Tuesday, January 4, 2011

Wheat: In Search of Scientific Objectivity and New Year's Resolutions

by Chris Masterjohn

Well it's that time again, so Happy New Year!

January is a great time for trying new things to improve our lives and make them a bit better than they were the year before.  A number of people in the blogosphere have offered some great dietary ideas for January.  Stephan Guyenet recently passed on Matt Lentzner's call for a Gluten-Free January.  If you're up for a challenge, and a potentially bigger bang for a bigger buck, take on John Durant's 2011 Paleo Challenge and go "Paleo" for January. 

As Melissa McEwen recently pointed out in her post about the 2011 Paleo Challenge, "Choosing plant foods because of their history without taking biochemistry into account is dogma, not science." 

She was referring to the disproportionate demonization of white potatoes, but I'd like to take this opportunity to poke a few holes in the disproportionate demonization of wheat of all foods, while nevertheless supporting the concept of the January gluten-free and Paleo challenges.  

In particular, I'd like to provide a critical review of a study widely cited to show that wheat causes intestinal inflammation in people who do not have celiac disease, which in fact did nothing of the sort.

Since there are no validated tests for non-celiac gluten sensitivity (yes, I'm very prepared to defend this statement), going gluten-free for a while and reintroducing gluten is the best way to see whether you're sensitive.  If you feel a lot better while gluten-free, but regress to how you felt before when you reintroduce gluten, it's pretty reasonable to conclude your are likely to be gluten-sensitive.  

The main caveat to this approach is that most gluten products on the market are processed in ways that make them more toxic instead of less toxic, so getting rid of these nasty products doesn't necessarily indicate a problem with gluten per se

Another caveat is that gluten is among the most difficult proteins to digest, so anyone with digestive problems caused by something else is likely to have problems with gluten, and it may be the case that such a person could tolerate gluten at a later time.

Nevertheless, better to get rid of the nasty stuff now and sort out the details later.

I went gluten-free, casein-free (GFCF) for a year and a half.  My health got worse during that period.  In particular, I developed my first panic attack in years, and I experienced periodic jitters that seemed like they might be related to blood sugar or cortisol problems.  

I don't think I have enough evidence to definitively attribute these problems to the GFCF diet, and I was never able to separate the effects of going gluten-free from the effects of going casein-free, but I've been eating properly prepared gluten- and casein-containing foods again for years now and I no longer have these problems.  So I think I am justified in concluding that going GFCF is not essential and probably isn't even beneficial to my health.

Nevertheless, many other people report benefits from going gluten-free, and whether you're sensitive is a question you are much more equipped to answer than your doctor is, so if you haven't done it already, I'd recommend going gluten-free.  And while you're at it, might as well throw in a stab at a stricter Paleo diet as well.

While we're all being open-minded and non-dogmatic about this, I'd like to offer a brief critical review about a study that has been widely cited as showing that gluten causes intestinal inflammation in non-celiacs (1), when in fact it did nothing of the sort.

In this study, the researchers took intestinal biopsies from six individuals without celiac and then cultured them in laboratory dishes, and showed that adding wheat gluten or several difficult-to-digest fragments of the protein increased the production of interleukin-15 (IL15), an inflammatory signal.  All of the non-celiac subjects were sick with problems like hiatal hernia and chronic gastritis.

If we're going to use this study to hate on wheat, we should start hating on coconut oil, because that ol' "one meal of saturated fat will practically kill you" study (2) was of much higher quality than this one.  At least in that study they actually fed people coconut oil.  Nevertheless, their interpretation of the study was enormously flawed, and I published an extensive critique on my web site and published a much shorter letter in the Journal of the American College of Cardiology criticizing the authors' conclusions (3).

For the sake of objectivity, I'll have to offer a few critiques of the wheat study too, so here goes.

Here's a brief list of my problems with this study:
  1. This is not an in vivo study.
  2. There is no full report of the methods or data.
  3. The images supposedly demonstrating the data look awful.
  4. The study is completely uncontrolled, and there is no way to conclude that the effect is unique to gluten and no way to conclude that the effect is even attributable to gluten rather than to the solvent or to any inflammatory contaminants.
1.  This is not an in vivo study.

No one fed any wheat to anyone in this study.  Concluding something about eating wheat from this study is therefore complete nonsense.

That's not to say that such a finding wouldn't be interesting.  If it were convincing (and it isn't, for reasons described below), it would be a good reason to conduct a study feeding wheat to non-celiacs to see if it causes any inflammation.  Then again, they should conduct such a study anyway.

The investigators found six people who did not have celiac, but were otherwise pretty sick.  They took intestinal biopsies, incubated the cells in laboratory dishes, and challenged them with three proteins.  One was the full gluten protein (gliadin), one was a synthetic imitation fragment of this protein 19 amino acids in length (19-mer), and one was a fragment 33 amino acids in length (33-mer) that had been treated with the enzyme transglutaminase in order to render it toxic.

Had they fed wheat to these people, the people would have substantially digested the gliadin molecule.  Although the 19-mer and 33-mer fragments are particularly difficult to digest and are therefore thought to play a role in celiac, recent evidence suggests that microbial enzymes from bacteria in our mouths digest 33-mer (4) and evidence dating back seven years has suggested that in people who do not have active celiac disease, both 19-mer and 33-mer are totally degraded once they enter the cells that line the intestine (5).

On top of this, the authors state that the version of 33-mer they used was "deaminated."  This means that they treated it with an enzyme called tissue transglutaminase (TG).  

Ordinarily, TG remains within our cells in an inactive form, but when our tissues get damaged, the cells activate it and release it so that it can start repairing the damaged tissue.  However, it also modifies the 33-mer fragment of the gluten protein by stealing nitrogen from the amino acid glutamine and thereby converting it to the amino acid glutamate.  This is in all or almost all instances required to make 33-mer "immunogenic."  In other words, the immune system will only mount a response to the gluten fragment after it has been processed by TG (6).

Surely, we can all see now why this study is worthless for telling us how the patients would have responded had they actually eaten wheat.  Perhaps since these patients were all sick and were not in any remote sense a random sample of the population, they would have been producing some TG enzyme.  Or, perhaps they would have fully digested the gluten and all its protein fragments from a mixture of microbial and endogenous enzymes beginning in the mouth and ending inside the intestinal cell.

2.  There Is No Full Report of the Methods or Data

This study was published as a brief report, almost like a letter to the editor with pictures.

This suggests that the editors of the journal either found the study 1) only moderately interesting, or 2) too inconclusive to give it space for a full report.

If this study was the first of its kind to definitively show that wheat causes intestinal inflammation in non-celiacs, I would think that would be of great interest.  The lack of details provided in this short format makes it very difficult to critically evaluate.  Nevertheless, there are some things that stick out that suggest the study is almost uninterpretable.

3.  The Images Supposedly Demonstrating the Data Look Awful

You can take a look at their figure on the second page here.  Most of it looks like a blurry mess.  

Ideally what you would want to see in a Western blot is a clear, distinct, relatively thin black line demonstrating the protein, in this case IL15.  On one side you want to see a "ladder" showing various molecular weights and on the other a clean line representing your protein of interest, sometimes shown alongside a "positive control" that was purchased commercially. 

Here's an example of a good Western blot (7):

On the right we see a ladder with different protein fragments of known molecular weight, each shown as black lines.  On the left, we see several proteins that the authors isolated.  We are confident they are the correct proteins because 1) the staining is associated with an antibody demonstrating some specificity to what they are looking for and 2) the lines appear at the correct molecular weight, as judged by the ladder on the right.
In our study, what we would like to see is a clear absence of the line in our control cells and the clear presence of a line indicating our protein of interest in the gluten-treated cells.  Is that what we see?  In some cases, kind of.  In others, all I see is a blur.

Let's take a look:
Rather than a ladder, we just have a positive control on the upper left, marked IL15.  A ladder takes up a lot of space, so that's ok.  But that should be the best-looking line, and instead it looks like a blur.  We have the best-looking line in the third column showing a biopsy from a celiac patient treated with gluten.  But is there a response to gliadin in the non-celiac individual shown in the upper right?  I just see a massive blur

In the second row, we see the cells treated with the 19-mer and 33-mer fragments.  It kind of looks like there are some lines there, but they look pretty horrible.

Sometimes it's hard to get these images to copy into files or onto print.  The computer can produce objective quantitative data that can be presented as a bar graph next to the images of the blots, but we don't have that here, perhaps because the journal wouldn't give the authors space.  Still, I'd feel more confident about their findings if they could show us that the computer can see these lines, because they look pretty fuzzy to me.

Worst of all, you always submit your best images for publication.  That means the others were probably even worse.

4.  The Study Is Completely Uncontrolled

Even if we suspend our skepticism of the fuzzy lines and take the authors at their word that gliadin and its protein fragments caused the intestinal biopsies taken from sick non-celiac patients to produce IL15, the study is still completely uninterpretable because the authors did not use any appropriate controls.

Is this an effect specific to gluten and gluten fragments, or would virtually any protein or protein fragment have caused this effect?  We don't know, because they didn't use a negative protein control.

Actually, the authors state that they expected 33-mer to have no effect on IL15:
and, although not expected, the "non-toxic" immunodominant 33-mer was also able to induce an innate response.
One way of looking at this is that their negative control failed and turned out positive.  33-mer is known for stimulating the immune system in other ways, but they only expected 19-mer to cause the production of IL15.  Maybe many other proteins would elicit the same response.

But it gets worse.  Was this even an effect of the protein, or was it an effect of the solvent?  We don't know, because there was no vehicle control.  In fact, since there is no "methods" section, we don't even know what they dissolved the proteins in!

Or, was it an effect of contaminants?  The authors state that they discarded any contaminating endotoxin, but they do not state clearly whether they discarded it from the synthetic peptides or from the intestinal biopsies, or how they discarded it.  Sometimes endotoxin purification can introduce other contaminants.  

On the other hand, sometimes proteins purchased commercially are themselves already contaminated with endotoxin, which could produce an inflammatory response.  In fact, this is so potentially problematic that any study showing an inflammatory effect of incubating cells with a protein purchased commercially should be viewed with extreme skepticism if the authors do not verify that it is free of endotoxin.

Conclusion: Consider Going Gluten-Free or Paleo Anyway!

I hope I've convinced some of you that this particular study absolutely can not be used to justify any dietary conclusions, let alone "wheat is inherently toxic and evil."  

However, if we waited for conclusive scientific evidence for everything we believe in or act on, we would vegetate.  If it's possible that you're gluten-sensitive and you still have some unresolved health problems, why not go gluten-free?  Heck, why not go full Paleo?  It's just for January.  If you feel better, stick with it and see what happens!

What's more, share your results with the rest of us!  Let's fix up published literature and personal and clinical experience on a blind date.  Once they embrace, we'll all be better off.

Read more about the author, Chris Masterjohn, PhD, here.


1.  Bernardo D, Garrote JA, Fernandez-Salazar L, Riestra S, Arranz E.  Is gliadin really safe for non-coeliac individuals?  Production of interleukin 15 in biopsy culture from non-ceoliac individuals challenged with gliadin peptides.  Gut. 2007;56(6):889-90. [pubmed link]

2.  Nicholls SJ, Lundman P, Harmer JA, Cutri B, Griffiths KA, Rye KA, Barter PJ, Celermajer DS.  Consumption of saturated fat impairs the anti-inflammatory properties of high-density lipoproteins and endothelial function.  J Am Coll Cardiol. 2006. 15;48(4):715-20. [pubmed link]

3.  Masterjohn C.  The anti-inflammatory properties of safflower oil and coconut oil may bemediated by their respective concentrations of vitamin E.  J Am Coll Cardiol. 2007;49(17):1825-6. [pubmed link]

4.  Helmerhorst EJ, Zamakhchari M, Schuppan D, Oppenheim FG.  Discovery of a novel and rich source of gluten-degrading microbial enzymes in the oralcavity.  PLoS One. 201;5(10):e13264. [pubmed link]

5.  Matysiak-Budnik T, Candalh C, Dugave C, Namane A, Cellier C, Cerf-Bensussan N, Heyman M.  Alterations of the intestinal transport and processing of gliadin peptides in celiac disease.  Gastroenterology. 2003;125(3):696-707. [pubmed link]

6.  Tjon JM, van Bergen J, Koning F.  Celiac disease: how complicated can it get?  Immunogenetics. 2010;62(10):641-51. [pubmed link]

7.  Moron B, Cebolla A, Manyani H, Alvarez-Maqueda M, Megias M, Thomas Mdel C, Lopez MC, Sousa C.  Sensitive detection of cereal fractions that are toxic to celiac disease patients by using monoclonal antibodies to a main immunogenic wheat peptide.  Am J Clin Nutr. 2008;87(2):405-14. [pubmed link]


  1. This is very interesting. I've gone gluten free for over a month before, and have felt no different adding some back in. I've still kept it to a minimum, assuming that it's one of those things that effects us "silently." Maybe not?

    As a non-scientific person, I appreciate these breakdowns of the science. I often read that "the studies are out there" and "do your own research" about grains, gluten, lectins, etc., but I'm not quite that capable of dissecting them, at least not at my patience level.


  2. Chris,

    Can you think of any reason why removal of wheat and/or casein could cause a problem for you or someone else?

  3. A gluten free test for me (and probably many others) is useless, since I did not had any apparent problem nor felt much better without it. But, what I know now for sure it's that it definitely increases my thyroid TPO antibodies.

  4. Chris, what about the apparent atherogenic properties of wheat? Dr. Davis blogs about this a lot.

    Also that it's not wheat per se, but the high-yield semi-dwarf variety that is grown now.

    Also do you consume fresh wheat? I've heard that most wheat is stored for a long time and becomes rancid? I think that was one of dr. price's recommendations that wheat should be freshly ground.

  5. Yes, some people are paleo purists or 'fascists' and recommend avoiding wheat and legumes based on a cautionary principle in relation to substances considered as dangerous toxins. When somebody without training in biochemistry/medicine/nutrition is trying to make their mind on how to consider these claims that go 'against the grain' one ends up with the usual issue of whom to consider as an authority on the subject, the paleo revolutionaries/paradigm shifters or the conventional 'experts' representing government agencies.
    Finding out if you or a family member has a sensitivity to gluten is rather tricky. I don't know what to think anymore. I avoid wheat because I've accepted the idea that wheat is poison and after more than 2 years I don't miss it at all. But I would like to make sure that my children (6 and 7) are and will be healthy. Is a negative tTG antibody test the last word in clarifying this issue? Or even then there might be potential problems in the future? Could you help?

  6. At a time when I was eating a modest amount of whole wheat, a Metametrix GI Effects stool test showed extremely low levels of inflammation markers (Lactoferrin the lowest my doc had seen and no white blood cells or mucus). My doc thought this pretty much ruled out any sort of wheat sensitivity. I still wonder 1) if Lactoferrin/WBC/mucous levels are sufficient to rule out GI inflammation and 2) if wheat can cause non-inflammatory problems, outside or inside the GI tract.

  7. As always, thanks for sharing your insight Chris!!!

  8. Fully agree - I gave up gluten free a year ago when I notices no difference.

    That said, I still eat very little bread since it usually is made with, as you said it, toxic ingredients. If I see a good bread made without vegetable oil or folic acid fortification, I have no problem eating it.

    If it's made in a traditional way, like sourdough, even better but that's not a requirement for me.

  9. It's interesting that you started with this Chris:

    "Choosing ... foods because of their history without taking biochemistry into account is dogma, not science."

    I think there's actually quite a nice irony here - because cereals actually were Palaeolithic food. One recent study even found fragments of them between Neanderthaler teeth, which was a turn up for the books. People had wrongly assumed that gathering and cooking plant-food was too complex a task for Neanderthal Man

    On the other hand it seems highly unlikely that dairy foods were exploited in the Palaeolithic era (except for women's milk for infants).

    However, I'd think it's probably a safe bet that cereal grains (which were Palaeolithic food) are more problematic for more people than dairy products (which weren't). So much for what the lady you quotes calls the "historical" approach.


  10. Chris,

    Given your cortisol remark: what was your protein and carb consumption like during your gluten-free and casein-free period?
    It seems that high protein consumption stimulates cortisol [1][2]. Carbohydrate consumption seems to lower it. [3][4][5]

    Note that I only scanned the abstracts of the given references, so I don't know how solid the science behind them is.


    [1] Slag M.F. et al. Meal stimulation of cortisol secretion: a protein induced effect. Metabolism. 1981 Nov;30(11):1104-8. http://pmid.us/6270500
    [2] Gibson E.L. et al. Increased salivary cortisol reliably induced by a protein-rich midday meal. Psychosom Med. 1999 Mar-Apr;61(2):214-24. http://pmid.us/10204975
    [3] Fernández-Real J.M. et al. Lower cortisol levels after oral glucose in subjects with insulin resistance and abdominal obesity. Clin Endocrinol (Oxf). 1997 Nov;47(5):583-8. http://pmid.us/9425398
    [4] Markus R. et al. Effects of food on cortisol and mood in vulnerable subjects under controllable and uncontrollable stress. Physiol Behav. 2000 Aug-Sep;70(3-4):333-42. http://pmid.us/11006432
    [5] Stimson R.H. et al. Dietary macronutrient content alters cortisol metabolism independently of body weight changes in obese men. J Clin Endocrinol Metab. 2007 Nov;92(11):4480-4. Epub 2007 Sep 4. http://pmid.us/17785367

  11. Yeah, that study is weak. Probably not worth citing anymore. There is a more convincing in vivo study suggesting gut immune reactions in non-celiac individuals. They used large but not impossible doses of gluten. "Gluten-induced mucosal changes in subjects without overt small bowel disease" The Lancet 1(8219):517. 1981. I'll send it to you as it's difficult to get online.

    I have to say, I'm skeptical that the proteases secreted by oral bacteria are relevant to gluten digestion. They're probably secreted in inconsequential amounts and likely get denatured as soon as they hit the stomach.

  12. Before my time, 1700's in Finland they grew rye and barley. 1700 - 1720 were the coldest years, 1740 was cold, 1750's was a cold dip, the 1760's was the century's hot peak years and 1780 was also quite warm.

    Harvests correlate with growing season and cold years the grain was less. The Fins kept church birth records and wrote later on who begat.

    If you were a peasant (poor) born in a year with below average grain harvest only 50% of those males and females went on to have a child. If you were poor and born in an above average harvest year then 95% of those boys and girls went on to have a child.

    Having grain was always more important than not having it. This does not deny some people's bodys are different or undergo changes in their lifetime.

    Glutamine endo-peptidase (gliadin cleaving enzyme) in our mouths works best at pH 4 and up. It has trace activity at pH 3, and so once we swallow it the low stomach pH staunches benefit.

    Finnish peasants did not gulp their food. The truely hungry break bread, savour it and chew it with delight; especially since their saliva level usually takes a while to cope.

    The exposure time in the mouth for gliadin to that cleaving enzyme is a limiting factor. We moderns have plenty of meals and scarf food down. Many diners dilute their mouths with readily available fluids as well.

  13. Responses to Roland, Todd, Mario, Sam, lightcan, Anonymous, Eric, Daniel, Mike, John, Stephan, and ...AL.

    Hey Roland, A month might not always be enough time, but if you don't have any problems you're trying to resolve, I doubt it's worth trying longer. I once took seriously the claim in _Dangerous Grains_ that the first sign of gluten sensitivity might be cancer. Upon reflection, the very nature of the claim makes it almost impossible for there to be evidence of it. I'm glad my posts are helpful, and you're welcome!

    Todd, the main reason would be not getting enough of a certain nutrient or set of nutrients. For some people, including myself, restrictive diets also make it sometimes hard to get enough calories.

    Mario, yes, I think that is a good reason why it is a worthwhile personal experiment, and why such an experiment is much better than getting a test of dubious value.

    SamAbroad, I don't eat a lot of wheat. I do have a grain grinder and will grind spelt or other grains if I make my own grain. I tend to buy French Meadows European Style 100% Rye Bread more often, which is not very good untoasted but is quite delicious toasted and butterred. Dr. Davis impresses me very much as a clinician and I find his blog very useful, but I'm not very impressed with his experimental techniques. I think it is possible that wheat is atherogenic but I don't think he has provided much evidence of this.

    Lightcan, anti-tTG antibody is an important part of the blood test for celiac, but it misses a small but substantial portion of people who would be caught on biopsy. If there are strong symptoms of celiac, biopsy should be done even in the presence of a negative blood test. It is possible that some people who are not celiac are gluten sensitive, and indeed there are a lot of anecdotes supporting this, so trying gluten-free and looking at the results is useful.

    Anonymous, it's possible but 'if it ain't broke don't fix it' might be useful to apply here. What kind of diet makes you feel best?

    Eric, you're welcome!

    Daniel, good points.

    Mike, good points. I wrote about that Neanderthal study in my review of Perfect Health Diet: https://www.cholesterol-and-health.com/Paul-Shou-Ching-Jaminet-Perfect-Health-Diet-Review.html And Melissa also wrote about it here: http://huntgatherlove.com/content/neanderthal-diets-included-some-grains

    John, thanks for the references. My macronutrient intakes were pretty balanced I think, and I don't have hard evidence cortisol was involved. But I do find that carbohydrates provide a calming effect and I often feel wired without enough of them.

    Stephan, thanks for sending the paper along. For the sake of others, it looks like this paper provides some evidence that high doses of gluten could be harmful for first relatives of celiacs. The enzyme paper said the enzyme was active at pH 3-8 and they suggested these enzymes are likely to be produced after the mouth as well. Just because an enzyme becomes inactive in certain parts of the stomach does not mean it gets permanently denatured. I think it is possible that these act both before, in certain parts of, and after the stomach. In any case, in non-celiacs there is evidence I cited that both these peptides are completely degraded intracellularly. All that is necessary to make my point, though, is to demonstrate the plausibility of variation in digestion, so as to communicate part of the need for an in vivo study.

    ...AL, very good points. Chewing long almost certainly helps digestion and maybe helps with this, although as I noted above I think these enzymes are likely to be active outside the mouth.


  14. Chris,

    Thanks for posting this. I have not closed my mind to the possibility that gluten is not the major player in the decline of health for everyone. I am fairly certain that there are many people suffering because of it - undiagnosed celiacs or people with gluten allergies, but they may not represent the majority.

    The way I see it, there are a lot of factors that confound the issue. Is it gluten, fructose, or over consumption of carbs that are the cause of the problem? How are they related? Does gluten cause carb intolerance? Does fructose cause gluten intolerance? Does a low-vitamin and mineral carb diet lead to problems with gluten and fructose?

    It's a mess since gluten = carbs and fructose = carbs.

    The reason I chose to focus on gluten is that we have the Kitavans and others that seem to thrive on carb heavy diets. I know of no culture that has done well with wheat. Of course, fructose has been around forever, but not in the levels we see it today.

    It just seemed to me that gluten was the most likely factor. So I browbeat a bunch of people to go without it for a month and am waiting to see what happens.

  15. Thank you,
    if there are no symptoms of celiac, no point in having a biopsy. The problem is I don't know how does the disease develop, what are the first symptoms. It depends on so many things. At the moment I can think of nutrient malabsorption in the case of my children but there is no clear evidence. I give them vit D.

    Could you maybe in the future write about greek orthodox fasting again suggesting some meals? I am a bit short of ideas for Lent as the people I know, including monks, would base their meals on dry beans, bread, polenta, vegetables and potatoes.

  16. Go back with me, if you would, to Chris' enigmatic "periodic jitters", "panic attacks". Grain carbohydrates are usually feel good foods, they involve dopamine neuro-biology.

    After dopamine is put into play the enzyme catechol-o-methyl-transferase (COMT) outside the cell renderes the mono-amine metabolite 3 meth-oxy-tryramine. This works on us extra-cellularly even at trace concentrations.

    Although it is not a proper dopamine pathway tryramine is it's own neuro-transmitter. It is involved in emotions, heart regulation (as in panic attack), abnormal involuntary tweaks (dyskinesia, as in jitters) and hyper/hypo activity.

    The enzyme catechol-omethyl-transferase (COMT) is involved in tyramine processing. If this enzyme is inhibited, due to the number of genetic copy numbers or diet, then the metabolite meth-oxy-tryamine level is low.

    If the enzyme mono-amine-oxidase (MAO) is inhibited, due to the number of genetic copy numbers or diet, then the same metabolite level is high. It too is integral to the pathways under discussion.

    COMT goes on to activate our trace amine associated receptor (TAAR1 in this case). Humans have 9 genes for these receptors. An individual response is what occurs from fluctuations of trace concentrations of that dopamine metabolite.

  17. Responses to Matt, lightcan, AND ...AL.

    Reply to Matt

    Hi Matt, I agree with you that in general the carbohydrate issue is confounded by total carb, gluten, and fructose. It is also confounded by processing, as processing methods that detoxify gluten have been abandoned in favor of processing methods that make flour more toxic. I agree that your call for gluten-free self-experiments will provide useful data for helping to sort this out, although some of the confounders will remain without additional experimentation with differently processed wheat products. Nevertheless, I think the important thing in the short-term is to identify toxic foods and get rid of them to allow healing, so I think what you're doing is good.

    On Crete, the traditional diet is based largely off wheat and dairy. Studies in the 1960s suggested their rate of myocardial infarction in men over the age of 45 was 0.7%. See here http://www.ncbi.nlm.nih.gov/pubmed/14263030 . There was a somewhat higher rate of murmurs that were considered possible evidence of arrhythmia due to aortic atherosclerosis (7-8%), but they also had a very high rate of smoking -- 55% of the men smoked and 35% smoked more than a pack per day. I think these numbers are pretty impressive and consistent with their wheat-based diet being most likely healthy for them.

    There may be other examples. It's difficult to say, because heart disease has not been studied with any rigor until the modern era, when the spread of wheat has occurred in the form of a global spread of white flour and sugar. Even worse, during the first half of the century when this spread was rapidly initiated, wheat was treated with nitrogen trichloride, which created toxic inhibitors of biosynthesis of glutamine and glutathione and led to hysteria in dogs. It was abandoned in US and UK due to concerns of potential human hysteria and in Canada because it was explosive and thus a risk to mill workers. Trying to tease out all these factors using a historical or epidemiological worldview would be incredibly difficult, so we need rigorous science in the form of publication-worthy literature, self-experimentation, and careful clinical practice. Thanks for being part of the solution!

    Reply to lightcan

    lightcan, you're welcome. I think if your kids are healthy, you are healthy, and there are no signs of disease, than not worrying about it is much, much, much healthier than worrying about it. I would just feed foods traditionally prepared that make you and your family feel well. I would not feed toxic white flour junk foods, of course, but if long-rise breads, preferably of older varieties if you can find them, seem health-promoting and there are no signs otherwise, I think you are in good shape.

    I will post more on Orthodox fasting in the future. Briefly, I would suggest emphasizing shellfish, coconut products, fruits, and fermented vegetables. If you tolerate them, leafy greens like cruciferous vegetables are a great idea for calcium. Red palm oil is a good idea for vitamin A. Bananas are one of the best plant sources of B6. And spinach, while its calcium is poorly bioavailable, and while it is a source of oxalate (that should be tolerated by most people due to its high calcium content), is an excellent source of betaine that can substitute for the choline missing from egg yolks and liver. Hope that helps!

    Reply to ...AL

    ...AL, I kind of follow you but can't quite tell what your conclusion is. I have a suspicion, with a very small amount of evidence, that elevated levels of histamine in the brain can contribute to panic attacks, and the rate-limiting step of histamine detoxification is methylation, so it makes sense that foods rich in folate, B12, choline, and betaine would help. Wheat does have quite the mega-dose of betaine, although clearly liver and egg yolks are king here.


  18. Might-o'chondri-ALJanuary 7, 2011 at 10:10 AM

    Trace metabolites aren't taught about in text book bio-chemistry, but they are also doing things. My suggestion is that our individual genetics and environment (diet, emotions included) combine to make us influenced by trace metabolites - even if we are not 100% of the time showing any symptoms of them.

    Dietary habits are not free from long cycles of influence on us. We don't easily pick up those nuances because the process of nutrition seems like cause and effect are running the show. Since your reported type of annoyances were unpredictable, I suggest the trace metabolite derived from dopamine as your particular "trickster".

    Why your dietary changes and re-incorporations of foods alleviated the episodes I am not sure of. If that was due to an epigenetic "re-write", with full on histone acetylation changes opening up DNA for methylation programming, is not certain (to me).

  19. curious about your view of plant-free diets

  20. Really your post is very informative and I enjoyed your opinions. Do you use twitter or stumbleupon? So I can follow you there. I am hoping you post again soon.


  21. Responses to ...AL, Anonymous, and Imgenex.

    ...AL, I kind of get you, but I guess your hypothesis is kind of loosely formulated, and that's why I wasn't too clear on what you meant.

    Anonymous, I don't know that plant-free diets are harmful, but as far as I know, no human groups in the entire universe have ever eaten them, so I don't know why anyone would bother unless they find themselves hypersensitive to plant chemicals, or just really hate the taste or texture of plant foods.

    Imgenex, I'm on facebook and twitter. You should be able to find me either place easily by searching my name. Glad you're enjoying the blog!


  22. Hi Chris,

    Just thought I'd add to Stephan's link ... Bernardo et al followed the 2007 Gut paper with a much more extensive 2008 paper in Clinical and Experimental Immunology with better western blot data and, more importantly, PCR data of mRNA expression. The paper is here.

    Our book cites both. I think the China Study results show that wheat consumption strongly correlates with poor health, and these papers show widespread inflammatory responses to it, so there's reason to believe that it will be health improving to avoid it.

    Best, Paul

  23. Hi Chris, I think the main reason because you got worse on GFCF is that you were missing some important nutrients.

    Dairy can be very healthy, did you eat ghee/clarified butter?

  24. Paul,

    I saw that paper before writing my blog post, but after perusing it, it did not seem relevant so I did not include it. I just perused it again, and I do not see anything relevant here. They stimulate IL15's receptor with IL15, not with gliadin peptides, and they report that "No detectable levels of IL-15 were found in the non-CD patients."

    Paul, the China Study not only has no ability to suggest cause-and-effect as it is observational, but it is also an ecological study, which is widely considered the lowest level of epidemiological study. It's and excellent design for relating factors that occur at the group level -- say, correlating sizes of the national budget with tax laws -- but not so great for relating factors that occur in individuals.

    The work that Denise and others have done on wheat is important, but the take-home message from it will ultimately be that Campbell displayed enormous bias in ignoring a very strong correlation because it did not support his own hypothesis, while pursuing other correlations that supported his hypothesis but were much weaker. To read cause-and-effect between wheat and disease into it, beyond merely making a case that such a cause-and-effect phenomenon has some biological plausibility, would not be a proper use of the data.

    Perhaps wheat causes intestinal inflammation in most people -- but if so, good and properly interpreted research should be used to show that.


  25. snaider,

    I agree that my experience confounded GF with CF. I can't remember for sure, but I was probalby using a verified casein-free ghee.


  26. Hi Chris,
    Your response is much appreciated. The problem generally is that 'traditional' foods are not available. I don't make fermented vegetables, but I try to only give them shop bought sourdough bread and overall nutrient rich food. Even that bread is not perfect, as I gather, only the starter is fermented for a longer period and then they add the actual flour that sits together with the starter for a few hours.
    The kids seem healthy, however my daughter has mild scoliosis and my son is shorter than the others for his age, although we are not of short stature. Their new permanent front teeth seem much bigger than the milk teeth and came on top of the old ones and will be maybe crowded. That remains to be seen. That's why I thought there might be a problem with vit D and minerals. (plus there are two cases of celiac in my husband's family, his aunt and her daughter and a case of alopecia areata, which could be an autoimmune disease linked to wheat)

  27. Hi Chris,

    You're right, they say the cultures were prepared as in an earlier paper (http://www.ncbi.nlm.nih.gov/pubmed/1582589) which did cultures of biopsies with a peptic-tryptic digest of gliadin, but they don't show any data from that, they only cite the 2007 paper to support the gliadin upregulation of IL-15.

    The zonulin effects discussed here http://perfecthealthdiet.com/?p=873 seem a lot more solid.

    The problems of epidemiological studies are great but China's cultural differences are helpful in this case. Whole swathes of the country are pretty nearly exclusive in the use of either rice or wheat. This is probably why the correlations between wheat or rice and health were the strongest in the study: the provincial aggregate data much more closely resembled the individual situation than for other foods.

    Unfortunately there's been a disturbingly small amount of research on food toxicity in general. A few researchers like Arpad Pusztai account for a large fraction of the literature on food toxins. When we searched the literature while writing our book it was hard to find molecular and cell biology papers on food toxins. Yet this is by far the largest source of toxin exposure for most people, as Bruce Ames points out.

    Best, Paul

  28. Chris, I like that you don't discount a gluten-free experiment just because you had a bad experience with it. It's easy to assume that your own experience will apply to everyone.

    Regarding panic and jitters in your experiment, could it have been caused by lack of magnesium? I've read that insufficient Mg can cause these and other problems, but without a background in biochemistry, I don't know how good the science is.

    I do know that after I dropped wheat and started a low-carb diet, my swallowing problems came back and I had trouble with constipation. (But I felt so much better in so many other ways that I didn't consider returning to my old diet.) Both problems disappeared with Epsom salts or a big daily dose of a Mg supplement. Is it possible that humans need more Mg on a high-fat diet--or maybe it's just me?

  29. Hi, regarding your panic attack maybe I found an explanation. Gluten and casein have opiates activity.


    "Paradoxically, some substances labelled depressants such as alcohol or opiates can increase T3 levels by impairing the breakdown of T3 in the brain, thus lifting mood. This may be one reason why these substances are so addictive."

  30. Chris,

    Another intelligent post! I like the fact that you keep it real and scientific and don't get tangled up in your own bias.


  31. Chris - what about the "leaky gut" effects of WGA/gluten? Even though this study is pretty much worthless - are there not others that make a stronger link to unfortunate responses to gluten in non-celiac persons?

    I have seem lots of pretty damning "could be" arguments/research pointing at gluten for thing form schizophrenia to MS, IBS to Rheumatoid arthritis (and auto-immune disorder) - are these not more frightening postulations than the study you just effectively deconstructed?

    Discoveries for a Full Life

  32. If you're that worried about gluten, but don't want to give up bread try some traditionally made artisan bread:


  33. Chris and Matt L, the Sikhs ate fresh ground whole wheat with robust health. Robert McCarrison studied and wrote about the indigenous people of India around the same time Weston Price traveled and wrote. Some of RM's books are available online. For a summary, see Matt Stone's blog, 180 Degree Health, and search for posts tagged Robert McCarrison or just McCarrison.

    I think the Hunza and some other healthy groups ate wheat, as well as the people on Crete that Chris mentions. To say you are not aware of any healthy people eating wheat is ignorant, as they have been brought up repeatedly on various blogs. Even Stephan conceded that the rancidity of flour, esp whole wheat, and the toxc chemical bleaching that creaes alloxan, and the synthetic vitamins and minerals used in enriching, could be large factors in whea related problems.

    Also, Matt, you ignore other confounders that could be at fault like the pufa oils, canola oil, hydrogenated oils, and so on that are almost ubiquitous in store bought breads. Even the health food store breads mosty use refined and/or rancid pufa oils.


  34. Chris, thanks for this post. Gluten can be a of the many complex proteins ingested by man - and is therefore extremely hard to digest. This is why babies first introduced to solid meals are not given wheat. They are started on a thin porridge of rice because their small digestive tract can process it very easily.

    Most people with Gluten intolerance are incapable to digest gluten - a protein found in wheat, rye, barley and oats. In fact in Celiacs this protein actually attacks the lining of the small intestine producing injury that flattens out the tiny villi

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  36. i just want to say that this is a fantastic dialogue, with a very impressive group of participants, and I'm not referring to myself; naturally, I'm talking about input from people like Paul Jaminet and Chris Masterjohn.

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