#87 Daily multivitamins to reduce mortality, cardiovascular disease, and cancer

CLINICAL QUESTION

QUESTION CLINIQUE

Does daily multivitamin supplementation reduce mortality, cardiovascular disease (CVD), and/or cancer?

BOTTOM LINE

RÉSULTAT FINAL

Present evidence does not support the routine use of multivitamins to reduce mortality, cardiovascular disease, or cancer for people in developed countries.

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EVIDENCE

DONNÉES PROBANTES

A meta-analysis and one Randomized Controlled Trial (RCT). Meta-analysis¹ of 21 RCTs (including RCT below) with 91,074 patients (54% males) randomized to multivitamins or placebo for 3.5 years. Most are primary prevention studies from Europe or North America

No effect on overall mortality: Relative Risk (RR)=0.98 (0.94-1.02).
- No effect on cancer mortality: RR=0.96 (0.88-1.04).
- No effect on CVD mortality: RR=1.01 (0.93-1.09).
- Multiple subgroup testing found no differences.
No evidence of publication bias or meaningful heterogeneity.

Physicians’ Health Study II: Heavily publicized RCT^2,3 of 14,641 men (mean age 64.3) randomized to Centrum Silver™ or placebo, followed 11.2 years.

No effect on overall mortality: Hazard Ratio (HR)=0.94 (0.88-1.02).
- No effect on cancer mortality: HR=0.88 (0.77-1.01).
- No effect on CVD mortality: HR=0.95 (0.83-1.09).
- No effect on CVD events: HR=1.01 (0.91-1.10).
- Reduced cancer incidence: HR=0.92 (0.86-0.998).
  - These were adjusted (for unclear reasons).
  - Unadjusted is not significant RR=0.94 (0.87-1.003).
Multiple issues: Lots of exclusion including run-in to remove non-compliant patients, adjustments (without clear reason) always in favor of multivitamins.

Context:

Multiple cohort studies have found no mortality reduction with multivitamins.
Vitamin supplementation may help reduce overall mortality in undernourished populations (like rural China). ⁸
- However, in this RCT⁸ of four different vitamin interventions, only one reduced mortality RR=0.91 (0.84-0.99).
Meta-analyses of different vitamin components on mortality:
- B-Vitamins:⁹ No effect.
- Anti-oxidants:¹⁰ Increase mortality RR=1.04 (1.01-1.07).
  - Increase with vitamin E, beta-carotene and high-dose vitamin A.
  - No effect from vitamin C and selenium.
- Vitamin D:¹¹ Decrease mortality RR=0.97 (0.94-1.00)
- Increases and decreases are small [Numbers Needed to Harm (NNH) or treat around 200 over five years].