What are the best supplements for improved cognition?

Best Supplements for Improved Cognition

Primary Recommendation

Omega-3 fatty acids (combined EPA and DHA) are the only supplements with meaningful evidence for cognitive enhancement in healthy adults, particularly when achieving an omega-3 index ≥4%, with doses of 2-3g daily showing benefits in verbal fluency, memory, and processing speed over 6-30 months. 1, 2

Omega-3 Fatty Acids: The Evidence-Based Choice

Dosing and Formulation

• Combined EPA and DHA supplementation at 2-3g daily is superior to either component alone for cognitive outcomes, though DHA appears more critical than EPA due to comprising 25% of cerebral cortex fatty acids 1, 2
• The HEARTS trial demonstrated that 3.36g combined EPA+DHA daily produced significant improvements in verbal fluency, language, and memory at both 12 and 30 months in adults with coronary artery disease 1
• Achieving an omega-3 index (blood level) ≥4% is necessary for cognitive benefits—those below this threshold showed no improvement in cognitive testing 1, 2

Who Benefits Most

• Cognitively healthy adults, especially those with cardiovascular risk factors (coronary artery disease increases dementia risk), show the strongest evidence for benefit 1, 3
• Individuals with mild cognitive impairment may benefit in specific domains (immediate recall, attention, processing speed) when supplemented for 6-12 months 4, 2, 3
• Do NOT use omega-3 supplements in established dementia—multiple high-quality trials show no benefit when cognitive decline is already advanced 1, 4, 2

Sex Differences Matter

• Men with higher omega-3 levels demonstrate better executive functioning and processing speed 1
• Women show enhanced verbal and nonverbal episodic memory with omega-3 supplementation 1
• Total omega-3 intake was particularly protective against Alzheimer's disease in women (P interaction=0.02) 1

Timing Is Critical

• Start supplementation before cognitive decline occurs—prospective studies show fish intake of 2 portions weekly associates with 30% reduction in Alzheimer's disease risk 1
• Benefits require sustained supplementation for at least 6-12 months to manifest 2, 3, 5

What NOT to Supplement

B Vitamins (B6, B12, Folic Acid)

• Do not supplement B vitamins unless documented deficiency exists 1, 4, 6
• Multiple high-quality RCTs show B vitamin supplementation effectively lowers homocysteine but produces zero cognitive benefit in non-deficient individuals 1, 6
• The ESPEN guidelines provide low-grade evidence against B vitamin supplementation for cognitive decline prevention 1, 6
• Exception: If serum B12 <150 pmol/L or homocysteine >19.9 μmol/L, treat the deficiency with 1mg B12 daily 6
• Interesting caveat: One study suggests omega-3 fatty acids may enhance B vitamin effects in MCI when both are present, but this requires confirmation 7

Vitamin E

• Do not recommend vitamin E supplementation—a large RCT using 2000 IU daily showed no effect on cognitive decline or progression from MCI to Alzheimer's over 3 years 1, 4
• The evidence grade is moderate against its use 1

Other Micronutrients

• No controlled trials demonstrate cognitive benefit from vitamin D, vitamin C, selenium, or copper supplementation in persons without documented deficiency 4
• High-dose supplementation carries toxicity risks that outweigh unproven benefits 4

Clinical Algorithm

Step 1: Screen for True Deficiency

• Assess for malnutrition, malabsorption disorders (celiac, Crohn's), strict vegan diet, pernicious anemia, or medications affecting absorption (metformin, PPIs) 6
• If cognitive symptoms present with risk factors, test B12, folate, vitamin D levels 6
• If deficiency confirmed, supplement that specific nutrient at therapeutic doses 4, 6

Step 2: Risk Stratification for Omega-3 Supplementation

• High priority: Adults with cardiovascular disease, family history of dementia, early memory complaints, or mild cognitive impairment 3
• Moderate priority: Cognitively healthy adults >55 years seeking prevention 2, 3
• Do not use: Established dementia patients 1, 4, 2

Step 3: Omega-3 Implementation

• Prescribe combined EPA+DHA at 2-3g daily (approximately 1.5g DHA + 1.5g EPA) 2, 5
• Alternative: Recommend fatty fish consumption 2-3 times weekly 1, 4, 2
• Set expectations: Benefits emerge after 6-12 months of consistent use 2, 3
• Consider checking omega-3 index if available—target ≥4% 1, 2

Common Pitfalls to Avoid

• Don't supplement "just in case" with B vitamins—the evidence is clear they don't work without deficiency, and you risk creating false reassurance 1, 4, 6
• Don't use EPA-only formulations (like icosapent ethyl)—DHA is more important for brain health than EPA alone 1
• Don't expect rapid results—cognitive benefits require months of supplementation 2, 3
• Don't continue omega-3 supplementation in advanced dementia—it won't help and wastes resources 1, 4, 2
• Don't ignore the omega-3 index threshold—supplementation without achieving adequate blood levels (≥4%) shows no benefit 1, 2

Safety Considerations

• Omega-3 supplementation up to 5g daily is well-tolerated with minimal side effects (mild GI upset, fishy aftertaste) 2
• Monitor for bleeding risk in patients on anticoagulation, though clinically significant bleeding is rare 2
• High-dose vitamin E (>400 IU daily) may increase all-cause mortality—another reason to avoid it 1