These associational studies have certain limitations regarding the establishment of a causality between vitamin D status and a reduced risk of cancer, e.g., as low serum 25(OH)D levels are also linked with confounding factors related to higher cancer risk, including obesity (vitamin D is sequestered in adipose tissue), and lack of physical activity (correlated with less time outdoors and less solar exposure) [138]. However, a population-based, double-blind, randomized placebo-controlled trial of 4 years duration with more than thousand postmenopausal women, whose principal secondary outcome was cancer incidence, showed that the supplementation with calcium (1400–1500 mg/day) and vitamin D3 (1100 IU/day) reduced the relative risk (RR) of cancer by ~60% (p < 0.01). The repetition of a cancer free survival analysis after the first 12 months revealed, that the relative risk for the calcium + vitamin D group was reduced by ~77% (confidence interval [CI]: 0.09–0.60; p < 0.005). Multiple regression models also showed that both treatment and serum 25(OH)D concentrations were significant, independent predictors of cancer risk [137].