The traditional diet of Greece and cancer.

[R.B.]

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



Hi KDR

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

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

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

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

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

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

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

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

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

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

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

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

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

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

In summary

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

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

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

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

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

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

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

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

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

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

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

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

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

[R.B.]

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


LA is the plant based Omega 6 linoleic acid

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

PGE2 is a downstream product of Omega 6

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


Also see following post



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

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

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

© 2013 Japanese Cancer Association.

[R.B.]

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

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

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


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

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

The whole article is available on the link above

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

[Andrea Barnett Budin]

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

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

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

Andi