Original Research
9 April 2019

Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults: A Cohort Study

Publication: Annals of Internal Medicine
Volume 170, Number 9



The health benefits and risks of dietary supplement use are controversial.


To evaluate the association among dietary supplement use, levels of nutrient intake from foods and supplements, and mortality among U.S. adults.


Prospective cohort study.


NHANES (National Health and Nutrition Examination Survey) data from 1999 to 2010, linked to National Death Index mortality data.


30 899 U.S. adults aged 20 years or older who answered questions on dietary supplement use.


Dietary supplement use in the previous 30 days and nutrient intake from foods and supplements. Outcomes included mortality from all causes, cardiovascular disease (CVD), and cancer.


During a median follow-up of 6.1 years, 3613 deaths occurred, including 945 CVD deaths and 805 cancer deaths. Ever-use of dietary supplements was not associated with mortality outcomes. Adequate intake (at or above the Estimated Average Requirement or the Adequate Intake level) of vitamin A, vitamin K, magnesium, zinc, and copper was associated with reduced all-cause or CVD mortality, but the associations were restricted to nutrient intake from foods. Excess intake of calcium was associated with increased risk for cancer death (above vs. at or below the Tolerable Upper Intake Level: multivariable-adjusted rate ratio, 1.62 [95% CI, 1.07 to 2.45]; multivariable-adjusted rate difference, 1.7 [CI, −0.1 to 3.5] deaths per 1000 person-years), and the association seemed to be related to calcium intake from supplements (≥1000 mg/d vs. no use: multivariable-adjusted rate ratio, 1.53 [CI, 1.04 to 2.25]; multivariable-adjusted rate difference, 1.5 [CI, −0.1 to 3.1] deaths per 1000 person-years) rather than foods.


Results from observational data may be affected by residual confounding. Reporting of dietary supplement use is subject to recall bias.


Use of dietary supplements is not associated with mortality benefits among U.S. adults.

Primary Funding Source:

National Institutes of Health.

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Information & Authors


Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 170Number 97 May 2019
Pages: 604 - 613


Published online: 9 April 2019
Published in issue: 7 May 2019




Fan Chen, MS, MPH
Friedman School of Nutrition Science and Policy, Tufts University, and Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts (F.C.)
Mengxi Du, MS, MPH
Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts (M.D., J.B.B., L.Z., F.F.Z.)
Jeffrey B. Blumberg, PhD
Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts (M.D., J.B.B., L.Z., F.F.Z.)
Kenneth Kwan Ho Chui, PhD, MPH
Tufts University School of Medicine, Boston, Massachusetts (K.K.C.)
Mengyuan Ruan, MS
Friedman School of Nutrition Science and Policy and School of Medicine, Tufts University, Boston, Massachusetts (M.R.)
Gail Rogers, MA
Friedman School of Nutrition Science and Policy and Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts (G.R.)
Zhilei Shan, MD, PhD
Friedman School of Nutrition Science and Policy, Tufts University, and Harvard T.H. Chan School of Public Health, Boston, Massachusetts (Z.S.)
Luxian Zeng, MD, MPH
Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts (M.D., J.B.B., L.Z., F.F.Z.)
Fang Fang Zhang, MD, PhD
Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts (M.D., J.B.B., L.Z., F.F.Z.)
Note: Dr. Zhang had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Grant Support: By grant 1R01MD011501 from the National Institute on Minority Health and Health Disparities, National Institutes of Health (Dr. Zhang).
Disclosures: Dr. Blumberg reports other support from AdvoCare International, Pfizer Consumer Healthcare, and Pharmavite 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=M18-2478.
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.
Reproducible Research Statement: Study protocol and data set: Not available. Statistical code: Available from Dr. Zhang (e-mail, [email protected]).
Corresponding Author: Fang Fang Zhang, MD, PhD, Friedman School of Nutrition Science and Policy, Tufts University, 150 Harrison Avenue, Boston, MA 02111; e-mail, [email protected].
Current Author Addresses: Ms. Chen: The Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA 02131.
Ms. Du and Drs. Blumberg, Zeng, and Zhang: Friedman School of Nutrition Science and Policy, Tufts University, 150 Harrison Avenue, Boston, MA 02111.
Dr. Chui and Ms. Ruan: Department of Public Health and Community Medicine, School of Medicine, Tufts University, 136 Harrison Avenue, Boston, MA 02111.
Ms. Rogers: Nutritional Epidemiology Program, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111.
Dr. Shan: Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115.
Author Contributions: Conception and design: F. Chen, F.F. Zhang.
Analysis and interpretation of the data: F. Chen, M. Du, J.B. Blumberg, K.K.H. Chui, M. Ruan, Z. Shan, F.F. Zhang.
Drafting of the article: F. Chen, F.F. Zhang.
Critical revision of the article for important intellectual content: F. Chen, J.B. Blumberg, M. Ruan, Z. Shan, F.F. Zhang.
Final approval of the article: F. Chen, M. Du, J.B. Blumberg, K.K.H. Chui, M. Ruan, G. Rogers, Z. Shan, L. Zeng, F.F. Zhang.
Statistical expertise: K.K.H. Chui, G. Rogers, F.F. Zhang.
Obtaining of funding: F.F. Zhang.
Administrative, technical, or logistic support: F. Chen, G. Rogers, L. Zeng, F.F. Zhang.
Collection and assembly of data: F. Chen, M. Du, M. Ruan, F.F. Zhang.
This article was published at Annals.org on 9 April 2019.

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Fan Chen, Mengxi Du, Jeffrey B. Blumberg, et al. Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults: A Cohort Study. Ann Intern Med.2019;170:604-613. [Epub 9 April 2019]. doi:10.7326/M18-2478

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