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

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...

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Main Authors: Api Chewcharat, Pol Chewcharat, Kathryn M. Rexrode, Robert J. Glynn, Julie E. Buring, John Michael Gaziano, Howard D. Sesso
Format: Article
Language:English
Published: Elsevier 2024-06-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924016218
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author Api Chewcharat
Pol Chewcharat
Kathryn M. Rexrode
Robert J. Glynn
Julie E. Buring
John Michael Gaziano
Howard D. Sesso
author_facet Api Chewcharat
Pol Chewcharat
Kathryn M. Rexrode
Robert J. Glynn
Julie E. Buring
John Michael Gaziano
Howard D. Sesso
author_sort Api Chewcharat
collection DOAJ
description 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.
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spelling doaj-art-36986714c8ba4e00a1dfc13c80430c092025-08-20T03:45:03ZengElsevierKidney International Reports2468-02492024-06-01961633164010.1016/j.ekir.2024.04.001The Effect of Randomized Beta-Carotene Supplementation on CKD in MenApi Chewcharat0Pol Chewcharat1Kathryn M. Rexrode2Robert J. Glynn3Julie E. Buring4John Michael Gaziano5Howard D. Sesso6Division of Nephrology, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA; Correspondence: Api Chewcharat, Brigham and Women’s Hospital, Department of Medicine, Harvard Medical School, 75 Francis St, Boston, Massachusetts 02115, USA.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USADivision of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USADepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USADepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USADivision of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA; Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA; Department of Medicine and MAVERIC, VA Boston Healthcare System, Boston, Massachusetts, USADepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA; Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USAIntroduction: 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.http://www.sciencedirect.com/science/article/pii/S2468024924016218beta-carotenekidney diseaserandomized controlled trials
spellingShingle Api Chewcharat
Pol Chewcharat
Kathryn M. Rexrode
Robert J. Glynn
Julie E. Buring
John Michael Gaziano
Howard D. Sesso
The Effect of Randomized Beta-Carotene Supplementation on CKD in Men
Kidney International Reports
beta-carotene
kidney disease
randomized controlled trials
title The Effect of Randomized Beta-Carotene Supplementation on CKD in Men
title_full The Effect of Randomized Beta-Carotene Supplementation on CKD in Men
title_fullStr The Effect of Randomized Beta-Carotene Supplementation on CKD in Men
title_full_unstemmed The Effect of Randomized Beta-Carotene Supplementation on CKD in Men
title_short The Effect of Randomized Beta-Carotene Supplementation on CKD in Men
title_sort effect of randomized beta carotene supplementation on ckd in men
topic beta-carotene
kidney disease
randomized controlled trials
url http://www.sciencedirect.com/science/article/pii/S2468024924016218
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