Friday, March 12, 2010

Paleo Diet Q & A - Epigenetics, Flaxseed Oil


Q: What do you think about epigenetics? Many scientists (in Germany) believe that the concept of the Paleo Diet is no longer tenable.

Thanks a lot, Michael

A: Dear Michael,

Epigenetics is defined as the science studying changes in phenotype or gene expression by mechanisms other than changes in DNA nucleotide sequence1. The phenotype is someone's appearance which it's determined by the genotype (stable and heritable) and the environment (nutrition and other lifestyle factors) which give place to the epigenotype (heritable, labile and rapid)1. Epigenetic changes are controlled, among other mechanisms, by methylation and histone modification. Altered methylation pattern and histone modification may lead to increased susceptibility to disease. E.G. cancer is associated to generalized hypomethylation and localized promoters hypermethylation1. Histone manipulation may also increase or decrease disease susceptibility2.

Both, methylation and histone manipulation are under the control of dietary substances. For example, methylation depends on SAMe availability, which in turn is influenced by vitamin B6, vitamin B12 and folate intake3, and long chain polyunsaturated fatty acids such as DHA4. On the other hand, certain substances such as garlic, horseradish, fiber, blueberries, apple, onion, nuts, berries, red grapes, broccoli, etc. are known nutrients involved in histone modification2.

The Paleo Diet is rich is all of these nutrients5, hence it may exert positive effects upon epigenetics machinery leading to decreased disease susceptibility. Decreased availability of micronutrients is associated to disease severity, probably, through complex epigenetic mechanisms, and supplementation could improve those symptoms3. Improved epigenetic is influenced by metabolic programming during foetal and early life. These two periods are crucial for the developing newborn and future adult's health. Hence, The Paleo Diet may confer protection against several diseases improving the epigenetic programming.

We hope this is helpful.

Maelán Fontes Villalba
Pedro Carrera Bastos


  1. van Vliet J, Oates NA, Whitelaw E. Epigenetic mechanisms in the context of complex diseases. Cell Mol Life Sci. 2007 Jun;64(12):1531-8.
  2. Delage B, Dashwood RH. Dietary manipulation of histone structure and function. Annu Rev Nutr. 2008;28:347-66.
  3. Kemperman RF, Veurink M, van der Wal T, Knegtering H, Bruggeman R, Fokkema MR, Kema IP, Korf J, Muskiet FA. Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 2006 Feb;74(2):75-85.
  4. Muskiet FA, Kemperman RF. Folate and long-chain polyunsaturated fatty acids in psychiatric disease. J Nutr Biochem. 2006 Nov;17(11):717-27.
  5. Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O'Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr. 2005 Feb;81(2):341-54.
  6. Kemperman RF, Veurink M, van der Wal T, Knegtering H, Bruggeman R, Fokkema MR, Kema IP, Korf J, Muskiet FA. Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 2006 Feb;74(2):75-85.

Flaxseed Oil

Q: I recently visited family and my brother is a new advocate of the paleo diet. For breakfast he made us "fakecakes" which had about 1-2 tablespoons of flaxseed in them that he ground in a coffee grinder. I had few a questions regarding the use of flaxseed in the Paleo Diet.

First, why are flaxseeds ok in the Paleo Diet but other grains (seeds) are not? My understanding for eliminating grains from the diet is the toxins that they contain, but flaxseed contains large amounts of cyanogenic glycosides, producing up to 139 mg/kg of hydrogen cyanide in raw human-grade flaxseed. I am sure flaxseeds are processed somehow before selling them but I don't know what process that is or what effect it has on the HCN concentration.

So, you know of any studies on the amount of HCN in meals containing ground flasxseed and the chronic oral exposure of those amounts on humans? My understanding here is the HCN that isn't hydrolysed to formic acid in the stomach and doesn't bind to hemoglobin is converted to thiocyanate which hinders thyroid function.

Thank you for your time and any information you can supply.


A: Hi Tim,

We think your thoughts are on the right track.

When Dr. Cordain wrote The Paleo Diet book, the advice to consume flaxseed oil was an attempt to balance the increased omega-6/omega-3 fatty acid ratio due to the exaggerated intake of omega-6 vegetable oils, especially linoleic acid, in the typical western diet.

Nevertheless, animal foods (fish, muscle meat and organs from wild animals) are good sources of w3 fatty acids. Therefore, when people eat these foods regularly along with vegetables and nuts, and avoid vegetable oils (especially oils rich in Linoleic Acid – Omega 6), they get a balanced intake of omega 3, omega 6, monounsaturated and saturated fatty acids. In this situation, there is no need for flax seeds to provide Omega 3 fatty acids and balance the Omega 3/Omega 6 ratio.

Here are some facts that support the notion that animal foods, vegetables and nuts provide the necessary Omega 6 and Omega 3 fatty acids in the right proportion:

  1. Hunter-gatherers do not eat ALA from seeds or vegetable oils.
  2. Nuts, green leafy vegetables and animal foods contain ALA.
  3. The conversion of ALA to EPA+DHA is limited, due to low delta-6 and delta-5 activity, although ALA is highly oxidized (twice that of LA) (see paper by Freemantle et al). This means that at some point in history we included preformed sources of EPA and DHA and still need to do so. Animal foods (especially brain from wild ruminants and fish) are very good sources of these fatty acids.
  4. The essentiality of LA & ALA in human metabolism has been questioned (see paper by Le et al.), as we relied almost on LCPUFA (Arachidonic Acid, EPA and DHA) during the Palaeolithic era (see Dr. Cordain’s papers on that here and here). Moreover, there is already some evidence showing that human metabolism could re-convert AA and DHA into LA and ALA respectively, hence AA and DHA would be the true essential fatty acids.
  5. The possible toxicity from seeds and vegetable oils (HCN, saponins, lectins).
  6. They are not used by current HG societies, and these populations show no signs of western disease, so this means that flax seeds are not necessary.
  7. The well known positive health effects of fish oil supplementation (among other factors to improve omega-6/omega-3 ratio) in contrast with some possible adverse effects of flaxseed oil (like the epidemiological evidence that points towards increased risk of prostate cancer with flax oil consumption – see paper by Brouwer et al).

The bottom line from an evolutionary perspective is that flax seeds and/or flaxseed oil would not have been consumed by pre-agricultural humans. However, having said that, hunter gatherers always would have preferentially sought high oil plant foods as per optimal foraging theory. But, most high fat plant foods contain high MUFA (with the exception of coconut and palm oils).

Hope this helps,
Maelán Fontes Villalba

Additional reading: Effectiveness of different processing methods in reducing hydrogen cyanide content of flaxseed, Feng, et al.

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