The traditional diet of Greece and cancer.

[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.