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Systematic review

Effect of vitamins, fatty acids, and other dietary supplements on schizophrenic symptoms in people with schizophrenia

There is considerable scientific disagreement about the possible effects of dietary supplements on mental health and illness. Do dietary supplements (possibly in megadoses) have an effect on symptoms and consequences of schizophrenia?

There is considerable scientific disagreement about the possible effects of dietary supplements on mental health and illness. Do dietary supplements (possibly in megadoses) have an effect on symptoms and consequences of schizophrenia?


Key message

There is considerable scientific disagreement about the possible effects of dietary supplements on mental health and illness. Do dietary supplements (possibly in megadoses) have an effect on symptoms and consequences of schizophrenia?

We critically appraised randomized controlled trials about supplemental vitamins, fatty acids and other dietary supplements given to people diagnosed with schizophrenia. The primary outcome was symptoms of schizophrenia.

We evaluated the evidence to be of low or very low quality. It is therefore difficult to draw strong conclusions about the effects of vitamins, minerals and other dietary supplements on symptoms of schizophrenia. The evidence shows the following:

  • Vitamin C and the fatty acid EPA may have a beneficial effect on schizophrenic symptoms (low quality evidence) 
  • Vitamin B6 and the fatty acid DHA may have no effect on schizophrenic symptoms (low quality evidence) 
  • We are uncertain of the effect of the fatty acid GLA and of vitamin E on schizophrenic symptoms (very low quality evidence) 
  • No studies about minerals fulfilled our inclusion criteria

Patients in most studies had few symptoms as a result of using antipsychotic medications. It was, thus, not much room for improvement, and this could have caused an underestimation of the effects of dietary supplements. The risk of adverse effects from the supplements is uncertain. Some adverse effects have been reported, but we could not tell whether the adverse effects were caused by the supplements.
    No evidence of effect does not imply evidence of no effect.
The included studies did not provide the highly individualized and long-term treatment regimens typically provided by orthomolecular medicine.

Summary

Background
There is considerable scientific disagreement about the importance of dietary supplements in relation to mental health and illness. Do dietary supplements (possibly in megadoses) have an effect on symptoms and consequences of schizophrenia?
The Norwegian Directorate of Health commissioned a summary of available re-search on the effects of dietary supplements for people diagnosed with mental illnesses.
 
Objective
This report collects, critically appraises and summarizes the available knowledge from randomized controlled clinical trials on the effects of dietary supplements on schizophrenic symptoms in people diagnosed with schizophrenia or schizoaffective disorder. The review is part of a larger project about dietary supplements for mental health.
 
Method
We systematically searched for randomized controlled trials in the Cochrane Library, Medline, Embase, and PsycINFO up to September 2010. In addition, we searched reference lists of included studies and reviews and hand searched all issues of the Journal of Orthomolecular Medicine (1967-2007). We also hand searched the book “Nutritional Influences on Mental Illness” by Melvyn R. Wehrbach. Inclusion criteria were studies with people who were diagnosed with schizophrenia or schizoaffective disorder and who received dietary supplements in the form of vitamins, minerals, fatty acids or other dietary supplements thought to relieve symptoms of schizophrenia. Outcomes were the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Symptoms Scale (PANSS) plus other measures of severity of schizophrenia. Positive symptoms are those that most individuals do not normally experience but are present in people with schizophrenia (delusions, disordered thoughts, and speech, and hallucinations. Negative symptoms are deficits of normal emotional responses or of other thought processes. They commonly include flat or blunted affect and emotion; poverty of speech, inability to experience pleasure, lack of desire to form relationships, and lack of motivation. We assessed risk of bias with the Cochrane Collaboration’s risk of bias tool, and graded the documentation using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Results are represented as forest plots, and meta-analyses were performed when two or more studies assessed the same supplement and the same outcome. 

Results
We included 33 randomized controlled trials published between 1957 and 2008. They studied vitamins B, C, E, multivitamins, fatty acids, and other dietary supplements (Mianserin, Benzopyrone).

The main results are listed below: We evaluated the evidence to be of low or very low quality. It is therefore difficult to draw strong conclusions about the effects of vitamins, minerals and other dietary supplements on symptoms of schizophrenia. The evidence shows the following:

  • Vitamin C and the fatty acid EPA may have a beneficial effect on schizophrenic symptoms (low quality evidence) 
  • Vitamin B6 and the fatty acid DHA may have no effect on schizophrenic symptoms (low quality evidence)
  • We are uncertain of the effect of the fatty acid GLA and of vitamin E on schizophrenic symptoms (very low quality evidence)
  • No studies about minerals fulfilled our inclusion criteria

The risk of adverse effects from the supplements is uncertain. Some adverse effects have been reported, but we could not tell whether the adverse effects were caused by the supplements.
 
Discussion
We summarized the evidence for possible effects of dietary supplements on symptoms of schizophrenia in people diagnosed with schizophrenia or schizoaffective disorder. We searched for randomized, placebo-controlled trials that had adhered to the instructions described by the adherents of orthomolecular psychiatry. The included studies had a treatment duration ranging from five days to two years. Only three studies used individual doses of supplements, and only six studies delivered more than one supplement. In sum, most studies delivered only one supplement in equal doses to all participants regardless of their individual needs, and the duration of treatment might have been too short in many of the studies.

From the electronic searches we found only 20 of the 33 studies. The remaining studies were located in the book by Wehrbach (n=4), in the review by Kleijnen (n=4), from personal contact with authors (n=2) and from reference lists (n=3). This might indicate that much of the literature in this field is not published in journals that are indexed in the common electronic databases. The hand search of the Journal of Orthomolecular Medicine failed to find any additional studies. We may have missed some studies because they are hard to locate.

There are few studies evaluating the effects of each supplement, and the trials are typically very small. Many of the trials are old. Patients in most studies had few symptoms as a result of using antipsychotic medications. It was, thus, not much room for improvement, and this could have resulted in an underestimation of the effects of supplements.

We do not have sufficient information to assess the risk for adverse effects.

Conclusion
The documentation on dietary supplements for schizophrenia is of low to very low quality. There are randomized controlled trials on a number of supplements, but the trials are few and small, and most have a number of methodological shortcomings. However, the lack of evidence for an effect must not be equated with evidence of no effect. There is a need for large, randomized, blinded, placebo-controlled trials that follow the CONSORT (CONsolidated Standards of Reporting Trials) criteria for reporting of trials. The intervention delivery should follow the principles of orthomolecular medicine which suggest that the treatment duration should be individually adjusted and the supplements should be delivered in individual combinations and doses.

    About this publication

  • Year: 2011
  • By: Norwegian Knowledge Centre for the Health Services
  • Authors Smedslund G, Berg RC.
  • ISSN (digital): 1890-1298
  • ISBN (digital): 978-82-8121-431-6