Vitamins for Schizophrenia

Megavitamin therapy was promoted for schizophrenia in the 1970's and the "orthomolecular psychiatry" promoters are still alive but virtually ignored since research found no value to their favorites: niacin and vitamin B-6.  However, there is a small amount of research suggesting that folate and vitamin C might be of value.  Vitamin D in pregnancy or infancy may have a preventive value. Also, for general health, taking niacin and B-6 supplements have not yet been proven of value, folate, vitamin C, and vitamin D are supplements that I recommend for everyone because of their proven health benefits. 

Niacin (B-3): No Evidence for Mental Disorders: Of 53 controlled trials of the effects of niacin, vitamin B6, and multivitamins on mental functions reviewed, virtually all trials show serious short-comings: in the number of participants, the presentation of baseline characteristics and outcomes, and the description of changes in concomitant treatments. Only in autistic children are some positive results are found with very high dosages of vitamin B6 combined with magnesium, but further evidence is needed before more definitive conclusions can be drawn. Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans. Kleijnen et al. University of Limburg, The Netherlands. Biol Psychiatry. 1991 May 1;29(9):931-41.

Niacin and B-6 Useless for Schizophrenia: As part of the Canadian Mental Health Association Collaborative Study, in a 48-week study in which supplementation of neuroleptic treatment with a single vitamin, i.e., nicotinic acid or pyridoxine, was done for schizophrenic patients in a DB PC design, no benefit from the vitamins was found. The use of nicotinic acid and pyridoxine in the treatment of schizophrenia. Petrie WM, et al. Int Pharmacopsychiatry. 1981;16(4):245-50; Arch Gen Psychiatry. 1973 Mar;28(3):308-15; Lancet. 1962 Feb 10;1:316-9.

Vitamin B-6 Doesn't Help Schizophrenia: In a 9-week, 15-patient DB PC study of vitamin B6 starting at 100 mg/day and increasing to 400 mg/day by the fourth week, PANSS scores revealed no differences between vitamin B6- and placebo-treated patients in amelioration of their mental state. Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients: a double-blind, placebo-controlled study. Lerner V, Miodownik C, Kaptsan A, Cohen H, Loewenthal U, Kotler M. Ben-Gurion University J Clin Psychiatry. 2002 Jan;63(1):54-8.

Vitamins B-6 No Benefit in DB: This was a DB PC crossover study of 4 weeks on 100-400 mg/d with an intervening washout period befor the crossover. J Clin Psychiatry 2002 Jan;63(1):54-8

Folate (B-9): Methylfolate DB Helps Depression & Schizophrenia: A DB PC study of 41 patients (33%) of 123 patients, major depression (24) or schizophrenia (17), had low RBC folate [<200microg/l] or borderline folate) and were treated with placebo or 15 mg methylfolate in addition to their regular medications for 6 months. Folate patients had a better social recovery and the difference grew with time. HAM-D increased in depressed from 8.0 to 11.25 with placebo but decreased 9.62 to 8.31 with folate. Schizophrenic symptoms decreased with folate from 5.22 to 3.44 (3 mo) to 2.22, but no change with placebo 5.63 to 5.87. Two-thirds of people with megaloblastic anemia have psychiatric difficulties. Low folate is found in 22% in the average study and low B-12 in 5%. Researchers have not been able to prove that low folate is due to inadequate dietary intake. All schizophrenics and 19 of the depressed patients were also on psychotropics. Few of the patients had macrocytosis which is an inadequate screen. SAMe gets its methyl group from methylfolate via methionine and both affect serotonin and dopamine turnover. Godfrey, King’s College, Lancet ’90;336:392; Br J Psychiatry 8/91

Folate Might Help: Several placebo-controlled studies have not demonstrated therapeutic effects, possibly because the doses they used (15-20 mg/day) are known to be toxic and to cause mental symptoms. 6. Two placebo-controlled studies have demonstrated beneficial effects of folic acid administration, one in patients with a syndrome of psychiatric and neuropsychological changes associated with folate deficiency and the other in patients on long-term lithium therapy. McGill, Prog Neuropsychopharmacol Biol Psychiatry 1989;13(6):841-63

Folate Low in Pregnancy May Increase Schizophrenia: Many different lines of research support the hypothesis that schizophrenia is a disorder of development with etiological factors implicated as early as the second trimester in utero. A research review by the authors supports the hypothesis that maternal low folate and high homocysteine levels may provide a potential teratogenic mechanism that increases the risk for developing schizophrenia. Do maternal folate and homocysteine levels play a role in neurodevelopmental processes that increase risk for schizophrenia? Picker JE, Coyle JT. Harvard-McLean. Harv Rev Psychiatry. 2005 Jul-Aug;13(4):197-205.

Folate: Homocysteine Elevated But Significance Unclear: Elevated plasma homocysteine is a risk factor for Alzheimer's disease as well as cerebral vascular disease. In measuring the homocysteine levels of 193 schizophrenic patients vs. 762 controls, the effect of schizophrenia was marked (p<0.0001) 16.3 muM vs. 10.6 muM in healthy controls. The increase was almost entirely in young male schizophrenic patients. In another study of homocysteine levels in 184 consecutively admitted schizophrenic patients and 305 control subjects, homocysteine levels were markedly increased in this population of newly admitted schizophrenic patients, especially in young males. However, no difference was found for CSF homocysteine levels between schizophrenia patients and controls. In an attempt to develop a model of homocysteine neurotoxicity, mice were fed homocysteine in water at a dose of 200 mg/kg/day. Homocysteine levels were elevated up to 800% at months 5 and 6, but no homocysteine-induced defects were found. High homocysteine serum levels in young male schizophrenia and bipolar patients and in an animal model. Levine J, et al. Ben Gurion University, Beersheva, Israel. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Aug 19

Vitamins: B-12 Low: 20% Israeli psychiatric patients were low in B-12 with 10% definitely deficient and 70% of these had a diagnosis of schizophrenia. Diet was adequate and there was nothing which distinguished them. Isr J Psychiatry Relat Sci 2000;37(1):41-5; Similar in England.

Vitamin C Helped Schizophrenics: In an 8-week DB PC crossover study of 40 schizophrenic patients, increased serum MDA and decreased plasma ascorbic acid levels were found in schizophrenic patients. These levels were reversed significantly after treatment with vitamin C along with atypical antipsychotics compared to placebo with atypical antipsychotics. BPRS change scores at 8 weeks improved statistically significant with vitamin C as compared to placebo. Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia. Dakhale GN, et al. Government Medical College, Nagpur, India. Psychopharmacology (Berl). 2005 Aug 13:1-5

Vitamin D Supplement in Infancy Linked to Lower Schizophrenia in Males; 2000 IU Best: In a Finnish study of 9,114 newborns followed for 31 years, males given vitamin D supplements in the first year of life, either irregular or regular vitamin D supplements, had a 90% reduced risk of schizophrenia (Risk ratio (RR)=0.10) compared with no supplementation. In males, the use of at least 2,000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR=0.23) compared to those on lower doses. There was no link for females or for other psychiatric difficulties for either sex. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. McGrath J, Saari K, et al. Schizophr Res. 2004 Apr 1;67(2-3):237-45. Ed: No one has studied whether vitamin D helps adults with schizophrenia.  While I would not expect these huge benefits, I personally think vitamin D supplementation is a very good idea.  In any case, developing diabetes was 700% more common in schizophrenic patients on medication in one study and vitamin D helps prevent diabetes. (VA study, 2004, 4.4% annual rate vs. 0.63% in normal population.)

Vitamin D: Schizophrenia May be Increased with Vitamin D Deficiency in Infancy: People who develop schizophrenia in Europe and North America are more likely to be born in the spring, according to an article in the New Scientist. They are also roughly four times as likely to be born to Afro-Caribbean immigrants living in England as they are to have parents of other ethnic origins living in the same areas. Australian psychiatrist John McGrath found adult rats deprived of vitamin D from conception are more startled than normal by a loud noise preceded by a soft noise. He also found ventricles in the brains of vitamin-deprived baby rats are also unusually large, a feature seen in people with schizophrenia. A U.S. survey suggests serious vitamin D deficiency affects 12% of women of childbearing age. BBC News 2/7/02.

Vitamin D: Mothers Tended to be Deficient in Vitamin D During Pregnancy: There was no statistically significant difference in levels using banked sera in third trimester maternal vitamin D in a very small sample of 26 cases and 51 controls. However, within the subgroup of Afro-Australian individuals (n = 21), there was a trend level difference in the predicted direction, i.e., lower vitamin D, more schizophrenia in the children after they grew up. Low maternal vitamin D as a risk factor for schizophrenia: a pilot study using banked sera. McGrath J, Eyles D, Mowry B, Yolken R, Buka S. Schizophr Res. 2003 Sep 1;63(1-2):73-8

Vitamin D: In Utero or Infant Vitamin D Deficiency Affects Adult Brain in Rats: The brains of newborn rats from Vitamin D(3) deficient dams are larger than controls, have increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The brains of adult rats at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). Developmental Vitamin D(3) deficiency alters the adult rat brain. Feron F, Burne TH, et al. Griffith University, Brisbane, Australia. Brain Res Bull. 2005 Mar 15;65(2):141-8.

Vitamin D or K: Osteoporosis More Common in Small Study: Decrease in bone mineral density may lead to osteopenia or osteoporosis. In premenopausal patients with schizophrenia it may be attributed to medication-related hyperprolactinemia and hypogonadism, low physical activity, smoking, dietary deficiencies, low exposure to sunshine and polydipsia. Bone mineral density is 60 schizophrenic patients (risperidone 26, olanzapine 34) and 38 healthy volunteers found 38% patients (28.3% had osteopenia i 9.4% osteoporosis) vs. 16% controls (13.2% osteopenia i 2.6% osteoporosis) deficient. There was no difference between groups treated with risperidone or olanzapine. Hyperprolactinemia was established in 92% patients treated with risperidone and in 76% patients treated with olanzapine and in 3% subjects of the control group. Decrease in mineral bone density in schizophrenic patients treated with 2nd generation antipsychotics. Wyszogrodzka-Kucharska A, et al. Lodzi. Psychiatric Pol 2005 Nov-Dec;39(6):1173-84. Ed Vitamin K ($2/mo) is very good for treating osteoporosis. Fractures were increased only 20% with anti-psychotics in a nationwide Danish study of 125,000 fractures and 375,000 controls. Osteoporosis Int 2006 Mar 7. For anti-depressants, it was 15%. In 8 studies on bone mineral density in males with schizophrenia (2 case reports, 3 controlled studies), patients had significantly lower BMD than nonschizophrenic controls or population norms, with osteopenia ranging from 40-72%. Ann Clin Psychiatry 2006 Jan-Mar;18(1):43-8.

Vitamins: Megavitamin and RAST Diet No Help: DB 5 month trial, experimental group received amounts of megavitamins based on their individual serum vitamin levels plus dietary restriction based on Radioallergosorbent (RAST) tests. Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial. Vaughan K, McConaghy N. Aust N Z J Psychiatry 1999 Feb;33(1):84-8