What Are the Top 10 Supplements for Brain Health?

Last Updated: November 2025

In this FAQ, Dr. Jessica Knape of HealthSpan Internal Medicine in Boulder, CO, explains that supplements can support cognitive health but must be tailored to each person’s underlying metabolic, inflammatory, and genetic factors. Guided by IntellxxDNA genomics and advanced labs, she uses supplements as part of a comprehensive, personalized brain-health plan.

Supplements can play a meaningful role in supporting cognitive health — but they are supportive tools, not substitutes for a medical evaluation. Brain health is influenced by many systems at once: inflammation, metabolism, hormones, toxins, vascular function, nutrient status, mitochondrial health, sleep, genetics, and more. This means the “best” supplements for one person may not match what another person needs.

As a ReCODE 2.0 Certified Practitioner with more than 10 years of experience caring for adults with Alzheimer’s, dementia, and cognitive decline, Dr. Jessica Knape uses supplements strategically, guided by IntellxxDNA genomic testing and advanced lab work. Supplements are most effective when used within a comprehensive, individualized brain-health plan that also includes nutrition, sleep, stress management, vascular support, detoxification (when needed), and metabolic repair.

Below are 10 evidence-based supplements commonly used to support brain health, along with how they work and what science tells us.

In a HealthSpan Minute

• Supplements can boost cognitive health, but only when matched to your biology.

• Top brain-supportive supplements include: omega-3 fatty acids, creatine, magnesium threonate, curcumin/Theracurmin, lithium orotate, folinic acid, lion’s mane mushroom, ashwagandha, phosphatidylserine, and vitamin D3 + K2.

• Evidence supports their roles in mitochondrial energy, inflammation reduction, neuroplasticity, stress resilience, BDNF production, and membrane support.

• Supplements work best when personalized to labs and genomics — especially methylation, inflammation, detox, and APOE patterns.

• Quality matters: clinical-grade, third-party tested supplements ensure safety and effectiveness.

Key Points

• Supplements are not a replacement for personalized medical care.

• They work best alongside lifestyle and metabolic interventions.

• Genomic testing (IntellxxDNA) guides personalized supplement selection.

• Evidence supports the use of several nutrients and botanicals for memory, focus, mood, and neuroprotection.

• Dosing must account for safety considerations, drug interactions, and individual biology.

The Top 10 Evidence-Supported Supplements for Brain Health

1. Omega-3 Fatty Acids (DHA + EPA)

Why it matters: DHA is a critical structural fat in the brain, making up nearly 30% of neuronal membrane phospholipids. EPA reduces systemic inflammation.

Evidence shows omega-3s may:

• Improve memory and processing speed

• Reduce neuroinflammation

• Support mood regulation

• Improve vascular health and endothelial function

• Benefit individuals with APOE4 (when properly dosed)

Key mechanisms:

• Enhances membrane fluidity

• Increases BDNF (brain-derived neurotrophic factor)

• Reduces amyloid aggregation in some studies

Important: Quality matters. Choose high-purity, triglyceride-form fish oil with a DHA emphasis for cognitive benefit.

2. Magnesium L-Threonate

Why it matters: Magnesium L-threonate is the only form shown to significantly raise magnesium levels in the brain.

Evidence shows it may:

• Improve working memory and executive function

• Enhance synaptic plasticity

• Reduce stress-related cognitive decline

Mechanisms:

• Supports NMDA receptor balance

• Helps regulate excitatory neurotransmission

• Promotes neuroplasticity

Many adults are magnesium deficient due to stress, poor soil quality, and medications (e.g., PPIs, diuretics).

3. Creatine Monohydrate

Why it matters: Creatine supports cellular energy production (ATP). The brain requires massive amounts of ATP for thinking, memory, and repair.

Evidence shows creatine may:

• Improve short-term memory

• Enhance processing speed

• Support mood, particularly in older adults

• Improve mitochondrial resilience

Mechanisms:

• Buffers cellular ATP

• Supports mitochondrial energy output

• Enhances neuroprotection during metabolic stress

Creatine is especially helpful for vegetarians, vegans, and individuals with mitochondrial gene variants (identified via IntellxxDNA).

4. Theracurmin (Highly Bioavailable Curcumin)

Why it matters: Curcumin is one of the most powerful natural anti-inflammatory compounds, and Theracurmin is a highly bioavailable form.

Evidence shows Theracurmin may:

• Reduce neuroinflammation

• Improve memory in older adults

• Support mood and decrease anxiety

• Act as an antioxidant

Mechanisms:

• Lowers inflammatory cytokines

• Reduces oxidative stress

• May reduce amyloid and tau pathology in animal models

Curcumin also supports liver detoxification pathways.

5. Lithium Orotate (Low Dose)

Why it matters: Lithium, in low nutritional doses, appears to protect the brain, regulate mood, and support mitochondrial health.

Evidence shows low-dose lithium may:

• Reduce dementia risk

• Enhance neurogenesis

• Improve mood and emotional resilience

• Support mitochondrial stability

Mechanisms:

• Increases BDNF

• Modulates glycogen synthase kinase-3β (GSK-3β)

• Promotes neuroplasticity

Safety note: Must be used with clinician oversight, especially for individuals with kidney disease, thyroid issues, or on interacting medications.

6. Folinic Acid (Activated Folate)

Why it matters: Folinic acid supports methylation — a process essential for neurotransmitter production, DNA repair, and detoxification.

Evidence shows folate deficiencies may contribute to:

• Memory decline

• Mood disorders

• Elevated homocysteine (a vascular and cognitive risk marker)

Key mechanisms:

• Supports methylation cycles

• Supports neurotransmitter synthesis

• Lowers homocysteine

Using activated folate is important, especially for individuals with MTHFR or methylation gene variants, identifiable via IntellxxDNA.

7. Lion’s Mane Mushroom (Hericium erinaceus)

Why it matters: Lion’s mane stimulates nerve growth factor (NGF), a critical protein for neural repair and myelination.

Evidence shows lion’s mane may:

• Improve memory and focus

• Support mood

• Reduce mild cognitive impairment

• Enhance nerve regeneration

Mechanisms:

• Increases NGF

• Supports neurogenesis

• Reduces neuroinflammation

Lion’s mane is one of the few natural compounds with demonstrated impact on neurotrophic pathways.

8. Ashwagandha (Withania somnifera)

Why it matters: Chronic stress and elevated cortisol impair memory, sleep, and hippocampal function.

Evidence shows ashwagandha may:

• Reduce cortisol levels

• Improve sleep quality

• Enhance memory and cognitive performance

• Reduce anxiety and stress-related inflammation

Mechanisms:

• Regulates the HPA axis

• Reduces oxidative stress

• Supports GABAergic activity

Best used in individuals with elevated stress or cortisol dysregulation.

9. Phosphatidylserine

Why it matters: Phosphatidylserine (PS) is a major component of neuron membranes and supports cell signaling.

Evidence shows PS may:

• Improve attention, focus, and processing speed

• Improve memory in older adults

• Enhance mood stability

• Support cortisol regulation

Mechanisms:

• Enhances neuronal membrane fluidity

• Supports neurotransmitter receptor function

• Aids synaptic communication

PS is especially helpful in individuals with high stress, ADHD-like symptoms, or early cognitive changes.

10. Vitamin D3 + K2

Why it matters: Vitamin D is essential for immune health, brain signaling, mood, and inflammation regulation. Vitamin K2 helps direct calcium into bones and away from arteries.

Evidence shows vitamin D deficiency is linked to:

• Higher dementia risk

• Brain fog and low mood

• Increased inflammation

Mechanisms:

• Regulates immune function

• Supports brain hormone pathways

• Modulates neuroinflammation

Genomics can reveal whether someone needs higher doses due to receptor variants (VDR polymorphisms).

Safety, Personalization, and Quality Matter

Not all supplements are right for everyone. Labs and genomics help determine:

• Correct dosing

• Safety based on drug interactions

• Absorption differences

• Methylation needs

• Detoxification vulnerabilities

• APOE-related considerations

• Vascular or inflammatory risks

As a clinician, I also emphasize third-party testing, purity, and standardized extracts to ensure consistent benefit.

Supplements Work Best Within a Whole-Person Plan

Supplements alone cannot replace:

• Nutrition

• Sleep

• Stress management

• Physical activity

• Insulin resistance reversal

• Detoxification

• Vascular optimization

• Hormonal balance

In ReCODE and precision medicine, supplements are tools — not the foundation.

Supplements work best when they’re personalized.

Schedule a Brain & Nutritional Optimization Evaluation with Dr. Knape to determine which supplements truly support your cognition, metabolism, and long-term brain health.

👉 Book your Discovery Call today.

Sources

🧠 Omega-3 Fatty Acids & Cognitive Function

Yurko-Mauro K et al., Journal of Alzheimer’s Disease, 2010 — PMC
Demonstrates improvements in memory and cognitive performance with DHA supplementation in adults with age-related cognitive concerns. Foundational evidence for omega-3 fatty acids as a brain-health supplement.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC3815792/

🧬 B Vitamins, Homocysteine & Brain Atrophy

Smith AD et al., PLoS ONE, 2010 — PMC
High-dose B6, B12, and folate significantly slowed brain atrophy and cognitive decline in adults with elevated homocysteine — a key biomarker for neurodegeneration.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC2946134/

⚡ Curcumin (Turmeric) & Neuroinflammation

Small GW et al., American Journal of Geriatric Psychiatry, 2018 — PMC
Double-blind RCT showing that daily curcumin supplementation improved memory performance and reduced amyloid/tau accumulation on PET scans.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC6016595/

🔋 Coenzyme Q10 & Mitochondrial Brain Support

Garrido-Maraver J et al., Antioxidants, 2014 — PMC
Review of CoQ10’s role in mitochondrial function, antioxidant defense, and neuroprotection — especially relevant for brain aging and cognitive fatigue.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC3886970/

🌿 Lion’s Mane Mushroom & Nerve Growth Factor (NGF)

Mori K et al., Phytotherapy Research, 2009 — PMC
Clinical trial showing that Lion’s Mane significantly improved cognitive function in adults with mild cognitive impairment, likely by stimulating NGF pathways.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC6886891/

💥 Creatine as a Neuroprotective Agent
Beal MF, Neuromolecular Medicine, 2011 — PMC
Summarizes research on creatine reducing oxidative stress, supporting mitochondria, and improving neuronal survival.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC3165939/

🌿 Ashwagandha Improves Memory & Cognitive Function
Choudhary D et al., Journal of Dietary Supplements, 2017 — PMC
Randomized, double-blind, placebo-controlled study showing significant improvements in memory, executive function, and information processing speed with ashwagandha extract.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC6979308/

Medically reviewed by
Dr. Jessica Knape, MD, MA Board Certified in Internal Medicine and Integrative and Holistic Medicine
Healthspan Internal Medicine — serving patients in Boulder, CO

Book a Discovery Call | About Dr. Knape

This content is for educational purposes and does not replace personalized medical advice.