Tuesday, December 8, 2009

Paleo Diet Q & A - 8 December 2009

Dear Readers,

Here's today's edition of Paleo Diet Q & A. Thank you for your contributions!

Q: I just listened to an interview of Cordain. He mentions that Huntington Chorea seems to be an autoimmune disease. I have Huntington Chorea in my family. So obviosly I'd like to know more about your or his findings. Could you please explain if there is any study showing this and what foods one should eliminate from the diet? I'd be so grateful.


A: Hi Tim,

Huntington's Chorea or Huntington's Disease (HD) results from lesions (alpha synuclein crosslinks) occurring in the brain which cause the characteristic symptoms (tremors and paralysis) of HD. It is well documented that a genetic basis underlies the development of HD. HD patients inherit a specific gene which causes increased expression of a protein called mutant huntingtin protein (mHTT). Whereas people without HD have inherited a gene which expresses the normal version of this protein, simply called, huntingtin protein (HTT). The over expression of mHTT at the expense of HTT is thought to cause the brain lesions of HD.

So, can diet have anything to do with whether or not a person with the mHTT genetic makeup goes on to develop the disease? Yes, and let me explain the underlying rationale. The imbalance in the mHTT to HTT ratio that occurs in HD patients requires the inheritance of the mHTT gene, however the gene cannot make its product without the presence of an enzyme called transglutaminase (TG). Transglutaminase is a post-translational enzyme (meaning that it is required to produce the gene product after the gene has been translated within a cell's nucleus). TG is a ubiquitous post translational enzyme that is found throughout the body's tissues, particularly in the gut, nervous tissue and brain. Without the presence of adequate concentrations of TG in the brain, mHTT cannot be produced in sufficient quantity to imbalance the mHtt to HHT ratio that results in HD.

So the $64,000 question in HD: what is the environmental trigger that causes over expression of TG in the brain? Plain and simple, it is wheat. More specifically, a storage protein in wheat called Gliadin. Unlike other dietary proteins, Gliadin is an unusual protein because it is resistant to the enzymes in the human gut (proteases) which normally degrade proteins into their constituent amino acids. Consequently, Gliadin arrives in the small intestine intact where it has recently been shown to bind a gut receptor (the CRX2 chemokine receptor). When Gliadin from wheat binds CRX2 it causes the intestinal cells to release a recently discovered enzyme known as zonulin. Zonulin release by gut cells causes the gut to become "leaky" and allow passage of intact proteins across the gut barrier -- including Gliadin itself.

Once Gliadin bypasses the gut barrier, it is immediately catalyzed by transglutaminase (TG) which is expressed by local intestinal cells. When you eat wheat on a daily basis, there is so much dietary Gliadin bypassing the gut barrier that it overwhelms the ability of the intestinal cells to produce the enzyme (TG) to catalyze the substrate (Gliadin). Intestinal cells as well as all other cells in the body react to this overload of circulating Gliadin by up-regulating (increasing) TG production.

The proof of the pudding lies in the experimental evidence. Unfortunately no randomized controlled trials of Gliadin free diets in HD patients have been examined to date. Having said this, I am aware of a single HD patient in S. California who was a member of a local CrossFit Gym, and who had been diagnosed with HD by a group of University neurologists employing MRI technology to detect the characteristic brain lesions. After approximately 8 months following adoption of a Paleo Diet (Gliadin free), this patient experienced a dramatic reduction in disease symptoms and subsequent MRI evaluation indicated a reduction in lesion volume. In addition to HD, numerous ataxia patients respond favorably to Gliadin free diets.


Loren Cordain, Ph.D., Professor

Q: In response to the idea that high glycemic foods can cause insulin resistance, what would be your response to people like Dr. John McDougall that claim there are plenty or cultures in Asia who live on diets consisting of high glycemic foods such as potatoes and rice but have little to no rates of diabetes or other chronic illnesses?

Here's a link to his article http://www.drmcdougall.com/misc/2006nl/july/glycemic.htm.



A: Hi James.

I believe (and we have evidence backing that up - see links below) that not all people will develop insulin resistance on a high glycemic load diet and not all people will see the same improve their body composition and/or insulin sensitivity on a low glycemic load diet. It appears to be dependant on your genotype (links to a few papers below). We have some examples of that: for instance, the aborigines don’t tolerate a high carb diet very well and the Kitava do better. But don’t forget that low glycemic load doesn’t automatically mean very low carb and high carb or normal carb doesn’t necessarily mean high glycemic load, as the glycemic load depends on the amount of carbs on a given serving of a certain food and the Glycemic Index of that food, so saying that the Asians eat a high glycemic load diet may not necessarily be true.

Another possibility that some people will develop insulin resistance on a high glycemic load diet (and some will not) is that a deprived fetal environment (which normally, but not always, leads to an underweight baby) may lead to a specific metabolic programming that has been called the trify phenotype, which means that these babies will develop various diseases of civilization when exposed to the postnatal environment (western diet and sedentary lifestyle) that is characteristic for affluent societies and of rapidly developing countries.

What I mean here is that depending on your genotype and/or epigenotype you may or may be not react adversely to a high carb diet. Moreover, there are also various variables that need to be considered when we want to know why certain populations suffer more from the diseases of insulin resistance, such as (among many other variables):
  • Exercise (it has a huge impact on insulin sensitivity and sarcopenia, a typical consequence of inactivity), leads to insulin resistance and an increased risk of the metabolic syndrome).

  • Vitamin D and/or ultraviolet exposure (for instance, in Kitava they don’t suffer from Vitamin D deficiency, whereas in the western world many of us do and there is evidence linking Vit D deficiency to an increased risk of Type 2 Diabetes and the Metabolic Syndrome, among various other diseases).

  • Magnesium deficiency is strongly associated to an increased risk of the Metabolic Syndrome and Cardiovascular diseases. Presumably this wasn’t a problem for our ancestrors and to many non-westernized populations, but it is a huge problem in the US.

  • Fructose intake – although our ancestors and many non-westernized populations around the world eat fruit, which is a source of fructose, fruit also has Vitamin C (which counteracts some of the adverse effects of fructose) and they don’t eat as much fructose as the Americans do, because HFCS has been added to many foods and because of the American eating habits (I’m Portuguese and I always get amazed when I go to the US and see what the people eat and the amount of sodas they drink and the amount of obese people I se there). In Dr. Cordain’s papers and in his lectures (I attended several) he mentions fructose as a cause of elevated uric acid and insulin resistance. And we have a spreadsheet with the fructose content of various foods for those who need to cut back on fructose intake (those who are already insulin resistant or have elevated blood uric acid levels and/or have been eating a very high fructose diet, which upregulates certain enzymes that need to be downregulated in order to reverse the effects of this high fructose intake and the only way to do it is by eating a very low fructose diet for a few weeks, before resuming a normal fructose diet (whose main sources are mainly fruit).

  • Bioactive peptides and antinutrients in Neolithic foods (see Dr. Cordain’s scientific paper on cereal grains here and Dr. Staffan Lindeberg’s research team paper on lectins and leptin resistance (link below).

  • Visceral fat – cytokines derived from visceral adipose tissue will cause insulin resistance.

  • Sleep deprivation – it may set off a hormonal cascade that may ultimately result in insulin resistance and Obesity.

  • Etc, etc…
We have to realize that many Americans have already the signs and symptoms of the Metabolic Syndrome and/or Type 2 Diabetes insulin resistance and many more have some degree of insulin resistance and for these people a low glycemic load diet may be very beneficial. But, as you may infer from our newsletters and from Dr. Cordain books and scientific papers, eating a low GL diet it is not enough and it is only a characteristic of the many general universal characteristics of pre-agricultural diets that Dr. Cordain and his research team have been deciphering over the past 15 to 20 years. AS so, if one wants to achieved optimal health, he shouldn’t focus only on one dietary characteristic, but on all of them plus the lifestyle that presumably shaped our genome during the Pliocene and Pleistocene (exercise, sun exposure or vitamin D supplementation + sleep + stress management + avoidance of environmental toxins).

All this sheds light on why some Asian populations live on a high carb diet, but do not develop the Metabolic Syndrome. Perhaps because they don’t overeat (remember that caloric restriction is the only proven way to increased longevity in many animal models and presumably one of the main reasons why you have so many centenarians in Okinawa), they don’t eat much fructose, they exercise, they don’t suffer from Vitamin D deficiency (and perhaps also magnesium deficiency), have “normal” sleeping patterns, etc, etc, etc.

Nevertheless, I would like to mention that apparently healthy people from India (living in India and eating their traditional vegetarian diet) have more visceral fat than healthy Caucasians and are more prone to Type 2 Diabetes and other diseases associated with the Metabolic Syndrome.

Finally, even in healthy people with no signs or genetic predisposition for insulin resistance, a high glycemic load diet may not be ideally, as it will increase glycolysis and it will decrease beta-oxidation (aging is associated with an increased glycolysis and decreased beta-oxidation and one of the mechanisms why caloric restriction increases longevity is believed to be a decrease in glycolysis and in increase in beta-oxidation). Moreover, it may increase inflammation (see link to paper) and, it may also cause several hormonal disturbances (elevated IGF-1 and androgens and decreased Sex Hormone Binding Globulin and IGFBP-3), which then increase our risk for various diseases, as you can see here, here and here.

I hope it helps


Links to additional papers:


  1. Very interesting theory about Huntington's Disease. What strikes me as odd is that I haven't heard of anyone preventing this disease. Isn't there a place on earth where they don't eat grains?

    Are there other foods besides grains that contain gliadin?

    I guess that that CrossFit member never made a genetic test? We probably can't be 100% sure it was HD then.

    Many thanks for this theory. It's definately worth a shot!

  2. I was interested in reading the following article, but the link is not working. Can you fix please?

    The article...
    Energy-restricted diets based on a distinct food selection affecting the glycemic index induce different weight loss and oxidative response

  3. Hi Brian,

    Thanks for pointing out the problem with the link on the article. The link to that article (and a couple of others) are working now.


  4. Hello. I have read that Inulin is a beneficial food, a probiotic and promotes a healthy gut. Also that it doesn't count as a carbohydrate. So does this mean that Jerusalem Artichokes (which I love) can be eaten as part of a paleo diet?

    I am currently eating lots of vegetables, lots of organic meat and fresh fish, eggs and some fruit. Today's lunch was a soup made of onion, Jerusalem Artichoke and smoked salmon - delicious. My question - is it acceptable?

    many thanks,


  5. Hi Paleo Team,
    I am athlete and have been doing Paleo for the past three months and love everything about it. I do have one question though that I have not been able to find an answer in the Paleo books or website. What are your thoughts on preserving meat bought at the store? I have recently bought some bison and game meat at the store and want to know if it will effect the nutritional value of the meat if I freeze it vs. just the refrigerator vs. just letting it sit at room temp. Thank you for your time.


  6. Posted on behalf of Pedro:


    Yes, Inulin is a prebiotic and has numerous benefits for GI health.

  7. Posted on behalf of Maelán:

    There are some studies showing the effects of processing upon nutritive value of foods. De Groot et al. showed that freezing and drying, in particular, does not alter significantly the biological value of beef, fish, chicken or eggs. Sauvegeot et al. reported deterioration of protein quality as a result of protein or aminoacid aggregation during freezing.

    On the other hand, pork chops stored during 6 months at -18º and -26º, respectively, retained 60% of thiamine and 69% of riboflavin, and all nicotinic acid (Lehrer et al.). No differences were shown between temperatures. Similar results were found by another group research (Westerman et al.), at in pork loins stored at -18º.

    Little or no loss of nutrients was reported during storage of tinned meat at 37º during 31 weeks, however, storage during 43 weeks at 27º reduced thiamine retention to 52%.

    Freezing may induce fat oxidation, producing adverse effects upon vitamins A and E. One of the methods to avoid fats oxidation is vacuum which maintains the properties of fresh product during 2 months. The method of freezing seems to affect fat oxidation being rapid freezing more prone to fat oxidation than slow freezing. However, this has no effect on thiamine, riboflavin, nicotinic acid, pantothenic acid or pyridoxine values.

    Taken together, we recommend people buy fresh meats in first place rather than frozen meats and canned meats as the last choice. Of course, the more time the food has been storage the higher the probability it has deteriorated.

    I hope this helps.


  8. I recently came accross your blog and have been reading along. I thought I would leave my first comment. I dont know what to say except that I have enjoyed reading. Nice blog. I will keep visiting this blog very often.




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