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Vitamin D in Cancer Prevention, Therapy, and Survival Pharmacological Perspectives, Clinical Evidence and the Cancer Incidence–Mortality Paradox


Authors : Dr. Pasham Uma; Ch. Kheroda Devi; Dr. R. L. Manisha; Muvvala Sudhakar

Volume/Issue : Volume 11 - 2026, Issue 7 - July

Google Scholar : https://tinyurl.com/4c9rmpar

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DOI : https://doi.org/10.38124/ijisrt/26jul700

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Abstract : Vitamin D, classically known for its role in calcium homeostasis and bone health, has attracted enormous interest as a potential anticancer agent following the discovery of the vitamin D receptor (VDR) in numerous tissues and the demonstration of antiproliferative, pro-differentiating, pro-apoptotic, anti-angiogenic, and immunomodulatory effects of its active metabolite, 1,25-dihydroxyvitamin D, in preclinical models. A large body of observational epidemiological evidence has consistently associated higher vitamin D status (serum 25-hydroxyvitamin D) and higher sunlight/vitamin D intake with lower cancer incidence and mortality, particularly for colorectal cancer, generating substantial enthusiasm for vitamin D supplementation as a cancer-prevention strategy. However, this review emphasizes a critical and frequently under-appreciated distinction: the large randomized controlled trials of vitamin D supplementation (notably VITAL, D-Health, and ViDA) have largely FAILED to demonstrate a reduction in cancer INCIDENCE, contradicting the observational associations and suggesting that low vitamin D may be a marker of poor health rather than a cause of cancer (confounding and reverse causation). In contrast, a more consistent — though still debated — signal has emerged for a reduction in cancer MORTALITY with vitamin D supplementation, supported by meta-analyses suggesting an approximately 12-13% reduction in cancer death, and for benefit in specific subgroups (normal-weight individuals, daily rather than bolus dosing, and possibly those with baseline deficiency). This review provides a comprehensive pharmacological analysis including vitamin D metabolism and the VDR, the preclinical antineoplastic mechanisms, the observational epidemiology, the critical appraisal of the major randomized trials and the incidence-versus-mortality distinction, vitamin D in cancer patients and survival, the distinctive Indian context of paradoxically high vitamin D deficiency despite abundant sunshine, and future directions including personalized supplementation and the targeting of baseline-deficient populations.

Keywords : Vitamin D; 25-Hydroxyvitamin D; Vitamin D Receptor; Cancer Prevention; Cancer Mortality; Colorectal Cancer; VITAL Trial; D-Health Trial; Calcitriol; Supplementation; Reverse Causation; Vitamin D Deficiency.

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Vitamin D, classically known for its role in calcium homeostasis and bone health, has attracted enormous interest as a potential anticancer agent following the discovery of the vitamin D receptor (VDR) in numerous tissues and the demonstration of antiproliferative, pro-differentiating, pro-apoptotic, anti-angiogenic, and immunomodulatory effects of its active metabolite, 1,25-dihydroxyvitamin D, in preclinical models. A large body of observational epidemiological evidence has consistently associated higher vitamin D status (serum 25-hydroxyvitamin D) and higher sunlight/vitamin D intake with lower cancer incidence and mortality, particularly for colorectal cancer, generating substantial enthusiasm for vitamin D supplementation as a cancer-prevention strategy. However, this review emphasizes a critical and frequently under-appreciated distinction: the large randomized controlled trials of vitamin D supplementation (notably VITAL, D-Health, and ViDA) have largely FAILED to demonstrate a reduction in cancer INCIDENCE, contradicting the observational associations and suggesting that low vitamin D may be a marker of poor health rather than a cause of cancer (confounding and reverse causation). In contrast, a more consistent — though still debated — signal has emerged for a reduction in cancer MORTALITY with vitamin D supplementation, supported by meta-analyses suggesting an approximately 12-13% reduction in cancer death, and for benefit in specific subgroups (normal-weight individuals, daily rather than bolus dosing, and possibly those with baseline deficiency). This review provides a comprehensive pharmacological analysis including vitamin D metabolism and the VDR, the preclinical antineoplastic mechanisms, the observational epidemiology, the critical appraisal of the major randomized trials and the incidence-versus-mortality distinction, vitamin D in cancer patients and survival, the distinctive Indian context of paradoxically high vitamin D deficiency despite abundant sunshine, and future directions including personalized supplementation and the targeting of baseline-deficient populations.

Keywords : Vitamin D; 25-Hydroxyvitamin D; Vitamin D Receptor; Cancer Prevention; Cancer Mortality; Colorectal Cancer; VITAL Trial; D-Health Trial; Calcitriol; Supplementation; Reverse Causation; Vitamin D Deficiency.

Paper Submission Last Date
31 - August - 2026

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