A recently-completed segment of the Physicians Health Study II (PHS II) has led investigators to conclude that vitamins C and E and beta-carotene do not help prevent cancer. This pronouncement follows similar reports from other studies that B vitamins (including folic acid), vitamin D, and calcium are not useful in cancer prevention, either.
PHS II was an extension of an ongoing longitudinal trial that had already shown no benefit from vitamin C or vitamin E in the prevention of cardiovascular disease. (Sesso H. Vitamins E and C supplements not effective for prevention of cardiovascular disease in men. JAMA. 300:2123-2133)
Dr. Howard Sesso, assistant professor of medicine at Brigham and Women’s Hospital and one of the study’s principal investigators, said, “…in the context of two very common outcomes—cardioprotection and chemoprevention—we see no compelling evidence to take vitamin E or C supplements.” (HealthDay News)
Physicians Health Study—Design and Outcomes
PHSII included 14,642 male physicians, all of them older than 50 years. All were pronounced “healthy” at the study’s onset, although 44% were past or current smokers, 77% were taking aspirin, 42% had a history of hypertension, 36% had a history of hypercholesterolemia, 6% were diabetic, and 5% had a history of cardiovascular disease.
The group was randomized in a multifactorial fashion to provide blinded exposure to vitamin C, vitamin E, beta-carotene, Centrum Silver multivitamin, or placebo. Vitamin C and the multivitamin (or their placebos) were taken daily. Vitamin E and beta-carotene (or their placebos) were taken every other day.
All of the vitamins used in this study were synthetic.
By the study’s end, participants experienced a total of 1,929 cases of cancer, 1,013 of which were prostate cancers. Overall risk for cancer was not statistically different in any of the groups. The study’s authors determined that this large, long-term trial demonstrated no benefit from supplemental vitamin C or vitamin E.
Limitations and Shortcomings of the Physicians Health Study
Results of PHS II cannot be extrapolated to the general population for the following reasons:
Only male physicians in the United States were included. Physicians experience a different level of access to both health care and health information—and therefore, possibly, a different risk profile—than other individuals.
Assessment of exposure (i.e., to other supplements, medications, medical care, or risks) was accomplished through a mailed questionnaire, as were some critical endpoints (i.e., cancer diagnosis). Such questionnaires are susceptible to bias.
Subjects were followed for a mean duration of eight years, but some members of the study group were retained from the previous PHS I, while others were recruited at the outset of PHS II. Thus, longitudinal exposures to vitamins varied considerably; a longer trial with simultaneous recruitment of subjects might yield different results.
Significant disagreement exists about the validity of results from studies that utilize synthetic forms of vitamins. Evidence suggests that people whose diets contain high levels of antioxidant vitamins do experience a lower overall risk for cancer and cardiovascular disease. (Byers T, Guerrero N. Epidemiologic evidence for vitamin C and vitamin E in cancer prevention. The Amer Journ Clin Nutr 1995;62(6):1385-1392)
In the end, well-designed studies may, indeed, show that supplementation with isolated vitamins is ineffective for preventing cardiovascular disease or cancer. One day we may be left with the knowledge that only a diet rich in fruits, vegetables, and grains is ultimately protective.
However, until a genuinely well-designed study is completed—one that employs vitamins from natural sources in a heterogeneous population—curious individuals are left to their musings.