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Structured Abstract
Background:
In the United States, dietary supplements are commonly used to prevent chronic diseases, including cardiovascular disease (CVD) and cancer.
Purpose:
To systematically review evidence for the use of multivitamins or single nutrients and functionally related nutrient pairs for the prevention of CVD and cancer in the general population (primary prevention).
Methods:
We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials to identify literature that was published between 2005 and January 29, 2013. We also examined the references from the previous reviews and other relevant reviews to identify additional studies; we also searched Web sites of government agencies and other organizations for grey literature. Two investigators independently reviewed identified abstracts and full-text articles against a set of a priori inclusion and quality criteria. One investigator abstracted data into an evidence table and a second investigator checked these data. We qualitatively and quantitatively synthesized the results for the four key questions and grouped the included studies by study supplement. We conducted meta-analyses using Mantel-Haenzel fixed effects models for overall cancer incidence, CVD incidence, and all-cause mortality.
Results:
We included 103 articles representing 26 unique studies. Very few studies examined the use of multivitamin supplements. Two trials showed a protective effect against cancer in men; only one of these trials included women and found no effect. No effects of treatment were seen on CVD or all-cause mortality. Beta-carotene showed a negative effect on lung cancer incidence and mortality among individuals at high risk for lung cancer at baseline (i.e., smokers and asbestos-exposed workers); this effect was persistent even when combined with vitamin A or E. Trials of vitamin E supplementation showed mixed results and altogether had no overall effect on cancer, CVD, or all-cause mortality. Only one of two included selenium trials showed a beneficial effect for colorectal and prostate cancer; however, this trial included a small sample size. The few studies addressing folic acid, vitamin C, and vitamin A showed no effect on CVD, cancer, and mortality. Vitamin D and/or calcium supplementation also showed no overall effect on CVD, cancer, and mortality. Harms were infrequently reported and aside from limited paradoxical effects for some supplements, were not considered serious.
Conclusions:
There are a limited number of trials examining the effects of dietary supplements on the primary prevention of CVD and cancer; the majority showed no effect in healthy populations. Clinical heterogeneity of included studies limits generalizability of results to the general primary care population. Results from trials in at-risk populations discourage additional studies for particular supplements (e.g., beta-carotene); however, future research in general primary care populations and on other supplements is required to address research gaps.
Contents
- 1. Introduction
- 2. Methods
- 3. Results
- Literature Search
- KQ 1 What Is the Efficacy of Multivitamin Supplement Use on Health Outcomes in the General Adult Population?
- KQ 2 What Is Known About the Safety of Multivitamin Supplement Use in the General Adult Population?
- KQ 3 What Is the Efficacy of Supplementation With Single Nutrients or Functionally Related Nutrient Pairs on Health Outcomes in the General Adult Population?
- KQ 4 What Is Known About the Safety of Single Nutrient Use in the General Adult Population?
- 4. Discussion
- References
- Appendix A Dietary Reference Intakes
- Appendix B Detailed Methods
- Appendix C Ongoing or Recently Completed Studies
- Appendix D Excluded Studies
- Appendix E Evidence Tables
- Appendix F Outcomes Reported by Original Randomized Arms Among the 2×2 Factorial-Designed Randomized, Controlled Trials
- Appendix G Additional Meta-Analysis Figures
- Appendix H Sensitivity Analysis: Random vs. Fixed Effects Models
Note: A journal article associated with this work was published in Annals of Internal Medicine. At the request of the journal, we featured fixed effects models for pooled outcomes reported in the manuscript. The fixed effects models produced very small changes compared with the random effects models and do not change the overall findings of the report. Appendix H provides a comparison between the fixed effects and random effects model results for selected outcomes.
Acknowledgments: The authors gratefully acknowledge the following individuals for their contributions to this project: Robert McNellis, MPH, PA-C, at AHRQ; Virginia Moyer, MD, MPH, Michael LeFevre, MD, MSPH, and Wanda Nicholson, MD, MPH, MBA, of the U.S. Preventive Services Task Force; JoAnn Manson, MD, DrPH, MPH, Thomas Trikalinos, MD, PhD, and Janelle Peralez-Gunn, MPH, for providing expert review; and Carin M. Olson, MD, MS, Daphne Plaut, MLS, and Heather Baird at the Kaiser Permanente Center for Health Research.
Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. HHSA 290-2007-10057-I. Prepared by: Kaiser Permanente Research Affiliates Evidence-based Practice Center, Kaiser Permanente Center for Health Research, Portland, OR
Suggested citation:
Fortmann SP, Burda BU, Senger CA, Lin J, Beil T, O'Connor E, Whitlock EP. Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Report No. 108. AHRQ Publication No. 14-05199-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2013.
This report is based on research conducted by the Kaiser Permanente Research Affiliates Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA 290-2007-10057-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information; that is, in the context of available resources and circumstances presented by individual patients.
This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
- 1
540 Gaither Road, Rockville, MD 20850; www
.ahrq.gov
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