Nonceliac wheat sensitivity: A new clinical entity

About 20 years ago I completed an internship in a small company specializing in the formulation of gluten-free bakery products for patients with celiac disease. At the time, celiac disease was pretty much unknown from the general population. Few people were affected, and few products existed to replace the staples of general diets that the affected individuals needed to avoid to remain symptom-free, such as bread, pasta, cookies, cakes, breakfast cereals, and all products containing (or made from) wheat, rye and barley.

Today, it is hard to escape discussions of intolerance to gluten. What happened? Did the frequency of the celiac disease suddenly skyrocket? Apart from an increased awareness of celiac disease per se, clinicians are starting to recognize the existence of another type of food intolerance triggered by wheat, namely nonceliac wheat sensitivity.

What is celiac disease?

Celiac disease is a reaction to gluten, the wheat protein, which affects the intestinal mucosa by inducing an atrophy of the microvillii, and thus reducing nutrient absorption. Accepted mechanisms for celiac disease involve an immune reaction mediated by T lymphocytes. Celiac disease exhibits many features of an autoimmune disorder, including an immune reaction to gluten leading to the destruction of intestinal cells, and a complex interaction between genetics (predisposition) and environmental exposure to triggers (gluten).

Celiac disease affects approximately 1 in 100 persons in the US, but is more prevalent in families with affected members, or in individuals with other genetic or autoimmune disorders, such as Down syndrome and Turner syndrome. In children, symptoms of celiac disease include abdominal bloating and pain, chronic diarrhea, vomiting, constipation, pale, foul-smelling or fatty stool, and weight loss. Adults may have less severe gastrointestinal symptoms, and more general manifestations such as unexplained iron-deficiency anemia, fatigue, bone or joint pain, arthritis, bone loss or osteoporosis, depression or anxiety, tingling numbness in the hands and feet, seizures, missed menstrual periods, infertility or recurrent miscarriage, canker sores inside the mouth, or itchy skin rash.

Celiac disease is diagnosed based on symptoms and confirmed by blood tests and intestinal biopsy.

Is there a new type of gluten intolerance?

Some people who present the symptoms of celiac disease don’t show the other clinical signs typical of the disease. These individuals exhibit celiac-like symptoms, such as intestinal symptoms (diarrhea, abdominal discomfort or pain, bloating, and flatulence) or extraintestinal symptoms (headache, lethargy, attention-deficit/hyperactivity disorder, or recurrent oral ulceration), which decrease or disappear on a gluten-free diet. However, they don’t show any sign of atrophy of their intestinal microvilli, have a negative serum response to markers of celiac disease, and a negative response to wheat allergy test. For a long time, these individuals have been given a diagnostic of IBS, or irritable Bowel Syndrome, which unifies under one name a series of symptoms with no identified cause or trigger, and no reliable treatment. However, the recent success of gluten-free diets has encouraged scientists to take a second look at gluten sensitivity. This condition was very recently recognized as a new and distinct clinical entity and has been named ‘nonceliac wheat sensitivity‘.

A recent study demonstrated the existence of such a distinct disease by using a double-blind placebo-controlled protocol: 1. neither researchers nor subjects knew who was getting which sample (test or placebo), 2. after four weeks of an elimination diet (no wheat), subjects received capsules containing wheat during two weeks, and a placebo during another two weeks (the order of the presentation was randomized), 3. two control groups were used to compare results, i.e. subjects with IBS and no sensitivity to wheat, and patients with celiac disease. The analysis of 276 patients with wheat sensitivity showed that nonceliac wheat sensitivity is a real and distinct phenomenon related to wheat consumption. In addition, the study identified at least two subgroups of individuals, namely those suffering only from intolerance to wheat, and those suffering from intolerance to several foods, such as wheat, cow’s milk proteins and other foods.

Characteristics of nonceliac wheat sensitivity

Individuals suffering from nonceliac wheat intolerance have a normal intestinal cytology and have negative blood responses to celiac markers and wheat allergy.

The prevalence of nonceliac wheat sensitivity is unknown but it is considered to be much higher than for celiac disease.

Individuals with nonceliac wheat sensitivity exhibit symptoms between 2 and 4 days after consumption of wheat – this delay is in itself an element that makes those conditions difficult to identify.

The exact cause of nonceliac wheat sensitivity is still unknown and while some researchers think that the responsible agent is gluten, others think that the fructans of wheat could also be involved.

Many individuals suffering from nonceliac wheat sensitivity also suffer from other food intolerances, in particular cow’s milk protein.

Identification and treatment of nonceliac wheat sensitivity

As for other food sensitivities, the identification of the disease is based on 1. the identification of possible causes through a food diary, 2. the elimination of the suspected foods from the diet for a period of 3 weeks to a month, then 4. on the reintroduction of the foods as a test for the return of symptoms. Every suspected food needs to be considered individually. A rest period of about a week is advised between tested foods.

The treatment of nonceliac wheat sensitivity relies on the elimination of all foods causing hypersensitivity from the diet, such as wheat (possibly gluten), and other foods identified as causing symptoms, such as cow’s milk protein.

Thankfully for people suffering from celiac disease or nonceliac wheat sensitivity, gluten-free products are much more common than they used to be, and awareness about possible disorders related to wheat or gluten has increased drastically. In my family, four of us are now gluten and dairy free, for various reasons, including chronic migraines, IBS and candidiasis. What about you? Do you know people who have decided to become gluten-free? For what reasons? Did it help them? Are you yourself considering it? Share your experience!

References used in this article

Pozo-Rubio T, Olivares M, Nova E, De Palma G, Mujico JR, Ferrer MD, Marcos A, Sanz Y. Immune development and intestinal microbiota in celiac disease. Clin Dev Immunol. 2012;2012:654143.

Megiorni F, Pizzuti A. HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular typing. J Biomed Sci. 2012 Oct 11;19:88. doi: 10.1186/1423-0127-19-88.

Carroccio A, Mansueto P, Iacono G, Soresi M, D’Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012 Dec;107(12):1898-906; quiz 1907. doi: 10.1038/ajg.2012.236. 

Di Sabatino A, Corazza GR. Nonceliac gluten sensitivity: sense or sensibility? Ann Intern Med. 2012 Feb 21;156(4):309-11. 

Aziz I, Hadjivassiliou M, Sanders DS. Does gluten sensitivity in the absence of coeliac disease exist? BMJ. 2012 Nov 30;345:e7907. 

Boettcher E, Crowe SE. Dietary proteins and functional gastrointestinal disorders. Am J Gastroenterol. 2013 May;108(5):728-36. doi: 10.1038/ajg.2013.97. 

Copyright (see copyright page): © “Food, Science and Health” ( by Barbara Cerf-Allen, 2013 All Rights Reserved

Disclaimer: I am not advocating any of the above mentioned diets, nor am I making any claim about their usefulness for your specific condition. I am not a medical doctor and I am not giving medical advice. This blog is about sharing scientific information and my personal anecdotal experiences.

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