Vitamin D & Cancer Incidence in Older Women

JAMA; 2017 Mar 28; Lappe, Watson, et al

April 11, 2017

Supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years among healthy postmenopausal older women, a recent study found. The randomized clinical trial included 2,303 women (mean age 65.2 years) with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL. The treatment group (vitamin D3 + calcium group) received 2,000 IU/d of vitamin D3 and 1,500 mg/d of calcium; the placebo group received identical placebos. Researchers found:

• At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group.
• A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D+ calcium group and 64 (5.58%) in the placebo group (difference, 1.69%; P = .06).

Citation:

Lappe J, Watson P, Travers-Gustafson D, et al. Effect of vitamin D and calcium supplementation on cancer incidence in older women. A randomized clinical trial. JAMA.2017;317(12):1234-1243. doi:10.1001/jama.2017.2115.

Commentary:

The Vitamin D Hypothesis (vitamin D protects against cancer) was proposed in 1980 after the observation that colon cancer mortality rates in the US were highest in areas with the least sunlight. Subsequently, a number of studies have shown an inverse relationship between risk of cancer and serum 25-hydroxyvitamin D (25[OH]D) levels. Looking only at this study's findings might lead to the conclusion that the epidemiologic association of low vitamin D levels with cancer was supported when examined with the rigor of randomized trial research, and that supplementing with vitamin D does not decrease the incidence of cancer. We should be careful before making this conclusion, however. The rate of the development of cancer was almost 40% higher in the placebo group than in the vitamin D group, just missing statistical significance (p=0.06). It may well be that there is a substantial benefit of vitamin D supplementation, but the number of patients enrolled in this study was not sufficient to detect this benefit. In addition, since many cancers have a prolonged preclinical phase, 4 years may not have been long enough to detect a benefit to supplementation, even if one exists. Finally, the average vitamin D level of women in this study was normal, so a lack of benefit in this group does not exclude a benefit in the large number of individuals who have low vitamin D levels. In my opinion, this study suggests that there may be a relation between low vitamin D levels and the development of cancer, and that vitamin D supplementation may help, but additional longer and larger studies are needed before this hypothesis can either be supported or refuted. —Neil Skolnik, MD