Gluten May be Causing Your Brain Problems!

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An interesting paper published in the Sept 2008 Annals of Neurology described a ‘new to science’ brain aggravating enzyme, triggered by reactivity to gluten, but acting independently of other coeliac symptoms.[1]

Most clinicians understand that overt gluten reactivity is classified under coeliac disease and the the classic constellation of symptoms and signs characterising  malabsorptive syndrome is a readily recognised manifestation  of  coeliac  disease. Frank malabsorptive symptoms include steatorrhea, weight loss or failure to thrive, bloating, and flatulence, with multiple deficiency states. More common but more difficult to recognise, however, are the other diverse ways in which coeliac disease presents.

Coeliac disease may also mimic many common clinical entities. These atypical modes of presentation include deficiencies of single micronutrients; nonspecific gastrointestinal complaints such as bloating, abdominal pain, diarrhoea, constipation, flatulence, secondary lactose intolerance, and dyspepsia; and non-gastrointestinal complaints such as fatigue, depression, arthralgia, milk intolerance, osteomalacia or osteoporosis, and iron deficiency anaemia.

One symptom not routinely screened for is neurological problems, although depression as an element of coeliac disease is well recognised.[2] Further elucidation of this issue has been provided through the extensive work of Fukudome and Yoshikawa, who have identified and characterised five distinct exorphins in the pepsin digests of gluten.[3],[4]

These morphine-like substances derived from the incomplete digests of dairy and cereal grain proteins are other dietary factors which may alter mood by depressing CNS serotonin, dopamine and norepinephrine levels.[5]

The authors of this paper state:

Gluten sensitivity typically presents as coeliac disease, a chronic, autoimmune-mediated, small-intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity.

The enzyme transglutamase in celiac disease will develop antibodies, and these are a cardinal indicator for diagnosing coeliac. This paper explains the role of an additional transglutamse isozyme in relation to brain health and function.

…a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction.

They found that:

Whereas the development of anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement.

‘Ataxia’ means ‘absence of order’. People with ataxia have problems of co-ordination. This is because parts of the nervous system that normally control co-ordination and balance are affected. So when discussing problems with gluten and other protein containing grains, the only symptom presenting may be one of mood disorders and a progressive loss of balance and co-ordination


The role of gluten and the mucosal immune system are slowly being picked apart, a recent post looked at the relationship between coeliac disease and local and systemic consequences.

Of course one of the questions we should be asking is the fact that it is relatively recently introduced grains that are causing the problem simply our bodies exerting a reasonable and normal response to antigens, or is it just that many people have become capable of eating these grains and can manage the immune challenges better than others?


[1] Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders DS, Woodroofe N, Aeschlimann  D.Ann Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Neurol. 2008 Sep;64(3):332-43. View Abstract

[2] Ludvigsson JF, Reutfors J, Osby U, et al. Coeliac disease and risk of mood disorders–a general population-based cohort study. J Affect Disord. 2007 Apr;99(1-3):117-26. View Abstract

[3] Fukudome S, Shimatsu A, Suganuma H, Yoshikawa M Effect of gluten exorphins A5 and B5 on the postprandial plasma insulin level in conscious rats. Life Sci. 1995;57(7):729-34. View  Abstract

[4] Fukudome S, Yoshikawa M Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Lett. 1992 Jan 13;296(1):107-11. View Abstract

[5] Hallert C et al. Psychic disturbances in adult coeliac disease III. Reduced central monoamine metabolism and signs of depression. Scand J Gastroenterol, 1982; volume 17: pages 25-28. View Abstract

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