Gluten Sensitivity Without Celiac Disease: Is It A Fad?

The following is a guest blog from my friend, Dr. Tom O’Bryan, specialist in the complications of Non-Celiac Gluten Sensitivity and Celiac Disease.


THE MYTH: Gluten Sensitivity without Celiac Disease is a Fad

THE TRUTH: Non-celiac gluten sensitivity (NCGS) is not only real, but experts also tell us it is the most common (and nonrecognized) condition in the family of gluten-related disorders

Recently, there has been a great deal of Internet chatter that gluten sensitivity, without celiac disease, is a fad and does not exist. This viral gobbletygook ramped up after a blogger commented on a study published in 2013 entitled ‘No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates’.

First let’s address this study. The title itself would suggest that gluten has no effect on people who ‘report’ being gluten sensitive. So if you don’t read the study and just read the title, it is understandable how a simple mind could conceive that gluten has no effect on the body. But the reality is that the researchers were looking at people with irritable bowel syndrome (IBS).

If there ever was an example of ‘cherry picking’ the data, this is a classic.

– the authors omitted 60% of the potential participants from the study because they carried a DQ2 or DQ8 gene, historically considered the celiac genes. However, roughly 35-40% of NCGS sufferers carry one or two of these genes with negative evidence of CD. Thus a significant number of subjects were omitted who may have demonstrated NCGS.

– another critical issue is the authors omitted anyone with increased inflammation markers in their intestines (Marsh 1). Previous studies have demonstrated that ‘a substantial number of patients (about 40%) with NCGS will demonstrate a Marsh 1 level of inflammation’. Thus another significant number of subjects were omitted who may have demonstrated NCGS.

– the patients included in this study were not complaining of NCGS, since they lacked the typical symptoms of this syndrome, represented by headache, joint/muscle pain, numbness, skin rash, dermatitis, depression, foggy mind and so on. The only extraintestinal manifestations were fatigue and sleep abnormalities, so it is difficult to regard these subjects as suffering from NCGS.

– 7% of the study subjects DID respond to eliminating the gluten proteins from their food, yet the authors chose to say ‘No Effect of Gluten….

– 37% of the patients in their study DID have an elevated immune reaction (antibodies) to the gliadin peptide of gluten. This clearly suggests a sensitivity to the protein with the immune system response. The authors not only ignored this finding, they constructed a new definition of NCGS compared to the definition they used in their earlier paper. In 2011, they wrote ‘NCGS has been defined as those without celiac disease but whose gastrointestinal symptoms improve on a gluten-free diet (GFD) and they included those patients with an immune reaction and elevated antibodies to gliadin.

In 2013 they acknowledged that they’ve changed their minds and are rewriting the definition of NCGS to one that does not include an immune reaction. “We have difficulty with the suggestion that patients with evidence of immune activation in the duodenum should be included in a study of non-celiac gluten sensitivity (NCGS). (Our) definition of NCGS encompasses the exclusion of both celiac disease and immune responses to wheat proteins”. How convenient.

Surprisingly, the authors have published a new study and reversed their definition once again. In ‘Non-celiac gluten sensitivity: literature review’ they discovered that GI symptoms may not respond as quickly as other symptoms (brain fog, depression, etc…) to gluten withdrawal, and they now recognize antibodies to gliadin as a biomarker of NCGS. “Short-term exposure to gluten specifically induced current feelings of depression. Gluten-specific induction of gastrointestinal symptoms was not identified. Such findings might explain why patients with noncoeliac gluten sensitivity feel better on a gluten-free diet despite the continuation of gastrointestinal symptoms”.

And they reinserted anti-gliadin antibodies as a biomarker of NCGS ‘Recent evidence shows that a positive test for immunoglobulin G (IgG) antigliadinn antibodies could be useful to identify NCGS patients’ and they demonstrate that. These are the same authors who last year said elevated antigliadin antibodies, an immune response should not be included in the scope of NCGS.


Two newly published papers put this question to rest.

In the first, Non-celiac gluten sensitivity: literature review.

‘It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients’.

And then, along comes the GrandFather study. The Big Kahuna that asks and then answers the question about NCGS. Entitled ‘An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity’, this study was performed in 38 Italian centers (all recognized as referral centers of the Italian Health Ministry for the diagnosis of gluten-related disorders). Of these 38 centers, 27 were centers of adult gastroenterology, 5 of internal medicine, 4 of pediatrics, and 2 of allergy. In total, 12,255 consecutively observed patients were clinically evaluated by the investigators, and underwent thorough diagnostic investigation, including blood tests and invasive procedures (when needed) in order to confirm or exclude NCGS and celiac disease.

During the 12 months of the prospective survey, the 38 participating centers (of which only 4 were pediatric centers) identified 486 patients with NCGS. The large majority of patients reported more than two associated gastrointestinal or extraintestinal symptoms. Of the gastrointestinal symptoms, the most frequent were bloating and abdominal pain, found in 87% and in 83%, respectively, of the patients with suspected NCGS. More than 50% of patients reported diarrhea, with the number of evacuations per day ranging from 3 to 10, while 27% had alternating bowel habits and 24% had constipation. After bloating and abdominal pain, epigastric pain was the most frequent symptom, being found in 52% of patients, followed with decreasing prevalence by nausea, aerophagia, gastroesophageal
reflux disease, and aphthous stomatitis. The most frequent extraintestinal manifestations were tiredness and lack of well being, reported by 64% and 68%, respectively, of the enrolled subjects. In addition, a high prevalence of neuropsychiatric symptoms including headache (54%), anxiety (39%), ‘foggy mind’ (38%), and arm/leg numbness (32%) were recorded. Other extraintestinal manifestations emerging from the analysis of the survey responses were joint/muscle pain resembling fibromyalgia (31%), weight loss (25%), anemia (due both to iron deficiency and low folic acid; 22%), depression (18%), dermatitis (18%) and skin rash (29%).


NCGS is a clinical entity with intestinal and extra-intestinal symptoms abounding. As much as we may wish we could ignore the findings, NCGS is real and can manifest in any tissue of the body.



1 Comment

  1. Jamie

    Your data are wrong:

    “Celiac disease was excluded either by absence of the HLA-DQ2 and HLA-DQ8 haplotype or by a normal duodenal biopsy (Marsh 0) performed at endoscopy while on a gluten-containing diet in individuals expressing the HLA-DQ2 or HLA-DQ8 haplotype.”

    Note the AND when discussing haplotypes, there is no evidence here to say they excluded those with HLA-DQ2 OR HLA-DQ8. Here they state they excluded those with HLA-DQ2 AND HLA-DQ8 as well as those with HLA-DQ2 OR HLA-DQ8 haplotype that also had a biopsy to confirm Celiac disease.

    “7% of the study subjects DID respond to eliminating the gluten proteins from their food, yet the authors chose to say ‘No Effect of Gluten….”

    I don’t think you understand how statistics work.

    “37% of the patients in their study DID have an elevated immune reaction (antibodies) to the gliadin peptide of gluten … This clearly suggests a sensitivity to the protein with the immune system response”

    Again, I don’t think you understand how statistics work. Also, I’m not sure where you’re getting 37% as that would equate to 14/37 patients in the study and this number is not mentioned in correlation with any result anywhere in the paper. Even if it was, this doesn’t ‘clearly suggest’ anything. By your same logic, with data in the study I could say that ~35% (13/37) of those on a no gluten diet have elevated gliadin, so CLEARLY no gluten causes an immune system response, but I won’t because that is junk statistics and junk science. The paper itself says: “There was no apparent trend for those patients who had elevated scores on any biomarker with those who demonstrated a gluten- or whey-specific symptom response.”

    I could go on but I won’t, this article is not surprising coming from someone who makes their living off promoting NCGS on a blog by another person who makes their living off of promoting NCGS.