Cancer

Two characteristics of cancer cells are their lack of differentiation (specialization) and their rapid growth or proliferation. Many malignant tumors have been found to contain vitamin D receptors (VDR), including breast, lung, skin (melanoma), colon, and bone. Biologically active forms of vitamin D, such as 1,25(OH)2D and its analogs, have been found to induce cell differentiation and/or inhibit proliferation of a number of cancerous and noncancerous cell types maintained in cell culture.

Colorectal Cancer

The geographic distribution of colon cancer is similar to the historic geographic distribution of rickets, providing circumstantial evidence that decreased sunlight exposure and diminished vitamin D nutritional status may be related to an increased risk of colon cancer. However, prospective cohort studies have not generally found total vitamin D intake to be associated with significant reductions in colorectal cancer when other risk factors are taken into account. One five-year study of more than 120,000 people found that men with the highest vitamin D intakes had a risk of colorectal cancer that was 29% lower than men with the lowest vitamin D intakes. Vitamin D intake was not significantly associated with colorectal cancer risk in women. Serum 25(OH)D level, which reflects vitamin D intake and vitamin D synthesis, was inversely associated with the risk of potentially precancerous colorectal polyps and indices of colonic epithelial cell proliferation, which are considered biomarkers for colon cancer risk.

Breast Cancer

Although breast cancer mortality follows a similar geographic distribution to that of colon cancer, direct evidence of an association between vitamin D nutritional status and breast cancer risk is limited.. A prospective study of women who participated in the first National Health and Nutrition Examination Survey (NHANES I) found that several measures of sunlight exposure and dietary vitamin D intake were associated with a reduced risk of breast cancer 20 years later. More recently, a 16-year study of more than 88,000 women found that higher intakes of vitamin D were associated with significantly lower breast cancer risk in premenopausal women but not postmenopausal women.

Prostate Cancer

Epidemiologic studies show correlations between risk factors for prostate cancer and conditions that can result in decreased vitamin D levels. Increased age is associated with an increased risk of prostate cancer, as well as with decreased sun exposure and decreased capacity to synthesize vitamin D. The incidence of prostate cancer is higher in African American men than in White American men, and the high melanin content of dark skin is known to reduce the efficiency of vitamin D synthesis. Geographically, mortality from prostate cancer is inversely associated with the availability of sunlight. Recent findings that prostate cells in culture can synthesize the 25(OH)D3-1-hydroxylase enzyme and that, unlike the renal enzyme, its synthesis is not influenced by PTH or calcium levels also provide support for the idea that increasing 25(OH)D levels may be useful in preventing prostate cancer. In contrast, prospective studies have not generally found significant relationships between serum 25(OH)D levels and subsequent risk of developing prostate cancer. Although a prospective study of Finnish men found that low serum 25(OH)D levels were associated with earlier and more aggressive prostate cancer development, another prospective study of men from Finland, Norway and Sweden found a U-shaped relationship between serum 25(OH)D levels and prostate cancer risk. In that study serum 25(OH)D concentrations of 19 nmol/L or lower and 80 nmol/L or higher were associated with higher prostate cancer risk. Further research is needed to determine the nature of the relationship between vitamin D nutritional status and prostate cancer risk.

Autoimmune Diseases

Insulin-dependent diabetes mellitus (IDDM), multiple sclerosis (MS), and rheumatoid arthritis (RA) are each examples of autoimmune disease. Autoimmune diseases occur when the body mounts an immune response to its own tissue, rather than a foreign pathogen. In IDDM, insulin producing beta-cells of the pancreas are the target of the inappropriate immune response. In MS, the targets are the myelin producing cells of the central nervous system, and in RA, the targets are the collagen producing cells of the joints. Autoimmune responses are mediated by immune cells called T cells. The biologically active form of vitamin D, 1,25(OH)2D, has been found to modulate T cell responses, such that the autoimmune responses are diminished. Treatment with 1,25(OH)2D has beneficial effects in animal models of IDDM , MS, and RA. Epidemiologic studies have found that the prevalence of IDDM, MS, and RA increases as latitude increases, suggesting that lower exposure to UVB radiation and associated decreases in vitamin D synthesis may play a role in the pathology of these diseases. The results of several prospective cohort studies also suggest that adequate vitamin D intake may decrease the risk of autoimmune diseases. A prospective cohort study of children born in Finland during the year 1966 and followed for thirty years found that those who received vitamin D supplementation in the first year of life had a significantly lower risk of developing IDDM, while children suspected of developing rickets (severe vitamin D deficiency) during the first year of life had a significantly higher risk of developing IDDM. Vitamin D supplement use was associated with a significant reduction in the risk of developing MS in two large cohorts of women followed for at least ten years. Similarly, postmenopausal women with the highest total vitamin D intakes were at significantly lower risk of developing RA after eleven years of follow up than those with the lowest intakes. Evidence from animal models and epidemiologic studies suggests that maintaining sufficient vitamin D levels may help decrease the risk of several autoimmune diseases.

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