Notes to Future-Me


Supplements for Long-term Brain Health

Posted:2023-12-27
Tags:Brain,Health

These supplements have good evidence supporting their usefulness in long-term brain health and in the prevention of cognitive decline.

Some promote better performance on cognitive tests in the short term, but that was not the primary selector for supplements on this list.

Supplements for short-term cognitive performance are listed here.

Actionable Takeaways

The following are recommended for supplementation.

Type Recommended Supplement
Vitamins A, B (complex), C, D, E, K
Minerals Magnesium, Selenium, Copper, Iron, Zinc, Calcium
Antioxidants Beta-carotene, Lutein, Lycopene, Co-Q10, Polyphenols, Curcumin (Turmeric), Acetyl-L-Carnitine
Other Choline, Omega-3s, Ginko Biloba, Lion’s Mane, Saffron

Deficiency as Risk Factor

Very few supplements show direct effectiveness against dementia and Alzheimer’s once symptoms begin. However, there is strong evidence that deficiencies in many of the listed items increase the risk of developing dementia and Alzheimer’s.

In these cases, supplementation is recommended as an effective form of prophylaxis.

Recommended supplements due to deficiency risk:
Choline, Copper, Iron, Vitamin A, Vitamin B (complex), Vitamin C, Vitamin D, Vitamin K, Zinc


Benefits by Supplement

Supplement / Intervention Result / Reference
Acetyl-L-Carnitine Neuro-protective and helps during injury recovery1.
No evidence for direct cognitive performance improvement2.
Beta-carotene Reduces risk of cognitive decline3.
Improved cognitive function (unclear if healthy adults)3.
Calcium Neuro-protective (when combined with Vitamin D)4.
Note: Alzheimer’s causes high serum levels5 6.
Choline Benefits attention, memory, executive function in early stage Alzheimer’s4.
Deficiency correlates with cognitive impairment7.
Co-Q10 Higher serum levels associated with reduced risk of cognitive decline8.
Caveats for neurological effectiveness of supplementation9.
Copper Deficiency (and excessive intake) increases cognitive decline risk4.
Curcumin Potentially protective against decline4.
Some evidence for improved memory4.
Ginko Biloba No evidence for effectiveness against existing Alzheimer’s10.
Iron Deficiency increases cognitive decline risk4.
Supplementation positively impacts IQ4.
Lion’s Mane Delays neuronal death in neurodegenerative diseases, prevent memory loss (mouse model), improved cognitive function in mildly impaired11.
Lutein Reduces risk of cognitive decline12.
Lycopene Weak evidence for reduced risk of cognitive decline13 14.
Magnesium Reduces risk of cognitive decline4.
Omega-3 Effective in prevention and treatment of Alzheimer’s4.
DHA may be more effective for prevention15.
Polyphenols
(berries, tea, and cocoa)
Effective in reducing dementia/Alzhiemer’s risk4.
Significant reduction in age-related memory and cognition decline16.
Saffron Improvement in cognitive function for mild to severe AD11.
Selenium Reduces risk of cognitive decline4.
Vitamin A Deficiency causes cognitive impairment17 18.
Vitamin B (complex) No evidence for effectiveness against existing Alzheimer’s10.
Deficiency increases cognitive decline risk4.
Improved memory and cognitive function4.
Vitamin C Deficiency increases cognitive decline risk4.
Vitamin D Deficiency increases cognitive decline risk4.
Improved mood and cognitive functions for 1500-4000 IU doses4.
Vitamin E anti-Alzheimer’s10
Protects cell membranes, effective in reducing dementia/Alzhiemer’s risk4.
Vitamin K Deficiency increases cognitive decline risk4.
Zinc Deficiency increases cognitive decline risk4.

Sources

  1. L-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain

    • Interesting quote: “Effective neuroprotection involves attenuating inflammation, preventing energy failure, preventing oxidative damage to key cellular and mitochondrial proteins, and maintaining neuronal and glial functions and biosynthetic capabilities.”
    • “acetyl-L-carnitine fulfills these requirements and also has the additional capability to provide an acetyl-CoA that can be oxidized for energy”

  2. L‐carnitine for cognitive enhancement in people without cognitive impairment
    Meta-analysis showed no evidence for cognitive enhancement in healthy adults, but author’s note that all studies (even those meeting minimum requirements for inclusion in the meta-analysis) were badly administered. 

  3. Carotenoids and Cognitive Outcomes: A Meta-Analysis of Randomized Intervention Trials
    Meta-analysis. Shows strong preventative role in cognitive decline, and cognitive improvements with supplementation.  2

  4. Improving Cognitive Function with Nutritional Supplements in Aging: A Comprehensive Narrative Review of Clinical Studies Investigating the Effects of Vitamins, Minerals, Antioxidants, and Other Dietary Supplements
    Very good and very recent, and with a table of specific recommendations.  2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

  5. Serum calcium and cognitive function in old age High serum calcium levels associated with worse cognitive performance and higher risk of cognitive decline. Appears to be a symptom of Alzheimer’s6

  6. Calcium Dysregulation in Alzheimer’s Disease: A Target for New Drug Development Calcium channels become disregulated in Alzheimer’s, resulting in high serum levels.  2

  7. Choline Intake Correlates with Cognitive Performance among Elder Adults in the United States Deficiency correlates with low cognitive function. 

  8. Coenzyme Q10 Levels Associated With Cognitive Functioning and Executive Function in Older Adults Unclear whether supplementation is helpful, but high levels are correlated with positive outcomes. 

  9. Coenzyme Q10, Ageing and the Nervous System: An Overview Endogenous production declines with age, but it is unclear whether exogenous Co-Q10 can cross the blood-brain barrier. However, still a very good supplement for non-neurological reasons. 

  10. Common Dietary Supplements for Cognitive Health
    Focused on dementia and Alzheimer’s. Mostly negative findings, but all specifically for effectiveness against already extand dementia and Alzheimer’s.  2 3

  11. The effects of twenty-one nutrients and phytonutrients on cognitive function: A narrative review Meta-analysis from 2021.  2

  12. Lutein Has a Positive Impact on Brain Health in Healthy Older Adults: A Systematic Review of Randomized Controlled Trials and Cohort Studies Meta-analysis. Positive findings for learning, memory, etc. Also may help prevent cognitive decline in aging. 

  13. Lycopene and cognitive function Meta-analysis. Weak positive findings for lycopene being protective against cognitive decline. 

  14. Lycopene attenuates western-diet-induced cognitive deficits via improving glycolipid metabolism dysfunction and inflammatory responses in gut–liver–brain axis Mouse model. Protective effect from cognitive impairment. 

  15. Effects of Omega-3 Polyunsaturated Fatty Acids on Brain Functions: A Systematic Review

    • Very recent publication, 2022.
    • Improved learning, memory ability, cognitive well-being, and blood flow in the brain.
    • EPA supplementation shows higher cognitive performance (vs DHA supplementation).
    • DHA displays more neuro-protective qualities.

  16. Effects of Nutrition on Cognitive Function in Adults with or without Cognitive Impairment: A Systematic Review of Randomized Controlled Clinical Trials Meta-analysis from 2021. 

  17. Vitamin A and Retinoic Acid in Cognition and Cognitive Disease Deficiency causes cognitive impairment. No effect on healthy adults. 

  18. Significance of vitamin A to brain function, behavior and learning Deficiency causes cognitive impairment (sometimes permanent if it occurs during critical stages of development).