A Patient’s Journey

Non-coeliac gluten sensitivity

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7982 (Published 30 November 2012)
Cite this as: BMJ 2012;345:e7982

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Non-coeliac disease wheat sensitivity diagnosed by food challenge is being a described in the UK and the USA as “new” clinical entity.1-3 This is not the case and I have 64 BMJ publications about food allergy and 38 about wheat allergy (Search - Ellen CG Grant).

Wheat has probably been the commonest cause of “masked” food allergy since hunter gatherers became farmers and started cultivated grasses. Excluding and reintroducing suspect foods was described by Hippocrates. In 1906 Von Pirquet defined allergy as specific changes in reactivity of an individual to a substance on the second or subsequent exposure to it. In 1931 Rowe described masked food allergy with withdrawal foods and later individual food reintroduction to identify those causing adverse reactions. Use of Stone Age diet has therefore long been a fundamental part of Ecological or Nutritional Medicine and is also used by homeopathic, complementary and alternative practitioners. Why has the medical establishment in general been so long to realize the importance of masked wheat allergy?

79% of 60 migraine patients reacted to wheat during an exclusion and reintroduction testing.4 Importantly, before starting the exclusion diet, patients stopped taking daily medications, including progestins, oestrogens, and ergotamine, and also stop smoking or drinking alcohol. This alone resulted in a 10 fold reduction in the number of migraine attacks.5 The result of avoiding individually diagnosed food allergens was a reduction in migraine medications from 115 tablets /month to only 0.5 tablets/ month. 85% of patients became headache free and those with hypertension became normotensive.4

The commonest “hidden or masked” food allergens were wheat (or corn), orange, eggs, coffee, (or chocolate for children), cow’s milk in several exclusion and re-introduction studies in a range of conditions studied in adults and children. 4-14 These included headaches, migraine, hypertension, irritable bowel syndrome, Crohn’s disease, gall bladder disease, rheumatoid arthritis, and osteoarthritis in adults; and also hyperactivity, eczema, migraine and serous otitis media in children.

The results of these studies have been unpopular with the medical establishment, perhaps because many drug treatments could become redundant. It is regrettable that advice to avoid common food allergens, especially wheat, has become a corner stone of alternative medicine while being mostly ignored by the medical profession.

1 Anonymous, Rostami K, Hogg-Kollars S. Non coeliac gluten sensitivity. BMJ 2012;345:e7982

2 Aziz I, Hadjivassiliou M, Sanders D. Does gluten sensitivity in the absence of coeliac disease exist? BMJ 2012; 45: e7907.

3 Carroccio A, Mansueto P, Iacono G, Soresi M, et al. Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity. The American Journal of Gastroenterology 107, 1898-1906 (December 2012) | doi:10.1038/ajg.2012.236

4 Grant ECG. Food allergy in Migraine. Lancet 1979; 2: 358-59.

5 Grant ECG. Oral contraceptives, smoking, migraine and food allergy. Lancet 1978;2:581-2.

6 Egger J, Carter CM, Wilson J, Turner MW, Soothill JF. Is migraine food allergy? A double-blind controlled trial of oligoantigenic diet treatment. Lancet 1983; 2(8355):215-9.

7 Breneman JC. Allergy elimination diet as the most effective gallbladder diet. Ann Allergy 1968;26:83-7.

8 Alun Jones V, Shorthouse M, Mclaughlan P, Workman E, Hunter JO. Food intolerance, a major factor in the pathogenesis of the irritable bowel syndrome. Lancet 1982;2:1117-1120.

9 Workman EM, Alun Jones V, Wilson AJ, Hunter JO. Diet in the management of Crohn's disease. Hum Nutr Appl Nutr. 1984; 38:469-73.

10 Darlington LG, Ramsay NW, Mansfield JR. Placebo-controlled, blind study of dietary manipulation therapy in rheumatoid arthritis Lancet 1986;1:236-8.

11 Carroll FM. Rheumatoid and osteoarthritis controlled by ecological management: a three and one-half year study. Paper given to the American Society for Clinical Ecology, November 1978.

12 Carter CM. Urbanowicz M, Hemsley R, Effects of few food diet in attention deficit disorder. Arch Dis Child 1993;69:564-8.

13 Steinman HA , Potter PC. The precipitation of symptoms by common foods in children with atopic dermatitis.1994 Allergy Proc 1994 ;15(4):203-10.

14 Nousli TM, Nsouli SM, Linde RE. O’Mara F, Scanlon RT, Bellanti JA. Role of food allergy in serous otitis media. Ann Allergy 1994;73:215-9.

Competing interests: None declared

Ellen CG Grant, Physician and medical gynaecologist

Retired, KT2 7JU

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Fascinating. A peruasive tale but a total lack of plausible explanatory mechanism for the many disparate symptoms. Who knows how this will all turn out? As always in medicine, it pays to be simultaneously open-minded and sceptical.
But we can say for sure that the patient can be relieved of one major symptom without recourse to a gluten-free diet. "The most important issue with my weight is that it can easily rise 4-7lb overnight if I accidentally eat gluten, as I fill up with fluid....". It is only possible to fill up with fluid by literally filling up with fluid, i.e. drinking lots, and so we can only assume this patient is in the habit of consuming 2 to 3 litres of fluid (and a bit more) overnight.
This can be effectively addressed by simple modest fluid restriction - possibly the only intervention in this tale which can be guaranteed to work every single time.

Competing interests: None declared

John Main, nephrologist

James Cook University Hospital, Middlesbrough, TS4 3BW

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I enjoyed the articles on non-gluten sensitivity (1,2). Publication of these articles in the BMJ gives respectability to an entity which has been recognised increasingly over the last 10 years. This is very different to the situation in the 1970s. The distinguished Birmingham gastroenterologist, Dr Trevor Cooke, recognised that not all gluten sensitive patients had coeliac disease. His group reported eight patients with diarrhoea who were shown to be gluten sensitive by gluten elimination and challenge but who did not have coeliac disease by the criteria of the time (3). These patients had minor abnormalities of jejunal mucosal cellularity but no evidence of villous atrophy. Anti-gluten antibodies were not present . Unfortunately this study predated the availability of endomyseal and tissue transglutaminase antibodies. There were no abnormalilties in serum IgE levels.

At that time, the attitude of the gastroenterological community to the concept of non-coeliac gluten sensitivity ranged from profoundly sceptical to ferociously hostile. It is gratifying that, after so many years, the concept of non-coeliac gluten sensitivity is accepted and is being actively studied.

Yours faithfully,
Brian Cooper

1. Anonymous, Rostami K, Hogg-Kollars S. Non coeliac gluten sensitivity. BMJ 2012;345:e7982
2. Aziz I, Hadjivassiliou M, Sanders D. Does gluten sensitivity in the absence of coeliac disease exist? BMJ 2012; 345: e7907.
3. Cooper BT, Holmes GKT, Ferguson R, Thompson RA, Allan RN, Cooke WT. Gluten sensitive diarrhoea without evidence of celiac disease. Gastroenterology 1980; 79: 801-6.

Competing interests: None declared

Brian T Cooper, Consultant gastroenterologist

City Hospital , Dudley Rd, Birmingham B18 7QH

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I read the article (the patient journey) by Rotsami et al with great interest.

Individuals with gastrointestinal symptoms are deriving benefit from a GFD even if they do not have CD. This has led to the scientific community considering the evidence for an emerging concept of non-coeliac wheat sensitivity (2).

Non-coeliac Gluten sensitivity (NCGS) is a well recognised condition and relates to one or more of immunological, morphological, symptomatic manifestations precipitated by the ingestion of gluten when coeliac disease (CD) has been excluded (3). It may be linked with innate immunity.

The recent surge in the number of cases may be linked with a change in the diet with increased wheat consumption. 10% of Australian are on a Gluten free diet (GFD), 50/50 partially GF vs. totally GF (4).

In my practice I have seen many patients with a variety of gastrointestinal symptoms (diarrhoea, bloatedness, nausea and vomiting) as well as non-gastrointestinal symptoms (tiredness, lethargy) in which coeliac disease has been excluded, by negative coeliac serology and normal Duodenal biopsies, but symptoms only respond to adherence to GFD.

A lack of laboratory biomarkers specific for gluten sensitivity makes it difficult to conduct proper scientific studies, hence diagnosis is based on exclusion criteria: elimination of gluten-containing foods from the diet and its impact on improvement in symptoms. Hence it is important to educate healthcare professionals about this extremely common but under-recognized condition.

1. Kamran Rostami , Sabine Hogg-Kollars. Non-Coeliac gluten sensitivity ( A patient journey): BMJ 2012
2. Sanders DS, Aziz I. Editorial: non-celiac wheat sensitivity: separating the wheat from the chat! Am J Gastroenterol. 2012 Dec;107(12):1908-12
3. Oslo definitions, Gut 2011, “The official CD Message.
4. Morell, CSIRO, Grain Summit Minneapolis 2012

Competing interests: None declared

Sauid Ishaq, Gastroenterologist

Russells Hall Hospital, ESK House, Dudley, DY12HQ

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