Summary: Until recently gluten intolerance has been believed to be typical of celiac disease (CD) and wheat allergy (WA). In the last few years, however, several study results have been published that have proved that gluten intolerance can also affect people who do not suffer from any of the above mentioned diseases. The new syndrome has been named non-celiac gluten sensitivity (NCGS) or gluten sensitivity (GS). It has been included in the new list of gluten-related disorders published in 2012. Researchers believe that NCGS is the most common syndrome of gluten intolerance. This review discusses many aspects of NCGS epidemiology, pathophysiology, clinical spectrum, and treatment and current tools to identify patients suffering from CD, WA, and NCGS.
Alex’s Notes: I suppose it was bound to happen sooner or later that non-celiac gluten sensitivity (NCGS) be recognized as a new syndrome of gluten intolerance. The first reports of it date back roughly three decades, but it hasn’t been until recently that numerous reports of self-diagnosis most common in young adults and females have sprung up.
While the true prevalence of NCGS is still unknown, about half the patients have the DQ2 or DQ8 genes that are present in 95% of celiac disease (CD) patients. Not surprisingly, NCGS typically leads to IBS-like symptoms (abdominal pain, nausea, bloating, gas, diarrhea, or constipation), but these people do not develop antibodies typical of CD or wheat allergy (WA) and do not suffer from intestinal lesions. Moreover, common systemic complaints include headaches, joint & muscle pain, numbness, fatigue, “foggy mind,” and behavior disturbances.
As we can see, much of the above is subjective and if you have been led to believe that gluten is bad for your health, then there is a strong chance for a placebo effect that manifests itself as these symptoms. The major challenge is determining that it is NCGS and not CD or WA, and there are no laboratory markers specific to NCGS. In fact, the only known antibodies observed in the NCGS patients are the IgG antigliadin antibodies which, unfortunately, occur in only a half of the patients. However, it appears that NCGS symptoms occur several hours or days after gluten consumption, whereas the antibody mediated immune responses to CD and WA occur within two hours.
“It has not been determined yet what grain ingredients are responsible for the symptoms of the disease. Upon incubation with gliadin, mucosa in the patients with NCGS – unlike the duodenal mucosa in the patients with CD – does not express markers of inflammation and their basophils are not activated by gliadin.”
It may even be that it is the poorly absorbed carbohydrates in wheat grains – fructo-oligosaccharides, fructans (FODMAPs) – that trigger the IBS-like symptoms in NCGS given that their elimination improves symptoms. Moreover,
“Contrary to CD, where the secondary immune response is up-regulation, the NCGS patients demonstrate mainly up-regulation of the primary response  and . There is no increased expression of the genes of the secondary immune response including IL-6, IL-21 and INFγ, which is characteristic of CD . In the intestinal mucosa there is an increased expression of tolk-like receptors 1, 2 and 4 of the primary immune response. Other relevant differences between the CD and NCGS patients are observed in the intestinal barrier function on the level of the epithelial cell tight junction. The CD subjects manifest increased intestinal permeability and raised claudin-1 and zonulin expression, while the NCGS patients demonstrate normal intestinal permeability and a normal level of the above proteins.”
Nonetheless, a gluten-free diet solves everything, and symptoms come back upon resuming gluten consumption. The bottom line while researchers still get this stuff sorted out is that simply going gluten-free for a month and then reintroducing it will tell you how you respond. It would be obvious if you had CD, but NCGS is much more discrete and may not be noticed until you eliminate the culprit.