Recent studies suggest that vitamin D, a vital nutrient primarily associated with bone health, may play a crucial role in the pathophysiology of endometriosis. Beyond its well-documented function in calcium and phosphorus homeostasis, vitamin D exhibits immunomodulatory and anti-inflammatory properties, which could influence the progression of endometriotic lesions. Emerging evidence indicates that vitamin D deficiency is prevalent among women with endometriosis and may contribute to disease severity.
Physiological Functions of Vitamin D
Vitamin D is essential for maintaining skeletal integrity by facilitating calcium absorption and bone mineralisation. However, its biological significance extends to immune regulation, inflammation control, and angiogenesis inhibition. These functions are particularly relevant in endometriosis, a chronic inflammatory disorder characterised by the ectopic proliferation of endometrial-like tissue outside the uterus.
Vitamin D modulates both innate and adaptive immunity by regulating the activity of macrophages, dendritic cells, and T lymphocytes, which are implicated in the persistence of endometriotic lesions. Additionally, it attenuates the secretion of pro-inflammatory cytokines while promoting anti-inflammatory responses, thereby reducing systemic and localised inflammation.
Sources and Requirements of Vitamin D
Endogenous synthesis of vitamin D occurs in the skin upon exposure to ultraviolet B (UVB) radiation, accounting for approximately 80–90% of total vitamin D production. The remaining 10–20% must be obtained from dietary sources. The German Nutrition Society recommends a daily intake of 20 µg (800 IU) of vitamin D in regions with limited sunlight exposure.
Dietary Sources of Vitamin D:
- Fatty fish (e.g., salmon, herring, mackerel)
- Egg yolks
- Dairy products and fortified foods
- Avocado
- Sun-exposed mushrooms
Despite these dietary sources, vitamin D deficiency remains highly prevalent, particularly among women with limited sun exposure, restricted diets, or predisposing medical conditions.
Clinical Implications of Vitamin D Deficiency
A transient insufficiency in vitamin D may present with non-specific symptoms, such as fatigue, decreased energy levels, and an increased susceptibility to infections. However, chronic deficiency has more profound implications, including:
- Skeletal complications: Increased risk of osteoporosis and bone demineralisation
- Immune dysfunction: Altered inflammatory responses, which may exacerbate autoimmune and inflammatory conditions
- Endometriosis progression: Potential aggravation of inflammatory pathways and enhanced lesion survival
Diagnostic Parameters for Vitamin D Deficiency
A serum concentration of 25-hydroxyvitamin D (25-OH-D) serves as the primary biomarker for vitamin D status. According to clinical guidelines:
- Sufficiency: ≥50 nmol/L
- Insufficiency: 30–50 nmol/L
- Deficiency: <30 nmol/L
Regular monitoring of vitamin D levels is advised for individuals at risk of deficiency, including women with endometriosis.
Potential Mechanisms Linking Vitamin D and Endometriosis
- Immunomodulation and Inflammation Control
Endometriosis is characterised by an altered immune response, wherein ectopic endometrial-like cells evade immune surveillance. In healthy physiological conditions, immune cells—particularly natural killer (NK) cells and macrophages—eliminate misplaced endometrial cells. However, in endometriosis, these immune defences are impaired, allowing lesions to persist and expand.
Vitamin D plays a pivotal role in immune regulation by suppressing pro-inflammatory cytokines and promoting anti-inflammatory mediators, mitigating local and systemic inflammation.
By restoring immune homeostasis, vitamin D may thus limit the progression of endometriotic lesions.
- Angiogenesis Inhibition
Angiogenesis, the formation of new blood vessels, is a critical process supporting endometriotic lesion survival and expansion. Ectopic endometrial tissue relies on angiogenesis to establish a blood supply for nutrient and oxygen delivery. Studies have demonstrated that vitamin D inhibits angiogenesis by downregulating vascular endothelial growth factor (VEGF) expression, a key mediator of blood vessel formation in endometriosis.
By modulating this process, vitamin D supplementation may reduce lesion vascularisation, thereby restricting disease progression.
Risk Factors for Vitamin D Deficiency in Endometriosis Patients
Several factors predispose individuals to vitamin D deficiency, including:
- Insufficient UVB exposure (e.g., seasonal variations, use of sunscreen, lifestyle factors)
- Dietary limitations (e.g., lactose intolerance, veganism)
- Gastrointestinal disorders affecting vitamin D absorption (e.g., Crohn’s disease, ulcerative colitis)
- Hepatic or renal dysfunction, which impairs vitamin D metabolism
- Medication interactions, including corticosteroids, anticonvulsants, and certain chemotherapy agents
Addressing these risk factors through dietary modifications, increased sun exposure, or supplementation may help optimise vitamin D levels.
Clinical Recommendations for Vitamin D Optimisation
For women with endometriosis, ensuring adequate vitamin D levels may be beneficial in reducing inflammation, modulating immune responses, and potentially mitigating disease progression.
Strategies for Optimising Vitamin D Status:
✔ Sunlight exposure: Spending 15–30 minutes outdoors daily, depending on skin type and UV index
✔ Dietary intake: Incorporating vitamin D-rich foods into daily meals
✔ Supplementation: If dietary intake and sun exposure are insufficient, targeted supplementation can help maintain optimal levels
Fertilovit® F Endo has been specifically formulated for women with endometriosis, providing 15 µg (600 IU) of vitamin D, along with 21 additional micronutrients to support reproductive and immune health.
Conclusion
Vitamin D plays an integral role in immune function, inflammatory regulation, and angiogenesis inhibition, all of which are relevant to the pathophysiology of endometriosis. Given the high prevalence of vitamin D deficiency among women with endometriosis, maintaining sufficient levels through sun exposure, diet, or supplementation may represent a potential adjunctive approach in disease management.
Further research is warranted to establish optimal dosing guidelines and therapeutic benefits of vitamin D supplementation in the clinical management of endometriosis.
Have You Checked Your Vitamin D Levels?
Have you noticed an increase in endometriosis symptoms during the winter months when vitamin D levels typically decline? Do you monitor your vitamin D status? Let us know in the comments below!
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References:
📌 Farhangnia P, Noormohammadi M, Delbandi AA. Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis. Reprod Health. 2024 May 2;21(1):61.
📌 Jennings BS, Hewison M. Vitamin D and Endometriosis: Is There a Mechanistic Link? Cell Biochem Funct. 2025 Jan;43(1):e70037.
📌 Rocha AL, Reis FM, Taylor RN. Angiogenesis and endometriosis. Obstet Gynecol Int. 2013;2013:859619.
📌 Xie B, Liao M, Huang Y, et al. Association between vitamin D and endometriosis among American women: National Health and Nutrition Examination Survey. PLoS One. 2024 Jan 12;19(1):e0296190.
