August 07, 2020
Among adults aged 50 years or older who were without clinically relevant depressive symptoms at baseline, vitamin D3 supplementation taken over 5 years did not reduce the risk for depression or make a difference in the quality of mood.
"The study is among the largest of its kind ever, and it was able to address whether vitamin D3 supplementation is useful for what we call 'universal prevention' of depression," Olivia Okereke, MD, Massachusetts General Hospital, Boston, told Medscape Medical News.
"These results tell us that there is no benefit to using vitamin D3 supplements for the sole purpose of preventing depression in the general population of middle-aged and older adults," said Okereke.
"Because of the high dose and long duration of treatment and the randomized placebo-controlled design, we can have high confidence in results," she added.
The study was published online August 4 in JAMA.
The VITAL-DEP Trial
The findings are based on 18,353 older adults (mean age, 67.5 years; 49% women) in the VITAL-DEP study; 16,657 were at risk for incident depression (ie, had no history of depression), and 1696 were at risk for recurrent depression (ie, had a history of depression but had not undergone treatment for depression within the past 2 years).
Roughly half were randomly allocated to receive vitamin D3 (2000 IU/d of cholecalciferol) and half to receive matching placebo for a median of 5.3 years. The participants' mean level of 25-hydroxyvitamin D was 31.1 ng/mL; for about 12%, levels were lower than 20 ng/mL.
The risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the vitamin D3 group (609 depression or clinically relevant depressive symptom events; 12.9/1000 person-years) and the placebo group (625 depression or clinically relevant depressive symptom events; 13.3/1000 person-years). The hazard ratio was 0.97 (95% CI, 0.87 – 1.09; P = .62).
"Cumulative incidence curves showed lack of separation between treatment groups over the entire follow-up," the researchers report.
There was also no significant between-group difference in the other primary outcome -- the mean difference in mood scores on the eight-item Patient Health Questionnaire depression scale (PHQ-8).
The mean difference for change between treatment groups in PHQ-8 scores was not significantly different from 0 over the entire follow-up (0.01 points; 95% CI, -0.04 to 0.05 points) or at any point during follow-up.
To date, 13 randomized clinical trials have examined the effects of vitamin D3 supplementation on depression or mood during middle age or in older adults, and all except one reported null findings, Okereke and colleagues note in their article.
The current study is the only one large enough to examine vitamin D3 supplementation for the universal prevention of depression, they point out.
Although the findings do not support vitamin D3 supplementation for depression prevention, Okereke told Medscape Medical News, "we cannot yet exclude the possibility of benefit of vitamin D3 for preventing depression among subgroups with certain health risk factors. We also know that vitamin D is essential for bone health, and this study does not tell us whether vitamin D3 is useful for prevention of other health outcomes."
VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pharmavite LLC donated the vitamin D3, matching placebos, and packaging in the form of calendar packs. Okereke reported receiving royalties from Springer Publishing for a book on the prevention of late-life depression.