Serum Beta Carotene and Overall and Cause-Specific Mortality: A Prospective Cohort Study

Circulation Research

Dec 2018

DOI: 10.1161/CIRCRESAHA.118.313409

Citations:65

Influential Citations:4

Observational Studies (Human)

Enhanced Details

Methods

29,133 male smokers from southwest Finland, aged 50–69 years. Study design: randomized, double-blind, placebo-controlled trial with a 2×2 factorial design evaluating alpha-tocopherol and beta-carotene supplementation.

Intervention

Daily oral supplementation for 5–8 years: alpha-tocopherol 50 mg; beta-carotene 20 mg; both alpha-tocopherol 50 mg and beta-carotene 20 mg; or placebo.

Results

Higher baseline serum beta carotene is associated with lower risk of all-cause mortality and death from major causes (CVD, heart disease, stroke, cancer, respiratory disease, diabetes mellitus, injuries/accidents, and other) over about 30 years, with a dose-response pattern. Highest vs lowest quintile hazard ratios: all-cause 0.64; CVD 0.64; heart disease 0.64; stroke 0.67; cancer 0.73; respiratory disease 0.71; diabetes mellitus 0.21; injuries/accidents 0.57; other causes 0.51 (all P trend < 0.0001). Associations persisted after adjusting for fruit/vegetable intake and were stronger in younger men, those with fewer smoking years, and BMI <25 kg/m2. Conclusion: higher beta carotene status within the normal range is associated with lower mortality; increasing fruit/vegetable intake to boost beta carotene could promote longevity. Prior high-dose beta carotene supplementation trials have shown no benefit or harm; results should be replicated in more diverse populations, including women.

Limitations

Generalizability limited to Finnish male smokers; observational analysis of baseline serum beta carotene; single baseline measurement; potential residual confounding; possible measurement error in dietary data; results may not apply to women or non-smokers.

Abstract

Rationale: Although the health effects of beta carotene have been studied extensively, a systematic examination of serum concentrations and long-term mortality, including cardiovascular disease mortality, has not been reported. Objective: Explore whether serum beta carotene is associated with overall and cause-specific mortality and to elucidate the strength and dose-response of the association. Methods and Results: We conducted a prospective serological analysis of 29 103 men in the ATBC study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). During 31 years of follow-up, 23 796 deaths occurred, including deaths because of cardiovascular disease (9869), cancer (7692), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2700). Serum beta carotene was assayed using high-performance liquid chromatography. Adjusting for major risk factors measured, men with higher serum beta carotene had significantly lower all-cause mortality (hazard ratios=0.81, 0.71, 0.69, and 0.64 for quintile 2 (Q2)-Q5 versus Q1, respectively; Ptrend<0.0001). Serum beta carotene was significantly associated with risk of death from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, diabetes mellitus, injuries and accidents, and other causes (Q5 versus Q1, hazard ratio=0.21–0.73, all Ptrend<0.0001). The all-cause mortality association was not materially impacted by adjustment for fruit and vegetable consumption (albeit, estimated with some measurement error) and was generally similar across subgroups of smoking intensity, alcohol consumption, trial supplementation, and duration of follow-up, but was significantly modified by age, years of smoking, and body mass index, with stronger inverse associations among men who were younger, smoked fewer years, and had a lower body mass index (all Pinteraction⩽0.0025). Conclusions: This study provides evidence that higher beta carotene biochemical status is associated with lower overall, cardiovascular disease, heart disease, stroke, cancer, and other causes of mortality. The dose-response associations over a 30-year period were not attenuated by adjustment for other important risk factors and support greater fruit and vegetable consumption as a means to increase beta carotene status and promote longevity. show less