Sunshine Connection: Exploring Vitamin D and Depression

21 Sep Sunshine Connection: Exploring Vitamin D and Depression

Over 10% of the population (21 million people in the US) struggle with Depression. This complex disease can be treatment resistant and it can significantly affect one’s quality of life. Depression is characterized by persistent feelings of sadness, a decline in interest in activities, fatigue, and cognitive problems. Research has connected depression to a number of causes, including metabolic abnormalities, environmental stressors, and genetic predispositions. The importance of evaluating Vitamin D levels in the work up for and treatment of depression is becoming well known. This blog will look into the mechanisms that support the correlation between depression and Vitamin D levels. We will also look at the impact of Vitamin D supplementation on symptoms of depression.

Vitamin D: Functions and Sources

Vitamin D is a critical fat-soluble vitamin that is essential for life. D3 is necessary for calcium absorption, bone health, hormones, nerve connections, brain function, mood and regulating the immune system. The two main forms of vitamin D are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol); D2 comes from plants, and D3 is produced in the skin by exposure to sunlight. After being produced in the skin or ingested through food, Vitamin D is transformed twice (by the liver and in the kidneys): in the liver, it becomes 25-hydroxyvitamin D [25(OH)D], and in the kidneys, it becomes calcitriol, which is the active form (Holick, 2007). 

Historically D3 has been appreciated for its roles in immune regulation and bone metabolism, however, recently Vitamin D has seen more attention as we have learned of its significance for brain function, hormone regulation and mood. Vitamin D receptors (VDRs) and the enzyme that activates vitamin D, are found in many brain regions, including those associated with mood regulation; this suggests that vitamin D may have an effect on mental health (Eyles et al., 2013).

The Relationship between Vitamin D and Depression

Over the last ten years, research has shown a correlation between low vitamin D levels and higher incidence of depression. Anglin et al. (2013) conducted a meta-analysis which demonstrated that there was a statistically significant increase in the risk of depression among those with low serum levels of vitamin D as opposed to those with appropriate levels. Ju et al. (2013) conducted another meta-analysis that provided additional evidence for this link, demonstrating that a vitamin D deficiency is consistently linked to an increased risk of depressive symptoms.

Seasonal Affective illness (SAD) is a mood disorder that is associated with vitamin D deficiency. “SAD” develops during the winter months when sunshine exposure is reduced. This has led researchers to hypothesize that inadequate sunlight, and subsequently low vitamin D levels, may play a role in the onset of depressive episodes (Melrose, 2015).

Mechanisms Linking Vitamin D to Depression

Although the exact mechanisms through which vitamin D influences depression remain unclear, several hypotheses have been proposed based on existing research:

1. Serotonin Production and Regulation
   The synthesis of serotonin, a neurotransmitter involved in mood stabilization, is in part regulated by vitamin D. Patrick and Ames (2014) state that the enzyme tryptophan hydroxylase, (which turns tryptophan into serotonin), is encoded by a gene that is activated by vitamin D. Vitamin D deficiency may hinder serotonin production, aggravating depressed symptoms since low serotonin levels have been intimately associated with depression.
2. Neuroinflammation and Oxidative Stress
   Chronic inflammation and oxidative stress have been implicated in the pathogenesis of depression. Vitamin D has anti-inflammatory properties and has been shown to reduce levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) (Bertone-Johnson, (2009). Reducing neuroinflammation may prevent neuronal damage and improve brain function, thereby lowering the risk of depression.
3. Hypothalamic-Pituitary-Adrenal (HPA) Axis Regulation
   The HPA axis regulates the body’s reaction to stress, and disruption of this axis is frequently observed in depressed people. Research indicates that vitamin D could influence the HPA axis’s activity, which would assist control cortisol levels and stress reactions. Low levels of vitamin D may cause the HPA axis to become hyperactive, which can make people more vulnerable to depression brought on by stress (Spedding, 2014). 
4. Neurogenesis and Brain Plasticity
   Recent research indicates that vitamin D may improve neurogenesis, or the brain’s process of producing new neurons.  This “neurotrophic” support is particularly significant in the hippocampus because this part of the brain is essential for memory and emotion control. Depression has been linked to impaired neurogenesis and brain atrophy. Improving neurotrophic support by consuming/providing enough vitamin D, helps to support brain function and may reduce symptoms of depression (Bivona et al., 2019).
   

Vitamin D Deficiency and Depression Risk

One billion individuals globally are thought to have suboptimal levels of vitamin D, making it a global health concern (Holick, 2007). Factors that contribute to deficiency include inadequate sun exposure, darker skin pigmentation, living at higher latitudes, advanced age, obesity, genetic SNPs that effect absorption and certain medical conditions like malabsorption syndromes.

Numerous studies have demonstrated the connection between depression and low vitamin D levels. According to Hoang et al. (2011), women who had low serum levels of D 25(OH) were more likely to have symptoms of depression than those who had sufficient D3. Similarly, a comprehensive review conducted in 2014 by Black et al. found a consistent link between vitamin D insufficiency and an increased risk of depression, especially in older people. 

Individuals with depression may have lifestyles factors that contribute to low Vitamin D. When people are depressed they may isolate and limit outdoor activities, additionally, with depression often appetite is suppressed and patients may not get enough D3 from food sources. 

Vitamin D Supplementation for Depression

Scholars have investigated the effectiveness of vitamin D supplementation as a therapeutic intervention for depression. Randomized controlled trials (RCTs) have yielded inconsistent results, with some demonstrating improvements in mood and others finding no discernible effects. It is suggested that the positive effects of supplementation are greater appreciated in those with significant deficiency.

Vitamin D supplementation dramatically enhanced mood in people with low baseline levels of vitamin D, according to a study by Jorde et al. (2008). Similar findings were made by Parker et al. (2017), who showed that vitamin D deficiency was linked to a decrease in depressive symptoms in people with major depressive disorder (MDD).

Clinical Implications

The relationship between vitamin D and depression underscores the importance of assessing vitamin D status in patients with depression. D3 Supplementation is an inexpensive and low-risk intervention with many health benefits and the potential to improve mood and general well-being.

The National Institutes of Health (NIH) recommends 600 to 800 IU of vitamin D per day for most adults, although the recommended amount varies depending on age and absorption. Higher doses are often required when correcting D3 deficiency, but high doses should be given under medical supervision as repeat levels/labs should be checked to assess for and prevent toxicity.

Vitamin D has a significant impact on mental and brain health. There is strong evidence that depression is associated with vitamin D deficiency. Evaluating for, and treating Vitamin D deficiency provides many health benefits; and it can be a tool and component in the complex treatment of depression. Understanding the importance of nutrients like vitamin D may lead to new approaches to therapy and prevention as we continue to investigate the complex causes of depression.

References

Anglin, R. E. S., Samaan, Z., Walter, S. D., & McDonald, S. D. (2013). Vitamin D deficiency and depression in adults: Systematic review and meta-analysis. The British Journal of Psychiatry, 202(2), 100-107.

Bertone-Johnson, E. R. (2009). Vitamin D and the occurrence of depression: Causal association or circumstantial evidence? Nutrition Reviews, 67(8), 481-492.

Bivona, G., Agnello, L., & Ciaccio, M. (2019). The immunological implication of the new vitamin D pathway in the pathophysiology of autoimmune diseases. Annals of Clinical and Laboratory Science, 49(1), 8-16.

Eyles, D. W., Smith, S., Kinobe, R., Hewison, M., & McGrath, J. J. (2013). Distribution of the vitamin D receptor and 1α-hydroxylase in human brain. Journal of Chemical Neuroanatomy, 29(1), 21-30.

Holick, M. F., & Chen, T. C. (2008). Vitamin D deficiency: A worldwide problem with health consequences. The American Journal of Clinical Nutrition, 87(4), 1080S-1086S.

Hoang, M. T., Defina, L. F., Willis, B. L., Leonard, D. S., Weiner, M. F., & Brown, E. S. (2011). Association between low serum 25-hydroxyvitamin D and depression in a large sample of healthy adults: The Cooper Center Longitudinal Study. Mayo Clinic Proceedings, 86(11), 1050-1055.