The traditional diet of Greece and cancer.

[R.B.]

Oops accidentally deleted.

Sorry

RB

[R.B.]

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

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

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

[julierene]

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

[R.B.]

***** 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%?

[R.B.]

Hi unregistered,

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

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

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

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

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

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

[R.B.]

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-6hgr-3 PUFA ratio of fat consumed is closer to 1. Melatonin has the potential to markedly delay the appearance of palpable mammary tumors. Studies are in progress with the TG.NK mouse model to understand the histological and molecular changes associated with the dose-response pattern of mammary tumor incidence and growth after treatment with a broad range of doses of melatonin.



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

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

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

[R.B.]

Full paper available free.

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

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

[R.B.]

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

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

University of North Carolina, Chapel Hill 27599, USA.

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

[R.B.]

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

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

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

[Andrea Barnett Budin]

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

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

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

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

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

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

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

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

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

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

[R.B.]

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

[R.B.]

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

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


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

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

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

[R.B.]

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).

[R.B.]

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

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

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

[R.B.]

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.

[Andrea Barnett Budin]

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

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

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

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

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

Andi

[Ellie F]

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

[chrisy]

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

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

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

Thanks for the smile

[Andrea Barnett Budin]

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...

Andi