Vitamin D Supplementation Linked to Fewer Suicide Attempts

Oral vitamin D supplementation nearly halved the rates of suicide and intentional self-harm in a study of US veterans, with an even stronger effect among Black veterans.

The retrospective cohort study also showed that higher daily vitamin D supplement dosages appeared to offer greater protection against suicide and self-harm risk than lower doses, that the effect was greater among those with baseline vitamin D deficiency or insufficiency, and that both vitamin D2 (ergocalciferol) and D3 (cholecalciferol) supplements were effective.

"As a relatively safe, easily accessible, and affordable medication, supplementation with vitamin D in the [Veterans Administration] may hold promise if confirmed in clinical trials to prevent suicide attempts and suicide," write Jill E. Lavigne, PhD, and Jason B. Gibbons, PhD, in their study, published online February 1 in PLoS One.

Pending those confirmatory trials, they advise: "Providers may wish to initiate low-dose vitamin D supplementation, for example, at the US [recommended dietary allowance] level of 600 IU per day, without screening in patients with a history of suicidal behavior or ideation or who exhibit warning signs of suicidal behavior."

The US Preventive Services Task Force advises against routine vitamin D screening, and in a review of 11 trials found no differences in mortality with vitamin D supplementation, nor in incident depression in different populations.

However, "the subjects in those studies had adequate levels of vitamin D, so they didn't have insufficiency. That was a big limitation and why there's been this call for further research. Our paper uses real-world data," Lavigne of the VA Center of Excellence for Suicide Prevention, Canandaigua, New York, told Medscape Medical News.

A Third of Military Members Are Vitamin D Deficient

Approximately a third of US military members have been shown to have 25-hydroxyvitamin D [25(OH)D] levels below 20 ng/mL, considered deficient.

Vitamin D deficiency is particularly common among males and among darker-skinned people. At the same time, servicemembers and veterans also have elevated suicide attempts and suicide rates, Lavigne and Gibbons note in their article.

Gibbons, a postdoctoral student in the Department of Health Policy & Management, Johns Hopkins University, Baltimore, Maryland, told Medscape Medical News: "There has been at least some indication around vitamin D as a potential supplement for depression and that those who are more severely depressed had greater benefits. So, it's possible that some of what we're seeing with these large effects is somewhat conditional on this being a more severely depressed population at baseline."

Asked to comment, Michael F. Holick, MD, PhD, professor of medicine, Boston University Chobanian & Avedisian School of Medicine, Massachusetts, told Medscape Medical News: "In my opinion, this is an incredibly important publication for a variety of reasons. For one, it's such a huge number."

Holick noted that there has been controversy in the literature as to whether vitamin D2 (ergocalciferol) is as effective as D3 (cholecalciferol), but that this study backs up his previous work showing that they have equal activity. "This now also demonstrates that Vitamin D2 is as effective as Vitamin D3 in this case of reducing risk of suicide."

Moreover, Holick said, "When you look at the plots showing the suicide rate versus controls, it's dramatic...an almost 50% reduced risk...This study is very powerful."

Suicide Attempt Rate With Vitamin D Versus Controls Is "Dramatic"

Using electronic health data, Lavigne and Gibbons conducted their retrospective cohort study of 1.3 million US veterans in 2010-2018. About 490,885 veterans who received vitamin D3 (cholecalciferol) and 169,241 veterans who received vitamin D2 (ergocalciferol) were compared one-on-one with veterans of similar demographics and medical histories who didn't receive supplementation.

Unadjusted suicide attempt/intentional self-harm rates in the D2 sample were 0.27% for those treated versus 0.52% for those untreated. The corresponding percentages for D3 were 0.20% versus 0.36%, respectively.

Vitamin D2 supplementation was associated with a 48.8% reduction in suicide/self-harm risks, and vitamin D3 with a 44.8% reduction, both highly significant (P < .001). Those risk reductions were similar between men and women.

There was a difference by race, however. The effect of supplementation was greater among Black versus White veterans, with suicide/self-harm attempt risk reductions of 57.9% versus 46.3%, respectively, for vitamin D2 and 63.8% versus 38.7%, respectively, for vitamin D3.

And by baseline serum vitamin D levels, among those with deficiency (0-19 ng/mL) vitamin D3 was associated with a significant 64.1% reduction compared with untreated controls. Each additional percentage point increase in average daily dose was associated with a 13.8% greater risk reduction, which was also significant.

For veterans with baseline blood vitamin D levels of 20-39 ng/mL, while the overall association was not significant, vitamin D3 supplementation was associated with a significant 9.6% reduction in suicide attempt and self-harm risk for each additional percentage point increase in average daily dosage.

Among those with vitamin D sufficiency (≥ 40 ng/mL), there were no significant overall or dose–response associations with vitamin D2 or D3 and suicide/self-harm attempt risk.

This study was supported, in part, with resources from the Department of Veterans Affairs Center of Excellence for Suicide Prevention. Support for VA/CMS data was provided by the Department of Veterans Affairs, VA Health Services Research and Development Service, VA Information Resource Center awarded to Lavigne and Gibbons. Holick has received research grants from Carbogen and Solius, and is a consultant for Pulse and Solius.

PLoS One. Published online February 1, 2023. Full text

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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