The traditional diet of Greece and cancer.

[R.B.]

1: Exp Biol Med (Maywood). 2008 Apr 11 [Epub ahead of print]Click here to read Links
The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases.
Simopoulos AP.

The Center for Genetics, Nutrition and Health.

Abstract Several sources of information suggest that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of ~1 whereas in Western diets the ratio is 15/1 - 16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a lower omega-6/omega-3 ratio), exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries.

[R.B.]

Hi all,

If you see "goodvevil 2" in the text it should be one of these.



You will find it on the Mozzilla free smileys section.

THIS ONE HAS DISAPPEARED TOO _ It was a smiley with good and evil represented on a see-saw. The fulcrum was a face that looked at good and evil as they rose and fell in turn. The balancing of goodness and badness is a very ancient human dilemma. I am not sure why somebody or some machine has seen fit to ban it.


Unfortunately a search will not refind each article and I do not have time at the moment to reread the posts to find where the images have disappeared and replace them.



RB

[ElaineM]

Hi,
Thanks for all the nutrition info everyone. I believe what we put in our bodies has a big impact on our overall health and our ability to keep cancer under control. Drugs are important, but they can't do all the work.

[R.B.]

Int J Cancer. 2007 Jul 15;121(2):377-85.Click here to read Links
Breast cancer risk and erythrocyte compositions of n-3 highly unsaturated fatty acids in Japanese.
Kuriki K, Hirose K, Wakai K, Matsuo K, Ito H, Suzuki T, Hiraki A, Saito T, Iwata H, Tatematsu M, Tajima K.

Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. kkuriki@aichi-cc.jp


"Dietary intake of fish rich in n-3 highly unsaturated fatty acids (HUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been proposed to decrease cancer risk. In contrast to results from laboratory studies, however, protective effects for breast cancer have proved equivocal in epidemiological studies. In the present case-control study, we examined associations between breast cancer risk and fatty acid compositions in erythrocyte membranes as biomarkers for those intakes. Dietary information and blood samples were collected from 103 incident breast cancer cases and 309 non-cancer controls (matched by age and season) and erythrocyte fatty acids were measured .....In conclusion, we showed that erythrocyte compositions of specific fatty acids derived from fish intake, as biomarkers, are associated with lower risk of breast cancer, but further studies are needed to investigate mechanisms linked to the etiology.

[R.B.]

This is not a trial for BC but there may be common factors like a role for COX2 in supporting cancers, and the blocking of COX 2 inhibiting cancer development.

Here they are suggesting a role for Omega 3 in support of chemo.

There have been an number of other trials that suggest this may be an interesting idea for further trialling.

RB

1: Pancreas. 2008 May;36(4):353-62.Click here to read Links
Opposing effects of n-6 and n-3 polyunsaturated fatty acids on pancreatic cancer growth.
Funahashi H, Satake M, Hasan S, Sawai H, Newman RA, Reber HA, Hines OJ, Eibl G.

Hirshberg Laboratories for Pancreatic Cancer Research, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

OBJECTIVES: Epidemiologic studies suggest that fish oil, rich in n-3 polyunsaturated fatty acids (PUFA), possesses antitumor activity, whereas n-6 PUFAs may stimulate the development of cancers. The aim of this study was to evaluate the effects of n-6 and n-3 PUFAs on the growth of pancreatic cancer. METHODS: The n-6 PUFA arachidonic acid (AA) stimulated the growth of cyclooxygenase (COX) 2 positive human pancreatic cancer (PaCa) cells, which was mediated by COX-2 generated prostaglandin E2 (PGE2) binding to EP2 and EP4 receptors. In contrast, the n-3 PUFA eicosapentaenoic acid decreased the growth of COX-2-positive and COX-2-negative PaCa cells. The COX-2-dependent mechanism of eicosapentaenoic acid was mediated by binding of PGE3 to EP2 and EP4 receptors. Dietary intake of n-3 PUFAs decreased the growth of pancreatic cancers in a xenograft model, which was accompanied by a decrease of PGE2 and an increase of PGE3 in the tumors. CONCLUSIONS: Our studies provide evidence that n-3 PUFAs possess antitumor activities, whereas n-6 PUFAs stimulate pancreatic tumor growth. The opposite effects of n-3 and n-6 PUFAs are mediated by the formation of different prostaglandin species. n-3 PUFAs may prove beneficial as monotherapy or combination therapy with standard chemotherapeutic agents in pancreatic cancer patients.

[R.B.]

Complicated and rather beyond me, but may suggest Omega 6 archidonic acid has an important role in early proliferation of cells in the BCs examined. The underline is mine.

Archidonic acid is made in the body from the mother Omega six linoleic acid, which is find in high levels in many vegetable oils (see rest of this thread)


RB


Arachidonic Acid-induced Ca2+ entry is involved in early steps of tumor angiogenesis.
Fiorio Pla A, Grange C, Antoniotti S, Tomatis C, Merlino A, Bussolati B, Munaron L.

Department of Animal and Human Biology, University of Torino, Via Accademia Albertina 13, 10123 Turin, Italy. alessandra.fiorio@unito.it.


http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Growth factor-induced intracellular calcium signals in endothelial cells regulate cytosolic and nuclear events involved in the angiogenic process. Among the intracellular messengers released after proangiogenic stimulation, arachidonic acid (AA) plays a key role and its effects are strictly related to calcium homeostasis and cell proliferation. Here, we studied AA-induced intracellular calcium signals in endothelial cells derived from human breast carcinomas (B-TEC). AA promotes B-TEC proliferation and organization of vessel-like structures in vitro. The effect is directly mediated by the fatty acid without a significant contribution of its metabolites. AA induces Ca(2+)(i) signals in the entire capillary-like structure during the early phases of tubulogenesis in vitro. No such responses are detectable in B-TECs organized in more structured tubules. In B-TECs growing in monolayer, AA induces two different signals: a Ca(2+)(i) increase due to Ca(2+) entry and an inhibition of store-dependent Ca(2+) entry induced by thapsigargin or ATP. An inhibitor of Ca(2+) entry and angiogenesis, carboxyamidotriazole, significantly and specifically decreases AA-induced B-TEC tubulogenesis, as well as AA-induced Ca(2+) signals in B-TECs. We conclude that (a) AA-activated Ca(2+) entry is associated with the progression through the early phases of angiogenesis, mainly involving proliferation and tubulogenesis, and it is down-regulated during the reorganization of tumor-derived endothelial cells in capillary-like structures; and (b) inhibition of AA-induced Ca(2+) entry may contribute to the antiangiogenic action of carboxyamidotriazole. (Mol Cancer Res 2008;6(4):535-45).

[R.B.]

Omega Six The Devils Fat

I have written a book that looks at the impact of EXCESS Omega 6 and lack of Omega 3 on health and behaviour. The subject has become a passion. It will be the diet subject of the next decade. The book is very much less technical than these posts. It is not light reading but has been understood by women from 20 to 80 who have absolutely no technical medical or scientific background. Even self confessed "non readers" have been sufficiently intrigued to spend the time to look at it, once they have dipped into the book.

The material specifically on breast cancer is no where near as comprehensive as this thread, and the book is very much wider, but helps you get a wider perspective of why this is such an important health topic and how it all fits together.

You can read a few pages on Amazon and my web site.

This is a subject that is particularly fundamental to women as women make 10 times as much DHA as men do. DHA is fundamental to women's health and arguably helps define what it is to be a woman.

"GOSH I didn't know that" an expression of genuine surprise and interest, is a generic common reaction of women to some of the material.

The message is simple balance the Omega 3s and 6s. To really appreciate why it is so important you really need to understand a little of why. There are lighter books but this one should leave you in no doubt how important the correct balance of EFAs is to mental and physical health at every level.

WWW.omegasixthedevilsfat.com

http://www.amazon.com/Omega-Six-Devi...5959567&sr=1-1

http://www.amazon.co.uk/Omega-Six-De...5959501&sr=1-1

[AlaskaAngel]

Hi Robert,

I heard this report this weekend on the radio, and thought I'd mention it for consideration:

http://www.npr.org/rss/podcast.php?id=510284

(Look for the July 11, 2008 report)

[R.B.]

Re Talapia - Thanks AA interesting that the subject of excess Omega 6 is making the main stream.

INFLAMMATION - Excess omega 6 and lack of omega 3 promotes inflammation in the body.

It is becoming more and more evident that inflammation is a big factor in the cancer process.

These are some fascinating links that make that point.

http://www3.interscience.wiley.com/j...22663/abstract

ABSTRACT
"In this review I would like to show the evidence that tumor development and progression are accelerated inevitably by inflammation caused from foreign bodies, and that reactive oxygen species derived from inflammatory cells are one of the most important genotoxic mediators to accelerate the process."

http://www3.interscience.wiley.com/j...22662/abstract

ABSTRACT
"Infection and chronic inflammation contribute to about 1 in 4 of all cancer cases. Mediators of the inflammatory response, e.g., cytokines, free radicals, prostaglandins and growth factors, can induce genetic and epigenetic changes including point mutations in tumor suppressor genes, DNA methylation and post-translational modifications, causing alterations in critical pathways responsible for maintaining the normal cellular homeostasis and leading to the development and progression of cancer."

http://www3.interscience.wiley.com/j...22664/abstract

ABSTRACT
" A wide array of chronic inflammatory conditions predispose susceptible cells to neoplastic transformation. In general, the longer the inflammation persists, the higher the risk of cancer. A mutated cell is a sine qua non for carcinogenesis. Inflammatory processes may induce DNA mutations in cells via oxidative/nitrosative stress. "



http://www3.interscience.wiley.com/j...22661/abstract

[R.B.]

http://her2support.org/vbulletin/sho...d=1#post167964

This is a link to Robins fascinating thread on activation of HER2 by a virus (EBV), and inhibition of that virus by long chain Omega 3s.

I thought it was worth re posting here for completeness.

RB

[R.B.]

Another mechanism by which long chain Omega 3 blocks BC, this time through BRAC1.



1: Oncol Rep. 2007 Apr;17(4):713-9.Click here to read Links
Increased BRCA1 protein in mammary tumours of rats fed marine omega-3 fatty acids.
Jourdan ML, Mahéo K, Barascu A, Goupille C, De Latour MP, Bougnoux P, Rio PG.


INSERM, E 0211; Université François Rabelais; CHU Bretonneau, Tours, F-37000, France.

Any factor affecting BRCA gene regulation may be of interest in the prevention of breast tumourigenesis. We studied the influence of dietary docosahexaenoic acid (DHA), a major omega-3 fatty acid present in marine products, on rat autochthonous mammary tumourigenesis. DHA-supplementation significantly reduced the incidence of tumours (30%, P=0.007) and led to a 60% increase (P=0.02) in BRCA1 protein level. Since DHA influences the product of a major tumour suppressor gene, this finding may contribute to the observation that high-fish consumption reduces the risk of breast cancer.

[Jackie07]

The current issue (Aug. 18/Aug. 25) of US News and World Report has an arrticle - "Making Sense of the Omega Fat Puzzle" by Sarah Baldaug and a health column by Bernadine Healy, former Director of NIH, entitled "From Fish Oil to Medicine".

Dr. Healy says that "... though eating fatty fish is the way to go, refined fish oil supplements with specified doses of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) can make for a more certain prescription, and one that alleviates concerns about fish being contaminated with mercury or PCBs. (Nasty fish burps can be avoided by freezing the gel capsules and taking them at bedtime.) "

[R.B.]

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.]

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=e...HJLU#PPA147,M1

[R.B.]

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.]

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.]

Another reason and a familiar cast of players.

RB
http://www.ajcn.org/cgi/content/abstract/81/4/934

ABSTRACT

There are a plethora of biologically plausible pathways whereby PUFAs may regulate the factors involved in bone metabolism, such as prostaglandins, cytokines, insulin-like growth factor I, and calcium. Reviewers have suggested that one or a combination of these factors may have an effect on bone (5, 6, 13, 23). For example, PGE2, the major prostaglandin involved in bone metabolism, is synthesized from n–6 fatty acids, whereas n–3 fatty acids inhibit its production (1, 13). Normal or moderate concentrations of PGE2 support bone formation, whereas greater quantities promote bone resorption (5). Fatty acids are also involved in calcium metabolism. Higher n–3 fatty acid intake enhances calcium absorption, decreases calcium loss, and increases bone calcium (13, 20,23). In addition, the inhibition of cytokine production has been implicated as a potential mechanism of the favorable effects of fatty acids on bone, with higher intakes of n–3 fatty acids inhibiting the synthesis of proinflammatory cytokines, such as interleukin 6, interleukin 1, and tumor necrosis factor {alpha} (24, 25). Kettler (6) suggested that bone loss is mediated by cytokines, and n–3 fatty acid supplementation in animals and humans reduces cytokine synthesis and increases calcium absorption.

In the present study, there was a significant interaction between hormone use and the ratio of dietary n–6 to n–3 fatty acids on BMD at the hip and spine. Fatty acids could potentiate the effect of HT on bone through increasing calcium absorption (26). A study in ovariectomized rats showed that estrogen plus a combination of n–6 and n–3 fatty acids increases bone formation and decreases bone resorption, whereas estrogen alone only increases bone formation (27).

To our knowledge, this is the first large epidemiologic investigation of the association between PUFAs and BMD in older, community-dwelling white men and women who had a wide range of dietary n–6 and n–3 fatty acid intake. The latest longitudinal study by Macdonald et al (11) investigated the association between total PUFAs and bone in women only and did not differentiate between various types of PUFAs (eg, n–3 versus n–6). Previous experimental studies had limited ability to assess a range of fatty acid intakes because of study design and small sample sizes.




http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

1: Altern Med Rev. 2001 Feb;6(1):61-77. Related Articles, Links
Click here to read
Can manipulation of the ratios of essential fatty acids slow the rapid rate of postmenopausal bone loss?

Kettler DB.

Sky Park Wellness Center, Irvine, CA 92614, USA dr.debra@home.com

The rapid rate of postmenopausal bone loss is mediated by the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor alpha. Dietary supplementation with fish oil, flaxseeds, and flaxseed oil in animals and healthy humans significantly reduces cytokine production while concomitantly increasing calcium absorption, bone calcium, and bone density. Possibilities may exist for the therapeutic use of the omega-3 fatty acids, as supplements or in the diet, to blunt the increase of the inflammatory bone resorbing cytokines produced in the early postmenopausal years, in order to slow the rapid rate of postmenopausal bone loss. Evidence also points to the possible benefit of gamma-linolenic acid in preserving bone density.

Publication Types:

* Review


PMID: 11207457 [PubMed - indexed for MEDLINE]

[R.B.]

http://www.jacn.org/cgi/content/full/19/4/478S

ABSTRACT

Conjugated Linoleic Acid and Bone Biology
Bruce A. Watkins, PhD, FACN and Mark F. Seifert, PhD

Purdue University, Department of Food Science, Lipid Chemistry and Molecular Biology Laboratory, West Lafayette, Indiana, and Department of Anatomy, Indiana University School of Medicine, Indianapolis, Indiana

Address reprint requests to: Dr. B.A. Watkins, Department of Food Science, Lipid Chemistry and Molecular Biology Laboratory, Purdue University, W. Lafayette, IN, 47907. E-mail: watkins@foodsci.purdue.edu.


Osteoporosis, osteoarthritis and inflammatory joint disease afflict millions of people worldwide. Inflammatory cytokines inhibit chondrocyte proliferation and induce cartilage degradation for which part of the response is mediated by PGE2. Excess production of PGE2 is linked to osteoporosis and arthritis and is associated with bone and proteoglycan loss. PGE2 also influences the IGF-I/IGFBP axis to facilitate bone and cartilage formation. Recent investigations with growing rats given butter fat and supplements of CLA demonstrated an increased rate of bone formation and reduced ex vivo bone PGE2 production, respectively...............




Anti-inflammatory diets, including nutraceutical n-3 fatty acids, are associated with decreased pathogenesis of rheumatoid arthritis (secondary osteoporosis), reduced inflammatory diseases [66–68] and lowered cancer risk [69]. The common link between these diseases resides in the regulation/expression of COX-2. For example, multiple lines of evidence indicate that up-regulation of COX-2 contributes to tumorigenesis and inflammation, providing tissue levels of prostanoid precursors that influence formation of the pro-inflammatory PGE2. In addition, chronic aspirin users (COX inhibitor) have reduced incidence of colorectal cancer. Both COX-1 and COX-2 inhibitors suppress experimental mouse skin carcinogenesis, and permanent overactivation of arachidonic acid metabolism appears to be a driving force for tumor development [70]. Moreover, metastasis of cancer to bone is a frequent outcome of breast (about two-thirds of patients with metastatic breast cancer have bone involvement) and prostate malignancies. The metastasis is often associated with significant morbidity (severe bone pain and pathologic fractures) due to osteolysis, and metastatic target bone is continually being remodeled under the influence of factors produced locally and systemically [71].

Interestingly, recent investigations suggest that both COX-2 induction and an increase in the supply of arachidonic acid are needed to greatly increase prostanoid production [72]. Supplying arachidonic acid appears to increase prostanoids to reduce the effects of nonsteroidal anti-inflammatory drugs, including NS-398 a specific COX-2 inhibitor. Therefore, in our view, n-3 fatty acids and CLA isomers may act as potent anticancer nutrients because they not only directly/indirectly affect the activity and expression of COX-2, but may also reduce the supply of arachidonic acid to diminish prostanoid biosynthesis. In any case, one mode of action for CLA appears to be anti-inflammatory with respect to reducing PGE2 production.

The data presented in this review describe consistent and reproducible effects of CLA isomers on decreasing ex vivo PGE2 production in bone organ cultures [33,34] and in various cell culture systems [51]. The potent beneficial anticancer effect of CLA is likely linked, in part, to down-regulation of COX-2 activity. Future investigations on CLA should evaluate isomeric effects on COX-1 and COX-2, for which over-expression of the latter is associated with carcinogenesis and inflammation. This research would lead to 1) important discoveries for bone modeling and remodeling, 2) development of delivery systems in designed/functional foods and 3) opportunities to identify a synergism between nutraceuticals and drug therapies to reduce cancer risk and control inflammatory bone/joint disease.

[R.B.]

Mr Menendez and Ruth Lupu are frequent authors on the subjects of fats and BC and have a particular expertise in the field.

This seems to be saying that the gene involved in the synthesis of fats by the body is key to aggressive cancers, and is suggesting that there should be a recognition that it relates to the body's metabolism (of which diet is an important factor in this case fats by implication of the FAS pathways my interpretation based on their previous studies).

Not the easiest to read but for me a "public" statement of some significance suggesting implicitly that fats and body "metabolism" have a significant role in aggressive cancers.

RB




http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

1: Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):346-357.Click here to read Links

Oncogenic properties of the endogenous fatty acid metabolism: molecular pathology of fatty acid synthase in cancer cells.

* Menendez JA,
* Lupu R.

aFoundation of the Recerca Bio-Medical Institute of Girona Dr Josep Trueta, University Hospital of Girona, Dr Josep Trueta, Girona, Catalonia, Spain bDepartment of Medicine, Evanston Northwestern Healthcare Research Institute, Evanston, Illinois, USA cNorthwestern University Feinberg School of Medicine, Chicago, Illinois, USA dRobert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.

PURPOSE OF REVIEW: This review documents our rapidly changing perspectives on the function of fatty acid synthase-catalyzed endogenous fatty acid biogenesis in cancer biology. RECENT FINDINGS: Up-regulation of fatty acid synthase gene expression and fatty acid synthase biosynthetic activity are molecular events accompanying the pathogenesis and natural history of cancer disease. First, the increased fatty acid synthase gene expression in precursor, preinvasive and invasive cancer lesions appears to represent an indirect, early epiphenomenon, occurring in response to a microenvironment containing regions of poor oxygenation and high acidity due to, for example, lack of an adequate angiogenesis and/or nutritional supply. Second, aberrant transduction cascades driven by cancer-associated oncogenic changes subvert the downregulatory effects of circulating fatty acids. Third, fatty acid synthase-dependent endogenous fatty acid metabolism actively contributes to cancer evolution by specifically regulating the expression, activity and/or cellular localization of proteins closely related to malignant transformation and/or cancer progression. SUMMARY: Fatty acid synthase-catalyzed endogenous fatty acid metabolism appears to be an obligatory acquisition selecting a biologically aggressive sub-group of cancer cells capable of growth and survival upon stresses such as hypoxia, low pH and/or nutritional deprivation. Considering that an ever-growing body of evidence demonstrates that fatty acid synthase-driven signalling actively regulates key cancer-controlling networks, we may hereafter redefine fatty acid synthase as a metabolic oncogene in human cancer cells.

PMID: 16778562 [PubMed - as supplied by publisher]

[RobinP]

Thanks for the precious, valued, VAST information on FA RB and for the answer to my unregistered post above about walnuts being both omega 3 and 6 FA.