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Not enough evidence to show that over-the-counter supplements prevent cognitive decline in healthy adults or people with mild cognitive impairment

Butler M, Nelson VA, Davila H, et al. Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2018;168:52-62.

Review questions

In adults without cognitive impairment, do supplements that don’t need a prescription (over-the-counter [OTC] supplements) prevent cognitive decline or dementia? Do OTC supplements work in adults with mild cognitive impairment?

Background

Cognitive function includes abilities such as thinking, remembering, using language, and making decisions. As we get older, our cognitive functions may decline. Mild cognitive impairment includes cognitive changes that are noticeable but usually don’t have much effect on daily living. Dementia is cognitive impairment that is serious enough to interfere with daily living.

Many people use OTC supplements to prevent or delay cognitive decline. However, we don’t know which supplements, if any, reduce risk for cognitive decline.

How the review was done

The researchers did a systematic review of studies available up to July 2017. They analyzed 38 studies; most were randomized controlled trials.

The key features of the studies were:

• people had normal cognition or mild cognitive impairment;
• people with dementia were excluded;
• OTC supplements included omega-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin E, vitamin D plus calcium, vitamin C, beta-carotene, and multivitamins;
• OTC supplements were mainly compared with placebo; some OTC supplements were compared with another supplement;
• people were followed up for at least 6 months; and
• about 33% of studies were funded by industry.

What the researchers found

Most of the evidence was of low strength (confidence in results was limited) or insufficient to reach any conclusions. Some evidence was of moderate strength (moderate confidence in results).

Results in adults with normal cognition

Compared with placebo (also see Table below):

• omega-3 fatty acids, gingko biloba, vitamin E, vitamin D plus calcium, and multivitamins did not reduce risk for dementia (low-strength evidence);
• folic acid plus vitamin B₁₂ improved memory (low-strength evidence);
• vitamin E and B vitamins did not improve cognitive function (moderate-strength evidence); and
• omega-3 fatty acids, soy, gingko biloba, folate plus vitamins B₆ and B₁₂, vitamin D plus calcium, vitamin C, beta-carotene, and multivitamins did not improve cognitive function (low-strength evidence).

Compared with other supplements:

• omega-3 fatty acid supplements, with or without B vitamins, did not improve global cognitive test results or memory compared with B vitamins alone at 4 years in 1 study with 884 people (low-strength evidence).

Results in adults with mild cognitive impairment

Compared with placebo:

• vitamin E did not reduce risk for dementia at 3 years in 1 study with 516 people (low-strength evidence); and
• evidence was insufficient to evaluate other supplements (6 studies).

Conclusion

In people with normal cognition or mild cognitive impairment, there isn’t enough evidence to show that any over-the-counter supplements prevent cognitive decline.

Over-the-counter supplements vs placebo in adults with normal cognition*

*The Table doesn’t include outcomes with insufficient evidence to evaluate supplement effects.

†Ratings: insufficient evidence or low- (limited confidence in results), moderate-, or high- (very confident in results) strength evidence.

‡Executive function includes activities such as problem-solving, judgment, and decision-making.