What supplements can improve memory and cognition?

Supplements for Memory and Cognition: Evidence-Based Recommendations

Most dietary supplements marketed for cognitive enhancement lack robust evidence for improving memory or cognition in healthy adults or those with cognitive impairment, and should not be routinely recommended for these purposes. 1

Key Recommendations by Supplement Type

Omega-3 Fatty Acids (Fish Oil)

• Do not use omega-3 supplements in persons with established dementia – high-quality evidence from multiple randomized controlled trials shows no benefit for cognitive or functional outcomes when combined EPA (600-975 mg/day) and DHA (675-1720 mg/day) are given for 6-18 months 1
• May consider in mild cognitive impairment (MCI) only – some evidence suggests potential benefits in specific domains (immediate recall, attention, processing speed, working memory) when used for 6-12 months, though this requires confirmation 1, 2
• For those considering supplementation: DHA appears more important than EPA for brain health due to its high concentration in brain tissue (comprising ~25% of cerebral cortex fatty acids), with doses of 2-3g/day combined omega-3s showing the most promise 2
• Critical threshold: Achieving an omega-3 index ≥4% in blood appears necessary for any cognitive benefits 2

B Vitamins (B6, B12, Folic Acid)

• Do not recommend B vitamin supplementation unless documented deficiency exists 1
• Evidence from multiple high-quality trials shows no benefit on cognitive decline, dementia incidence, or functional outcomes when B vitamins are given for 6-24 months, despite successfully lowering homocysteine levels 1, 3, 4
• Exception: One subgroup analysis suggested possible benefit in those with elevated baseline homocysteine levels, but this requires replication before clinical application 1, 4

Vitamin E

• Do not recommend vitamin E supplementation for cognitive protection 1, 4
• High-quality evidence from a large trial (n=516) showed no effect on progression from MCI to Alzheimer's dementia over 3 years with 2000 IU daily 1, 4
• While one study showed slower functional decline (not cognitive), this was a secondary outcome and vitamin E carries potential toxicity risks at high doses 1

Other Micronutrients

• Do not recommend routine supplementation with vitamin D, vitamin C, selenium, copper, or other single micronutrients for cognitive enhancement 1
• No controlled intervention studies have demonstrated cognitive benefit from supplementing any single micronutrient in persons without documented deficiency 1

Multi-Ingredient/Multivitamin Supplements

• Limited evidence of benefit – one meta-analysis found multivitamins improved immediate free recall memory but not delayed recall or verbal fluency 5
• Multi-nutrient combinations theoretically more promising than single nutrients, but current evidence remains unconvincing 1
• Insufficient evidence to recommend for cognitive protection 3, 6

Clinical Approach Algorithm

Step 1: Assess for Actual Deficiency

• Screen for malnutrition, malabsorption disorders, metabolic conditions, or severely unbalanced diets that could cause true nutrient deficiencies 1
• In persons with dementia or cognitive impairment, consider individual assessment for specific deficiencies given their higher risk of inadequate nutrition 1

Step 2: Correct Documented Deficiencies Only

• If specific deficiency identified, supplement that nutrient at normal therapeutic doses (not mega-doses) 1
• Monitor for potential toxic effects of high-dose supplementation 1

Step 3: Do Not Routinely Supplement

• Without documented deficiency, supplementation does not improve cognition or prevent cognitive decline 1
• This applies across the spectrum from normal cognition through MCI to established dementia 1, 3

Important Caveats and Pitfalls

Common Misconceptions to Address:

• Despite biological plausibility (vitamins/minerals serve as cofactors for brain metabolism and protect against oxidative damage), supplementation in non-deficient individuals does not translate to cognitive benefit 1
• Normalizing biomarkers (e.g., lowering homocysteine with B vitamins) does not necessarily improve clinical outcomes 1, 3

Quality of Evidence Considerations:

• The strongest evidence comes from 2024 Clinical Nutrition guidelines with 100% consensus recommending against micronutrient supplementation unless deficiency exists 1
• Most trials showing "positive" effects had methodological flaws, short follow-up periods, or findings of questionable clinical significance 1, 3, 6

Safety Concerns:

• High-dose supplementation carries potential toxicity risks that must be weighed against unproven benefits 1
• Adverse events are rarely systematically reported in supplement trials 3

Alternative Recommendation:

• Rather than supplements, the American Heart Association recommends consuming fatty fish 2-3 times weekly for general brain health 2
• Focus on correcting overall malnutrition with comprehensive nutritional support rather than isolated nutrient supplementation 1