Does Vitamin D Really Affect Depression?

Does Vitamin D Really Affect Depression?

Depression has been identified as a leading cause of disease worldwide, affecting 280 million people per year. Currently, antidepressant medication is readily prescribed despite the potential side effects and hazards. More recently there has been increased public and clinical interest in lifestyle factors affecting depressive symptoms, such as for example the role of vitamin D deficiency in depression. This article will discuss the roles of vitamin D in body and brain, compare different sources of vitamin D and their effectiveness, and summarize the currently available clinical data on vitamin D and depression.

Vitamin D is well-known for its role in maintaining bone health but also plays a very important part in immune and nervous system function. With its role in calcium and phosphate homeostasis, vitamin D is an important contributor to skeletal health and hence prevention of diseases such as osteoporosis. Furthermore, vitamin D also regulates both adaptive and innate immune responses by acting as both a transcription and growth factor. Due to the well-studied association between low-grade chronic inflammation and depression, this may be an underlying mechanism in which vitamin D could reduce depressive symptoms. Furthermore, the active form of vitamin D has been shown to enhance integrity of the intestinal epithelium, thus also modulating the gut-based immune system. Vitamin D receptors in the intestinal epithelium further control mucosal inflammation and the composition of the gut microbiome. Disruptions to the gut-based immune system and the corresponding translocation of LPS into the circulation is a well-known cause of low-grade chronic inflammation and has been associated with depression in many different clinical studies.

In addition to its indirect effects on mood through its role in the body, vitamin D has been shown to directly affect the central nervous system as well, by acting as a neuroactive steroid. Vitamin D receptors have been discovered in the brain which suggests a potential pathway through which vitamin D may affect mood. Furthermore, vitamin D has been shown to affect the growth of new neurons, the secretion of serotonin and dopamine by neurons, and modulate synaptic plasticity in the brain. Though these findings sound promising, there is a definite need for deeper research into the underlying mechanisms through which vitamin D levels can affect mood and mental health.

With all the immunological and neurological benefits vitamin D may bring about, it is important to shift our discussion to talking about vitamin D sources as well. Vitamin D can either be obtained via the diet or via the production in the skin following sunlight exposure, particularly UVB radiation. Dietary sources of vitamin D are subdivided into plant and animal-derived foods, due to plant sources such as mushrooms, soy, and yeast providing vitamin D2 and animal-derived foods such as oily fish like salmon or mackerel, or eggs providing vitamin D3. It is important to note here that vitamin D3 is approximately three times stronger than vitamin D2, hence animal sources of dietary vitamin D3 may be more effective in raising blood levels. However, dietary sources in general contribute only a small fraction to the overall vitamin D3 metabolized in the body. When Vitamin D is obtained through sun exposure, the sun’s UVB radiation stimulates vitamin D3 production in the skin from a molecule called 7-dehydrocholesterol. Still in its inactive form, vitamin D then undergoes two hydroxylation rounds, one in the liver and one in the kidney, to then become biologically active and exert its roles as discussed earlier. The last way in which vitamin D can be ingested is through the intake of supplements. Particularly vitamin D3 supplementation has been shown to be effective in improving mood in a variety of clinical studies.

Clinical research investigating the association between vitamin D and depression has demonstrated promising results regarding the role of vitamin D in depression treatment and prevention. A recent meta-analysis of 41 RCTs showed a positive effect of vitamin D on depressive symptoms. Several other systematic reviews and meta-analyses support the proposal that vitamin D supplementation can decrease symptoms of depression. On the other hand, meta-analyses from both longitudinal and cross-sectional studies have suggested an association between low levels of vitamin D and depressive symptoms, hence indicating a correlational relationship in addition to the causal relationship. Another recent review concludes that most clinical studies of vitamin D supplementation indicate a reduction of depressive symptoms as a result, with the need for further exploration of confounding factors such as age, sex, and symptom severity.

Overall, the literature of clinical studies conducted to this point suggests a promising therapeutic effect of vitamin D supplementation in depression and a potential preventive effect through the maintenance of healthy vitamin D levels. If supplements are to be taken, the recommended form of intake is vitamin D3 due to its enhanced effectiveness. Non-supplement sources of vitamin D include daily sun exposure (without sunscreen for a short amount of time to increase vitamin D production), as well as dietary sources of vitamin D in the form of D2 from plants or D3 from animals. Vitamin D has a variety of important roles in the body and brain in mediating immunity, bone health, and mental health and hence may be an important factor to consider for anyone looking to improve their overall health, happiness, and longevity.

Jill Horn is an international student from Switzerland on a pre-med track, currently majoring in Neuroscience at UCLA.