Practice changer
Increasing the dose of vitamin D3 from the current standard of 400–600 IU per day to 1000 IU per day lowers future risk of cancer in women older than age 55 who do not get adequate vitamin D from sun exposure or diet.1
Strength of recommendation (SOR)
A: Well done randomized controlled trial2
Lappe JM, Travers-Gustafson D, Davies KM et al. Vitamin D Supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85:1586–1591.
Illustrative case
A healthy 60-year-old Chicago woman who takes 1500 mg calcium and a multi vitamin daily tells you she has read that extra vitamins prevent cancer. She is particularly concerned about cancer because of her strong family history. Should you recommend that she take any additional vitamins to reduce her risk of cancer?
Background: Will this trial pass the test of time? We think so
Wouldn’t it be nice if we could recommend something as simple and safe as a daily vitamin to reduce the risk of cancer? Until now, we have had no definitive evidence to support such a recommendation. The Lappe et al trial, however, concluded that improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women.1 Will this single, relatively small study pass the test of time and be confirmed by future clinical trials? We think so.
- The estimated relative risk reduction was dramatic (0.232) and the 95% confidence interval was 0.09 to 0.60, meaning that the true relative risk reduction has a 95% probability of being in the range of 40% to 91%. The P value of <.005 suggests that the probability of this finding occurring by chance alone is less than 1 in 200.
- Our critical appraisal found no significant flaws in this randomized controlled trial.
- Vitamin D is known to have cancer protective effects at the cellular level.
- Prior population based studies support the association between vitamin D and cancer prevention.
For these reasons—and the fact that 1000 IU vitamin D is very safe for most patients—we find this single RCT convincing as a practice changer. For us, the potential benefit outweighs the potential harm.
United States Preventive services Task Force. A 2003 report on “routine vitamin supplementation to prevent cancer and cardiovascular disease” cited insufficient evidence to recommend the use of supplemental vitamins A, C, E, multivitamins with folic acid, or antioxidants to prevent cancer or cardiovascular disease; vitamin D is not mentioned.3
Institute of medicine. In 2005, the IOM suggested an Adequate Intake (AI) of vitamin D of 400 IU for women from 51 to 70 years of age, and 600 IU for women over 70 years of age, to maintain bone health and normal calcium metabolism in healthy women. The IOM cited epidemiologic studies showing an inverse association between either increased sun exposure or higher vitamin D levels and decreased risk of cancer, and included the caveat that it was premature to recommend taking vitamin D for cancer prevention until well-designed trials prove that vitamin D is protective against cancer.4
Electronic knowledge resources that are evidence-based and frequently updated did not recommend vitamin D for cancer prevention on the dates we searched.5-8
Clinical Context: Food, sun, supplements may not deter deficiency
Few people get enough vitamin D to match the dosage that reduced cancer incidence in this trial. In fact, inadequate vitamin D intake, even to meet current standards, is surprisingly common—even in people who are apparently conscious of their nutritional needs. A Boston hospital found that 32% of healthy students, physicians, and resident physicians were vitamin-D deficient, despite drinking a glass of milk daily, taking a daily multivitamin, and eating salmon at least once a week.9 An estimated 1 billion people worldwide have vitamin D deficiency or insufficiency.9
