Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia A Systematic Review

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 ω-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or β-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 ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, β-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.

Primary Funding Source:

Agency for Healthcare Research and Quality.

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