Monday, December 8, 2008

Gluten Sensitivity: Celiac Disease is the Tip of the Iceberg

Celiac disease is a degeneration of the lining of the small intestine caused by a sensitivity to gluten. Gluten is the protein portion of wheat, rye, barley, and wheat relatives (spelt, kamut, emmer, einkorn and triticale). I found an interesting paper recently on the impact of celiac disease on nutrient status and bone density. Researchers compared 54 Northern Italian children with untreated celiac disease to 60 presumably healthy children. The celiac patients had extremely poor vitamin D status, with a deficiency rate of 35.18% compared to 5% in the control group. This was using the lenient cut-off point of 20 ng/mL. Average serum 25(OH)D3 in celiac patients was less than half the level of the control group. The celiac patients also had low serum calcium and magnesium, and elevated parathyroid hormone. Celiac children had lower bone mineral density. All parameters returned to normal after 6 months on a gluten-free diet.

This confirms what has been shown numerous times before: celiac disease interferes with nutrient status, including the all-important fat-soluble vitamins. It's not surprising, since it flattens the villi, finger-like structures necessary for efficient nutrient absorption in the small intestine. But wait, the overwhelming majority of our vitamin D comes from the effect of sunlight on our skin, not through our small intestine! So gluten sensitivity must be doing something besides just flattening villi. Perhaps it does. Feeding wheat bran to "healthy" volunteers caused them to burn through their vitamin D reserves at an
accelerated rate. I think this underlines what I've come to believe about wheat: it's problematic for a large proportion of the population, perhaps the majority.

Approximately 12% of Americans can be diagnosed as gluten sensitive using blood antibody tests (anti-gliadin IgA or IgG). A subset of these have full-blown celiac disease. The vast, vast majority are undiagnosed. Gluten sensitivity associates with a dizzying array of diseases, including autoimmune disorders, cancer, and neurological problems. The problem with the blood tests is they aren't very sensitive. The most common blood tests for celiac disease look for a class of antibody called IgA. IgA is produced by the mucosa, including the gut. Unless gut damage is already extensive, the majority of IgA stays in the gut. This may cause the assay to overlook many cases of gluten sensitivity. A negative blood antibody test
does not rule out gluten sensitivity!

I recently discovered the work of Dr. Kenneth Fine of
EnteroLab. He has developed an assay that detects anti-gliadin IgA in stool. Gliadin is one of the problematic proteins in gluten that is implicated in gluten sensitivity. Dr. Fine has been conducting informal research using his fecal anti-gliadin IgA test (data here). He has found that:
  • 100% of untreated celiac patients are antigliadin IgA positive by fecal test, compared to only 76% by blood (n= 17).
  • 76% of microscopic colitis (a type of chronic diarrhea) patients are positive by the fecal test, compared to 9% by blood (n= 57).
  • 57% of symptomatic people (digestive problems?) are positive by the fecal test, compared to 12% by blood (n= 58).
  • 62% of people with autoimmune disease are positive by the fecal test.
  • 29% of asymptomatic (healthy) people are positive by the fecal test, compared to 11-12% by blood (n= 240).
  • Baby and cow feces are 0% positive by the stool assay.
It gets worse. Gluten sensitivity is determined in large part by genetics. A gene called HLA-DQ is intimately involved. It encodes a protein that is expressed on the surface of cells, that serves to activate immune cells when certain foreign substances are present. Different versions of the gene are activated by different substances. HLA-DQ2 and HLA-DQ8 are classically associated with celiac disease. Roughly 42% of the US population carries DQ2 or DQ8. According to Dr. Fine, every allele except DQ4 has some association with gluten-related problems! Only 0.4% of the U.S. population carries HLA-DQ4 and no other allele.

Not everyone who is genetically susceptible will end up developing health problems due to gluten, but it's impossible to estimate how many of the problems we attribute to other causes are in fact caused or exacerbated by gluten.

The immune system can be divided into two parts: innate and adaptive. The innate immune system is a nonspecific, first-line reaction to a perceived threat. The adaptive immune system is a more sophisticated, but slower system that produces a powerful response by particular cell types to a very specific threat. Antibody production is part of the adaptive immune system. Thus, if your gluten sensitivity test is looking for antibodies, it could still be missing an immune reaction to gluten mediated by the innate immune system!

This question has been addressed in a
preliminary study. Researchers took gut biopsies from celiac patients and asymptomatic controls. Five out of six asymptomatic controls showed elevated interleukin-15, a marker of innate immune activation, upon exposure to gliadin. An activated innate immune system (commonly called 'inflammation') is associated with a wide array of chronic diseases, from obesity to cancer to cardiovascular disease. Inflammatory cytokines are elevated in celiac patients and may play a role in their bone pathology. What I would like to see is some negative controls-- would the gut biopsies have produced interleukin-15 in response to benign foods or is it truly specific to gluten?

I don't intend to imply that everyone has gluten sensitivity, but I do think the totality of the data are thought-provoking. They also include the association between the introduction of wheat to non-industrial populations and the development of widespread health problems. Another thing to keep in mind is that traditional sourdough fermentation breaks down a portion of gluten, possibly explaining the rise in gluten sensitivity that has paralleled a shift to quick-rise yeast breads. I believe that gluten sensitivity is behind many modern ills, and should be on the short list of suspects in the case of unexplained health problems. This is particularly true of digestive, autoimmune and neurological disorders. Gluten sensitivity is easy to address: stop eating gluten for a few weeks. See how you feel. Reintroduce gluten and see what happens. You might learn something about yourself.

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