Data indicate that treatment with

vitamin D could be beneficial in reducing the risk of developing multiple sclerosis and diminishing its exacerbations [102]. Although contradictory ABT 888 data exist concerning supplementation benefits in rheumatoid arthritis (RA) and systemic lupus erythematosus, an association between low levels of 25(OH) vitamin D levels and activity of both diseases has been reported [103, 104]. Furthermore, an inverse association between higher intake of vitamin D and risk of rheumatoid arthritis was demonstrated in the Iowa Women’s Health Study [105]. However, we still lack non-biased large cohort studies that can sustain the proposed benefits of vitamin D supplementation for optimal immune function. Large-scale intervention trials in humans that support the findings in preclinical or observational studies are lacking [96]. Vitamin D and cancer treatment and prevention Many experimental data show that calcitriol stimulates apoptosis and differentiation and inhibits angiogenesis and proliferation in tumour cells [106]. Numerous association studies suggest that serum 25(OH) vitamin D levels are inversely associated with the risk of many types of cancer. Further, in some studies of patients with cancer, an association between low 25(OH) vitamin D levels and poor prognosis has been observed [107,

108]. A meta-analysis of available studies indicated that there is a trend for lower incidence of colorectal carcinoma and adenoma with 25(OH) vitamin D levels >20 ng/ml in a dose–response association [109]. For breast cancer, a pooled analysis of two studies Galeterone with 880 cases CDK and cancer and 880 controls demonstrated that individuals with sufficient serum 25(OH) vitamin D levels had 50% lower risk of breast cancer

than those with levels <13 ng/ml [110]. In addition, a large case–control study on 1,394 post-menopausal breast cancer patients and 1,365 controls also showed that the 25(OH) vitamin D level was significantly associated with lower breast cancer risk, particularly at levels above 20 ng/ml [111]. Most evidence concerning the link between vitamin D and cancer is derived from laboratory studies and observational investigations of 25(OH) vitamin D levels in association with cancer incidence and outcome. There are, however, several possible confounding factors and association cannot prove causation. Moreover, results from prospective studies only are more heterogeneous and do not support a significant association between vitamin D status and breast cancer [112]. There have been no clinical trials with cancer incidence or mortality as a primary outcome to support causality between vitamin D status and cancer. One population-based randomised clinical trial found that calcium plus vitamin D supplementation decreased cancer incidence as a secondary outcome. In that study including 1,179 healthy postmenopausal women aged >55 years, the mean level of 25(OH) vitamin D at baseline was 29 ng/ml.