The Effect of Randomized Beta-Carotene Supplementation on CKD in Men

Abstract

Introduction: Beta-carotene (BC) protects the body against free radicals that may damage the kidney and lead to the development of acute kidney injury and chronic kidney disease (CKD). Previous studies in animal models have demonstrated a potential protective effect of 30 mg/kg BC supplementation on renal ischemia or reperfusion injury and subsequently improved kidney function. The extension of these findings to humans, however, remains unclear.

Methods: Our study leverages previously collected data from the Physicians' Health Study I (PHS I), a large-scale, long-term, randomized trial of middle-aged and older US male physicians testing 50 mg BC every other day for primary prevention of cardiovascular disease and cancer. We examined the impact of randomized BC supplementation on self-reported incident CKD identified by self-reports stating "yes" to kidney disease from annual follow-up questionnaires from randomization in 1982 through the end of the randomized BC intervention at the end of 1995, and on CKD defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m² at the end of 1995. Analyses compared incident CKD between BC supplementation and placebo using Cox proportional hazards regression models and logistic regression. We also examined whether smoking status (current vs. former or never smoker) or other factors modified the effect of randomized BC supplementation on CKD.

Results: A total of 10,966 participants were randomized to BC, and 10,952 participants were randomized to a placebo group. Baseline characteristics between randomized BC groups were similar. There was no significant benefit between BC supplementation and self-reported incident CKD after adjusting for age and randomized aspirin treatment (hazard ratio [HR] = 0.97, 95% confidence interval [CI]: 0.86-1.08, P-value = 0.56). Stratified by smoking status, there was no significant benefit of BC supplementation and self-reported incident CKD either among former or never smokers (HR = 0.95, 95% CI: 0.84-1.07, P-value = 0.41) or current smokers (HR = 1.08, 95% CI: 0.78-1.50, P-value = 0.64). Smoking status did not modify the association between BC supplementation and incident CKD (P-interaction = 0.47). In subgroup analysis among those with available serum creatinine at the study end (5480 with BC and 5496 with placebo), there was no significant benefit between BC supplementation and CKD based on eGFR < 60 ml/min per 1.73 m² (odds ratio [OR] = 0.96, 95% CI: 0.85-1.08, P-value = 0.49).

Conclusion: Long-term randomized BC supplementation did not affect the risk of incident CKD in middle-aged and older male physicians.

Keywords: beta-carotene; kidney disease; randomized controlled trials.

Graphical abstract

Figure 1

Flow chart of randomized Physicians’ Health Study I participants for the primary outcome of self-reported chronic kidney disease.

Figure 2

Flow chart of Physicians’ Health Study I participants with serum creatinine available at the study end included in the analysis of the secondary outcome of eGFR < 60 ml/min per 1.73 m². eGFR, estimated glomerular filtration rate.