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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

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The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health State-of-the-Science Conference

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Review published: .

CRD summary

This review concluded that there was insufficient evidence to determine the presence or absence of benefits from the use of multivitamin and mineral supplements for the prevention of cancer and chronic disease. These conclusions reflect the results of the review and are probably reliable.

Authors' objectives

To assess the efficacy and safety of multivitamin and mineral supplements for the primary prevention of cancer and chronic disease in the general population.


MEDLINE, EMBASE and the Cochrane Library were searched from 1966 to February 2006. References of articles were checked, experts were contacted, and tables of contents for 15 relevant journals were searched from January 2005 to February 2006. Search terms were reported in the full report (see Other Publications of Related Interest). Only studies reported in English were eligible for inclusion.

Study selection

Randomised controlled trials (RCTs) which assessed the efficacy of a multivitamin/mineral supplement for the prevention of one or more of the following chronic diseases were eligible for inclusion: cancer; myocardial infarction or stroke; type 2 diabetes; Parkinson's disease or dementia; cataracts; macular degeneration or hearing loss; osteoporosis; osteopenia; rheumatoid arthritis; osteoarthritis; non-alcoholic steatorrheic hepatitis; non-alcoholic fatty liver disease; chronic renal insufficiency; chronic nephrolithiasis; HIV (human immunodeficiency virus) infection; hepatitis C; tuberculosis; and chronic obstructive pulmonary disease. Studies which included only the following types of participants were excluded from the review: pregnant women; people aged up to 18 years; people with a chronic disease or those receiving treatment for such a disease; patients in long-term care facilities; or people with a clinical nutritional deficiency. Studies which assessed only safety or which did not assess supplement use separately from dietary intake were also excluded. For the assessment of safety observational studies in adults and children were also eligible for inclusion.

Included trials were conducted in the USA, UK, France and China. Chronic diseases assessed included cancer, cardiovascular disease, cataracts, age-related macular degeneration and hypertension. Supplements included a range of vitamin and mineral combinations and doses.

Two reviewers assessed the studies for inclusion in the review. Disagreements were resolved through consensus

Assessment of study quality

Two reviewers independently assessed the trials for validity using criteria in the following categories: representativeness of participants (four items); bias and confounding (12 items); description of intervention (one item); adherence to treatment and follow-up (seven items); and statistical analysis (six items). Each item was scored between zero and two; each category was scored as percentage of the total possible score; an overall score was calculated as the mean of the category scores. In each category, trials were rated as good (80% or higher), fair (50% to 79%) or poor (under 50%).

Data extraction

Data to permit the calculations of relative risks (RR) with 95% confidence intervals (CI) were extracted by one reviewer and checked by a second reviewer. Disagreements were resolved through adjudication.

Methods of synthesis

The trials were combined in a narrative synthesis grouped by outcome.

Results of the review

Five RCTs (reported in 12 publications) were included in the review of effectiveness (n=47,289 participants). Sample size ranged from 71 to 29,584 participants. Study quality was generally fair for trials of cancer, cardiovascular disease, cataracts and age-related macular degeneration, and poor for trials of hypertension. The principal problems were poor reporting of allocation concealment, independent outcome evaluation and concomitant medication use. Four RCTs and three case reports were included in the assessment of safety.

Cancer: One very large RCT in a poorly nourished Chinese population found a reduced incidence of gastric cancer and a reduced overall cancer mortality rate (RR 0.87, 95% CI 0.75 to 1.00) in the groups given a multivitamin supplement containing beta-carotene, alpha-tocopherol and selenium, with or without other nutrients, compared with groups receiving supplements without these nutrients. No significant differences were found for any other cancer outcome. There was also a reduced incidence of noncardia stomach cancer in groups receiving supplements containing retinol and zinc. A large French RCT found no benefit for use of antioxidant supplements in women but a reduction in risk of cancer in men (RR 0.69, 95% CI 0.53 to 0.91).

Cardiovascular disease: The large Chinese RCT found a lowered risk of death from stroke in people receiving beta-carotene, alpha-tocopherol, selenium, retinol and zinc (RR 0.71, 95% CI 0.50 to 1.00). A second RCT found no differences between groups in incidence of ischaemic cardiovascular disease.

Hypertension: The large Chinese RCT found an increased rate of isolated diastolic hypertension in people receiving beta-carotene, alpha-tocopherol and selenium, but a lowered rate in people given riboflavin, niacin, vitamin C and molybdenum. No other significant findings were reported and a second large RCT found no differences in incidence of hypertension.

Total mortality rate: Inconsistent results were reported. A Chinese RCT found a decrease in overall mortality in people receiving beta-carotene, alpha-tocopherol and selenium (RR 0.91, 95% CI 0.84 to 0.99). A second trial found a decrease in mortality in men (RR 0.63, 95% CI 0.42 to 0.93), but not women given antioxidants; while a third study found a non-significant increase in mortality in such groups.

Cataracts and age-related macular degeneration: There was some evidence for the efficacy of antioxidants plus zinc in two trials (RR 0.73, 95% CI 0.54 to 0.99 for moderate visual acuity loss and for advanced macular degeneration (RR 0.72, 95% CI 0.52 to 0.98).

The strength of evidence for the efficacy of supplements in the general adult USA population was considered very low for all these indications.

Safety: No consistent pattern of increased adverse events was evident from four RCTs.

Authors' conclusions

There was insufficient evidence to determine the presence or absence of benefits from the use of multivitamin and mineral supplements for the prevention of cancer and chronic disease.

CRD commentary

The review question and the inclusion criteria were clear. The authors searched three relevant databases and other sources, but the restriction to studies reported in English may have increased the possibility of language bias and the omission of some relevant studies. Rigorous methodology was used at all stages of the review, which minimised the risk of reviewer error and bias. The validity assessment used appropriate criteria and was used to inform the synthesis. The decision to use a narrative synthesis was clearly appropriate, in view of the clinical heterogeneity between trials. The authors' conclusions accurately reflect the results of the review and, despite concerns about possible language bias, are probably reliable.

Implications of the review for practice and research

Practice: Practitioners advising patients should be aware that, although supplements are unlikely to have serious adverse effects, it remains unclear whether supplementation is effective in preventing major chronic diseases in the general adult population in the USA. Other health conditions such as pregnancy, where folic acid supplementation is beneficial, should also be considered when making recommendations.

Research: The authors stated that further research should be directed towards developing valid biomarkers which predict disease risk, and measuring them in RCTs to guide the search for the optimal composition and dose of multivitamin and mineral supplements. Research is also needed to examine how the effects of such supplements may vary with age, sex, adherence, dietary patterns and genetic polymorphisms of recipients, as well as duration of supplementation. Interactions between nutrients should be examined and attention given to controlling for co-interventions.


Agency for Healthcare Research and Quality, Contract number 290-02-0018.

Bibliographic details

Huang HY, Caballero B, Chang S, Alberg AJ, Semba RD, Schneyer CR, Wilson RF, Cheng TY, Vassy J, Prokopowicz G, Barnes GA, Bass EB. The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health State-of-the-Science Conference. Annals of Internal Medicine 2006; 145(5): 372-385. [PubMed: 16880453]

Other publications of related interest

Huang HY, Caballero B, Chang S, Alberg A, Semba R, Schneyer C, Wilson RF, Cheng TY, Prokopowicz G, Barnes GJ, Vassy J, Bass EB. Multivitamin/mineral supplements and prevention of chronic disease. Rockville, MD, USA: Agency for Healthcare Research and Quality. Evidence Report/Technology Assessment;139. 2006.

Indexing Status

Subject indexing assigned by NLM


Adult; Chronic Disease; Dietary Supplements /adverse effects /utilization; Humans; Minerals /administration & dosage /adverse effects; Neoplasms /prevention & control; Primary Prevention; United States; Vitamins /administration & dosage /adverse effects



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

Copyright © 2014 University of York.
Bookshelf ID: NBK72878


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