Epidemiological evidence suggests an association between low vitamin D status and risk for various outcomes including cardiovascular diseases, cancer, and type 2 diabetes mellitus (T2DM). Analyzing serum 25-hydroxyvitamin D [25(OH)D] is the most established means to evaluate an individual’s vitamin D status. However, cutoff values for 25(OH)D insufficiency as well as for optimal 25(OH)D levels are controversial. This systematic review critically summarizes the epidemiological evidence regarding 25(OH)D levels and the risk for colorectal cancer and T2DM. The meta-analytical calculation revealed a pooled relative risk (RR) of 0.62 (CI 0.56–0.70; I2 = 14.7%) for colorectal cancer and an RR of 0.66 (CI 0.61–0.73; I2 = 38.6%) for T2DM when comparing individuals with the highest category of 25(OH)D with those in the lowest. A dose–response analysis showed an inverse association between 25(OH)D levels and RR for both outcomes up to concentrations of about 55 ng/mL for colorectal cancer and about 65 ng/mL for T2DM. At still higher 25(OH)D levels the RR increases slightly, consistent with a U-shaped association. In conclusion, a higher 25(OH)D status is associated with a lower risk for colorectal cancer and T2DM; however, this advantage is gradually lost as levels increase beyond 50–60 ng/mL.
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