Is non-celiac wheat sensitivity real? A new study says yes.

 Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity.

Wait, based on some news articles I've read lately, I thought non-celiac wheat sensitives were a bunch of wilting prima donnas intent on eating an annoying hipster diet that excludes wheat, an important nutrient that people have been eating for a really long time or something like that. And since their diet excludes sandwiches and pizza, they must be UnAmerican. 

But in the medical research community, there is growing recognition that non-celiac wheat sensitivity is a real thing that affects quality of life and even mortality risk when it leads to intestinal inflammation. Stephan Guyenet posted about the last promising study.

This new study is very interesting, but highlights some limitations in dealing with problems like this. This study was on patients who already had been through the wringer test-wise and all had

  • IBS-like symptoms (Rome II criteria)
  • Negative serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) IgA antibodies (the common blood tests for celiac)
  • Negative duodenal histology (absence of intestinal villous atrophy)- requires a biopsy
  • Negative IgE-mediated immuno-allergy tests to wheat (skin prick tests and serum-specii c IgE — RASTs).
  • Resolution of the symptoms on gluten-free diet and their reappearance on double-blind placebo controlled wheat challenge, which means neither the person nor the patient knew whether or not they were giving or receiving a placebo

Um, how many people here with IBS have ever been offered this standard of care? Anyone had a doctor who offered to supervise a double-blind placebo controlled wheat challenge? Maybe things are different in Italy. 

Once they were in this study, these patients got more tests including biopsies of the duodenum and colon, HLA genotyping, as well as skin-prick and blood tests. Then these people had to eat a minimum quantity of wheat daily as they were observed. Then they did a regular elimination diet that excluded wheat, cow's milk, eggs, tomato, and chocolate. Then they got to do a fun exciting double-blind placebo controlled wheat challenge again.

Wheat challenge was performed administering a daily dose 13 g of flour, equal to about 20 g of bread. A total of 12 capsules daily were given subdivided in three times daily, away from meals.  DBPC for cow’s milk was performed by administering capsules coded as A or B containing milk proteins (casein from bovine milk, lactoalbumin, lactoglobulin – daily dose 6 g, equal to about 200 ml of cow’s milk) or xylose, respectively. A total of 6 capsules daily were given subdivided in three times daily, away from meals.

Patients used a survey to track their symptoms. They used celiac disease and IBS patients without wheat sensitivities as controls. 

Among those who were wheat sensitive, a high number of them tested positive on the cytomteric basophil activation test, and many also tested positive for serum IgG and IgA AGA tests. Many of these patients suffered from anemia and weight-loss. Biopsies showed eosinophil infiltration of the duodenal and colon mucosa.
, despite not having the type of villous atrophy damage associated with celiac. 

There seemed to be two groups of IBS wheat-sensitive patients- those with wheat sensitivity alone and those with wheat sensitivity AND multiple other sensitivities to cow's milk and other foods. The later group was also more likely to also have other types of allergies (non-food allergies, skin allergies, etc.) and a family history of allergies.

Further studies will have to look more into the mechanism in which wheat causes damage in these patients. The researches propose one mechanism in their conclusion

Obviously, other hypotheses must be considered; experimental  models have demonstrated that gluten sensitization of DQ8 mice increases acetylcholine release by the myenteric plexus and this can lead to consequent in vivo dysmotility ( 27 ). In this model, gluten did not cause villous atrophy, but there was evidence that coexistent triggers, e.g., intestine-damaging drugs or dysbacteriosis, can lead to a more severe intestinal impairment ( 28 ). Clearly, wheat  antigens may also act in a similar manner.

Acetylcholine is responsible for ahem, moving things along, so it might explain why wheat causes diarrhea in some people. 

Also, it is notable that this study used wheat rather than gluten, so it might be other components of wheat like fructans that are responsible for the symptoms. 

The researchers say

the very high frequency of self-reported wheat intolerance, which we observed in our patients, should induce clinicians to pay full attention to patient suggestions

I wonder how long it will take the average doctor to catch on?