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Re: Gluten Free Diets are backed by Science

As I've written before on my posts at, I'm not against the paleo diet - it's backed by a really shallow understanding of evolutionary theory and desperately needs a name change (Unprocessed/antigrain isn't very sexy, I guess), but overall, I don't see a huge worry for nutritional deficiencies - depending on the strictness/vigilance, an individual might be low in calcium, iodine, manganese and vitamin E. From a clinical perspective, I'm more concerned with those consuming standard American diets. From a scientific perspective, I'm mostly concerned with religious evangelization of a dietary mantra posing as science.

I had a friend send me this link, claiming that gluten free diets are backed by 'real' science and asked me for my thoughts. For one, i'm familiar with Robb Wolfe, and generally like his and Matt LaLonde's call for a harder science approach to the Paleo movement. I am a big critic of the dietetics education standards, particularly how little molecular/biochemical nutrition and cell biology is incorporated into the coursework. It's also worrisome to see dietitians critiquing these topics from a place of sentiment and not going to the literature - it's essential, in these days of self-named internet nutritionists, for RDs to be able to analyze claims and form scientifically backed rebuttals. But if we're going to call for Nutrition and paleo to be more scientific, it should actually be based on good science.

Extraordinary claims require extraordinary evidence. This link that was sent to me would not pass the critiques of a nutritional scientist, and would surely not hold enough weight to convince clinicians to start changing their recommendations. I understand wanting to disagree with current recommendations, and i've discussed some of the issues with recommendation interpretations in the past, but if there was known, solid evidence regarding the dangers of gluten, the scientific community would've already addressed it (and they have/continue to i.e. celiacs/gluten intolerance).

So back to Rob's article:
1. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac - The theory behind gut permeability is an exciting one, as it could explain aspects of the pathophysiology of several autoimmune diseases, including Celiac's, and maybe even type 1 Diabetes (1). However, this study that is put forth in Rob Wolfe's is nowhere near conclusive. Alpha-gliadin's effect on zonulin expression/activity was observed in cell lines. Cell lines, as well as the intestinal biopsies collected, pose a number of problems for conclusive evidence, especially in that they don't represent the rest of the intestinal environment or control for whole body factors. Several studies have shown that BMI independently effects circulating zonulin concentrations, as well being affected by serum glucose levels (2,3). One of the most important factors also appears to be the microflora/microbiota of the individual - an area that's currently receiving a lot of attention but is nowhere near being understood (3,4, 5). These factors are removed from cell lines exposed directly to alpha-gliadin, and while they are suggestive, they are by no means conclusive. The exposure of the alpha-gliadin was also not done in a controlled, dose-dependent manner, to see the different effects of different concentrations of gliadin. The discovery of zonulin was relatively recent in scientific history, and to understand aberrant expression levels, science will need to further elucidate what is normal patterning of zonulin expression, and all of the factors that affect it.

Rob makes the claim that because everyone has the cellular proteins involved in this proposed mechanism, everyone shouldn't be eating gluten. But if you read the paper, it only studied the intestinal tissue of individuals with treated/untreated Celiacs, and GI controls with persistent dyspeptic complaints. To show that gluten is not for everyone, one would at least need to start with a fourth control group of individuals who have no regular intestinal discomfort, and to have this all occurring in a working system. It has been shown that there is a genetic susceptibility, via specific HLA-DQ haplotypes, to Celiac's Disease and it has been suggested that gluten sensitivity is due to some underlying genetic cause, though I've discussed evidence that this may be due to other factors-if the groups chosen are those with potential genotypes underlying a gluten-induced phenotype, then the authors missed out on studying a large majority of the population that doesn't appear to be sensitive to gluten.

This one study surely does not control for a wide range of genetic/epigenetic susceptibility or other whole body/lumenal factors potentially involved regulating zonulin expression and intestinal permeability- and that will prove to be quite hard to study directly. 

2. Agrarian diet and diseases of affluence–do evolutionary novel dietary lectins cause leptin resistance? - If you read my blog, you're probably sick of me saying that Nutrition is Toxicology. Dosage is all that matters. Our brains love to compartmentalize foods/nutrients as 'good' or 'bad', but this is always an oversimplification. Are lectins good or bad, or do they take part in a larger complex system, dependent upon food processing techniques, other food components, the genetics of our immune system and the microbiota? This citation that Rob uses is based on interesting theory, though even the authors of this paper mention the potential benefits of consuming whole grains in reducing 'diseases of affluence'.  I have worked with leptin resistant mouse models, and it's quite easy to induce leptin resistance by overconsumption of a high fat diet (high fat diets are pleasurable to the rat palate and they overeat, inducing obesity). I worked in an epigenetics lab that induced this leptin resistance via overfeeding and obesity, and found interesting results implicating altered methylation affecting expressions of different carrier proteins that translocate the leptin receptor to the membrane- not necessarily having to do with a lectins binding affinity for the leptin receptor. 

If lectins are a problem, at what dosage? After how much cooking or fermentation? With the high consumption of them by lean/active individuals, why are some individuals not leptin resistant? I have not seen literature quantifying how much of specific dietary lectins are tolerable or what dosage may be beneficial. As was stated by Freed (6) in his article on the potential for lectins involvement in the pathophysiology of disease, many don't develop disease from lectins due to variability in the glycoconjugates that coat our cells, and the protective sialic acid attached to our glycoprotein tips, which can be stripped off, particularly by microorganisms - back to that microbiota again. This supports what I've said before - maybe some might be sensitive, but it is too multifactorial and science has not fully elucidated who should and should not be hyperaware of these in foods. It's imperative for clinicians to work with individuals, sympathize with their sentiments about specific foods, and address their symptoms accordingly. For a thorough, unbiased read about lectins, check out Cornell University's post about the history of plant lectins (10) - keeping in mind that studies showing they are toxic use uncooked beans/extracts, and that there are noted immune boosting/tumorcidal effects of lectins (even wheat lectins).

3.  A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease. - This study that is referenced would never be seen as conclusive by a scientist, and arguably not even provide implications for the benefits of Paleo - claiming that it's part of the scientific evidence that supports going Paleo makes it seem like only the title/abstract was read. The two diets studied in this study had drastically different macronutrient compositions - the Paleo diet was almost 100g lower in carbohydrates, had a significantly lower glycemic load, not isocaloric (over 400kcals lower - which lead to more weight loss) - let's all put on our shocked faces that this improved glucose intolerance moreso than the Mediterranean diet - plenty of evidence supports increasing protein content of the diet for individuals with impaired insulin sensitivity (7,8,9). If one wants to hint at the detrimental effects of gluten or grains on disease phenotypes, one would need to adequately control for macronutrient factors, and caloric intake/expenditure and weight loss.

So are gluten free diets supported by science? Maybe, for some. But scientists don't have these recommendations 'down to a science', for anyone except those with diagnosable Celiac's disease. 

To me, at the end of the day, this is all fighting over minute details. I think everyone agrees that getting a huge majority of your calories from grains, whole or not, is not ideal or well balanced, though many industrialized societies do this - only more research will tell the appropriate dosage. Nutritional scientists/dietitians have been saying for a long time to get your calories from varied sources, consume plenty of fruits and vegetables, lean meats, dairy, nuts, seeds, and legumes. While I like these Paleo pushers' focus on non-nutritive food components like lectins and phytic acid, saying that the science on this is so sound that public health officials should alter their recommendations is purely unscientific. I understand the evidence behind recommending the public to eat whole grains, and there's not good science (yet, at least, that i've seen) to say that we should all be avoiding gluten. On that same note, there is no dietary requirement for gluten, and if you can afford to not eat it, go for it. Grains aren't the most nutrient dense foods in the world, and if you feel fine not eating them, your lab work looks okay, you don't have to- no one is forcing you. Evangelizing doesn't change the fact that grains are a major dietary staple for the growing world population, and whole grains are an important source of nutrients and fiber for under-served/nutritionally compromised populations - don't expect changes to be made to recommendations based off cell line data, theoretical mechanisms, and poorly designed/controlled trials.



  1. Tactfully written!

    BTW - I'm a non-celaic successfully treating my arthritis (ankylosing spondylitis) with gluten and corn free diet. Drug free for 22 years now - and was doing this before the Internet was used for research.

    My biased view is that the health service (actually the government) could save billions by educating people on diet and it's possible effects on disease.

    There are other angles on gluten and proteins in wheat - such as Wheat Germ Agglutinin (used as an adjuvant in experiments) which I believe is the major culprit to trigger some disease.


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