Omega 6 not saturated fats looks like prime culprit for homrone rises in obesity.
 

Oops accidentally deleted.

Sorry

RB

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.

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

***** 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.co...h/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.

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

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.

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 µg/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 µg/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 µg 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 0.05–0.2thinspml of flaxseed oil as the source of ohgr-3 rich PUFA, or melatonin at 50–200thinspmg/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.

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.

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.

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.

Praise be omega 3!!!
 

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!

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-Devi...2251624&sr=1-1

This is the Amazon.co.uk http://www.amazon.co.uk/Omega-Six-De...2251888&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

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.

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/art...medid=19399184

AND within the paper

"As positive control for COX2 downregulation, cells were treated with the COX2-specific inhibitor Celecoxib® at 20 and 40 µM for 48 hours. 40 µM Celecoxib® 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).

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.

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/1...ubmed_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.

More good reasons to load up on omega 3
 

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

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

ANDI you crack me up!!
 

[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:)

Humor and t cells
 

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

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

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”"

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.

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.

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.

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]

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.

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.

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!!!!

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/Pro...8/?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/P.../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.

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

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/resea...er-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}§, Priscilla Ivester§1, Michael Seeds{ddagger}, L. Douglas Case¶, Jonathan P. Arm||, and Floyd H. Chilton§

From the From the {ddagger}Department of Internal Medicine, Section on Molecular Medicine, and , Departments of §Physiology and Pharmacology and , ¶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.

Re: The traditional diet of Greece and cancer.
 

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/...w/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.

Re: The traditional diet of Greece and cancer.
 

http://en.wikipedia.org/wiki/Plasmin...or_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/Rese...erBiology.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/dia...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.

Re: The traditional diet of Greece and cancer.
 

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

Re: The traditional diet of Greece and cancer.
 

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.

Re: The traditional diet of Greece and cancer.
 

http://www.ncbi.nlm.nih.gov/pmc/arti...3/?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.

Re: The traditional diet of Greece and cancer.
 

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

Re: The traditional diet of Greece and cancer.
 

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...ull/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."

Re: The traditional diet of Greece and cancer.
 

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