I’ve Got Sunshine on a Cloudy Day: Can Low Vitamin D Contribute to Depression?

By Randall D. Ordovich-Clarkson, MD

“Martinique” (2013–2014), by Randall D. Ordovich-Clarkson, MD. Digital illustration created while attending medical school in the Caribbean. Looking back, the winding road and distant destination seem fitting for a research journey that would take nearly a decade to complete.

Today, I am excited to share that our systematic review, Hypovitaminosis D and Depression: A Systematic Review of Randomized Controlled Trials, has officially been published in the Galician Medical Journal.

This publication represents the culmination of a long journey. The original concept dates back to 2017, when I first became interested in the relationship between vitamin D deficiency and depression. Over the years, the manuscript evolved through multiple revisions, expanded literature searches, peer review, and several rounds of methodological refinement before finally reaching publication.

At its core, the question was deceptively simple: Can low vitamin D contribute to depression, and if so, can vitamin D supplementation help? The answer, as is often the case in medicine, is more nuanced than a simple yes or no.

Why Vitamin D?

Vitamin D is best known for its role in bone health and calcium balance, but researchers have become increasingly interested in its effects throughout the body—including the brain. Unlike many vitamins, vitamin D functions more like a hormone. After being synthesized in the skin following ultraviolet B (UVB) exposure, it undergoes activation in the liver and kidneys before exerting effects on numerous tissues. Researchers have identified vitamin D receptors (VDRs) throughout the central nervous system, including regions involved in mood regulation, cognition, and emotional processing.

Figure 1. Ultraviolet B (UVB) radiation converts 7-dehydrocholesterol in the skin into vitamin D, which undergoes activation in the liver and kidneys before influencing neuronal signaling, calcium homeostasis, immune function, and mood regulation (Ordovich-Clarkson et al., 2026)

Potential mechanisms by which vitamin D may influence mood include:

• Modulation of serotonin synthesis

• Regulation of inflammatory pathways

• Neuroprotective and neurotrophic effects

• Calcium signaling within neurons

• Interactions with the hypothalamic-pituitary-adrenal (HPA) axis

These observations have led many researchers to investigate whether vitamin D deficiency may contribute to depressive symptoms.

Who Is at Risk for Vitamin D Deficiency?

One of the more interesting aspects of vitamin D research is that deficiency risk is influenced by numerous biological, environmental, and lifestyle factors.

Skin Complexion	Individuals with higher melanin levels require 3-5 times more sunlight exposure to synthesize adequate vitamin D compared to those with lighter skin tones. Lighter-skinned individuals (e.g., Type 2) experience a significant increase in calcitriol with UVB exposure, whereas darker-skinned individuals (e.g., Type 5) may not achieve sufficient levels even with increased exposure (Clemens et al., 1982). Additionally, SPF 30 sunscreen can reduce vitamin D synthesis by over 95%, suggesting that sunscreen use may contribute to deficiency (Matsuoka et al., 1987).
Pregnancy Status	Maternal vitamin D levels are essential for fetal development, with deficiencies linked to conditions such as multiple sclerosis, cancer, diabetes, and schizophrenia later in life. Higher vitamin D levels are especially necessary during the third trimester, and supplementation has been associated with lower postpartum depression rates (Gur et al., 2014; Wacker & Holick, 2013; Miller et al., 2013). Prenatal screening and treatment for vitamin D deficiency are critical for maternal and fetal health.
Body Mass Index (BMI)	Obese individuals (BMI ≥ 30) exhibit 57% lower vitamin D3 levels following UV exposure compared to non-obese individuals (BMI ≤ 25), likely due to vitamin D sequestration in adipose tissue, which limits bioavailability from sunlight and dietary sources (Wortsman et al., 2000).
Gender	Women are more likely than men to experience both hypovitaminosis D and depression, potentially due to higher body fat percentages that reduce vitamin D bioavailability (Blaak, 2001). This association underscores the importance of monitoring vitamin D levels in female populations with depression.
Age	While major depressive disorder (MDD) is more common in younger adults (18-29 years), older adults often exhibit lower vitamin D levels, partly due to reduced cutaneous synthesis as they age (Hoogendijk et al., 2008). Addressing vitamin D needs in older adults may help reduce age-related health disparities linked to deficiency.
Geographic Location and Season	UVB exposure decreases with distance from the equator and during winter months, leading to seasonal vitamin D deficiencies in areas above or below 33° latitude (Wacker & Holick, 2013). In regions with limited sunlight, a vitamin D-rich diet can help compensate for reduced synthesis.
Urbanization	Urban areas with high air pollution are associated with elevated rates of both depression and vitamin D deficiency. For example, women in highly polluted areas exhibited greater vitamin D deficiencies compared to those in less polluted regions (Hosseinpanah et al., 2010; Wacker & Holick, 2013).
Smoking Status	Smoking has been correlated with both lower serum vitamin D3 levels and higher depression rates. Research suggests that smoking may impair vitamin D metabolism, potentially disrupting the vitamin D-PTH system and affecting vitamin D and calcium bioavailability (Boden et al., 2010).
Medications	Certain medications, such as phenytoin and rifampin, accelerate vitamin D breakdown by inducing CYP24 enzyme activity, which can contribute to deficiency-related conditions like osteomalacia. Prescribers should inform patients of potential vitamin D depletion when using these medications (Dhaliwal et al., 2022).

Figure 2. Multiple factors influence vitamin D status, including skin pigmentation, geographic location, season, obesity, age, pregnancy status, smoking, and certain medications.

Some of the most important risk factors include:

• Limited sun exposure

• Living at higher latitudes

• Increased skin pigmentation

• Obesity

• Advanced age

• Pregnancy

• Smoking

• Certain medications that alter vitamin D metabolism

These variables can complicate research findings because two individuals receiving identical supplementation may achieve very different blood vitamin D levels.

What Did We Find?

Our review examined randomized controlled trials published between 2014 and 2024 that investigated vitamin D supplementation and depressive symptoms. After screening studies from PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials, we identified:

• 11 randomized controlled trials

• 1,693 participants

• Diverse populations including older adults, pregnant and postpartum women, individuals with major depressive disorder, type 2 diabetes, ulcerative colitis, chronic kidney disease, and prediabetes

The results were mixed. Several studies reported improvements in depressive symptoms following vitamin D supplementation, particularly among individuals with documented vitamin D deficiency at baseline. However, not all studies demonstrated significant benefits. In some cases:

• Improvements occurred only within specific subgroups

• Depression scores improved without reaching statistical significance

• Baseline vitamin D levels appeared to influence outcomes

• Different dosing strategies produced similar results

Importantly, vitamin D supplementation consistently increased serum vitamin D levels, but the relationship between those increases and improvements in mood was not always straightforward.

A Conceptual Overview

During the writing process, I also experimented with visual summaries of the biological pathways being investigated.

Figure 3. Conceptual illustration of proposed biological pathways linking vitamin D metabolism to mood regulation and depressive symptoms. This figure is intended as a visual summary of themes discussed within the literature and does not imply causation.

What We Still Don’t Know

One of the most important conclusions from our review is that substantial uncertainty remains. Although vitamin D supplementation appears promising in some populations, several questions remain unanswered:

• Which patients benefit most?

• Does baseline vitamin D deficiency predict treatment response?

• What is the optimal dose?

• How long should supplementation continue?

• Are benefits direct, or mediated through broader improvements in health?

Future large-scale randomized trials will be needed to answer these questions.

Reflections on a Nine-Year Journey

This paper took nearly nine years from concept to publication! Looking back, I find it somewhat fitting that this project centered on sunlight. The illustration featured at the beginning of this article was created while I was living in the Caribbean during medical school, years before this paper would eventually be published. At the time, I could not have imagined how long the journey would be. Research rarely follows a straight path. There are setbacks, revisions, rejections, and periods where progress seems invisible. Yet meaningful projects often require persistence beyond what we initially expect.

I am deeply grateful to my co-authors, Daniel Lara and Sera Trapani, as well as Dr. Taras Kotyk and the editorial team at the Galician Medical Journal for helping bring this project to completion. The road was longer than anticipated, but the destination was worth reaching.

Read the Full Publication

Ordovich-Clarkson R, Lara D, Trapani S.Hypovitaminosis D and Depression: A Systematic Review of Randomized Controlled Trials.Galician Medical Journal. 2026.

Publication available at:https://ifnmujournal.com/gmj/article/view/e-GMJ2026-A12

Citations

Clemens, T. L., Henderson, S. L., Adams, J. S., & Holick, M. F. (1982). Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. The Lancet, 319(8263), 74–76. https://doi.org/10.1016/S0140-6736(82)90214-8

Gur, E. B., Gokduman, A., Turan, G. A., Tatar, S., Hepyilmaz, I., Zengin, E. B., Eskicioglu, F., & Guclu, S. (2014). Mid-pregnancy vitamin D levels and postpartum depression. European Journal of Obstetrics & Gynecology and Reproductive Biology, 179, 110–116. https://doi.org/10.1016/j.ejogrb.2014.05.017

Hoogendijk, W. J. G., Lips, P., Dik, M. G., Deeg, D. J. H., Beekman, A. T. F., & Penninx, B. W. J. H. (2008). Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Archives of General Psychiatry, 65(5), 508–512. https://doi.org/10.1001/archpsyc.65.5.508

Hosseinpanah, F., Pour, S. H., Heibatollahi, M., Moghbel, N., Asefzade, S., & Azizi, F. (2010). The effects of air pollution on vitamin D status in healthy women: A cross-sectional study. BMC Public Health, 10, 519. https://doi.org/10.1186/1471-2458-10-519

Matsuoka, L. Y., Ide, L., Wortsman, J., MacLaughlin, J. A., & Holick, M. F. (1987). Sunscreens suppress cutaneous vitamin D3 synthesis. The Journal of Clinical Endocrinology & Metabolism, 64(6), 1165–1168. https://doi.org/10.1210/jcem-64-6-1165

Miller, B. J., Murray, L., Beckmann, M. M., Kent, T., & Macfarlane, B. (2013). Dietary supplements for preventing postnatal depression. Cochrane Database of Systematic Reviews, 2013(10), CD009104. https://doi.org/10.1002/14651858.CD009104.pub2

Ordovich-Clarkson, R., Lara, D., & Trapani, S. (2026). Hypovitaminosis D and Depression: A Systematic Review of Randomized Controlled Trials. Galician Medical Journal, 33(2), e-GMJ2026-A12.

Wacker, M., & Holick, M. F. (2013). Sunlight and vitamin D. Dermato-Endocrinology, 5(1), 51–108. https://doi.org/10.4161/derm.24494

Wortsman, J., Matsuoka, L. Y., Chen, T. C., Lu, Z., & Holick, M. F. (2000). Decreased bioavailability of vitamin D in obesity. The American Journal of Clinical Nutrition, 72(3), 690–693. https://doi.org/10.1093/ajcn/72.3.690