Over-the-counter supplement interventions to prevent cognitive decline, mild cognitive impairment, and clinical Alzheimer-type dementia

Mary E Butler, Torie Nelson, Heather W Davila, Edward Ratner, Howard A Fink, Laura S Hemmy, John R McCarten, Terry R. Barclay, Michelle Brasure, Robert L. Kane

Research output: Contribution to journalReview articlepeer-review

107 Scopus citations


Background: Optimal interventions to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia are uncertain. Purpose: To summarize the evidence on efficacy and harms of over-the-counter (OTC) supplements to prevent or delay cognitive decline, MCI, or clinical Alzheimer-type dementia in adults with normal cognition or MCI but no dementia diagnosis. Data Sources: Multiple electronic databases from 2009 to July 2017 and bibliographies of systematic reviews. Study Selection: English-language trials of at least 6 months' duration that enrolled adults without dementia and compared cognitive outcomes with an OTC supplement versus placebo or active controls. Data Extraction: Extraction performed by a single reviewer and confirmed by a second reviewer; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Data Synthesis: Thirty-eight trials with low to medium risk of bias compared -3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or -carotene, multi-ingredient supplements, or other OTC interventions with placebo or other supplements. Few studies examined effects on clinical Alzheimer-type dementia or MCI, and those that did suggested

no benefit. Daily folic acid plus vitamin B12 was associated with improvements in performance on some objectively measured memory tests that were statistically significant but of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of -3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, -carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength, suggesting that these supplements did not reduce risk for cognitive decline. Adverse events were rarely reported. Limitation: Studies had high attrition and short follow-up and used a highly variable set of cognitive outcome measures. Conclusion: Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI.

Original languageEnglish (US)
Pages (from-to)52-62
Number of pages11
JournalAnnals of internal medicine
Issue number1
StatePublished - Jan 2 2018

Bibliographical note

Funding Information:
This review was funded by the National Institute on Aging and the AHRQ. These agencies and members of the National Academies Committee on Preventing Dementia and Cognitive Impairment helped refine the scope and reviewed a draft report of findings. The authors are solely responsible for the content, preparation, and writing of the manuscript and the decision to submit it for publication.

Funding Information:
This manuscript is based on research conducted by the Minnesota Evidence-based Practice Center under AHRQ contract 290-2015-00008-I.


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