Vitamin D3 and cancer risk in healthy subjects: An umbrella review of systematic review and meta-analysis

Introduction: Vitamin D3, which originates from cholesterol, exerts its influence on immune cells and potentially cancer cells via the metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D3), impacting their proliferation, differentiation, and apoptosis. An umbrella review was conducted to evaluate the potential protective effect of vitamin D3 intake and serum levels on the incidence and mortality of cancer.

Material and methods: A systematic search was conducted in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE databases from their inception to October 1, 2023. We included meta-analyses of observational or randomized clinical trials that compared interventions (vitamin D3 intake) or blood levels in a healthy population, with cancer incidence or mortality as outcomes. The grading of evidence certainty followed established criteria, including strong, highly suggestive, suggestive, weak, or not significant.

Results: A total of 71 systematic reviews were included. Strong evidence indicated that vitamin D3 supplementation reduced total cancer mortality (odds ratio [OR], 0.9 [95% CI, 0.87-0.92]; P < 0.01). In the context of site-specific cancers, there exists highly suggestive evidence pointing towards the potential prevention of head and neck, breast, colorectal, lung, and renal cell cancers through the intake of vitamin D3. Furthermore, strong evidence suggests that maintaining sufficient levels of vitamin D3 may effectively lower the risk of renal cell and thyroid cancer (OR = 0.76 [95%CI 0.64-0.88]).

Conclusions: There is significant evidence that vitamin D3 intake may reduce the incidence of some cancers. Routine assessments to ensure sufficient levels of vitamin D3 and administering supplements to address deficiencies may serve as crucial preventive measures for healthcare systems.