The 6 Historical Trials of Schizophrenia and Gluten
Updated: Dec 16, 2019
The association between gluten-intolerance and schizophrenia isn't well known. In graduate school for Nutrition Diagnostics, and I spent hours of my time passionately researching this fascinating link of gluten-induced brain inflammation for a research project. The following are summaries of 6 historical research studies that deserve recognition.
I captured this picture from the Glore Museum housed in an old psychiatric hospital in St. Joseph, MO. The embroidery was completed by a patient with schizophrenia and is very telling of the inner workings of their mind.
The following are 6 historical trials on schizophrenia and gluten disorders. During the time these trials took place, lab testing for celiac disease wasn't nearly as advanced as it is today. A modern day trial is needed with the new knowledge the scientific community has now gained on this topic. There are no new trials within the last 3 decades! The following is written in an academic writing style as it was a part of a graduate level research project. I am currently writing a book on the topic that is easier to understand. Join the mailing list found on the home page to stay in the loop on when the book becomes available.
1. In a trial by Vlissides, Venulet, and Jenner (1986), 22 long-term male residents within a maximum security hospital ward with chronic psychosis, mainly schizophrenia, began an initial two week gluten-free diet at the beginning of the study to allow for staff and participants to adjust. The following six weeks was a continuation of the gluten-free diet as well as casilan drinks, a gluten-free protein drink. The following 6 weeks was an initiation of 15g gluten in drinks two times per day (total of 30g gluten).
Schizophrenic manifestations were measured using the Psychotic Inpatient Profile (PIP). Overall, PIP results did not show statistically significant change between gluten-free diet and gluten-containing diet. Though, all the participants showed clinical improvements in PIP scores, namely depressive mood, anxious depression, psychotic disorganization, and hostile belligerence in terms of statistical significance throughout entire study without effect to diet changes. Improvement was a result of more attention given to participants rather than intervention itself. With the exception of two of the 22 participants, both diagnosed with psychosis schizophrenia, had remarkable improvement during the gluten-free period. Improvement was demonstrated by specific PIP scores in the perceptual disorganization and depressive mood. And then subsequent relapses when the gluten was blindly added back into the diet.
2. Ten female patients, 19-63 yrs old with diagnosed chronic schizophrenia by Pacheco, Easterling, & Pryer (1965) underwent two weeks on the ketogenic diet, which happens to also be a gluten-free diet, and followed with one week discontinuation of the diet. To measure behavioral changes, Beckomburga Rating Scale (BRS) was utilized. The BRS resulted in a statistically significant decrease in schizophrenic symptomology after 2 weeks on the diet compared to 2 days on the diet. Clinical symptomology then increased again 1 week after discontinuation of the gluten-free diet in 7 out of 10 patients.
3. In research by Potkin et al (1981), 8 long-term residents of hospital ward with diagnosed schizophrenia in stable condition were on a gluten/cereal/milk-free diet with multivitamin for a 13 week span of the entire study. In 5 of those weeks, the participants had 30g gluten added daily (15g gluten powder in 1 drink and 1 snack). Participants then underwent 8 weeks placebo (gluten-free powder) into drink and snack. Serum α1 acid glycoprotein (gluten inflammation biomarker) and HLAB8-antigen (indirect marker of gluten inflammation) were measured as well as Brief Psychiatric Rating Scale (BPRS) to assess for clinical significance. No statistical or clinical differences were found between the gluten and gluten-free periods in BPRS scores, serum α1 acid glycoprotein, and HLAB8-antigens. Importantly, this study only had 8 participants and were all mostly well-stabilized schizophrenic participants at baseline. Also, gluten-inflammation biomarkers were not first measured at baseline.
4. Singh and Kay (1976) conducted a 14 week study within a locked hospital ward with 14 schizophrenic participants. During the length of the study, participants were maintained on a cereal grain/milk free diet, took a multivitamin, and given a “special drink” daily. Special daily drinks of koolaid, dextrose, and water, were given and either 30g soy flour (placebo) or 30g gluten powder (intervention) were added. Weeks 3-6 and 11-14 were placebo weeks and weeks 7-10 was the intervention. Participants met with a psychologist and a psychiatrist for 90 minutes every 2 weeks which involved 6 measures of social participation/avoidance and 33 dimensions of a psychopathology rating scale.
Participants maintained on gluten-free diet with blind initiation of gluten-containing “special drink”. Results of the psychopathology scale showed 26 out of 33 dimensions and 4 out of 6 social avoidance/participation measures were improved with gluten-free periods and then retracted during blinded gluten challenge. Specifically the statistically significant measures that were improved were: Preoccupied behavior p<0.01, Hostile or fearful social avoidance p<0.02, Tension state p<0.02, Anxiety p<0.05, Poor judgment and insight p<0.05, and Difficulty in abstract thinking p<0.02. These measures all have clinical significance on quality of life in the schizophrenic patient. Input graph here maybe.
5. In a locked ward stay of males with psychosis in a veteran's psychiatric facility, Dohan and Grasberger (1973) studied total length of stay (including both locked and open ward stay) when given a temporary gluten-free diet. The locked ward stays are for more severe and sometimes aggressive or unsafe schizophrenic manifestations. The open ward was granted when patients were not ready for discharge but were more cooperative and were in no apparent danger to self or others. And the gluten-free diet was only maintained during the locked ward portion of the hospital stay and was discontinued when patients advanced to the open ward. Total length of stay included all entire hospital stay. Dohan and Grasberger (1973) also secretly added gluten back into the diet in some participants for a blinded effect by participants and staff to ensure credibility of results.
Within 30 days, gluten/milk-free temporary diet group was discharged at 2 times the rate of the high cereal group. The trend of shorter total length of stay continued up to 180 day hospital stays in favor of gluten/milk-free diet. But, importantly, no participant remained on a gluten/milk-free diet 10 days past their locked ward stay (into the open ward stay). The shortest possible diet was 15 days. If patients stayed on gluten/milk-free diet throughout duration of hospital stay, the results may even be more significant and clinically relevant than they already were for this study.
6. Dohan's original research study of 1973 actually took place in 1969. The study was very similar to the first except length of stay in the locked ward was studied and not total length of stay. The high cereal diet in the control group ensured gluten at each meal. For example, potatoes were changed to spaghetti to ensure the hospital diet included gluten.
Of 47 schizophrenic participants on cereal/milk free diet, 62% were released <7 days. And of 55 schizophrenic participants on high cereal diet, 36% were released <7 days. This was a difference of p=0.0091. When gluten was secretly added back into the diet compared to the high cereal group, length of stay of locked ward were not significantly different.
Dohan, F., & Grasberger, J. (1973). Relapsed schizophrenics: earlier discharge from the hospital after cereal-free, milk-free diet. The American Journal Of Psychiatry, 130(6), 685–688.
Dohan, F., Grasberger, J., Lowell, F., Johnston, H., Jr, & Arbegast, A. (1969). Relapsed schizophrenics: more rapid improvement on a milk- and cereal-free diet. The British Journal Of Psychiatry: The Journal Of Mental Science, 115(522), 595–596.
Potkin, Weinberger, Kleinman, Nasrallah, Luchins, Bigelow, Linnoila, Fischer, Bjornsson, Carman, Gillin, Wyatt. (1981). Wheat gluten challenge in schizophrenic patients. American Journal of Psychiatry, 138(9), 1208–1211.
Pacheco, A., Easterling, W., & Pryer, M. (1965). A pilot study of the ketogenic diet in schizophrenia. American Journal of Psychiatry, 121(11), 1110-1111. doi:10.1176/ajp.121.11.1110
Singh, M., & Kay, S. (1976). Wheat gluten as a pathogenic factor in schizophrenia. Science (New York, N.Y.), 191(4225), 401–402.
Vlissides, D., Venulet, A., & Jenner, F. (1986). A double-blind gluten-free/gluten-load controlled trial in a secure ward population. The British Journal of Psychiatry: The Journal of Mental Science, 148, 447–452.