet may increase the risk of breast cancer and metastasis to the lungs, according to a study at The University of Texas MD Anderson Cancer Center. "

http://medicalxpress.com/news/2016-01-sugar-western-diets-breast-cancer.html

What's this got to do with Omega 3 and 6 is probably your first thought.

A pathway increased by sugar is the expression of an enzyme called LOX12, which is an enzyme that is one of the key pathways by which plant based Omega 6 linoleic acid and the longer chain arachidonic acid are converted to downstream oxidized products that are highly bio-active including 12HETE, which has roles in controlling cell growth and invasion.

http://www.nature.com/bjc/journal/v105/n2/full/bjc2011194a.html

The pathways are multiple and complex, and much remains to be determined, but several oxidized products of Omega 6s are associated with increased risks of cancer by multiple mechanisms.

So here it appears we have a cross amplification of relevant pathways by excess sugar and Omega 6s in the diet.

I see Lani has also posted the story. http://her2support.org/vbulletin/showthread.php?t=64352

This emphases how interlinked things are and that approaches need to be holistic.

R.B.

06-05-2016, 02:22 PM

An ACSO meeting presentation Mediterranean Diet v Other Diet - 3 years - return of cancer - 0 v 11

I will go and try and find the paper at some point - the details of the diets would be interesting.

News paper report

Yes a small study number but nonetheless thought provoking.

http://www.theguardian.com/society/2016/jun/05/mediterranean-diet-stop-breast-cancer-coming-back-study-italy-fruit-vegetables-fish-olive-oil

"Mediterranean diet may help stop breast cancer coming back, study says "

Abstract

"The study presented at the American Society of Clinical Oncology (ASCO) meeting in Chicago is a trial in Italy which compared the outcomes for 307 women who had been treated for early breast cancer. One group of 199 women were asked to eat a Mediterranean diet, involving four portions of vegetables, three pieces of fruit and one serving of grains a day, together with four or more servings of fish each week, some red and processed meat and plenty of olive oil. They were allowed up to one alcoholic drink a day.

The other group of 108 women were asked to eat their normal diet, but given advice on healthy food by a dietician.

The cancer researchers at Piacenza hospital, Italy, found that after three years, 11 women from the group eating a normal diet suffered a return of their breast cancer, while none of those eating a Mediterranean diet did."

Another papers perspective

http://www.independent.co.uk/life-style/health-and-families/health-news/mediterranean-diet-may-reduce-risk-of-breast-cancer-returning-healthy-eating-olive-oil-a7066056.html

R.B.

08-21-2016, 10:08 AM

Another paper adding support to the general contention that in the context of a western diet Omega 6s increase and Omega 3s decrease risk of breast cancer. :)

Positive tumors were found to have an association with a saturated fat, I have not seen the full paper but it occurs to given palmitic acid is also made in the body a plasma phospholipid content increase could in part or whole reflect wider dysbiosis in other lipid metabolic pathways.

http://www.foodconsumer.org/newsite/Nutrition/Diet/trans_fat_omega_6_fat_linked_to_breast_cancer_0808 160946.html

http://www.ncbi.nlm.nih.gov/pubmed/27146840
ABSTRACT

Cancer Causes Control. 2016 Jun;27(6):759-73. doi: 10.1007/s10552-016-0753-2. Epub 2016 May 4.
Plasma phospholipids fatty acids, dietary fatty acids, and breast cancer risk.
Bassett JK1, Hodge AM2, English DR2,3, MacInnis RJ2,3, Giles GG2,3,4.
Author information
Abstract
PURPOSE:

This study prospectively investigates associations between fatty acids assessed in plasma phospholipids (PPL) and diet, and breast cancer risk, including subgroups defined by hormone receptor status.
METHODS:

We performed a case-cohort analysis within the Melbourne Collaborative Cohort Study using a random sample of 2,021 women and 470 breast cancer cases. At baseline, fatty acids were assessed in PPL and estimated from diet using a 121-item food frequency questionnaire. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using Cox regression.
RESULTS:

Breast cancer risk was positively associated with %PPL saturated fatty acids (SFA); HRQ5vsQ1 = 1.64 (95 % CI 1.17-2.30); p trend = 0.004. Positive associations were found for ER+ or PR+ tumors for %PPL SFA and palmitic acid and for ER-/PR- tumors for %PPL n-6 polyunsaturated fatty acid (PUFA), TFA, TFA 16:1, and TFA 18:1n-7 (all p homogeneity <0.05). Breast cancer risk was inversely associated with dietary docosapentaenoic acid (DPA); HRQ5vsQ1 = 0.57 (95 % CI 0.40-0.82); p trend = 0.001 [with similar inverse associations observed for dietary docosahexaenoic (DHA) and eicosapentaenoic acid (EPA)] and positively associated with dietary n-6:n-3 PUFA. Inverse associations for ER-/PR- tumors were found for dietary dihomo-γ-linolenic acid (DGLA) for older women (p homogeneity = 0.04).
CONCLUSIONS:

Breast cancer risk was positively associated with %PPL SFA and the ratio of dietary n-6 to n-3 PUFA and inversely associated with dietary long-chain n-3 PUFA intake. Some associations between fatty acids and breast cancer varied by age and tumor phenotype defined by hormone receptor status. Increased intake of fish and other foods rich in long-chain n-3 PUFAs and reduced n-6 PUFA intake might reduce breast cancer risk.

R.B.

08-21-2016, 10:29 AM

The Role of n-3 Polyunsaturated Fatty Acids in the Prevention and Treatment of Breast Cancer

Full PDF available for free

Complex as ever but the general direction of travel seems clear

www.mdpi.com/2072-6643/6/11/5184/pdf

R.B.

09-26-2016, 02:37 AM

Just a quick post for the moment; this is what I have been up too for a while; having the honor of being asked to write some 6 chapters in a edited Springer Publication. (A university type reference book)

The chapters argue the physiological importance of plant based Omega 3 linolenic acid ALA and Omega 6 linoleic acid LA in evolutionary terms as well as on physiology and energetics.

There is a limited amount of material on cancer; the chapters look more widely at the impact of and implications of imbalances, and oxidation of LA and ALA, in the context of a western nutrient depleted diet, on the occurrence of western non-communicable diseases including cardiovascular, obesity dementia's, and more widely behavioral change, trends to aggression etc, set within an evolutionary framework.

Some of the ideas are new and arguably potentially of significant importance. As above the University Books are expensive, but may be found in some libraries. (just to be clear I and other contributors received no payment or reward beyond a free copy and the honor of contributing).

This thread that has been running since 2005 was in part the start of the journey that lead to these chapters being written. :) so thank you all very much for your interest and support over the years.

http://www.springer.com/gp/book/9783319404561?wt_mc=ThirdParty.SpringerLink.3.EPR6 53.About_eBook

http://link.springer.com/chapter/10.1007%2F978-3-319-40458-5_27
http://link.springer.com/chapter/10.1007%2F978-3-319-40458-5_28
http://link.springer.com/chapter/10.1007%2F978-3-319-40458-5_29
http://link.springer.com/chapter/10.1007%2F978-3-319-40458-5_30
http://link.springer.com/chapter/10.1007%2F978-3-319-40458-5_31
http://link.springer.com/chapter/10.1007%2F978-3-319-40458-5_32

R.B.

11-04-2017, 02:04 PM

As ever complicated stuff, but very simplistically 13HODE is an oxidised product of Omega 6 linoleic acid, (AKA 'FA oxygenases') and one of the most common oxidised lipids in plasma by a long way (exactly which is the most common differs between groups but they are all oxidized derivatives of linoleic acid - more research required as to why)

The preferred substrates of the 'LO' lipoxygenase enzymes are linolenic and linoleic (probably in that order - arguably an evolutionary consequence of their centrality in plant function), so simplistically if there is lots of linoleic acid (plant derived Omega 6) in the circulation, and not much linolenic acid (plant derived Omega 3) the the LO enzyme is going to work on oxidizing the linoleic acid including to 13HODE.

13HODE is found in oxidised vegetable oils along with other oxidised products, as well as being created by the activity of oxidizing enzyme activity, including that of LO, on ingested linoleic acid in the body (remember linoleic acid cannot be got from the diet and must be made in the body; it is an essential nutrient we must have enough to be healthy but arguably excess and more so where the Omega 3 linolenic acid is low, in the context of an overly processed, antioxidant depleted, western diet, is a significant factor in western diseases.)

The conclusion below needs to be mulled in the wider context of papers referred to in this thread, but adds more weight to the contention that excess Omega 6 in vegetable oils and other sources in the context of a nutrient depleted and nutrient damaged western diet is a factor in risk of cancer occurrence and progression.

The full free paper is accessible through the link below, and below is a abstract of the concluding paragraph at the end of the paper.

Fatty Acid Metabolites in Rapidly Proliferating Breast Cancer
Joseph T. Oâ€™Flaherty,1 Rhonda E. Wooten,2 Michael P. Samuel,2 Michael J. Thomas,2 Edward A. Levine,3 L. Douglas Case,4 Steven A. Akman,5 and Iris J. Edwards6,*
Anthony Peter Sampson, Editor

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642080/

"In conclusion, the metabolites and pathophysiology behind the contributions of FA oxygenases to poor survival in breast cancer has been ill-defined. We find that among the metabolites of the oxygenases known or found here to stimulate breast cancer cell proliferation, 13-HODE stands alone in associating with rapidly proliferating, rapidly dividing, aggressive grade, and perhaps metastasizing breast cancer. Three oxygenases make 13-HODE but correlation studies suggest that its major producer in rapidly proliferating breast cancer is 15-LO-1. Since 15-LO-1 makes other metabolites that are not characterized for proliferative activity in breast cancer cells or measured here, 13-HODEâ€™s contribution to proliferation, division, and metastasis may be complemented or even superseded by other products of 15-LO-1. This caveat also applies to the trends of PGE2 and D2 to be negatively associated with these parameters of aggressive disease. Nonetheless, our results indicate that 13-HODE is a marker for breast cancer severity and the 15-LO-1/13-HODE pathway is associated with a rapidly proliferating, dividing, and possibly metastasizing phenotype. We propose that the over expression of this pathway speeds breast cancerâ€™s growth and spread. Over expression of the other oxygenase-metabolite pathways, including the CO/PGE2/D2 pathways, do not use this specific mechanism to worsen the disease."