Sunshine in a bottle: trial illustrates vitamin D’s benefits for depression

Now that shorter days are here (at least in the UK), many of us will be taking additional vitamin D until sunny days return. Vitamin D, which our bodies create upon exposure to sunlight, is important for both our bones and maintaining a healthy immune system.

Recently, though, research has extended our understanding of this vitamin's potential benefits. Work has linked a deficiency in this vitamin with an increased risk of developing Major Depressive Disorder (MDD), and some studies have suggested that supplements may help reduce symptoms.

There has been a lack of gold-standard randomised controlled trials to investigate the effects of supplements on patients over time, however. But in a new paper in Psychological Medicine, Wenming Zhao Anhui Medical University, China, and colleagues report just such a study.

The participants consisted of 46 patients with MDD, plus healthy controls. At the start of the study, they gave blood samples for vitamin D analysis, completed questionnaires that assessed the severity of their depression and anxiety symptoms, and had their brains scanned using fMRI.

The patients were then randomised to take their regular anti-depressant medication plus either a daily dose of 1600 IU (40 mcg) of vitamin D3 (the type of vitamin D that's found in oily fish, and that we make in our skin) or a placebo that looked just like the vitamin tablet and was in the same packaging. After seven months, the two patient groups went back to the lab to repeat the tests and evaluations.

The results showed that levels of anxiety and depression symptoms in both patient groups improved. However, the team also found that among those in the vitamin group, patients whose blood contained higher levels of the vitamin at the seven-month follow-up point had a bigger improvement in clinical symptoms. The varying blood levels of the vitamin between patients taking the supplement could have been down to differences in diet, sun exposure or genetics, for example.

The brain imaging data also revealed some key differences between the two groups. Over the seven-month period, the patients who had been given the placebo experienced a reduction in white matter 'wiring' between brain regions in the right frontoparietal and medial visual networks. The patients who had taken vitamin D did not.

The frontoparietal network is known to play a central role in mental health, the team writes, while the medial visual network detects and processing visual stimuli. Earlier research has found abnormal connectivity between these two regions in patients with MDD, they add. The absence of these changes in the vitamin D group suggests that the vitamin supplement protected against this deterioration.

There is evidence from other studies that vitamin D can affect the brain in various ways — by reducing inflammation in the brain itself, for example, and affecting the regulation of neurotrophic growth factors, which promote the growth of new brain cells.

Vitamin D deficiency is common in many countries, including China and the UK. The team doesn't report on whether any of the patients with depression had a deficiency at the start of the study, so it's impossible to know whether patients with an initial deficiency might benefit more than others. However, exactly what blood level of vitamin D is ideal for immune and brain health, rather than bone health, is still being debated.

There are, in fact, still plenty of unanswered questions in this field, the team notes. Their study was small, and they would like to see it repeated with a larger group, as well as with patients who have been newly diagnosed with MDD, and who, as well as a vitamin D supplement, are also taking an anti-depressant drug for the first time.

Their finding that vitamin D seems to be neuroprotective in people with MDD should be taken as preliminary, they write. But it does add to a growing body of work suggesting that levels of this vitamin, and perhaps also some other micronutrients, can play a role in depression.

Read the paper in full:
Zhao, W., Zhu, D., Shen, Y., Zhang, Y., Chen, T., Cai, H., Zhu, J., Yu, Y. (2024). The protective effect of vitamin D supplementation as adjunctive therapy to antidepressants on brain structural and functional connectivity of patients with major depressive disorder: a randomized controlled trial. Psychological Medicine, 54(10), 2403–2413. doi:10.1017/S0033291724000539

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