Low vitamin D levels have been linked to increased risk of onset of depression—but are there implications for treatment?

More than half of GPs are checking Vitamin D levels as a routine investigation in depression, a Healthed survey suggests. But how does the evidence stack up?

“Major depression remains this huge public health problem for which we have incomplete answers,” says psychiatrist Professor Malcolm Hopwood of the University of Melbourne, “and we know that borderline low Vitamin D levels seem to be very common, and seasonal.”

“The evidence linking low Vitamin D with a higher risk of the onset of depression has accumulated and is now relatively clear,” he confirms. He says the link seems to get stronger as vitamin D levels get lower as well.

In a recent Healthed survey, 54% of more than 1200 GPs who responded said they would mostly or always check vitamin D levels when ordering blood tests for a female patient who they suspect might have depression.

However, Professor Hopwood says the jump from identifying low vitamin D as a risk factor to supplementing as part of treatment is a leap too far.

“It leads to an obvious line of thinking about the role of Vitamin D supplementation in the treatment of major depression, and unfortunately that’s where the story gets more complicated,” he says.

Trials examining Vitamin D supplementation for treatment of major depression have quite mixed results.

“This partly reflects very divergent methodology and populations that they’ve been studying, and a lot of variation in the dose used, with most using relatively low dose,” Professor Hopwood says. “It’s not clear that Vitamin D supplementation is effective.”

He refers us to the results of the VITAL-DEP study published in JAMA in 2020 where over 18,000 patients were supplemented with Vitamin D3 over a 5 year period. “Unfortunately there was no impact on the reduction of subsequent depression,” he says.

“An investigation is arguably only helpful if it leads to an effective therapy, and at the minute that’s not conclusively so,” Professor Hopwood says.

“The Vitamin D story is typical of a few non-traditional therapy stories in depression, that there’s often a wave of enthusiasm, and it’s very important we actually get properly controlled evidence to say, as intuitive as this might seem, is there actually evidence that it really does help?”

While there is clear evidence that low serum Vitamin D levels increase the risk of major depression, Professor Hopwood reiterates that there remains no evidence that supplementation treats the condition or decreases the risk of it developing.

“We still have a cause and effect problem,” he explains. “Do people with depression spend less time outside? We know the answer is yes.”

Professor Hopwood acknowledges that Vitamin D levels obviously play a role in pathologies outside of depression, and that GPs may use a blood test at the time of diagnosis to look at a range of issues that may not all be directly linked to the mental health presentation. He wonders if this in part accounts for the large number of survey responses stating they would regularly check it as part of the workup.

Regardless, he says replacing Vitamin D is very unlikely to cause harm.