Celiac.com 03/16/2018 - Celiac awareness has increased exponentially over the last decade among physicians and the general public alike. Increasing numbers of research publications and very active support groups and individuals have contributed to this growing awareness. Knowledge of the many and varied manifestations is also growing rapidly although some individuals continue to cling to the notion that celiac disease is characterized by malabsorption and that nutrient deficiency is the dominant feature of this ailment. This misses the broader understanding of the many ways in which gluten grains negatively impact on human health. From toes to head, any and all of our human body systems may be harmed by ingesting gluten under some circumstances. Although the wide range of signs and symptoms of celiac disease is impressive, a similar, even broader range of impacts may be attributed to gluten in the context of non-celiac gluten sensitivity. Those with celiac disease only comprise a small portion of the population of people who are afflicted by non celiac gluten sensitivity. Dr. Rodney Ford has offered the all encompassing term of 'gluten syndrome' to identify everyone whose health is compromised by gluten consumption (1).
From Dr. Fasano's most conservative estimate that 6% of the population is afflicted by non-celiac gluten sensitivity (2), to Dr. Rodney Ford's estimate that 10% is afflicted (3), to Dr. Kenneth Fine's finding that IgG class anti-gliadin antibodies are found in about 11% of the population (4), to this writer's assertion that non-celiac gluten sensitivity includes well more than 20% of the population, the paucity of research in this area offers a wide range of estimates without a solid basis for refuting any of them. Nonetheless, it is clear that those with non-celiac gluten sensitivity outnumber those with celiac disease by a ratio of somewhere between 6 to 1 and more than 20 to 1. The gluten syndrome may therefore include from seven percent to more than twenty percent of the population.
But this is just the tip of the iceberg. Dr. Fasano bases his estimate of non-celiac gluten sensitivity on those who mount an innate immune reaction to gluten grains. While there is likely some overlap between innate immune reactions and selective antibody reactions, most estimates of non-celiac gluten sensitivity are based on IgG class antibodies against one of the proteins of several protein families found in gluten. It makes eminent sense to me that when our bodies are mounting a measurable immune response against the most common food in our diets, whether the reaction is by the innate immune system or by creating selective antibodies, that food might be harmful to our health. I do not quarrel with the basis on which these sensitivities are identified. I simply argue that they are only identifying a sub-fraction of many more possible cases of non-celiac gluten sensitivity.
To put this issue into sharper focus, there are several protein families to be found in each of the gluten grains. In wheat, for instance, each family, glutelin, gliadin, and glutenin contains a number of individual proteins. The antibody test for gliadin ignores possible reactions to proteins in either of the other two families. Further, IgG class antibodies are the most common and widespread class of selective antibody we produce. But they form only one of five types of selective antibodies (known as immunoglobulins). Further, as is obvious from Dr. Fasano's conservative approach to identifying non-celiac gluten sensitivity, there are other facets of the immune system that do not involve selective antibodies, and can also be enlisted in a reaction against gluten grains.
Thus, when we test for IgG anti-gliadin antibodies, the most common test for non-celiac gluten sensitivity, positive results are identifying reactions against only one of the several protein families found in gluten, and only one of the five possible selective antibody reactions against this single protein family.
It therefore seems wholly improbable that testing for reactions against a single protein family in only a single class of selective antibody would identify all or even most cases of gluten sensitivity. Admittedly, some researchers test for IgA antibodies but those investigators usually do not test for IgG antibodies. However, even with testing for both classes of selective antibodies, which most published reports on this issue have not done, it is clear that many possible immune reactions to any other protein fractions of gluten might well be overlooked, either in the form of other selective antibodies or as other immune reactions and various innate reactions against gluten grains.
I'm sure that, by now, the reader will see that there are many possible immune reactions against this most common food, and that most of these reactions will go undetected, both in the context of standard medical testing and in most research conducted in this venue. On a more practical plane, when Dr. Curtis Dohan identified significant improvements among patients with schizophrenia patients eating a gluten-free, dairy-free diet (6), and Singh and Kay replicated their findings (7), many looked for celiac disease among patients with schizophrenia and found only a small increase.
Dohan and Singh's publications were followed by several sloppy studies that ignored the guiding principles expressed in this pioneering work. These weak studies further undermined acceptance of the connection between gluten and schizophrenia. The net result was a growing belief that Dohan had erred and his heroic work was widely dismissed. Yet, more than twenty years after his death, one of Dohan's most vigorous critics is listed among the authors of a paper that reports an immune reaction against gluten that, while different from the reaction seen in celiac disease, is common among people with schizophrenia (8).
Similarly, I think that we can expect, sometime in the future, to see research that identifies immune reactions and damaging dynamics caused by gluten consumption among people with learning disabilities. There is, for instance, one newspaper report of an informal study conducted at the Nunnykirk School in Northumberland, a school that serves only children with dyslexia, a condition that is reported to afflict about 10% of children in the United Kingdom. After six months of eating a gluten free diet, more than 80% of these children improved their reading at a rate of at least twice that of normal children. Some leaped ahead, in their reading skills, by as much as 2.5 years over this six month period (9).
Relatedly, I had the privilege of working with Dr. Rodney Ford on a retrospective analysis of indicators of school readiness among children who had celiac disease, non-celiac gluten sensitivity (as measured by selective antibody testing) and children who showed no signs of either reaction to gluten. A large majority of those who reacted to gluten improved dramatically. There was a small but significant sub-group whose school readiness improved following a gluten free diet, and these improvements happened within 6 months of avoiding gluten (unpublished data).
Autism, especially where normal development was curtailed after one or several years, is another condition in which excluding gluten seems to provide substantial improvements even in the absence of celiac disease. Some research in this area suggests that toxins (generated by bacteria resident in the intestines) are allowed access to the bloodstream and the brain (10). Perhaps exclusion of dietary gluten is the factor that limits access to the bloodstream through reducing zonulin production.
Similarly, although not as well supported, there is some evidence to suggest that gluten contributes to bi-polar disorder. Just how frequent and significant the contribution may be is still open to debate, but I have observed some evidence to support this hypothesis in my own family.
A range of types of epilepsy have been found in association with celiac disease, many of which are mitigated by the gluten free diet (11).
The manifestations of undetected non-celiac gluten sensitivity are not limited to brain function. We know that celiac disease is much more frequent in the context of other autoimmune diseases. We also know that antibody tests show even higher rates of non-celiac gluten sensitivity. Since we are only identifying a fraction of those who may be reacting to gluten, it seems reasonable to suggest that everyone with an autoimmune disease, or antibodies suggesting that an autoimmune disease is imminent, should begin a strict gluten free diet and follow it for at least one year. If there is any reduction of auto-antibodies or symptoms of autoimmunity, the diet should be continued. Although difficult in the early stages, it is an entirely benign intervention/treatment. There are no unwanted side effects or hazards.
There are more than 200 autoimmune and other medical conditions reported in association with gluten and are listed in Appendix D of Dangerous Grains (12). In each case, a lengthy trial of a gluten free diet would be well advised. Again, there are no negative side effects of the gluten free diet. It is an entirely benign intervention.
A significant proportion of those who suffer from IBS, Crohn's or any of the various types of colitis have also been reported to benefit from a gluten free diet on various websites. Similarly, many people with MS and a host of other neurological diseases have been shown to benefit from a gluten free diet (13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23).
Even many AIDS patients are helped by a gluten free diet. It reduces their diarrhea and improves nutrient absorption (24). This is an important discovery that can be harnessed in conjunction with the improved treatments now available for this very serious illness.
Overweight, obesity, and weight loss are contentious issues with regard to the gluten free diet. Until quite recently, there were two reports of small studies of changes in body mass index in the USA and one report from Ireland, following institution of a gluten free diet. The two American studies showed weight loss among overweight subjects on a gluten free diet. The study from Ireland showed only weight gain among overweight subjects after following a gluten free diet. In November of 2011, another small study was published. Their conclusion states "The GFD (gluten free diet) has a beneficial effect upon the BMI (body mass index) of overweight children with celiac disease" (25), which is congruent with the earlier two American studies. I have previously suggested that the discrepancy between the findings may be due to the acceptance of wheat starch as part of the gluten free diet in the United Kingdom. However, regardless of the cause, the preponderance of evidence supports the notion that a gluten free diet can be used as an effective weight loss strategy in some cases of celiac disease. Other evidence suggests it may be a more broadly effective weight loss tool.
Thus, my estimate of the prevalence of non-celiac gluten sensitivity includes the 6% who show signs of innate immune reactions to gluten, in addition to those who show IgG antibodies against gluten, at about 11% of the population (although there may be some overlap between these 6% and 11% groups). My estimate also includes many of those with schizophrenia who number about 1% of the general population, and a portion of those with autism who are quickly approaching 1% of the population. I am also including 80% of the approximately 10% of the population with some degree of dyslexia. Because of overlaps between groups, and because gluten's impact is often only demonstrable through a gluten free diet, I only assert that non-celiac gluten sensitivity is a factor in more than 20% of the general population. However, I remain open to findings that will show a much greater negative impact from eating foods derived from gluten grains. The portion of the human population that may be negatively impacted by gluten consumption can range as high as the 80% portion that produce haptaglobin 2, for which zonulin is the precursor.
The take away point here is that the gluten free diet may aid overall health for up to as much as 80% of the general population. In that context, my estimate that 20+% of the population is showing signs that they are variously mounting immune reactions against gluten or are otherwise harmed by gluten appears modest. The overlapping symptoms make it extremely difficult to narrow my estimate further. Nonetheless, gluten is one of the most harmful substances in our diet. Yet it is the most ubiquitous factor in our diets.
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3. personal communication
4. personal communication
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