No role for vitamin D supplementation in late-life depression

Vitamin D₃ supplementation does not reduce the risk of late-life depression, according to the results of the VITAL-DEP* study.

“There was no significant benefit from the supplement for this purpose. It did not prevent depression or improve mood,” said Dr Olivia Okereke from Massachusetts General Hospital, Boston, Massachusetts, US.

The study population comprised 18,353 individuals aged ≥50 years (mean age 67.5 years, 49.2 percent female) without clinically relevant symptoms of depression. Of these, 16,657 were at risk for incident depression (no history of depression) and 1,696 at risk for recurrent depression (history of depression but untreated in the past 2 years). They were randomized 1:1 to receive vitamin D₃ (2000 IU/day of cholecalciferol) and fish oil (1 g/day capsule containing 840 mg omega-3 fatty acids) or placebo and were treated for a median 5.3 years. Mean 25-hydroxyvitamin D level was 31.1 ng/mL, with 11.6 percent of the participants having levels <20 mg/mL. Treatment adherence was high at ≥90 percent in both groups.

The risk of depression or clinically relevant depressive symptoms (incident and recurrent cases) did not significantly differ between vitamin D₃ and placebo recipients (n=609 vs 625; 12.9 vs 13.3 per 1,000 person-years; hazard ratio [HR], 0.97, 95 percent confidence interval [CI], 0.87–1.09; p=0.62). [JAMA 2020;324:471-480]

The between-group findings were consistent when the outcomes were assessed separately (incident depression: HR, 0.99; recurrent depression: HR, 0.95).

Change in mood score, assessed using the 8-item Patient Health Questionnaire depression scale (PHQ-8), also did not significantly differ between groups (mean difference, 0.01 points**, 95 percent CI, -0.04 to 0.05 points).

“Depression is often undertreated in older persons, who frequently experience residual symptoms even with treatment. Thus, late-life depression prevention is a public health priority,” said the authors.

“[However,] the findings [from this study] do not support a role for supplemental vitamin D₃ in depression prevention among adults,” they said, noting that the findings conflict with those from observational studies which suggested a potential benefit.

“It’s not time to throw out your vitamin D yet though, at least not without your doctor’s advice,” said Okereke.

“Vitamin D is known to be essential for bone and metabolic health, but randomized trials have cast doubt on many of the other presumed benefits,” added senior author Professor JoAnn Manson from Brigham and Women’s Hospital, Boston, Massachusetts, US.

The authors noted that serum 25-hydroxyvitamin D levels were adequate at baseline. “[As such,] the ability to observe effects of vitamin D₃ supplementation may have been attenuated,” they said. Larger studies using higher doses of vitamin D₃ for longer periods may be necessary to establish the effects of supplementation in individuals with vitamin D₃ deficiency.