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Evidence Summary

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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*

Supplements

Number of studies and people

Effect of supplements

Strength of evidence†

Omega-3 fatty acids

7 studies (21,027 people)

No benefits for preventing dementia at 6.2 years (1 study) or for overall cognitive tests, memory, executive function‡, attention, or processing speed at 2 to 6 years (1 to 5 studies)

Low

Soy

5 studies (829 people)

No benefits for memory, executive function‡, attention, or processing speed at 2.5 years

Low

Gingko biloba

3 studies (5,559 people)

No benefits for preventing dementia (3 studies) or for overall cognitive test results, memory, executive function‡, attention, or processing speed (1 study) at 6 years

Low

B vitamins (folic acid + vitamin B12)

2 studies (3,819 people)

Improved memory at 2 years

Low

 

 

No benefits for executive function‡, attention, or processing speed at 2 years

Moderate

B vitamins (folate + vitamins B6 and B12)

2 studies (1,524 people)

No benefits for overall cognitive test results or memory at 3.3 to 4 years

Low

Vitamin E

3 studies (12,830 people)

No benefits for preventing dementia at 10 years (1 study)

Low

 

 

No benefits for overall cognitive test results or memory at 4 years (2 studies)

Moderate

Multivitamins

4 studies (27,613 people)

No benefits for preventing dementia or mild cognitive impairment at 5 years (1 study) or for overall cognitive test results (1 study) or memory, executive function‡, attention, or processing speed (2 studies) at 1 year or an undefined time

Low

Vitamin D + calcium

1 study (4,143 people)

No benefits for preventing dementia or mild cognitive impairment or for memory, executive function‡, attention, or processing speed at 7 years

Low

Vitamin C

1 study (2,471 people)

No benefits for overall cognitive test results or memory at 4 years

Low

Beta-carotene

1 study (2,471 people)

No benefits for overall cognitive test results or memory at 4 years

Low

*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.




Glossary

Cognitive function
Mental processes, including thinking, learning and remembering.
Cognitive impairment
Trouble remembering, learning new things, concentrating, or making decisions that affect everyday life.
Placebo
A harmless, inactive, and simulated treatment.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

Related Web Resources

  • Alzheimer's Disease: Do Ginkgo products help?

    Informed Health Online
    Gingko supplements (240 mg per day) may help reduce symptoms of Alzheimer's disease and enable you to perform daily tasks better. Be aware that gingko could interact with other medications, so talk to your doctor before taking any supplements.
  • Worried about dementia? Here are 5 ways to cut your risk

    HealthLine
    Dementia affects millions of people around the world, and there is no current treatment. There are a few ways to lower your risk. Eat a well-balanced diet, exercise, stay social, and limit alcohol and smoking.
  • High blood sugar can increase cognitive decline

    Berkeley Wellness
    New research shows that if you have high blood sugar, you might be more at risk for cognitive decline as you age. Whether or not you have diabetes, it is important to keep your blood sugar under control.
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