Vitamin D Deficiency Linked to Schizophrenia

Deborah Brauser

July 29, 2014

Vitamin D deficiency has been linked to an increased risk for schizophrenia, new research shows.

Dr. Ahmad Esmaillzadeh

A review of 19 studies, which included more than 2800 participants, showed that those with vitamin D deficiency were more than twice as likely to be diagnosed with schizophrenia compared with their counterparts who were not vitamin D deficient.

In addition, 65% of the patients who had schizophrenia also had lower levels of vitamin D.

Coinvestigator Ahmad Esmaillzadeh, PhD, associate professor in the Department of Community Nutrition in the School of Nutrition and Food Science at the Isfahan University of Medical Sciences in Iran, told Medscape Medical News that although lower levels of serum vitamin D were expected in these patients because of earlier ecologic and epidemiologic studies, "we were surprised by the significant 2.16 times increased risk of schizophrenia in vitamin D deficient individuals. We did not expect such a significant increase," he added.

Dr. Esmailzadeh noted that the findings support the importance of vitamin D in brain function and psychological health.

"As vitamin D deficiency is a global issue, more attention should be drawn to assessment of serum vitamin D levels in order to screen and support individuals that are at higher risk of having deficiencies. Moreover, our findings might help psychiatrists in the healing process of patients with schizophrenia," he said.

"However, controlled clinical trials are needed to confirm the effects of vitamin D supplementation," he added.

The study was published online July 22 in the Journal of Clinical Endocrinology and Metabolism.

Global Issue

Dr. Esmailladeh noted that vitamin D deficiency is "relatively prevalent" globally and is associated with several disorders. For instance, previous studies have reported a link between these lower levels and depression.

"We were interested in the role of vitamin D in psychiatric health and, due to conflicting data on the association between serum levels of vitamin D and schizophrenia and no comprehensive meta-analysis in this regard, we aimed to conduct this study," he added.

The investigators examined data from 19 studies, published between 1988 and 2013, that assessed serum vitamin D levels in adult patients with schizophrenia. They then conducted 3 separate meta-analyses.

The number of patients in each study ranged from 17 to 848, for a total of 2804. In addition, 11 of the studies were conducted in European countries, and 8 were conducted in non-European countries.

The first meta-analysis included 13 of the studies and examined mean levels of 25-hydroxyvitamin D. The second included 8 studies and examined vitamin D deficiency prevalence; and the third included 8 studies and focused on odds ratios.

Some of the studies were included in overlapping meta-analyses.

First Meta-analysis

Results from the first meta-analysis showed an overall mean difference in serum 25-hydroxyvitamin D levels of -5.91 ng/ML in patients with schizophrenia vs those without (95% confidence interval [CI], -10.68 to -1.14).

Subgroup analyses also showed significant mean differences in levels between the 2 patient groups specifically in the studies that had a case-control design, included inpatients, and were conducted in either European or non-European countries.

However, the mean difference was no longer significant when examining just the studies that had a cross-sectional design and/or included outpatients.

Interestingly, there was some degree of heterogeneity between studies that assessed 25-hydroxyvitamin D vs 25-dihydroxyvitamn D3 biomarkers.

Still, "findings from the sensitivity analysis revealed that none of the studies significantly influenced the overall effect," write the researchers.

In the second meta-analysis, the investigators found that those with schizophrenia had a 65.3% overall prevalence of vitamin D deficiency (95% CI, 46.4% - 84.2%).

The third meta-analysis showed that the participants who were vitamin D deficient were 2.16 times more likely to also have schizophrenia than their counterparts who were not vitamin D deficient (95% CI, 1.32 - 3.56).

"Based on the findings, we found a strong association between vitamin D deficiency and schizophrenia," write the researchers.

"More research is [now] needed to determine how the growing problem of vitamin D deficiency may be affecting our overall health," added Dr. Esmaillzadeh in a release.

Suspicions Confirmed

"For the most part, this confirms what we've long been expecting, based on all of the other epidemiologic data out there," Michael F. Holick, MD, PhD, from the Department of Medicine; the Section of Endocrinology, Nutrition, and Diabetes; and the Vitamin D, Skin, and Bone Research Laboratory at Boston University Medical Center in Massachusetts, told Medscape Medical News.

Dr. Michael Holick

The investigators "took into account sunlight exposure and a whole variety of variables and concluded that schizophrenic patients are more likely to be vitamin D deficient. And that is consistent with the concept that vitamin D deficiency is associated with increased risk for schizophrenia," said Dr. Holick, who was not involved with this research.

He noted that approximately 30% of children and adults around the world are vitamin D deficient ― and 60% are deficient or insufficient.

"So we recommend vitamin D supplementation across the board. The Endocrine Society recommends for children 1 year and older, 600 to 1000 units a day; for adults, 800 to 2000 units a day; and for people who are overweight or obese, they need 2 to 3 times more to both treat and satisfy their deficiency," he said.

Dr. Holick noted that both the Institute of Medicine and the Endocrine Society do not have specific recommendations for this type of supplementation in pregnant women. However, he recommends 2000 units per day along with other dietary sources of vitamin D, such as milk, and normal prenatal vitamins.

"We know from a study recently done in South Carolina that pregnant women taking 4000 units of vitamin D a day had robust, healthy levels of 25-hydroxyvitamin D and no untoward toxicity. So 4000 units were easily tolerated and may be preferred by pregnant women," he said.

He added that although it may not be possible to prevent schizophrenia, there is hope to decrease the risk for the disorder.

"The [current] investigators conclude, which is consistent with a lot of literature, that there is a 2-fold higher risk of having schizophrenia based on being vitamin D deficient. And I think that is the major message," he said.

"Vitamin D deficiency is extremely common in this population. Therefore, physicians caring for these patients should be aggressive in treating the deficiency, and then they may actually improve how [patients] respond to their medication, making them feel better as their mood improves, all for the benefit of their mental health."

The study authors and Dr. Holick have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online July 22, 2014. Full text

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