What supplements, besides omega-3 fatty acids (Omega-3), can support cognitive performance?

Supplements for Cognitive Performance Beyond Omega-3

Do not routinely use dietary supplements for cognitive enhancement in healthy adults or those with dementia, as high-quality evidence shows no benefit for most supplements when no documented deficiency exists. 1, 2

Evidence-Based Approach to Supplementation

B Vitamins (B1, B6, B12, Folic Acid)

• Do not recommend B vitamin supplementation for cognitive enhancement unless documented deficiency exists, as multiple high-quality trials show no benefit on cognitive decline, dementia incidence, or functional outcomes 1, 2
• Vitamin B1 (thiamine) supplementation in persons with dementia shows no reliable evidence of benefit when no deficiency is present (very low grade evidence) 1
• Vitamin B6, B12, and folic acid supplementation does not improve cognition in persons with dementia despite their role in homocysteine metabolism (low grade evidence) 1
• These vitamins are commonly promoted online in proprietary blends, but this marketing does not reflect the scientific evidence 3

Vitamin E

• Do not recommend vitamin E supplementation for cognitive protection, as high-quality evidence from large trials showed no effect on progression from mild cognitive impairment to Alzheimer's dementia over 3 years with 2000 IU daily 2
• Despite antioxidant properties that theoretically protect brain tissue from oxidative damage, intervention trials have failed to demonstrate efficacy 1

Vitamin D

• Do not recommend routine vitamin D supplementation for cognitive enhancement in the absence of documented deficiency 2
• No controlled intervention studies have demonstrated cognitive benefit in persons without deficiency 2

Herbal Supplements with Limited Evidence

Bacopa monnieri

• Some evidence suggests Bacopa may improve memory free recall in healthy adults when used at 300-450 mg daily over 12 weeks 4, 5
• A systematic review found improvement in 9 of 17 tests in the domain of memory free recall, but little evidence for enhancement in other cognitive domains 4
• Bacopa is frequently included in proprietary blends marketed for brain health, often combined with B vitamins and Ginkgo biloba 3, 5
• The evidence remains inconsistent and of low certainty, making firm recommendations difficult 6

Ginkgo biloba

• Commonly promoted in online supplements for brain health, often in combination products 3
• Evidence for cognitive enhancement is inconsistent and imprecise across studies 6
• Frequently appears in multinutrient formulas but lacks robust evidence as a standalone cognitive enhancer 5

Ginseng

• Identified as a frequently marketed ingredient for cognitive performance 6
• Evidence is inconsistent with methodological flaws across studies 6

Other Herbal Supplements

• Rhodiola rosea, valerian root, and lion's mane mushroom have been studied but lack sufficient high-quality evidence for recommendation 6, 7
• Saffron, turmeric, and Withania somnifera show promise in some trials but require confirmation 7

Other Nutrients

Choline and Cholinergic Precursors

• Studied for cognitive performance but evidence remains inconsistent 6, 7
• Insufficient data to make firm recommendations 6

Creatine

• Some studies suggest potential cognitive benefits, but evidence is limited and inconsistent 6

Tyrosine

• Evaluated in multiple studies but lacks consistent evidence for cognitive enhancement 6

Selenium and Copper

• Despite antioxidant properties, no controlled intervention studies demonstrate cognitive benefit without documented deficiency 1, 2

Clinical Algorithm for Supplement Decisions

Step 1: Screen for True Deficiencies

• Assess for malnutrition, malabsorption disorders (celiac disease, inflammatory bowel disease, bariatric surgery), metabolic conditions, or severely unbalanced diets 1, 2
• Consider individual assessment for specific deficiencies in persons with dementia or cognitive impairment, as they are at higher risk 1
• Order appropriate laboratory testing when clinical suspicion exists 1

Step 2: If Deficiency Identified

• Supplement the specific deficient nutrient at normal therapeutic doses (not mega-doses) 1, 2
• Monitor for potential toxic effects of high-dose supplementation 1, 2
• Reassess after appropriate treatment duration 1

Step 3: If No Deficiency Exists

• Do not recommend systematic supplementation for cognitive enhancement or dementia prevention 1, 2
• Recommend providing adequate amounts of all essential nutrients through a balanced dietary pattern instead 1
• Counsel patients that marketed "brain health" supplements lack robust evidence and are expensive 3

Critical Pitfalls to Avoid

Marketing vs. Science Gap

• The most commonly promoted online products (Prevagen®, Procera®, Neuro Health®, Focus Factor®) contain proprietary blends of Ginkgo biloba, B vitamins, huperzine-A, Bacopa monnieri, and phosphatidylserine 3
• These products have insufficient evidence of efficacy despite aggressive marketing 3
• Claims made on product bottles and through advertising do not match the science 6

Methodological Concerns

• Most supplement studies are inconsistent, imprecise, and methodologically flawed 6
• The low level of certainty in the science, coupled with unknown product contents, makes weighing risks and benefits difficult 6
• Baseline nutrient status and dietary intake are generally not considered in studies, yet these are important determinants of supplementation effects 1

Population-Specific Considerations

• Evidence suggests that diet quality prior to supplementation may influence outcomes, with some studies showing benefits only in those with already "optimal" diets 5
• This paradoxical finding supports the concept of "co-nutrient optimization" and interdependency of nutrients 5
• However, this does not justify routine supplementation in well-nourished individuals 1, 2

Toxicity Risks

• High-dose supplementation carries potential toxicity risks that must be weighed against unproven benefits 1, 2
• Mega-doses should be avoided even when treating documented deficiencies 1

Strength of Evidence Summary

• The strongest evidence comes from ESPEN guidelines (2015) and synthesized evidence (2024-2025) recommending against micronutrient supplementation unless deficiency exists 1, 2
• For all nutrients examined to date, present evidence from intervention trials suggests that supplements are unlikely to be effective in the treatment of dementia 1
• The evidence for cognitive enhancement in healthy adults remains of low certainty across all supplement categories reviewed 6