{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:24:41Z","timestamp":1790717081195,"version":"4.1.0"},"reference-count":416,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure. Methods: This systematic review (SR) examines the relationship between vitamin D and the reduction of cancer risk and mortality, and the mechanisms involved in cancer prevention. This SR followed the PRISMA and PICOS guidelines and synthesized evidence from relevant studies. Results: Beyond genomic actions via calcitriol [1,25(OH)2D]-receptor interactions, vitamin D exerts cancer-protective effects through mitigating inflammation, autocrine, paracrine, and membrane signaling. The findings reveal a strong inverse relationship between serum 25(OH)D levels and the incidence, metastasis, and mortality of several cancer types, including colon, gastric, rectal, breast, endometrial, bladder, esophageal, gallbladder, ovarian, pancreatic, renal, vulvar cancers, and both Hodgkin\u2019s and non-Hodgkin\u2019s lymphomas. While 25(OH)D levels of around 20 ng\/mL suffice for musculoskeletal health, maintaining levels above 40 ng\/mL (100 nmol\/L: range, 40\u201380 ng\/mL) significantly lowers cancer risks and mortality. Conclusions: While many observational studies support vitamin D\u2019s protective role in incidents and deaths from cancer, some recent mega-RCTs have failed to demonstrate this. The latter is primarily due to critical study design flaws, like recruiting vitamin D sufficient subjects, inadequate dosing, short durations, and biased designs in nutrient supplementation studies. Consequently, conclusions from these cannot be relied upon. Well-designed, adequately powered clinical trials using appropriate methodologies, sufficient vitamin D3 doses, and extended durations consistently demonstrate that proper supplementation significantly reduces cancer risk and markedly lowers cancer mortality.<\/jats:p>","DOI":"10.3390\/nu17142333","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T15:48:22Z","timestamp":1752680902000},"page":"2333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Vitamin D\u2019s Impact on Cancer Incidence and Mortality: A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-8595","authenticated-orcid":false,"given":"Sunil J.","family":"Wimalawansa","sequence":"first","affiliation":[{"name":"CardioMetabolic & Endocrine Institute, North Brunswick, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4161\/derm.24494","article-title":"Sunlight and Vitamin D: A global perspective for health","volume":"5","author":"Wacker","year":"2013","journal-title":"Derm. 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