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  • A new study has investigated the effects of vitamin D supplementation on depression.
  • The researchers found that vitamin D supplements have a small to moderate effect on depressive symptoms in adults.
  • The findings indicate that further research is needed to investigate the effects of combining vitamin D with standard treatments for depression.

According to the World Health Organization (WHO), around 5% of adults around the world live with depression.

While there is no available cure for depression, symptoms are often manageable through treatments including psychotherapy and prescription antidepressants.

Prior research has explored the causal relationships between vitamin D, inflammation, and depression. For instance, a 2013 study linked low levels of vitamin D to depression. Another study from 2011 suggested that vitamin D levels may help regulate inflammation, which is linked to depression.

Until now, however, systematic reviews and meta-analyses investigating the link between vitamin D levels and depression have delivered mixed results.

But a new study has systematically reviewed and meta-analyzed randomized controlled trials (RCT) that examined the efficacy of vitamin D supplements in reducing depressive symptoms compared to a placebo.

The researchers found that vitamin D supplementation equal to or exceeding 2,000 individual units (IUs) per day may help reduce depressive symptoms, although they noted their results have “very low certainty.”

The study was recently published in Critical Reviews in Food Science and Nutrition.

For the study, the researchers examined 41 RCTs including 53, 235 people in their analysis. They looked at data including age, vitamin D levels at baseline and post-treatment, and data on depressive symptoms.

They also included details of vitamin D supplementation, including:

  • duration
  • dose
  • type
  • frequency
  • possible calcium supplementation or add-on medications

Overall, the researchers found that vitamin D supplementation had a small to moderate effect on depressive symptoms.

Effect sizes were slightly larger among people with baseline vitamin D levels below 50 nanomoles per liter (nmol/L) — the borderline for low vitamin D levels — than those with vitamin D levels above this threshold at baseline.

The researchers also noted that while doses up to 2,000 IU daily had a small to moderate effect, those who took over 4,000 IU daily had a larger effect.

What’s more, vitamin D supplementation appeared to have a larger effect when taken for less than 12 weeks compared to longer periods of time.

The researchers noted that vitamin D supplementation had an overall positive effect on the 1,116 subjects diagnosed with major depressive disorder (MDD), also known as clinical depression.

Vitamin D supplements also had a positive effect on depressive symptoms among 407 people with perinatal depression.

The researchers further found that patients who used antidepressants alongside vitamin D supplements experienced small yet statistically significant positive effects.

However, they found placebo was slightly more beneficial than vitamin D supplements in a subgroup of healthy individuals without a diagnosis of clinical depression.

They noted this could be because a reduction in depression symptoms was more challenging to detect when the baseline symptoms levels were already very low in this subgroup.

Vitamin D supplements also had no significant effect on seasonal affective disorder (SAD) among a subgroup of three studies and did not seem to affect depressive symptoms in older adults.

The researchers also acknowledged that their results carry a “very low certainty,” as 36.6% of studies had a high risk of bias, and overall results were very diverse.

When asked how vitamin D supplementation may be linked to inflammation and depression, Dr. Monique Aucoin, ND, MSc, naturopathic doctor and senior research fellow at the Canadian College of Naturopathic Medicine, not involved in the study, told Medical News Today:

“The exact mechanism of how vitamin D impacts the brain and mental health is not entirely clear. There is evidence that vitamin D may modulate, or balance, parts of the immune system that are involved in inflammation.”

Dr. Aucoin added that an emerging body of evidence suggests that mental health disorders may be related to increased inflammation in the body and that a reduction of inflammation levels may have a therapeutic benefit.

“A 2019 meta-analysis, which combined the results of studies providing vitamin D supplements to participants with depression, reported significant decreases in several laboratory values related to inflammation. However, it is unclear if these changes were responsible for an antidepressant effect or were simply other benefits that occurred at the same time.”

– Dr. Monique Aucoin, ND, MSc, naturopathic doctor and senior research fellow at the Canadian College of Naturopathic Medicine

Tuomas Mikola, a doctoral researcher at the Institute of Clinical Medicine at the University of Eastern Finland and lead author of the study, explained to MNT:

“Depression has been associated with low-grade inflammation in the form of elevated cytokine levels. The body’s innate and adaptive immune responses have been shown to be partially dependent on circulating vitamin D levels. Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA axis) and hypersecretion of the stress hormone cortisol are common physiological abnormalities in patients with depression. Vitamin D may regulate the secretion of cytokines in the immune system and normalize the secretion of cortisol.”

The researchers concluded that further studies should investigate the possible benefits of augmenting standard treatment options for depression with vitamin D supplements.

When asked about the study’s limitations, Dr. Aucoin said that one limitation of the new research is that among the studies with a low risk of bias, no antidepressant effect was observed.

“While these studies make up a small sub-section of the research, it suggests that more high quality studies are needed before clinical recommendations can be made,” she noted.

“The authors of this meta-analysis looked at the data in many different ways to identify which factors (like participant diagnosis, vitamin D status, or vitamin D dosage) impacted the results. However, because most of the studies had unique combinations of these different factors, it was very hard for the researchers to clearly pinpoint who is most likely to benefit or which dose of vitamin D treatment might be most effective.”

According to Dr. Mikola, another limitation of the new research is that their meta-analyses “focused on change in depressive symptom scores rather than examining the associations between serum vitamin D levels and depressive symptoms.”

“A certain dosage of vitamin D may not increase the circulating concentrations of vitamin D similarly in all participants in heterogeneous populations.”

– Dr. Tuomas Mikola, doctoral researcher at the Institute of Clinical Medicine at the University of Eastern Finland, and lead author of the study

When asked whether vitamin D supplementation could be used alongside other treatments for depression or as an alternative, Dr. Aucoin noted that it is hard to draw any conclusions due to a lack of current research available.

She added, however, that “there are no concerns about providing a vitamin D supplement to a person who is also receiving other treatments for depression.”

“In this new meta-analysis, I was surprised to see a smaller antidepressant effect from vitamin D supplementation in studies where participants were also taking antidepressants. However, as the authors suggest, this is likely due to other characteristics of the participants in those studies.”