Vitamin D and Immunity: What Research Shows

Medically Reviewed by Ian Nathan, MBChB, on 11th January 2026

Vitamin D, commonly known as the “sunshine vitamin,” is traditionally recognized for its role in bone health and calcium regulation. However, research over the past few decades has revealed that vitamin D is crucial for a wide range of physiological processes beyond skeletal maintenance, particularly in modulating the immune system. Evidence now suggests that vitamin D influences both innate and adaptive immunity, affecting how the body responds to infections, inflammation, and autoimmune challenges. This article delves into the scientific evidence on vitamin D and immunity, exploring mechanisms of action, clinical research findings, deficiency implications, and population-level guidance.

Understanding Vitamin D

Vitamin D is a fat-soluble vitamin that also functions as a hormone. There are two main forms: vitamin D2 (ergocalciferol), primarily obtained from plant sources and fortified foods, and vitamin D3 (cholecalciferol), which is synthesized in the skin when ultraviolet B (UVB) light converts 7-dehydrocholesterol into vitamin D3. Both forms are metabolized in the liver to 25-hydroxyvitamin D (25(OH)D), the circulating form commonly measured to assess vitamin D status. The kidneys then convert 25(OH)D into the active form, 1,25-dihydroxyvitamin D (calcitriol), which exerts effects in multiple tissues, including immune cells.

Vitamin D Receptors and Immune Cells

A key discovery linking vitamin D to immunity is the widespread expression of vitamin D receptors (VDRs) and the enzyme 1-alpha-hydroxylase in immune cells, including macrophages, dendritic cells, T lymphocytes, and B lymphocytes. This enables local conversion of 25(OH)D into active calcitriol within immune tissues. By binding to VDRs, calcitriol modulates the transcription of numerous genes involved in immune regulation, antimicrobial peptide production, and cytokine signaling. This direct influence on immune cell behavior suggests vitamin D is a critical modulator of both innate and adaptive immunity. (Prietl et al., Nutrients)

Innate Immunity: Strengthening the First Line of Defense

Innate immunity provides immediate, non-specific defense mechanisms against pathogens. It includes physical barriers like skin and mucous membranes and immune cells such as macrophages, neutrophils, and natural killer cells. Vitamin D supports innate immunity in multiple ways:

• Antimicrobial peptides: Vitamin D upregulates antimicrobial peptides, including cathelicidins and defensins, which can directly neutralize bacteria, viruses, and fungi.
• Macrophage activation: Active vitamin D enhances macrophage pathogen recognition and phagocytic activity, boosting the ability to clear infections. Nature Communications
• Epithelial barrier maintenance: Vitamin D contributes to the integrity of epithelial tight junctions in the respiratory and gastrointestinal tracts, preventing pathogen entry.

These effects demonstrate that sufficient vitamin D levels enable innate immune cells to respond rapidly and effectively to invading pathogens.

Adaptive Immunity: Modulation of Targeted Responses

Adaptive immunity provides antigen-specific responses involving T and B lymphocytes. Vitamin D influences adaptive immunity by:

• T cell regulation: Vitamin D suppresses excessive Th1 and Th17 pro-inflammatory T cell activity while promoting regulatory T cells (Tregs), helping prevent autoimmune reactions. (Johnson et al.)
• Dendritic cell maturation: Calcitriol inhibits full dendritic cell maturation, reducing overactivation of T cells but promoting immune tolerance.
• B cell function: Vitamin D can modulate B cell proliferation, differentiation, and antibody production, though findings are variable across studies. (Hewison, 2012)

Vitamin D and Inflammation

Chronic or dysregulated inflammation contributes to tissue damage and disease. Vitamin D exerts anti-inflammatory effects by:

• Reducing pro-inflammatory cytokines such as IL-6 and TNF-alpha.
• Enhancing anti-inflammatory cytokines such as IL-10.
• Modulating immune pathways to prevent prolonged inflammatory responses. (Ao et al., 2021)

This immunomodulatory function is particularly relevant in autoimmune diseases, chronic infections, and conditions characterized by excessive inflammation.

Vitamin D Deficiency and Immune-Related Disorders

Observational studies consistently show associations between low vitamin D levels and increased susceptibility to infections and immune-related diseases:

• Respiratory infections: Low 25(OH)D levels are linked to higher rates of respiratory tract infections, including influenza and viral illnesses. MDPI Review
• Autoimmune conditions: Lower vitamin D status is associated with diseases such as type 1 diabetes, multiple sclerosis, inflammatory bowel disease, and systemic lupus erythematosus.
• Chronic inflammatory states: Vitamin D deficiency correlates with elevated inflammatory markers, contributing to cardiovascular, metabolic, and musculoskeletal conditions. Bikle, 2022

It is important to note that while these associations are strong, observational studies cannot prove causation; low vitamin D may reflect poor health rather than being the primary cause of disease.

Vitamin D Supplementation and Immune Outcomes

Clinical trials and meta-analyses have investigated whether supplementation affects infection risk and autoimmune diseases:

• Acute respiratory infections: Meta-analyses of randomized controlled trials suggest vitamin D supplementation modestly reduces the risk of acute respiratory infections, particularly in individuals who are deficient. Martineau et al., 2017
• COVID-19: Some studies associate low vitamin D levels with severe COVID-19 outcomes, though evidence that supplementation directly prevents or mitigates infection remains under investigation.
• Autoimmune disorders: Evidence is emerging that adequate vitamin D may help manage autoimmune disease activity, though benefits vary depending on dosage, disease, and individual factors.

Overall, supplementation appears most beneficial in individuals with low baseline levels. In populations with sufficient vitamin D, supplementation has limited effects on infection prevention.

Optimal Vitamin D Levels and Safety Considerations

Serum 25(OH)D concentrations of at least 50 nmol/L (20 ng/mL) are commonly cited as minimum levels for general health. Some research suggests higher levels may optimize immune function, although definitive targets remain under debate. Vitamin D toxicity is rare but can occur with extremely high doses, leading to hypercalcemia, nausea, and kidney complications. Safe supplementation should be guided by population-level recommendations rather than individual prescriptions. WHO Vitamin D Fact Sheet

Vitamin D and Aging Immune Systems

Aging is associated with immunosenescence — diminished immune response and increased chronic inflammation. Evidence suggests vitamin D may counteract aspects of immunosenescence by modulating T cell responses, reducing inflammation, and supporting gut microbiota diversity. Ensuring sufficient vitamin D levels in older populations may contribute to better immune resilience.

Global Vitamin D Status

Vitamin D deficiency is a global health concern. Estimates suggest that approximately 1 billion people worldwide have insufficient or deficient vitamin D levels. Factors include limited sun exposure, higher latitudes, skin pigmentation, age, and dietary insufficiency. Population-level strategies, including food fortification and public health guidance, aim to reduce deficiency rates and improve overall immune health. Holick et al., 2017

Conclusion

Vitamin D is a crucial regulator of both innate and adaptive immunity. Immune cells express vitamin D receptors and locally activate vitamin D to modulate pathogen response, inflammation, and immune tolerance. Observational studies link low vitamin D to increased susceptibility to infections and immune-related diseases, and clinical trials indicate that supplementation may reduce infection risk, particularly in deficient individuals. Maintaining adequate vitamin D levels via sun exposure, diet, and safe supplementation supports optimal immune function as part of a holistic approach to health.

References

1. Prietl et al., 2013. Vitamin D and immune function. Nutrients.
2. Johnson et al., 2023. Vitamin D: immune function, inflammation, infections, and auto-immunity.
3. Hewison, 2012. Vitamin D and immune function: an overview.
4. Bikle, 2022. Vitamin D Regulation of Immune Function.
5. Ao et al., 2021. Effects of Vitamin D on Immune System and Inflammatory Diseases.
6. Nature Communications, 2021. Vitamin D upregulates macrophage innate immunity.
7. Martineau et al., 2017. Vitamin D supplementation to prevent acute respiratory infections.
8. Holick et al., 2017. Global vitamin D status and public health implications.
9. World Health Organization. Vitamin D Fact Sheet.
10. MDPI Review, 2023. Infections and autoimmunity—Vitamin D systematic review.