Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial

Abstract

Context: Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality.

Objective: To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men.

Design, setting, and participants: A large-scale, randomized, double-blind, placebo controlled trial (Physicians" Health Study II) of 14 641 male US physicians initially aged 50 years or older (mean [SD] age, 64.3 [9.2] years), including 1312 men with a history of cancer at randomization, enrolled in a common multivitamin study that began in 1997 with treatment and follow-up through June 1, 2011.

Intervention: Daily multivitamin or placebo.

Main outcome measures: Total cancer (excluding nonmelanoma skin cancer), with prostate, colorectal, and other site-specific cancers among the secondary end points.

Results: During a median (interquartile range) follow-up of 11.2 (10.7-13.3) years, there were 2669 men with confirmed cancer, including 1373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (multivitamin and placebo groups, 17.0 and 18.3 events, respectively, per 1000 person-years; hazard ratio [HR], 0.92; 95% CI, 0.86-0.998; P=.04). There was no significant effect of a daily multivitamin on prostate cancer (multivitamin and placebo groups, 9.1 and 9.2 events, respectively, per 1000 person-years; HR, 0.98; 95% CI, 0.88-1.09; P=.76), colorectal cancer (multivitamin and placebo groups, 1.2 and 1.4 events, respectively, per 1000 person-years; HR, 0.89; 95% CI, 0.68-1.17; P=.39), or other site-specific cancers. There was no significant difference in the risk of cancer mortality (multivitamin and placebo groups, 4.9 and 5.6 events, respectively, per 1000 person-years; HR, 0.88; 95% CI, 0.77-1.01; P=.07). Daily multivitamin use was associated with a reduction in total cancer among 1312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56-0.96; P=.02), but this did not differ significantly from that among 13 329 men initially without cancer (HR, 0.94; 95% CI, 0.87-1.02; P=.15; P for interaction=.07). Conclusion In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.

Trial registration: clinicaltrials.gov Identifier: NCT00270647.

Figure 1

Flow diagram of participants from screening to completion of the multivitamin component of the Physicians’ Health Study (PHS) II.* * Those classified as “unforwardable” were not able to be contacted by mail.

Figure 2

Cumulative incidence rates of (part A) total cancer, (part B) prostate cancer, and (part C) colorectal cancer by randomized multivitamin assignment in the Physicians’ Health Study II. * The reduction in the number at risk from 10 to 11 years reflects the two phases of PHS II recruitment; PHS I physicians initially enrolled in Phase 1 starting in 1997 were followed longer on average (mean of 13 years) than new physicians recruited in Phase 2 starting in 1999 (mean of 10 years). Crude log-rank P=0.05 for total cancer, P=0.78 for prostate cancer, P=0.38 for colorectal cancer, and P=0.26 for lung cancer.

Figure 2

Cumulative incidence rates of (part A) total cancer, (part B) prostate cancer, and (part C) colorectal cancer by randomized multivitamin assignment in the Physicians’ Health Study II. * The reduction in the number at risk from 10 to 11 years reflects the two phases of PHS II recruitment; PHS I physicians initially enrolled in Phase 1 starting in 1997 were followed longer on average (mean of 13 years) than new physicians recruited in Phase 2 starting in 1999 (mean of 10 years). Crude log-rank P=0.05 for total cancer, P=0.78 for prostate cancer, P=0.38 for colorectal cancer, and P=0.26 for lung cancer.

Figure 2

Cumulative incidence rates of (part A) total cancer, (part B) prostate cancer, and (part C) colorectal cancer by randomized multivitamin assignment in the Physicians’ Health Study II. * The reduction in the number at risk from 10 to 11 years reflects the two phases of PHS II recruitment; PHS I physicians initially enrolled in Phase 1 starting in 1997 were followed longer on average (mean of 13 years) than new physicians recruited in Phase 2 starting in 1999 (mean of 10 years). Crude log-rank P=0.05 for total cancer, P=0.78 for prostate cancer, P=0.38 for colorectal cancer, and P=0.26 for lung cancer.

Figure 2

Cumulative incidence rates of (part A) total cancer, (part B) prostate cancer, and (part C) colorectal cancer by randomized multivitamin assignment in the Physicians’ Health Study II. * The reduction in the number at risk from 10 to 11 years reflects the two phases of PHS II recruitment; PHS I physicians initially enrolled in Phase 1 starting in 1997 were followed longer on average (mean of 13 years) than new physicians recruited in Phase 2 starting in 1999 (mean of 10 years). Crude log-rank P=0.05 for total cancer, P=0.78 for prostate cancer, P=0.38 for colorectal cancer, and P=0.26 for lung cancer.

Figure 3

Hazard ratios (HRs) and 95% confidence intervals (CIs) of total cancer among 13,329 men with no baseline history of cancer (part A; Primary Prevention) and 1,312 men with a baseline history of cancer (part B; Secondary Prevention) in the Physicians’ Health Study II. * Crude log-rank P=0.018 for 13,329 men with no baseline history of cancer, and crude log-rank P=0.19 for 1,312 men with a baseline history of cancer.