Longitudinal Studies

The authors indicated that there are few published longitudinal studies examining the association between vitamin D and depression. They cited three:

·         A six-year prospective study of 954 adults aged 65 or older, which reported that individuals with low 25(OH)D3 levels at baseline had significantly higher depression scores at the two follow-up periods (3 and 6 years), compared with those who had high levels at baseline.11

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·         A study of 1102 subjects with current depressive disorders, 790 with remitted depressive disorders, and 495 healthy controls found that in currently depressed subjects, 25(OH)D was inversely associated with symptom severity, suggesting a dose-response gradient. These patients had a higher risk of having a depressive disorder at 2-year follow-up.12

·         An observational study examined retrospective, cross-sectional, and prospective association between vitamin D concentration and depressed mood in a community sample of 2105 older men. Vitamin D concentration <50 nmol/L was associated with greater odds of current but not past depression. The researchers concluded that their results did not “support a role for vitamin D in the causation of depression,” although “a small antidepressant effect of vitamin D” could not be “entirely discarded.”13 

Randomized Controlled Trials (RCTs)

The authors noted that RCTs have “yielded inconsistent results.” They hypothesized that this might be due design limitations (eg, varying study criteria, sample size, age range of subjects, vitamin D dosage and method of administration, depression measures used, and the assessment of outcome.) The inconsistency makes it “difficult to generalize findings across studies.”

While most studies report on the effect of vitamin D supplementation, there has been a more recent focus on the potential role of vitamin D augmentation, the authors observed. They added that few studies “have examined for the multiple salient confounding factors that may create non-causal associations, while not all studies have limited intervention to those who are formally deficient or insufficient in vitamin D.”

The authors stated that several systematic reviews and meta-analyses suggest that vitamin D supplementation can benefit individuals with depression, but the benefit may or may not reflect the type and severity of the depression, whether vitamin D is prescribed alone or in conjunction with an antidepressant drug, and whether the benefit is restricted to those who were deficient in vitamin D prior to the intervention.