Gluten: a protein in grains

J Am Diet Assoc 2003 Mar;103(3):376-9
Oats and the gluten-free diet.
Thompson T T. Thompson is a nutrition consultant in Manchester, MA.

  Whether oats should be included in a gluten-free diet has been debated for half a century. In 1995, the largest and most scientifically rigorous study on the safety of oats was published. Investigators concluded that the consumption of oats was safe for adults with celiac disease. Since 1995, several additional studies have been published. Without exception, these investigations found no adverse effects associated with the regular consumption of moderate amounts of oats. However, there are concerns among some authorities on celiac disease that even if oats themselves are safe, they nonetheless may be contaminated with wheat, rye, or barley. Unfortunately, the extent to which contamination of commercial oat products occurs is not known. Ideally, if a patient appears likely to use oats, they should be advised to consume only those products tested and found to be free of contamination.

PMID: 12616264

Science 1976 Jan 30;191(4225):401-2
Wheat gluten as a pathogenic factor in schizophrenia.
Singh MM, Kay SR.

  Schizophrenics maintained on a cereal grain-free and milk-free diet and receiving optimal treatment with neuropleptics showed an interruption or reversal of their therapeutic progress during a period of "blind" wheat gluten challenge. The exacerbation of the disease process was not due to variations in neuroleptic doses. After termination of the gluten challenge, the course of improvement was reinstated. The observed effects seemed to be due to a primary schizophrenia-promoting effect of wheat gluten.

PMID: 1246624

J Intern Med 1997 Nov;242(5):421-3
Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet.
De Santis A, Addolorato G, Romito A, Caputo S, Giordano A, Gambassi G, Taranto C, Manna R, Gasbarrini G. Department of Internal Medicine, Catholic University, Rome, Italy.

  A 33-year-old patient, with pre-existing diagnosis of 'schizophrenic' disorder, came to our observation for severe diarrhoea and weight loss. Use of single photon emission computed tomography, (99mTc)HMPAO SPECT, demonstrated hypoperfusion of the left frontal brain area, without evidence of structural cerebral abnormalities. Jejunal biopsy showed villous atrophy. Antiendomysial antibodies were present. A gluten-free diet was started, resulting in a disappearence of psychiatric symptoms, and normalization of histological duodenal findings and of (99mTc)HMPAO SPECT pattern. This is the first case in which, in an undiagnosed and untreated coeliac patient with psychiatric manifestations, the (99mTc)HMPAO SPECT demonstrated a dysfunction of frontal cortex disappearing after a gluten-free diet.

PMID: 9408073

Prog Neuropsychopharmacol Biol Psychiatry 1996 Oct;20(7):1083-114
Could schizophrenia be reasonably explained by Dohan's hypothesis on genetic interaction with a dietary peptide overload?
Reichelt KL, Seim AR, Reichelt WH. Institute of Pediatric Research, Univ of Oslo, Rikshopsitalet, Norway. 1.

  Dohan has proposed that schizophrenia is a genetic disposition which interacts with an overload of dietary proteins such as casein and gluten or gliadin. 2. A systematic attempt is made to see if this hypothesis is possible faced with aspects of schizophrenia that must be accounted for. 3. The authors conclusion is that it is possible, but more serious work in this field is urgently needed.

PMID: 8938813

Biol Psychiatry 1995 Mar 15;37(6):410-3
Specific IgA antibody increases in schizophrenia.
Reichelt KL, Landmark J. Department of Pediatric Research, Rikshospitalet, University of Oslo, Norway.

  IgA antibody levels in serum were examined in two groups of schizophrenic patients. All were diagnosed according to DSM-III-R criteria. One group of 36 males and 12 females were compared to historical controls. The other group consisted of 13 males off drugs for at least 3 months; these were compared with age- and sex-matched controls. An increase in specific IgA antibodies was found. More schizophrenics than controls showed IgA antibody levels above the upper normal limit to gliadin, beta-lactoglobulin, and casein.

PMID: 7772650

Schizophr Bull 1988;14(4):489-94
Genetic hypothesis of idiopathic schizophrenia: its exorphin connection.
Dohan FC. Medical College of Pennsylvania, Eastern Pennsylvania, Psychiatric Institute, Philadelphia 19129.

  This brief overview proposes a testable oligogenic model of the inheritance of susceptibility to idiopathic schizophrenia: "abnormal" genes at each of a few complementary loci. The model is based on my assumptions as to the likely genetic abnormalities at possibly four or five interacting loci that would permit exorphins, the opioid peptides from some food proteins, especially glutens and possibly caseins, to go from gut to brain and cause symptoms of schizophrenia. Exorphins may reach the brain cerebrospinal fluid (CSF) in harmful amounts because of their genetically increased, receptor-mediated transcellular passage across the gut epithelial barrier plus decreased catabolism by genetically defective enzymes. A schizophrenia-specific, genetically enhanced affinity for exorphins by opioid receptors influencing dopaminergic and other neurons would permit sustained dysfunction at low CSF exorphin concentrations. Tests of each postulated genetic abnormality are suggested. This model is supported by a variety of evidence, including a significant effect of gluten or its absence on relapsed schizophrenic patients, the high correlation of changes in first admission rates for schizophrenia with changes in grain consumption rates, and the rarity of cases of schizophrenia where grains and milk are rare.

PMID: 2851166

Br J Psychiatry 1986 Apr;148:447-52
A double-blind gluten-free/gluten-load controlled trial in a secure ward population.
Vlissides DN, Venulet A, Jenner FA.

  A double-blind control trial of gluten-free versus a gluten-containing diet was carried out in a ward of maximum security hospital: 24 patients were studied for 14 weeks. Most suffered from psychotic disorders, particularly schizophrenia. Various dimensions of behaviour were rated on the Psychotic In-Patient profile (PIP) at different stages. There were beneficial changes in the whole group of patients between pre-trial and gluten-free period in five dimensions of the PIP, maintained during the gluten challenge period; these changes could be attributed to the attention the patients received. Two patients improved during the gluten-free period and relapsed when the gluten diet was reintroduced.

PMID: 3524724

Peptides 1984 Nov-Dec;5(6):1139-47
Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates.
Huebner FR, Lieberman KW, Rubino RP, Wall JS.

  Because of a possible relationship between schizophrenia and celiac disease, a condition in some individuals who are sensitive to wheat gluten proteins in the diet, there has been interest in observations that peptides derived from wheat gluten proteins exhibit opioid-like activity in in vitro tests. To determine the origin of the peptides exhibiting opioid activity, wheat proteins were fractionated by size (gel filtration), by charge differences (ion exchange chromatography) and by differences in hydrophobicity (reversed-phase HPLC). These fractions were hydrolyzed by pepsin or pepsin and trypsin and the resulting peptides separated by gel filtration chromatography. The separated peptides were tested for opioid-like activity by competitive binding to opioid receptor sites in rat brain tissue in the presence of tritium-labeled dihydromorphine. The peptides showed considerable differences in activity; while some peptides exhibited no activity, 0.5 mg of the most active peptides were equivalent to 1 nM of morphine in the binding assay. The most active peptides were derived from the gliadin fraction of the gluten complex.

PMID: 6099562

Nutr Health 1984;3(3):137-51
Psychological and behavioral effects of food and chemical exposure in sensitive individuals.
King DS.

  Dietary influences on behavior are of increasing scientific interest. In some cases, the effects appear limited to sensitive individuals. Thus, research on the role of wheat gluten in schizophrenia has produced conflicting results, but not all schizophrenics respond to wheat. Therefore, differences in statistical power may be a factor in these discrepant findings. Similarly, only a subset of hyperactive children seem to be affected by food colors. Another dietary influence on behavior may be sucrose consumption which was found to be directly correlated with behavior in children. In addition, the possible relationship of allergy to behavior is reviewed. Double-blind findings of the production of cognitive-emotional symptoms by sublingual provocative food and chemical challenges are described, with treatment follow-up data. Finally, a methodological note on provocative testing is included.

PMID: 6400044

Am J Psychiatry 1979 Oct;136(10):1306-9
Immunologic reaction of psychotic patients to fractions of gluten.
Ashkenazi A, Krasilowsky D, Levin S, Idar D, Kalian M, Or A, Ginat Y, Halperin B.

  Production of a leukocyte migration inhibition factor by peripheral blood lymphocytes in response to challenge with gluten fractions was studied in hospitalized patients with schizophrenia and other psychoses compared with normal individuals and with children and adolescents with celiac disease. The schizophrenic and other psychotic patients could be subdivided into two groups, one that responded in the leukocyte migration inhibition factor test as the celiac patients did and one that responded as the normal control subjects did. The psychotic and schizophrenic patients did not show any evidence of malabsorption. The authors speculate that gluten may be involved in biological processes in the brain in certain psychotic individuals.

PMID: 384809

CRC Crit Rev Food Sci Nutr 1977 Mar;8(4):383-456
The nutritional and physiological impact of cereal products in human nutrition.
Lorenz K, Lee VA.

  There is a need for reeducation of the population, especially in developed countries, as to the value of cereals in the diet. Cereals provide calories and important nutrients to the diet. Refined cereal products and unrefined cereals have certain advantages and disadvantages. With refinement, some nutrients and fiber are removed, but the body is better able to make use of certain nutrients. Essential nutrients are being replaced through fortification to compensate for losses in processing. The high fiber content of unrefined cereal products is believed to aid in the prevention of certain diseases. Special dietary bakery products have been introduced for the treatment of conditions generally exacerbated by standard food items. The increased consumption of cereal products appears warranted as a means of decreasing the saturated fat and cholesterol consumption. Cereals and cereal products have been mentioned in connection with allergies, celiac disease, schizophrenia, obesity, dental caries, cancer, atherosclerosis, goiter, and diverticulosis. This review discusses the possible role of cereals in the prevention or cause of these health problems.

PMID: 338251


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