Vitamin D Protects Against Various Cancers

Cancer cells are characterised by two features: 1/ lack of differentiation (specialisation) and 2/ rapid growth or proliferation. It was found that many malignant tumors contain vitamin D receptors (VDR), including breast, skin (melanoma),lung, colon and bone. Biologically active forms of vitamin D, such as 1,25-dihydroxyvitamin D and its analogs, appear to induce cell differentiation and/or inhibit proliferation of a number of cancerous and noncancerous cell types maintained in cell culture (57).

Some human epidemiological studies suggest that vitamin D may protect against various cancers.

Colorectal Cancer

The geographic distribution of colon cancer mortality resembles the historical geographic distribution of rickets (58), 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 risk of colorectal cancer when other risk factors are taken into account (59-62). However, some more recent studies have reported that higher vitamin D intakes and serum 25-hydroxyvitamin D levels are associated with reductions in colorectal cancer risk. 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 (63). Vitamin D intake in this study was not significantly associated with colorectal cancer risk in women. Moreover, serum 25-hydroxyvitamin D level, which reflects vitamin D intake and vitamin D synthesis, was inversely associated with the risk of potentially precancerous colorectal polyps (64) and indices of colonic epithelial cell proliferation (65), two biomarkers for colon cancer risk. More recently, a case-control analysis from the Nurses’ Health Study cohort reported that plasma 25-hydroxyvitamin D levels were inversely associated with colorectal cancer (66). A randomized, double-blind, placebo-controlled trial in 36,282 postmenopausal women participating in the Women’s Health Initiative study found that a combination of supplemental vitamin D (400 IU/day) and calcium (1,000 mg/day) did not lower incidence of colorectal cancer (67). However, it has been suggested that the daily vitamin D dose, 400 IU, was too low to detect any effect on cancer incidence (68). In fact, a recent dose-response analysis estimated that 1,000 IU of oral vitamin D daily would lower one’s risk of colorectal cancer by 50% (69).

Breast Cancer

Although breast cancer mortality follows a similar geographic distribution to that of colon cancer (58, 70), 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 (71). 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 (72). Garland et al. conducted a pooled, dose-response analysis of two case-control studies in which women with breast cancer had significantly lower plasma 25-hydroxyvitamin D levels compared to controls (73, 74). These authors reported that women with a 25-hydroxyvitamin D level of 52 ng/ml (130 nmol/L) experienced a 50% lower risk of developing breast cancer compared to women with 25-hydroxyvitamin D levels lower than 13 ng/mL (32.5 nmol/L) (75). The authors state that to obtain a 25-hydroxyvitamin D level of 52 ng/mL, around 4,000 IU of vitamin D3 would need to be consumed daily, or 2,000 IU of vitamin D3 daily plus very moderate sun exposure (75). The current tolerable upper limit of intake (UL) for adults, set by the Food and Nutrition Board of the Institute of Medicine, is 4,000 IU/day (see Safety).

Prostate Cancer

Epidemiological studies show correlations between risk factors for prostate cancer and conditions that can result in decreased vitamin D levels (57). 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. Findings that prostate cells in culture can synthesize the 25-hydroxyvitamin 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-hydroxyvitamin D levels may be useful in preventing prostate cancer (76). In contrast, prospective studies have not generally found significant relationships between serum 25-hydroxyvitamin D levels and subsequent risk of developing prostate cancer (77-80). Although a prospective study of Finnish men found that low serum 25-hydroxyvitamin D levels were associated with earlier and more aggressive prostate cancer development (81), another prospective study of men from Finland, Norway and Sweden found a U-shaped relationship between serum 25-hydroxyvitamin D levels and prostate cancer risk. In that study serum 25-hydroxyvitamin D concentrations of 19 nmol/L or lower and 80 nmol/L or higher were associated with higher prostate cancer risk (82). Further research is needed to determine the nature of the relationship between vitamin D nutritional status and prostate cancer risk.