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The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear.
To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults.
PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists.
English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease.
Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence.
Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low– to moderate-certainty evidence).
Suboptimal quality and certainty of evidence.
Use of omega-3 LC-PUFA and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke.
Primary Funding Source:
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Author, Article, and Disclosure Information
Safi U. Khan,
West Virginia University, Morgantown, West Virginia (S.U.K., M.U.K., S.V.)
Cleveland Clinic, Cleveland, Ohio (H.R.)
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (D.Z.)
East Carolina University, Greenville, North Carolina (L.V., V.O.)
Mayo Clinic, Rochester, Minnesota (I.B.R., M.H.M.)
John H. Stroger, Jr. Hospital of Cook County, Chicago, Illinois (M.S.K.)
Guthrie Robert Packer Hospital, Sayre, Pennsylvania (E.K.)
Johns Hopkins School of Medicine, Baltimore, Maryland (M.J.B.)
Johns Hopkins Bloomberg School of Public Health and Johns Hopkins School of Medicine, Baltimore, Maryland (E.G.)
Johns Hopkins School of Medicine and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (E.D.M.)
Financial Support: Drs. Zhao, Guallar, and Michos are funded by the Blumenthal Scholars Fund in Preventive Cardiology at Johns Hopkins University.
Disclosures: Dr. Blaha reports grants from the National Heart, Lung, and Blood Institute, the Food and Drug Administration, the American Heart Association, Amgen, and the Aetna Foundation and personal fees from the Food and Drug Administration, Amgen, Sanofi, Novartis, Novo Nordisk, and Bayer outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-0341.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Corresponding Author: Safi U. Khan, MD, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26505; e-mail, safinmc@gmail.
Current Author Addresses: Drs. S.U. Khan, M.U. Khan, and Valavoor: West Virginia University, One Medical Center Drive, Morgantown, WV 26508.
Dr. H. Riaz: Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195.
Drs. Zhao and Guallar: Johns Hopkins Bloomberg School of Public Health, Welch Center, 2024 East Monument Street, Suite 2600, Baltimore, MD 21205.
Drs. Vaughan and Okunrintemi: East Carolina University, 2100 Stantonsburg Road, Greenville, NC 27834.
Drs. I.B. Riaz and Murad: Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55901.
Dr. M.S. Khan: 903 South Ashland Avenue, Apt 1206, Chicago, IL 60607.
Dr. Kaluski: Guthrie Robert Packer Hospital, One Guthrie Square, Sayre, PA 18840.
Dr. Blaha: Johns Hopkins School of Medicine, 600 North Wolfe Street, Blalock 524-D1, Baltimore, MD 21287.
Dr. Michos: Johns Hopkins School of Medicine, 600 North Wolfe Street, Blalock 524-B, Baltimore, MD 21287.
Author Contributions: Conception and design: S.U. Khan.
Analysis and interpretation of the data: S.U. Khan, D. Zhao, E. Guallar, E.D. Michos.
Drafting of the article: S.U. Khan, H. Riaz, L. Vaughan, V. Okunrintemi, E. Guallar, E.D. Michos.
Critical revision of the article for important intellectual content: S.U. Khan, I.B. Riaz, M.S. Khan, M.H. Murad, M.J. Blaha, E. Guallar, E.D. Michos.
Final approval of the article: S.U. Khan, M.U. Khan, H. Riaz, S. Valavoor, D. Zhao, L. Vaughan, V. Okunrintemi, I.B. Riaz, M.S. Khan, E. Kaluski, M.H. Murad, M.J. Blaha, E. Guallar, E.D. Michos.
Provision of study materials or patients: S.U. Khan, M.U. Khan, S. Valavoor.
Statistical expertise: S.U. Khan, M.H. Murad, D. Zhao, E. Guallar, E.D. Michos.
Administrative, technical, or logistic support: E.D. Michos.
Collection and assembly of data: S.U. Khan, M.U. Khan, S. Valavoor.
This article was published at Annals.org on 9 July 2019.