At one time or another, dozens of substances—beta-carotene, vitamin E, folate, and selenium, to name a few—have been touted as cancer preventatives, only to become more questionable in rigorous clinical trials. One of the most persistent candidates for cancer prevention has been vitamin D. Animal, ecological, and epidemiologic studies suggest an inverse relationship between serum 25(OH)D level and risk of certain cancers, especially colorectal cancer. Nevertheless, evidence from clinical trials evaluating whether or not high 25(OH)D levels, or high intake of vitamin D, is associated with reduced cancer risk has been elusive.
- The Japan Public Health Center-based Prospective Study measured plasma 25(OH)D in 375 patients with newly diagnosed colorectal cancer and in matched controls. The investigators found no significant association between 25(OH)D levels and colorectal cancer, but the subjects with the lowest level of plasma 25(OH)D did have an elevated risk of rectal cancer.
- The European Prospective Investigation into Cancer and Nutrition Study (EPIC) compared pre-diagnostic 25(OH)D levels in 1248 colorectal cancer patients with those of matched controls. There was a strong inverse relationship between 25(OH)D and colorectal cancer risk—people in the highest quintile of serum 25(OH)D had a 40% lower risk than people in the lowest quintile; however, this result was not statistically significant. In contrast to the Japan Public Health Center study, the protective effect was shown, to some degree, for colon cancer, but not for rectal cancer.
- Another EPIC study assessed the relationship between 25(OH)D levels and the risk of prostate cancer. This study matched 652 men with prostate cancer with 752 healthy controls; ultimately, the results found no evidence of a link between 25(OH)D levels and cancer risk.
- The Prostate, Lung, Colorectal, and Ovarian Cancer study included a substudy of 1005 women with breast cancer and an equal number of matched controls to evaluate the relationship of breast cancer to 25(OH)D or 1,25(OH)(2)D. Overall, no relationship was found between 25(OH)D or 1,25(OH)(2)D and breast cancer risk in older or younger women.
Studies of the relationship between cancer and supplementation with vitamin D and calcium have been equally disappointing. The Women’s Health Initiative randomized >36,000 postmenopausal women to a daily dose of 1000 mg of calcium and 400 IU of vitamin D or placebo and followed them for 7 years. No difference was found between the treatment group and the control group in the incidence of colorectal cancer or breast cancer.
Case closed? Hardly. The National Institutes of Health Clinical Trials database currently lists 184 studies investigating the relationship between vitamin D and cancer.
The Vitamin D and Omega-3 Trial (VITAL), now nearing the end of patient recruitment, is the most ambitious attempt yet to nail down the relationship of vitamin D and cancer. This randomized, double-blind, placebo-controlled, 2 x 2 factorial trial will assign a multi-ethnic population of 20,000 men aged ≥50 years and women aged ≥55 years to 2000 IU/day of vitamin D (as vitamin D(3) cholecalciferol) plus 1 g/day of omega-3 fatty acid; vitamin D alone; fish oil alone; or neither. Subjects will be followed for 5 years. The primary end points of the study are cancer and major cardiovascular events (myocardial infarction, stroke, death from cardiovascular disease). Secondary aims are to test whether vitamin D or omega-3 supplementation reduces the risk of specific cancers, including colorectal, breast, and prostate cancer; cancer mortality; revascularization procedures; and death from cardiovascular disease.
We want to hear from you!
- Do you recommend that your patients increase their intake of vitamin D?
- Do you take a vitamin D supplement in the hope of preventing cancer?