Depression is tricky to treat because many patients do not respond to antidepressant medications. A growing body of evidence suggests that zinc deficiency may be a factor underlying depression in some cases—and zinc supplements can be an effective treatment for people whose levels are low.

A meta-analysis published in December 2013 in Biological Psychiatry analyzed 17 studies and found that depressed people tended to have about 14 percent less zinc in their blood than most people do on average, and the deficiency was greater among those with more severe depression. In the brain, zinc is concentrated in glutamatergic neurons, which increase brain activity and play a role in neuroplasticity, explains one of the paper's co-authors, Krista L. Lanctôt, a professor of psychiatry and pharmacology at the University of Toronto. “Those neurons feed into the mood and cognition circuitry,” she says.

Newer results increasingly point to a causal relation. Last September researchers at the University of Newcastle in Australia reported findings of two longitudinal studies that demonstrated an inverse relation between depression risk and dietary zinc intake. After adjusting for all known potential confounders, they found that the odds of developing depression among men and women with the highest zinc intake was about 30 to 50 percent lower than those with the lowest intake. Although previous studies have shown that zinc supplementation can augment the effects of antidepressant medications, research published in May in Nutritional Neuroscience is the first to investigate the effects of zinc alone on depressive symptoms. In the double-blind, randomized, placebo-controlled trial, researchers assigned participants to one of two groups: every day for 12 weeks, one group received 30 milligrams of zinc; the other group received a placebo. At the end of the study period, the zinc group showed a steeper decline in its scores on a rigorous inventory of depression symptoms.

“The future treatment of depression is zinc sulfate,” says Atish Prakash, a postdoctoral fellow in the department of pharmacy at the MARA University of Technology in Malaysia, who co-authored a thorough review of studies on the role of zinc in brain disorders, published in April in Fundamental and Clinical Pharmacology. Researchers strongly caution against people trying zinc supplements on their own, however—when levels are too high, zinc can cause other complications. Working with a doctor is essential, and in most cases, eating a healthier diet is probably a better way to ensure optimal zinc levels than supplementation. Yet for those with depression who are also at high risk for zinc deficiency, including vegetarians, people with alcoholism, gastrointestinal issues or diabetes, and pregnant or lactating women, zinc may be just what the doctor ordered.