Gluten-free has been stigmatized as a ‘fad’ diet and an example of woo science gone overboard. Nonetheless, the backlash against the gluten-free fad is difficult to justify based on the scientific literature.

While a common mantra is that only those diagnosed with celiac disease or a wheat allergy need to avoid gluten, the list of gluten-related disorders is actually quite long (e.g. some forms of epilepsy, ataxia, and liver disorders). As well, the underdiagnosis of celiac disease will likely continue to be a problem as (A) antibody and biopsy tests generate false negatives and (B) celiac disease is often difficult to diagnose.

More importantly, it may very well be the case that it’s not just wheat that’s the issue. Emerging evidence suggests that a long list of autoimmune conditions could be treated with diet. However, removal of gluten alone is often not enough as there seems to be many other foods that also cause problems.

Known problems with wheat and/or gluten

Celiac disease is frequently under-diagnosed .

. 2 small studies suggest that non-celiac gluten/wheat sensitivity (NCGS/NCWS) can result in depression and brain fog . Other symptoms of NCGS/NCWS include abdominal pain , eczema , rash , headache , fatigue , anemia , numbness in legs/arms/fingers, and joint pain .

and . Other symptoms of NCGS/NCWS include , , , , , , in legs/arms/fingers, and . Rare cases of epilepsy respond to a gluten-free diet. See Appendix A.

respond to a gluten-free diet. See Appendix A. Gluten can lead to gluten ataxia and dermatitis herpetiformis . See Appendix B and C.

and . See Appendix B and C. A few types of liver disease and liver disorders respond to a gluten-free diet. See Appendix D.

respond to a gluten-free diet. See Appendix D. Wheat allergies are one of the most common allergies. See Appendix E.

are one of the most common allergies. See Appendix E. Neurological manifestations such as peripheral neuropathy, inflammatory myopathies, myelopathies, headache, and white matter abnormalities. There are also some reports of gluten encephalopathy, ADHD, anxiety, schizophrenia, and autism being treated successfully by gluten-free diets. See the review “Neurologic and Psychiatric Manifestations of Celiac Disease and Gluten Sensitivity” ( Psychiatr Q. 2012 Mar; 83(1): 91–102. ). For movement disorders, see this review.

Certain conditions are caused/triggered by gluten as well as other foods:

Gluten has been proven to impair intestinal permeability and therefore cause a ‘leaky gut’. Impaired intestinal permeability is a suspected cause of autoimmune disease . It is likely that many other foods also impair intestinal permeability. See Appendix F.

. It is likely that many other foods also impair intestinal permeability. See Appendix F. Wheat and many other foods are known to trigger rheumatoid arthritis in some patients. (See my post on the dietary causes of rheumatoid arthritis.)

in some patients. (See my post on the dietary causes of rheumatoid arthritis.) Hard-to-digest fibres (FODMAPs), which are found in wheat and many other foods, can lead to irritable bowel syndrome (IBS) and other GI issues such as diarrhea and constipation .

and other GI issues such as and . Grains/cereals such as wheat can cause cavities if the total amount of phytic acid consumed is sufficiently high.

Why celiac disease is under-diagnosed

We’ve been slowly learning that many people with celiac disease do not exhibit the most stereotypical symptoms (from page 3 of this paper):

Chronic diarrhea.

Iron-deficient anemia.

Growth faltering (in children) and weight loss (in adults).

Other less common symptoms of celiac disease include:

Bloating

Gas

Fatigue

Constipation (which is the opposite of diarrhea)

Depression

Itchy rash and/or dermatitis herpetiformis

Most celiacs do not exhibit the symptoms most ‘typical’ of celiac disease, leading to under-diagnosis. A multi-center study on the prevalence of celiac disease (by Alessio Fasano and his colleagues) found that only 35% of newly-diagnosed patients exhibited chronic constipation, which was the most frequent symptom of celiac disease (CD). Among first and second-degree relatives of those with CD, the rate of CD was almost identical between those exhibiting symptoms and those not exhibiting symptoms: 4.32% of symptomatic relatives had CD while 3.91% of relatives without symptoms had CD.

Furthermore, common practices in diagnosing celiac disease can lead to under-diagnosis. While antibody tests are known to have false negatives (and frequent false positives), many doctors will not order a biopsy if the antibody tests come back negative. And while biopsies are often considered to be the gold standard in terms of diagnosis, they may miss borderline cases. Of the patients in multi-center study mentioned previously, 350 tested positive for EMA antibodies. Out of those 344, 116 had biopsies performed (71 of the 350 had their biopsy request denied by their physician or insurance company). Of those 116, only 34% showed classic signs of celiac disease in their biopsy results (Marsh stage 3b marked villous atrophy or Marsh stage 3c flat mucosa). The remaining 66% were borderline cases that exhibited hyperplastic changes or mild villous flattening.

A 2010 paper by Alessio Fasano and Carlo Catassi argues that celiac disease should be diagnosed based on a “4 out of 5” rule, which would broaden the definition of celiac disease and reduce the amount of undiagnosed celiac disease.

Screening for celiac disease

People with epilepsy or ataxia (of unknown cause) should be screened for gluten sensitivity as a gluten-free diet may also treat the epilepsy or ataxia.

As far as high-risk populations go, the general pattern is that those with an autoimmune condition are more likely to have other different autoimmune disorders. For example, somebody with type 1 (autoimmune) diabetes is more likely to have celiac disease (and vice versa). To check the scientific literature, go to Google Scholar and search for the name of both autoimmune diseases. You will likely find a paper with statistics on the correlation between the two diseases.

Non-celiac gluten/wheat sensitivity (NCGS/NCWS) and its connection to Irritable Bowel Syndrome (IBS)

NCGS is a controversial condition because it has been difficult to research. To understand some of the controversy, let’s look at the history of Monash University researchers on gluten.

Controversy as to NCGS’ existence relates to the conflicting research results and the strong placebo/nocebo effects that researchers face when investigating IBS, depression, and brain fog / foggy mind. In a 2017 paper, Peter Gibson and 2 co-authors take a more skeptical stance towards the existence of NCGS and dance around the issue of whether or not it exists.

A review paper on gluten disorders provides some figures on NCGS from the University of Maryland’s Center for Celiac Research. 347 of 5,896 (6%) patients seen fulfilled their criteria for NCGS. Symptoms included:

Abdominal pain (68%)

Eczema and/or rash (40%)

Headache (35%)

“Foggy mind” (34%)

Fatigue (33%)

Diarrhea (33%)

Depression (22%)

Anemia (20%)

Numbness in the legs, arms or fingers (20%)

Joint pain (11%)

The data implies that the clinicians are of the opinion that only a small fraction of their patients have a medically-identifiable problem with gluten.

At the moment, NCGS/NCWS remains a controversial topic.

Autoimmune disease and diet: it’s not just gluten

Surprisingly, the scientific literature has many instances of various autoimmune conditions being successfully treated with diet.

Rheumatoid arthritis (RA) has multiple dietary causes, with wheat and corn being the most common food intolerances. Food intolerances vary widely from patient to patient. Roughly 35-40% of RA patients can be treated with diet according to Dr. Gail Darlington.

of RA patients can be treated with diet according to Dr. Gail Darlington. Some cases of ataxia respond to gluten-free diets.

Rare cases of epilepsy respond to gluten-free diets. Many cases of epilepsy also respond to ketogenic diets. While the reported success rates of ketogenic diets vary (with some as low as 10-15% for seizure-free recovery), Livingston’s textbook on epilepsy (according to this review) suggested that 52% had complete control of seizures. Success rates for diets are significantly higher when >90% reductions in seizures are included. Other diets such as the modified Atkins, low glycemic index, and paleo ketogenic diet have also been used for epilepsy.

for seizure-free recovery), Livingston’s textbook on epilepsy (according to this review) suggested that had complete control of seizures. Success rates for diets are significantly higher when >90% reductions in seizures are included. Other diets such as the modified Atkins, low glycemic index, and paleo ketogenic diet have also been used for epilepsy. There is a single case study of type 1 diabetes responding to a gluten-free diet. The disease seems to have reversed completely: HbA1c levels were stabilised at 5.8%–6.0% without insulin therapy (!). Unfortunately, other larger T1D populations do not exhibit such dramatic success. Some studies (e.g. here and here) show that patients still have elevated HbA1c levels characteristic of poorly-managed type 1 diabetes while on gluten-free diets. Paleomedicina, a Hungarian clinic, has posted 2 case studies (here and here) on their patients whose T1D reversed while on their paleo ketogenic diet, which consists of fatty meat (and eggs). While their patients are able to discontinue insulin, Paleomedicina also reports that some of their patients decide to go off their diet and lose their remaining insulin-producing cells forever.

In studies on mice and rats, research results are inconsistent. Some studies (here and especially here) implicate gluten in the development of type 1 diabetes. Other studies found that the animal models developed type 1 diabetes less frequently while on diets that include gluten (see here and here). Surprisingly, the latter studies strongly suggest that a diet containing gluten isn’t the worst diet in the world (for non-obese diabetic mice). Commercial mice chow seems to be far worse than gluten and Pregstimil (Pregstimil is a synthetic diet where proteins have been extensively broken down / hydrolyzed).

The general picture is that there seems to be other dietary components that also cause autoimmune disease. Gluten (or wheat) isn’t the only villain. This might explain why gluten-free diets rarely succeed for certain autoimmune diseases and health conditions.

Unfortunately, mainstream medicine is often unsupportive of the idea that diet can treat particular health conditions (e.g. most autoimmune diseases such as rheumatoid arthritis). The big picture is that mainstream medicine often clings to ideas that aren’t supported by scientific evidence. The scientific literature clearly describes a long list of conditions that can be resolved by a gluten-free diet, yet many medical professionals claim otherwise. Hopefully there will be a day when the medical establishment changes its ways so that patients are told about treatment options that could potentially reverse their health problems.

Grains can cause nutrient deficiencies

While those criticizing the gluten-free fad argue that a gluten-free diet can lead to nutritional deficiencies, the irony is rich as the phytic acid in grains is known to cause nutritional deficiencies.

In the 20th century, the husband and wife team of May and Edward Mellanby performed research into various nutritional topics such as rickets and cavities. Rickets is a skeletal disorder caused by poor nutrition. Both rickets and cavities are disorders in bone development and are both caused by similar nutritional deficiencies. While Edward Mellanby is notable for his role in discovering the causes of rickets (see his biography), the Mellanbys’ work on cavities is not as well known.

The Mellanbys identified the main factors in the development of cavities:

Calcium and phosphorous. As phosphorous deficiencies are rare in Western diets, it is typically calcium that is deficient. Fat-soluble vitamins, especially vitamin D. Phytic acid, which is typically found in grains/cereals, nuts, plant seeds, and legumes. Phytic acid binds to minerals such as calcium and prevents our bodies from using those minerals, potentially causing mineral deficiencies.

In 1932, May Mellanby and C. Lee Pattison published the results of a study on hospitalized children looking at the effect of a grain/cereal-free diet on cavities: “Remarks on the influence of a cereal-free diet rich in vitamin D and calcium on dental caries in children“. At the time, they knew from animal studies that grains/cereals cause cavities but scientists had yet to determine the exact mechanism (phytic acid). What May Mellanby and Pattison found was that the removal of all grains from the diet led to the “healing” of almost all cavities:

While any missing bone will not grow back, cavities can “heal” when the surface of the tooth hardens and becomes a protective layer. Edward Mellanby’s 1949 paper (“The rickets‐producing and anti‐calcifying action of phytate“) is a treatise on phytates (phytic acid compounds) and how their cavity-inducing properties were discovered.

Unfortunately, mainstream dentistry at the time marginalized the Mellanbys’ views due to politics. Prominent dentists were promoting the idea that cavities were prevented by eating fibrous foods, which have a ‘detergent’ teeth-cleaning effect when the fibrous food is chewed. The paper “Scientific knowledge and clinical authority in

dentistry: James Sim Wallace and dental caries” describes dental theories in the Mellanbys’ era. By today’s standards, the detergent effect theory seems absurd and misguided. The same paper on the history of dentistry also argues that dentists attacked the Mellanbys’ work to protect their reputations:

The leading British dentists found themselves in a position in which their claim to professional status and their claim to distinctive therapeutic and preventive expertise were both under intense scrutiny. It is in this context that the adoption of a form of discourse that emphasised their possession of a special sort of authority, primarily clinical but secondarily scientific, was particularly advantageous.

Nowadays, the Mellanbys’ experimentally-proven ideas remain ignored due to the popularity of the current theories regarding fluoride and oral hygiene on cavities. The scientific evidence is largely unfavourable towards those theories. A Cochrane Collaboration review estimates that conventional toothpaste (e.g. with 1000/1055/1100/1250 parts per million of fluoride) lowers the rate of cavities by roughly 23%. The ineffectiveness of modern dentistry is not great for patients’ bank accounts as the standard of care is to treat cavities with a lifetime of dental fillings (and eventually tooth extractions and dentures).

Note that the total avoidance of grains is not necessary if the only goal is dental health (this is stated in May Mellanby’s 1932 paper). It is only the excessive consumption of phytic acid that leads to the development of cavities. Phytic acid can be reduced through food preparation techniques such as lengthy sourdough fermentation. This was known several decades ago as Edward Mellanby’s 1949 paper discusses how phytases (enzymes that break down phytates) found in yeast (as well as the bran of a grain) will affect the phytate content of food.

The advice that conventional grains should be a regular part of a ‘balanced’ diet (e.g. grains forming the base of the USDA food pyramid) is not supported by scientific evidence. May Mellanby’s studies indicate that regular consumption of bread will lead to cavities in some people. Unfortunately, this scientific knowledge has been ignored and cavities remain a common problem today.

Further reading:

Treating cavities through nutrition

Elmer McCollum’s 1941 paper “Diet in relation to caries”. McCollum was a leading nutritionist in his day and a contemporary to the Mellanbys. He believed in the detergent effect of chewing fibrous foods. His paper is reproduced on the Weston A Price Foundation website with editorializing in the beginning that points out the wackiness of the dental theories in his paper, e.g. the idea that fats coat the teeth and protect them from decay. Scientists used to promote some strange ideas.

What we know and don’t know

Multiple components of wheat (e.g. gluten, α-amylase inhibitors, phytic acid, and potentially others) cause problems in humans. Unfortunately, there isn’t a lot of science that quantifies exactly how bad these components are. We do know that many autoimmune diseases can be reversed through diet (in at least some people). It is unclear as to how much of that can be attributed to the removal of gluten and wheat. That research simply hasn’t been done yet (and sadly, such research remains unfashionable). At the end of the day, we don’t fully understand how detrimental gluten is to human health. Perhaps the intestinal permeability theories are correct and gluten is one of the many foods that lead to autoimmune disease (see Appendix F). Or perhaps gluten is only a minor player in the health problems that human beings face. We simply don’t know yet.

In the meantime, medical professionals could do a better job in informing the public about known risks of gluten and wheat.

Celiac disease is underdiagnosed.

In those who can’t tolerate trace amounts of gluten, it is easy to accidentally ingest it. There is some science as to how such risks can be minimized (e.g. unintuitive sources of cross contamination)- see my post on eating gluten-free for some references to that literature.

Certain autoimmune diseases respond to dietary treatments (!).

Some clinicians now recognize non-celiac gluten sensitivity as a real health condition.

Cavities are often caused by problems with phytic acid as well as deficiencies in vitamin D and calcium.

Currently, we are in an age where the Internet provides access to most of the scientific literature. It becomes obvious that the medical community often gives out (self-serving) advice with little or no evidence behind their recommendations. This needs to stop as bad advice can hurt patients. Instead of telling patients that diet won’t treat rheumatoid arthritis, doctors need to be educated about how elimination diets have been proven to work for some people.

The stigmatization of those eating gluten-free diets needs to stop as well. Some people really do benefit from a gluten-free diet even if the science is unclear as to why they benefit. People with health problems should not be socially encouraged into harming themselves.

Lastly, we need more research into how diet affects our health. Despite evidence that diet can put autoimmune disease into remission, such research is often unfashionable as it goes against ideologies within the medical field. Nonetheless, the current evidence points towards gluten and a long list of other foods as problematic in the onset of autoimmune disease. We currently have a poor understanding as to what all of those other foods/substances are and why they cause disease. People with autoimmune disease or other health problems deserve the best that science can offer.

Appendix A: Epilepsy

In a very small segment of epilepsy patients, there is a triad of specific symptoms: occipital calcifications, seizures originating from a number of brain locations, and celiac disease or gluten sensitivity. A gluten-free diet reduces symptoms in about 53% of these cases. See the following reviews:

This 2018 review: Gluten sensitivity and epilepsy: a systematic review. Journal of neurology (2018): 1-9.

(2018): 1-9. The “Epilepsy and Seizure Disorders” section in this review (Psychiatr Q. 2012 Mar; 83(1): 91–102).

Unfortunately, epilepsy is a condition where money and politics play a role in ignoring the science on dietary treatments. In the 1920s, it was discovered that the ketogenic diet was a treatment option that worked in some patients. However, when pharmaceutical drugs hit the scene, doctors slowly stopped telling patients about the ketogenic diet and there were close to zero research papers being published on the diet. In a 1994 TV segment from Dateline (10:47 into the video), Dr. Donald Shields explains that the ketogenic diet lost popularity because there wasn’t a pharmaceutical company selling it to doctors.

Currently, recognition of the role that gluten plays in epilepsy remains low. One 2011 literature review on drug-resistant epilepsy does not even mention gluten at all (or celiac disease or CEC syndrome), despite papers going back a few decades on that topic.

Appendix B: Gluten ataxia

Ataxia is a degenerative disease of the nervous system whose symptoms can resemble those of somebody who is drunk – slurred speech, stumbling, falling, and a lack of coordination. In individuals with celiac disease or a gluten sensitivity/intolerance, ataxia can be treated with a gluten-free diet. One online article highlights the importance of diagnosing gluten ataxia early:

Hadjivassiliou recommends neurologists routinely screen patients with unexplained ataxia for gluten sensitivity. Those with gluten ataxia have no time to waste, he warns. The gluten-free diet—the mainstay of treatment for gluten ataxia—can result in a stabilization of symptoms. But often, significant damage is already done. The neurologic system tends to heal very poorly and very slowly, says Murray. Unlike the small bowel lining, Purkinje cells of the cerebellum have no capacity for regenerating, explains Hadjivassiliou. Once ataxia is well established, which can happen in as few as six months, it’s rare to make a full recovery.

More recent papers by Hadjivassiliou and his colleagues (see below) argue for a broader definition of gluten ataxia in patients who don’t fully meet the diagnostic criteria for celiac disease. This fits the broader pattern of gluten-related disorders being underestimated and underdiagnosed.

Further reading:

Gluten-Related Disorders: Gluten Ataxia. (Abstract.) This 2015 paper reviews gluten ataxia and its diagnosis. It notes: “Gastrointestinal symptoms are seldom prominent and are not a reliable indicator for the presence of enteropathy”.

Effect of gluten-free diet on cerebellar MR spectroscopy in gluten ataxia. (Abstract.)

“[…] patients with positive serology and negative duodenal biopsy should still be treated with strict GFD”

“[…] patients with positive serology and negative duodenal biopsy should still be treated with strict GFD” The Significance of Low Titre Antigliadin Antibodies in the Diagnosis of Gluten Ataxia. (Full paper.)

“Patients with ataxia and low titres of AGA benefit from a strict GFD. The results suggest an urgent need to redefine the serological cut-off for circulating AGA in diagnosing GA.”

Appendix C: Dermatitis herpetiformis

You can use Google Image Search to see what the characteristic skin rash looks like (warning: it’s not that pretty).

For some more information on the skin condition, see this review on diet in dermatology.

Appendix D: Liver disease and disorders

It is not well-known that certain liver conditions respond to gluten-free diets while others do not seem to do so. For example, a review published in Feb 2012 on the spectrum of gluten-related disorders does not mention liver disease (or epilepsy) at all.

For a review of the topic, see “The Liver in Celiac Disease” in Hepatology 46.5 (2007): 1650-1658. Those with liver disease are generally at higher risk of celiac disease so they should be screened for it.

Appendix E: Wheat allergies

Wheat allergies are one of the most common types of allergies. One type of wheat allergy, baker’s asthma, is caused by prolonged exposure to airborne wheat from working in a bakery. Baker’s ashtma is thought to be caused by α-amylase inhibitors found in wheat. So, it’s not just the gluten component of wheat that seems to cause problems in humans. See the aptly-named paper “Members of the α-amylase inhibitors family from wheat endosperm are major allergens associated with baker’s asthma” (FEBS letters 261.1 (1990): 85-88) for more information.

A review on gluten-related disorders also points the finger at other wheat components:

a number of other proteins present in wheat, including germ agglutinin, peroxidase and non-specific lipid transfer proteins (LTPs), have been reported to bind to IgE from patients with baker’s asthma […] It is of interest that both peroxidase and LTP have also been reported to be active in food allergy to wheat

“Allergic to exercise”

In the uncommon condition known as exercise-induced anaphylaxis (EIA), an allergic reaction happens when an individual ingests a sensitizing food and engages in exercise. The wheat-specific version of EIA, wheat-dependent exercise-induced anaphylaxis (WDEIA), is thought to be caused by omega-5 gliadins and high molecular weight glutenins. (Gluten is made up of gliadins and glutenins.)

Surprisingly, there is evidence that exercise isn’t always healthy as there are some individuals who have one of the many forms of EIA.

Appendix F: Intestinal permeability theory (or, why ‘gluten causes everything’)

For many decades, researchers have noticed that autoimmune diseases are associated with elevated intestinal permeability or a ‘leaky gut’. While the intestine normally does not let large molecules enter the body, an abnormally high intestinal permeability allows foreign proteins to enter the body. The theory is that the immune system mounts an attack on these foreign proteins and that somethings goes wrong, causing the immune system to also attack the body’s own cells in the process.

Alessio Fasano and his colleagues have discovered that the giladin in gluten binds to the CXCR3 receptor and causes the body to produce zonulin. Zonulin is a signalling molecule that causes the gut to ‘open up the castle gate’ and allow large molecules through, leading to an increase in intestinal permeability. See “Zonulin and Intestinal Barrier Function” for a review of the research on the subject.

These researchers have also linked zonulin to the onset of type 1 diabetes (T1D), though only in mice. In BioBreeding diabetic-prone rats, elevated levels of zonulin and increased intestinal permeability precede the development of type 1 diabetes. (See the discussion of T1D on page 14 of the paper mentioned earlier for more details.)

When these rats were given a zonulin inhibitor, Larazotide Acetate (also known as FZI/0 or AT-1001), the intestinal permeability was restored and the rats developed T1D at a much lower rate. The relevant study found that:

Without the inhibitor, 11 out of 15 rats developed type 1 diabetes (73%). With the inhibitor, 3 out of 15 rats developed type 1 diabetes (20%).

Despite Fasano’s enthusiasm, these results could not be replicated in humans as that particular zonulin inhibitor doesn’t affect intestinal permeability in humans (see here and here for the results of 2 different trials reported in 2012).

There is another line of evidence that suggests that intestinal permeability leads to T1D in humans. Paleomedicina, a clinic in Hungary, has figured out that their paleo ketogenic diet is highly effective in restoring intestinal permeability in humans.

Zsofia Clemens’ conference presentation (available on Youtube) goes over the diet and why they believe it works. At the 6:15 mark, she explains that pathological intestinal permeability (and that of other membranes) are the suspected cause of autoimmune diseases and cancer.

Pages 13-15 from the presentation slides contain examples of intestinal permeability measurements before and after placing patients on their treatment diet (lower is better).



So far, Paleomedicina has published case studies on treating (and reversing) diseases such as type 1 diabetes. To fully prove the link between intestinal permeability and autoimmune disease, more research such as randomized controlled trials would be needed to provide stronger evidence in favour of the theory. Sadly, such trials do not currently exist. Right now, we only have case studies (and anecdotes) showing that many autoimmune diseases can be reversed in some patients. Paleomedicina has published their case studies on various health conditions:

Paleomedicina argues that their diet can treat a multitude of other autoimmune conditions (see Appendix D in this post for a list). If the theory is correct, then we would expect that:

Gluten and other foods (yet to be fully identified) lead to elevated intestinal permeability which leads to disease.

Some fruits and vegetables can be unhealthy when they increase intestinal permeability (!). Paleomedicina has observed that removing paleo-friendly fruits and vegetables can improve patient outcomes.

Please bear in mind that there needs to be more research. It may very well be the case that the mechanism is something other than intestinal permeability. There are various other alternative theories such as an unhealthy balance of gut bacteria (dysbiosis), early exposure to antigens (too little / too much), an environment that is too clean (due to c-section delivery of babies, overuse of antibiotics, etc.), and many more. We have evidence that diet works but we don’t fully know why or how it works. We also don’t know how much disease is caused by diet.