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‘Gluten Brain’: Wheat Cuts Off Blood Flow To Frontal Cortex

As far back as 1954, reports of the full or partial resolution of schizophrenia following a gluten free diet began to surface in the medical literature. We covered this remarkable pattern of associations in a previous article titled, 60 Years of Research Links Gluten Grains to Schizophrenia”.

Thanks to Sayer Ji,


Gluten_Effect
Starting with a 1997 case study published in the Journal of Internal Medicine involving a 33-year-old patient, with pre-existing diagnosis of ‘schizophrenic’ disorder, who first came to medical attention for severe diarrhea and weight loss (classical symptoms of gluten intolerance), brain scan technology determined that cerebral hypo-perfusion (decreased blood flow to the brain) was occurring within the patient’s frontal cortex.[i] A gluten free diet resulted not only in the normalization of intestinal damage and autoantibodies, but the return of blood flow to the frontal cortex, and the resolution of schizophrenic symptoms.



Celiac Disease and Blood Flow to the Brain



Then, in 2004, a follow up study was performed to verify if the 1997 case study was just a fluke, or perhaps a widespread effect of untreated celiac disease. Published in the American Journal of Medicine, researchers from the Institute of Internal Medicine, Catholic University, Rome, Italy, compared 15 untreated celiac patients without neurological or psychiatric disorders other than anxiety or depression, with 15 celiac patients who were on a gluten-free diet for almost 1 year, and 24 healthy volunteers of similar sex and age. All subjects underwent cerebral single photon emission computed tomography examination.

The results were remarkable, with dramatically increased incidence of impaired brain blood flow in untreated celiac patients, reported as follows:

Of the 15 untreated celiac patients, 11 (73%) had at least one hypo-perfused brain region, compared with only 1 (7%) of the 15 celiac patients on a gluten-free diet and none of the controls (P = 0.01). Cerebral perfusion was significantly lower (P <0.05) in untreated celiac patients, compared with healthy controls, in 7 of 26 brain regions. No significant differences in cerebral perfusion were found between celiac patients on a gluten-free diet and healthy controls.”

They concluded: “There is evidence of regional cerebral blood flow alteration in untreated celiac patients.”

[i] A De Santis, G Addolorato, A Romito, S Caputo, A Giordano, G Gambassi, C Taranto, R Manna, G Gasbarrini. Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet. J Intern Med. 1997 Nov ;242(5):421-3. PMID: 9408073

Wartime Reduction In Gluten Grain Rations Reduces Schizophrenia Prevalence


Gluten-Free-Diet_0For instance, in 1966, a remarkable epidemiological study was published in The American Journal of Clinical Nutrition titled,“Wheat “Consumption” and Hospital Admissions for Schizophrenia During World War II,“ (<– Click here) which sought to confirm the possible relationship between schizophrenia and celiac disease by investigating the reported decrease in the number of admissions to mental hospitals during some wars.

The author of the study, F. C. Dohan, M.D., looked at the number of women admitted to the mental hospitals in Finland, Norway, Sweden, Canada and the United States before and after World War II. These figures were then compared to volume of wheat and rye consumed during those two periods. As Dohan explains:

The percent change in the mean annual number of first admissions for schizophrenia to the hospital in each of the five countries from the respective pre-war mean was compared to the percent change in the “consumption” of wheat and wheat plus rye.”

The results can be view in the figure below:

Wheat Consumption Data and Psychiatric Problems

As you can see above, the percent change from prewar values during World War II in the number of patients admitted to hospitals for the first time with schizophrenia in five countries was found to be significantly correlated to the percent change in the amount of wheat and wheat plus rye consumed.


As gluten grain rations decreased, so did the worldwide rate of first-time admission to psychiatric institutions.


Increasing Body of Research Implicates Gluten Grains in Schizophrenia Pathogenesis


gluten-warningSince then, a number of studies have been published linking the consumption of gluten-containing grains to schizophrenia:

  • Schizophrenia Bulletin, 2011: Persons with schizophrenia have higher than expected titers of antibodies (7 fold increased prevalence) related to celiac disease and gluten sensitivity.[iv]

[iv] Nicola G Cascella, Debra Kryszak, Bushra Bhatti, Patricia Gregory, Deanna L Kelly, Joseph P Mc Evoy, Alessio Fasano, William W Eaton. Prevalence of celiac disease and gluten sensitivity in the United States clinical antipsychotic trials of intervention effectiveness study population. Schizophr Bull. 2011 Jan;37(1):94-100. Epub 2009 Jun 3.

  • Schizophrenia Research, 2010: Individual with schizophrenia have a novel immune response to gliadin distinct from those with celiac disease (i.e. absence of antibodies to the transglutaminase enzyme and the HLA-DQ2/DQ8 genetic locus of susceptibility.[v]

[v] Diana Samaroo, Faith Dickerson, Donald D Kasarda, Peter H R Green, Chiara Briani, Robert H Yolken, Armin Alaedini. Novel immune response to gluten in individuals with schizophrenia.Schizophr Res. 2010 May;118(1-3):248-55. Epub 2009 Sep 11.

  • Acta Psychiatra Scandinavica, 2006: A review of the literature found a drastic reduction, if not full remission, of schizophrenic symptoms after initiation of gluten withdrawal has been noted in a variety of studies.[vi]

[vi] A E Kalaydjian, W Eaton, N Cascella, A Fasano. The gluten connection: the association between schizophrenia and celiac disease. Acta Psychiatr Scand. 2006 Feb;113(2):82-90.

  • Biological Psychiatry, 1984: Only two chronic schizophrenics were found among over 65,000 examined or closely observed adults in remote regions of Papua New Guinea (PNG, 1950-1967) and Malaita , Solomon Islands (1980-1981), and on Yap , Micronesia (1947-1948), who do not consume grains. Researchers noted that when these peoples became partially westernized and consumed wheat, barley beer, and rice, the prevalence reached European levels.[vii]

[vii] F C Dohan, E H Harper, M H Clark, R B Rodrigue, V Zigas. Is schizophrenia rare if grain is rare? Biol Psychiatry. 1984 Mar;19(3):385-99.

  • Science, 1976: Schizophrenics maintained on a grain-free and milk-free diet challenged with gluten saw interruption of their therapeutic progress. After termination of the gluten challenge, the course of improvement was reinstated.[viii]

[viii] M M Singh, S R Kay. Wheat gluten as a pathogenic factor in schizophrenia. Science. 1976 Jan 30;191(4225):401-2.

New Research Confirms Gliadin-Schizophrenia Link

The latest study to confirm the gluten-schizophrenia link was published this month in the World Journal of Biological Psychiatry and titled, “Elevated gliadin antibody levels in individuals with schizophrenia.” Researchers compared the blood work of 950 schizophrenics with 1,000 healthy controls. They discovered that the odds ratio of having anti-gliadin IgG antibodies was 2.13 times higher in schizophrenics, indicating that t the least schizophrenics are more likely to experience an adverse immune response to wheat proteins.

Gliadin is the alcohol soluble complex of proteins found within what is known colloquially as gluten (the term is misleading as wheat technically contains over 23,000 different proteins, not one), and is considered the primary immunotoxic class of proteins in wheat. For instance, in celiac disease, a genetically mediated immune process unfurls where upon exposure to gliadin, the enzyme tissue transglutaminase modifies the protein, and the immune system cross-reacts with the small-bowel tissue, causing an inflammatory reaction that results in the destruction of the intestinal villi.

The discovery of antibodies to gliadin in the blood of both celiac disease patients and schizophrenics implies several things:

  • The Wheat Protein Gliadin Doesn’t Break Down During Digestion: Undigested wheat-derived macromolecules can act as antigens, provoking an antibody-mediated immune response, particularly if they get through the intestinal lining and into the blood. The fact that antibodies to wheat protein gliadin can be found in the blood indicates that it is not being fully broken down into constituent amino acids.
  • Wheat Proteins In the Blood Stimulate Auto-Immunity: The presence of gliadin in the blood also indicates intestinal permeability. It turns out that gliadin has been found to up-regulate the protein zonulin in the gut of those either with or without celiac disease, which essentially opens “pandora’s box” of intestinal permeability, and subsequent autoimmunity.[ix] In another essay, we also described the intestinal permeability generating effects of wheat lectin, also known as Wheat Germ Agglutinin (WGA) – [see Opening Pandora's Bread Box]
  • Wheat Protein May Cause The Immune System To Attack the Nervous System: Anti-gliadin antibodies appear to cross react with neurological self-structures, which may explain how they contribute to schizophrenia. A study published in 2007 in the Journal of Immunology found that anti-gliadin antibodies bind to neuronal synapsin I, a protein found within nerve terminal of axons, which the study authors believe may explain why gliadin contributes to “neurologic complications such as neuropathy, ataxia, seizures, and neurobehavioral changes.”[x] Another example of anti-gliadin antibodies possibly contributing to the formation of autoantibodies against neurological self-structures is in autism. A 2004 study in Nutritional Neuroscience found that children with autism show antibody elevations against gliadin and cerebellar (brain) proteins simultaneously. In other words, wheat proteins may simulate antibodies that cross-react, resulting in neurological damage.[xi] Learn more on the topic by reading our article: Wheat: A Missing Piece In the Autism Puzzle.


[ix]
Sandro Drago, Ramzi El Asmar, Mariarosaria Di Pierro, Maria Grazia Clemente, Amit Tripathi, Anna Sapone, Manjusha Thakar, Giuseppe Iacono, Antonio Carroccio, Cinzia D’Agate, Tarcisio Not, Lucia Zampini, Carlo Catassi, Alessio Fasano. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006 Apr;41(4):408-19.

[x] Armin Alaedini, Haruka Okamoto, Chiara Briani, Kurt Wollenberg, Holly A Shill, Khalafalla O Bushara, Howard W Sander, Peter H R Green, Mark Hallett, Norman Latov. Immune cross-reactivity in celiac disease: anti-gliadin antibodies bind to neuronal synapsin I. J Immunol. 2007 May 15 ;178(10):6590-5.


[xi] A Vojdani, T O’Bryan, J A Green, J Mccandless, K N Woeller, E Vojdani, A A Nourian, E L Cooper. Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr Neurosci. 2004 Jun;7(3):151-61.


[xii] M Hadjivassiliou, A Gibson, G A Davies-Jones, A J Lobo, T J Stephenson, A Milford-Ward .Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.