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Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S

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Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S Annals of Internal Medicine ORIGINAL RESEARCH Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults A Cohort Study Fan Chen, MS, MPH; Mengxi Du, MS, MPH; Jeffrey B. Blumberg, PhD; Kenneth Kwan Ho Chui, PhD, MPH; Mengyuan Ruan, MS; Gail Rogers, MA; Zhilei Shan, MD, PhD; Luxian Zeng, MD, MPH; and Fang Fang Zhang, MD, PhD Background: The health benefits and risks of dietary supple- tamin K, magnesium, zinc, and copper was associated with ment use are controversial. reduced all-cause or CVD mortality, but the associations were restricted to nutrient intake from foods. Excess intake of calcium Objective: To evaluate the association among dietary supple- was associated with increased risk for cancer death (above vs. at ment use, levels of nutrient intake from foods and supplements, or below the Tolerable Upper Intake Level: multivariable- and mortality among U.S. adults. adjusted rate ratio, 1.62 [95% CI, 1.07 to 2.45]; multivariable- Ϫ Design: Prospective cohort study. 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 Setting: NHANES (National Health and Nutrition Examination intake from supplements (≥1000 mg/d vs. no use: multivariable- Survey) data from 1999 to 2010, linked to National Death Index adjusted rate ratio, 1.53 [CI, 1.04 to 2.25]; multivariable-adjusted mortality data. rate difference, 1.5 [CI, Ϫ0.1 to 3.1] deaths per 1000 person-years) rather than foods. Participants: 30 899 U.S. adults aged 20 years or older who answered questions on dietary supplement use. Limitations: Results from observational data may be affected by residual confounding. Reporting of dietary supplement use is Measurements: Dietary supplement use in the previous 30 subject to recall bias. days and nutrient intake from foods and supplements. Out- comes included mortality from all causes, cardiovascular disease Conclusion: Use of dietary supplements is not associated with (CVD), and cancer. mortality benefits among U.S. adults. Results: During a median follow-up of 6.1 years, 3613 deaths Primary Funding Source: National Institutes of Health. occurred, including 945 CVD deaths and 805 cancer deaths. Ever-use of dietary supplements was not associated with mortal- Ann Intern Med. doi:10.7326/M18-2478 Annals.org ity outcomes. Adequate intake (at or above the Estimated Aver- For author affiliations, see end of text. age Requirement or the Adequate Intake level) of vitamin A, vi- This article was published at Annals.org on 9 April 2019. recent study found that more than half of U.S. plement and the nutrient source (foods vs. supplements) A adults reported use of dietary supplements in the can play critical roles in determining the benefits or risks previous 30 days (1). Whether dietary supplement use of nutrient intake. is associated with health benefits or risks is controversial. Using a nationally representative sample of U.S. The overall evidence suggests no benefits or harms, but a adults, we evaluated the association between dietary sup- few randomized controlled trials have reported adverse plement use and mortality from all causes, cardiovascular outcomes associated with dietary supplement use, espe- disease (CVD), and cancer. We further assessed whether cially at high doses (2, 3). For example, the ATBC (Alpha- adequate or excess nutrient intake was associated with Tocopherol, Beta-Carotene Cancer Prevention) study and mortality and whether the associations differed by nutri- CARET (Beta-Carotene and Retinol Efficacy Trial) found ent intake from foods versus supplements. that ␤-carotene supplements (20 or 30 mg/d) increased risk for lung cancer among smokers (4, 5), and SELECT METHODS (Selenium and Vitamin E Cancer Prevention Trial) re- ported that supplemental use of vitamin E (400 IU/d) in- Study Design and Population creased risk for prostate cancer among men (6). We used data from U.S. adults aged 20 years or Although randomized controlled trials usually assess older who participated in 6 cycles (1999–2000 to 2009– dietary supplement use at a specific dose, prospective co- 2010) of NHANES (National Health and Nutrition Exam- hort studies allow for evaluation of dose dependence ver- ination Survey). Exclusion of pregnant or lactating sus threshold effects and potential heterogeneous effects women resulted in 30 958 participants, among whom of nutrient intake from supplements versus foods (7). For 30 899 provided complete information on dietary sup- example, the CPS-II (Cancer Prevention Study II) Nutrition plement use in the previous 30 days. Those who re- Cohort found that higher doses of supplemental calcium (≥1000 mg/d) were associated with increased risk for all- cause death in men, but lower doses (<1000 mg/d) or See also: calcium intake from foods were not associated with mor- Editorial comment ...........................1 tality outcomes (8). Therefore, both the dose of the sup- Annals.org Annals of Internal Medicine © 2019 American College of Physicians 1 Downloaded from https://annals.org by Jules Jules Levin on 04/16/2019 ORIGINAL RESEARCH Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults sponded “refused” or “don't know” or did not answer cancer was defined as codes C00 to C97 being listed as the questions on dietary supplement use were ex- the underlying cause. Follow-up length was defined as cluded (n = 59). Among the 30 899 participants who the interval from the interview date to the date of death provided information on dietary supplement use, or to the end of 2011 for those who were censored. 27 725 with 1 or 2 valid 24-hour diet recalls were in- Demographic Characteristics, Lifestyle Factors, cluded in the analysis that estimated nutrient intake and Comorbid Conditions from foods versus supplements and its association with Demographic characteristics and lifestyle factors, mortality outcomes. NHANES was approved by the re- including age, sex, race/ethnicity, education, income, search ethics review board of the National Center for smoking, and physical activity, were collected during Health Statistics, and all participants provided written household interviews. Alcohol intake, weight, and informed consent. height were obtained during physical examinations at Dietary Supplement Use the Mobile Examination Center. Smokers were defined NHANES participants were asked during an in- as participants who reported smoking at least 100 cig- house interview whether they had used any dietary sup- arettes during their lifetime, and former smokers were plements in the previous 30 days. Those who reported defined as those who reported smoking at least 100 supplement use were asked about the product name, cigarettes but were not currently smoking. Drinkers frequency (for example, how many times each day), du- were defined as participants who consumed at least 12 ration (for example, how many days in the previous 30 alcoholic drinks in a given year. Moderate versus heavy days), and serving form (for example, capsules, tablets, drinkers were defined as participants who consumed pills, softgels, or drops). For each nutrient, the daily fewer than 1 versus 1 or more drinks per day (women) dose was calculated by combining the frequency (for or fewer than 2 versus 2 or more drinks per day (men). example, the number of capsules taken each day) with Participants were classified as physically active if they the product information on the ingredient (for example, had at least 150 minutes of moderate to vigorous phys- vitamin D or calcium), the amount per serving, and the ical activity per week and were classified as physically units (for example, international units or milligrams). Nu- inactive otherwise (12). Diet quality was assessed using trient intake from each product was summed to estimate the Healthy Eating Index-2015, which measures adher- the total daily dose of each supplemental nutrient for ence to the 2015–2020 Dietary Guidelines for Ameri- each participant (Appendix 1, available at Annals.org). cans (13). A higher score corresponds to a healthier Nutrient Intake From Foods diet. Comorbid conditions, including cancer, conges- tive heart failure, coronary heart disease, myocardial in- Nutrient intake from foods was assessed using 24- farction, and stroke, were defined if participants re- hour diet recalls conducted by trained interviewers. ported having ever been told by a physician that they One diet recall was done in person at the Mobile Ex- had these conditions and/or if they had ever been told amination Center; from 2003 to 2010, a second recall to take or were currently taking prescription medication was added by telephone interview approximately 3 to to treat high cholesterol, hypertension, or diabetes. 10 days after the first one. Using the Automated Multiple-Pass Method, all foods and beverages con- Statistical Analysis sumed the previous day were recorded. A standard set We first estimated the prevalence of supplement of measuring guides was used to help the respondent use among the participants. Multivitamin and mineral report the volume and dimensions of the items con- (MVM) supplement use was defined as use of a product sumed. Food intakes were coded and nutrient values formulated with 3 or more vitamins with or without min- were determined using the U.S. Department of Agricul- erals (14). We then compared the distribution of demo- ture Food and Nutrient Database for Dietary Studies graphic characteristics, lifestyle factors, and comorbid (FNDDS), versions 1.0 to 5.0 (9). conditions between participants who used any dietary Inadequate and Excess Nutrient Intake supplements and those who did not, using t tests for continuous variables and ␹2 tests for categorical vari- Inadequate nutrient intake was defined as levels of ables. We further estimated total nutrient intake by total nutrient intake (foods plus supplements) below summing intake from foods and supplements and the the Estimated Average Requirement or the Adequate percentage of participants with inadequate or excess Intake level specified in the Dietary Reference Intakes intake.
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