Vitamin D Deficiency: Impact on Immunity and Rheumatic Diseases

Vitamin D has long been known for its role in maintaining bone health and calcium metabolism. However, decades of recent research have significantly expanded our understanding of its functions, revealing its critical importance for the immune system. Vitamin D deficiency is now considered a potential risk factor for the development and exacerbation of many autoimmune and inflammatory diseases, including rheumatic conditions. Understanding this relationship opens new perspectives for prevention and treatment.

Vitamin D: A Hormone with Immunomodulatory Properties

Vitamin D is not just a vitamin, but a steroid hormone with powerful immunomodulatory properties [1, 7]. Its active form, 1,25-dihydroxyvitamin D, plays a key role in regulating the immune response. It is capable of stimulating innate immunity and inducing immune tolerance, which is crucial for preventing autoimmune reactions [1].

Immune cells, such as dendritic cells, macrophages, as well as T and B lymphocytes, express vitamin D receptors (VDR) and the 1α-hydroxylase enzyme, which converts the inactive form of vitamin D into the active one [3]. This means that vitamin D can directly influence the functions of these cells, regulating their activity and the production of inflammatory mediators. In vitro studies have shown that the active form of vitamin D exhibits pronounced anti-inflammatory effects [3].

Vitamin D Deficiency and Autoimmune Diseases: The Big Picture

Epidemiological data strongly indicate a significant link between vitamin D deficiency and an increased incidence or worsening of infectious and inflammatory autoimmune diseases [3, 5]. Low vitamin D levels may contribute to the development of autoimmune conditions, and its deficiency is recognized as a risk factor for many of them [5, 7].

Overall, patients with autoimmune diseases often demonstrate lower levels of 25(OH)D (the main circulating form of vitamin D) compared to healthy individuals [5]. This underscores the importance of maintaining adequate vitamin D levels for overall immune system health and reducing the risk of developing autoimmune pathologies.

Vitamin D and Rheumatic Diseases

Vitamin D deficiency is widespread among patients with various autoimmune rheumatic diseases, and its role in their pathogenesis is being actively studied:

• Rheumatoid Arthritis (RA): Vitamin D deficiency is frequently observed in patients with RA and is inversely correlated with disease activity. It is suggested that it may be involved in the pathogenesis of RA [1, 3].
• Systemic Lupus Erythematosus (SLE): As with RA, vitamin D deficiency has been identified in patients with SLE and is inversely associated with disease activity and renal involvement. Vitamin D receptor (VDR) polymorphisms in SLE are also being studied [1, 3].
• Sjögren's Syndrome: Patients with Sjögren's syndrome also experience vitamin D deficiency, which may be associated with the development of neuropathy and lymphoma in the context of this disease [1].
• Ankylosing Spondylitis: Vitamin D deficiency has also been noted in patients with ankylosing spondylitis [1].

These findings indicate that vitamin D plays an important role in regulating the immune processes that underlie these chronic inflammatory conditions.

The Impact of Vitamin D on Autoimmune Thyroid Diseases and Other Conditions

In addition to rheumatic diseases, vitamin D deficiency is closely linked to other autoimmune pathologies:

• Autoimmune Thyroid Diseases (AITD): These include Hashimoto's thyroiditis and Graves' disease. Studies show that patients with AITD have significantly lower vitamin D levels compared to healthy individuals, which is especially pronounced in Hashimoto's thyroiditis [2, 5]. Vitamin D deficiency is a risk factor for the development of AITD [7]. VDR gene polymorphisms (such as FokI) have also been studied, which may be associated with specific AITD subtypes, such as Graves' disease [2].
• Multiple Sclerosis (MS): This is a chronic immune-mediated neurodegenerative disease of the central nervous system. Vitamin D plays a key role in immune regulation, and its deficiency is a significant risk factor for MS [3, 8].
• Other Conditions: Vitamin D deficiency is also associated with increased inflammation and adverse outcomes in ST-segment elevation myocardial infarction (STEMI), affecting ventricular function [4]. Furthermore, studies show a link between vitamin D deficiency and certain eye diseases, such as myopia, age-related macular degeneration, diabetic retinopathy, and dry eye syndrome [6].

The Importance of Maintaining Optimal Vitamin D Levels

Given the widespread influence of vitamin D on the immune system and its link to the development and course of numerous autoimmune and inflammatory diseases, maintaining adequate levels of this hormone becomes a priority. Regular monitoring of blood vitamin D levels and, if necessary, correction under medical supervision can play a vital role in the prevention and comprehensive treatment of many conditions, improving patients' quality of life.

Sources

1. Vitamin D and Autoimmune Rheumatic Diseases. (Biomolecules, 2023) https://pubmed.ncbi.nlm.nih.gov/37189455/
2. Vitamin D deficiency is common in Hashimoto's thyroiditis, while VDR FokI shows subtype-specific association with gravis disease in Jordan: a case-control study. (Clinica chimica acta; international journal of clinical chemistry, 2026) https://pubmed.ncbi.nlm.nih.gov/42603581/
3. The Effects of Vitamin D on Immune System and Inflammatory Diseases. (Biomolecules, 2021) https://pubmed.ncbi.nlm.nih.gov/34827621/
4. Association of Serum Vitamin D Levels and Ventricular Dysfunction Among Patients With Acute ST-Segment Elevation Myocardial Infarction in a Tertiary Care Hospital. (Cureus, 2026) https://pubmed.ncbi.nlm.nih.gov/42326140/
5. Meta-analysis of the association between vitamin D and autoimmune thyroid disease. (Nutrients, 2015) https://pubmed.ncbi.nlm.nih.gov/25854833/
6. Vitamin D and Ocular Diseases: A Systematic Review. (International journal of molecular sciences, 2022) https://pubmed.ncbi.nlm.nih.gov/35457041/
7. Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease. (Frontiers in immunology, 2021) https://pubmed.ncbi.nlm.nih.gov/33679732/
8. Vitamin D status, supplementation, and multiple sclerosis: a systematic review and meta-analysis. (Frontiers in immunology, 2026) https://pubmed.ncbi.nlm.nih.gov/41983136/

The information provided in the article is for reference purposes only and cannot replace the consultation of a qualified specialist. Before starting any treatment or changing your supplement regimen, you must consult a doctor.