Nutritional Influences on Illness: Vitamins for Treating Schizophrenia


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There are four vitamins whose nutriture may be particularly relevant to the schizophrenic syndrome:

1. Folic Acid

Folic acid deficiency occurs in 10 to 30% of hospitalized psychiatric patients.[ 1] In addition to psychosis, the deficiency is associated with depression, confusion, disorientation and dementia as well as with neurological symptoms such as numbness, stiffness, spasticity and weakness, both with and without muscular atrophy.

In a randomized double-blind study reported in the Lancet, schizophrenics with low red cell folate levels, but without a deficiency of vitamin B 12 or significant cognitive impairment, received either methylfolate 15 mg daily or placebo in addition to standard psychotropic drugs. After 6 months, there were significant differences in mean clinical outcome scores between groups in favor of the folate group.[ 2]

Specific mechanisms by which folate deficiency may be implicated are starting to be identified. Folic acid may be an essential cofactor in the conversion of the omega-6 fatty acids to prostaglandins,[ 3] and early evidence suggests that impaired prostaglandin metabolism may provoke a schizophrenic picture.

Also, hyperhomocysteinemia due to an inborn error of folate metabolism may present as a schizophrenic syndrome sometimes accompanied by neurological signs. Case reports suggest that folic acid supplementation, usually along with either vitamin B6[ 4] or vitamin B12,[ 5] appears to be effective.

A Warning: For schizophrenics, supplementation with as little as 3 mg of folic acid daily can cause an exacerbation of psychotic behavior if blood folate levels become elevated. Thus, blood levels should be followed during a therapeutic trial.[ 6]

2. Niacin

Megadoses of niacin for treating schizophrenia, advocated by Hoffer and Osmond, launched the orthomolecular psychiatry movement four decades ago.[ 7] Today, such treatment remains controversial, as both positive[ 8] and negative[ 9] double-blind studies have appeared in the scientific literature. Although the consensus of mainstream academicians is that niacin therapy is ineffective,[ 10] Hoffer notes that niacin is primarily effective for early and acute schizophrenics, while it is ineffective - especially when given alone - for the chronic schizophrenics who were included in the negative trials.[ 11] In any case, the possibility of adverse side-effects from high-dosage niacin supplementation must be considered.

Patients with sub-clinical pellagra, who may develop perceptual changes and neurasthenia, could be mistakenly labeled as schizophrenic, yet would clearly benefit from niacin.[ 12] Blood niacin levels would help to identify such cases. Whether other sub-groups who present with schizophrenic syndromes would benefit from niacin therapy remains unknown.

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3. Vitamin B6

Pyridoxal-5-phosphate, the activated form of the vitamin, is important for normal brain function. In fact, isoniazid, an antituberculous drug which antagonizes vitamin B6 activity, produces a variety of neuropsychiatric symptoms that remit with B6 supplementation.

A few open trials of supplementation with the vitamin have reported good results. Perhaps the most interesting concerned a group of women who presented with paranoid ideation, emotional lability, irritability, depression and fatigue. The patients were taking oral contraceptives, drugs which may foster depletion of the vitamin.[ 13] Following pyridoxine supplementation, three-quarters of the group improved.[ 14]

The lack of placebo-controlled studies, and the failure of published studies to ascertain vitamin B6 nutriture at baseline, makes it impossible to reach a conclusion about the efficacy of the vitamin in treating schizophrenia.

4. Vitamin C

There appears to be an inverse correlation between ascorbic acid intake and the risk of schizophrenia.[ 15] Even when the dietary vitamin C intake is adequate for normals, schizophrenics may have depressed plasma levels and may demonstrate a greatly reduced urinary excretion of ascorbic acid after an ascorbic acid load,[ 16, 17] suggesting that the utilization of vitamin C in schizophrenics may be enhanced.

Results of an animal study suggest that vitamin C may block the behavioral response to dopamine and enhance the effects of neuroleptic drugs.[ 18] Supplementation with high doses produced improvement in mood and paranoid ideation in a randomized double-blind study,[ 19] results that have been confirmed in subsequent open trials.

For example, 21 long-term hospitalized patients who were taking the neuroleptics (even though they were ineffective) were started on ascorbic acid supplements for at least one month. Two of the patients showed a favorable response on 2 grams daily. One of them, who had been floridly psychotic, went into a full remission within 2 weeks. Ten of the non-responders were then raised to 6 grams daily. Within one month, 4 of them showed progress. All responders subsequently maintained their progress.[ 20]

Doctor Werbach cautions that the nutritional treatment of illness should be supervised by physicians or practitioners whose training prepares them to recognize serious illness and to integrate nutritional interventions safely into the treatment plan.

1. Greenblatt JM et al. Folic acid in neurodevelopment and child psychiatry. Prog Neuropsychopharmacol Biol Psychiatry 18:647-60, 1994

2. Godfrey PS et al. Enhancement of recovery from psychiatric illness by methylfolate. Lancet 336:392-5, 1990

3. Horrobin DF. Interrelationships between folic acid and prostaglandins in epilepsy, schizophrenia, and peripheral neuropathies, in MI Botez & EH Reynolds, Eds. Folic Acid in Neurology, Psychiatry, and Internal Medicine. New York, Raven Press, 1979a

4. Freeman JM et al. Folate-responsive homocystinuria and schizophrenia. A defect in methylation due to deficient 5,10-methylene-tetrahydrofolate reductase activity. N Engl J Med 292:491-6, 1975

5. Regland B et al. Homocysteinemia and schizophrenia as a case of methylation deficiency. J Neural Transm Gen Sect 98(2):143-52, 1994

6. Prakash R, Petric WM. Psychiatric changes associated with an excess of folic acid. Am J Psychiatry 139(9):1192, 1982

7. Hoffer A. Niacin Therapy in Psychiatry. Springfield, Illinois, Charles C. Thomas, 1962

8. Osmond H, Hoffer A. Massive niacin treatment in schizophrenia: Review of a nine-year study. Lancet i:316-20, 1962

9. Wittenborn JR et al. Niacin in the long-term treatment of schizophrenia. Arch Gen Psychiatry 28:308-15, 1973

10. American Psychiatric Association, Task Force on Vitamin Therapy in Psychiatry. Megavitamin and Orthomolecular Therapy in Psychiatry. Washington, DC, American Psychiatric Association, 1973

11. Hoffer A. The vitamin paradigm wars. Townsend Letter for Doctors and Patients, June, 1996:56-60

12. Green RG. Subclinical pellagra: Its diagnosis and treatment. Schizophrenia 2:70-79, 1970

13. Roe DA. Drug-induced Nutritional Deficiencies. Second Edition. Westport, CT, Avi Publishing, 1985:270-3

14. Baumblatt MJ, Winston F. Pyridoxine and the pill. Letter to the Editor. Lancet i:832-3, 1970

15. Singh RB et al. Dietary intake and plasma levels of antioxidant vitamins in health and disease: a hospital-based case-control study. J Nutr Environ Med 5:235-42, 1995

16. Suboticanec K. Vitamin C status in schizophrenia. Bibl Nutr Dieta 38:173-81, 1986

17. Suboticanec K et al. Vitamin C status in chronic schizophrenia. Biol Psychiatry 28(11):959-66, 1990

18. Rebec GV et al. Ascorbic acid and the behavioral response to haloperidol: Implications for the action of antipsychotic drugs. Science 227:438-40, 1985

19. Milner G. Ascorbic acid in chronic psychiatric patients: A controlled trial. Br J Psychiatry 109:294-9, 1963

20. Kanofsky JD et al. Ascorbate: An adjunctive treatment for schizophrenia. Abstract. J Am Coll Nutr 8(5):425, 1989

Excerpted from Textbook of Nutritional Medicine by Melvyn R. Werbach with Jeffrey Moss. Tarzana, California, Third Line Press, Inc., 1999.

Schizophrenia is only one of the 82 illnesses discussed in Dr. Werbach's Textbook of Nutritional Medicine. For information, or a free brochure on all of his books, contact Third Line Press Inc., 4751 Viviana Drive, Tarzana, CA 91356, USA. (Phone: 818-996-0076; Fax: 818-774-1575; internet:; e-mail:


By Melvyn R. Werbach

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