Good morning Beautiful Self-aware Brain,
Welcome to the fifth edition in the Structural Brain Health series.
Relative to most of the advice we get from the interwebs (web and social/video channels), some might say we’re overbuilding structural brain health in this series. But there’s a reason for it. The reason is you.
We’re not leveraging supplements to compensate for lack of exercise and dietary self-care. My high-achieving, highly health-sensitive reader wants to perform at work and play at their very, very best. And I’m here to help them (you) do exactly that.
This is why we're building our brain’s health first on a solid deep health foundation, first. When our sleep, physical training, and social connection habits are reasonably consistent and stable, and whole food nutrition is as close to the MIND diet as we can sustain, we then extend our self-care to supplements, as supplements, for holistic Structural Brain Health.
Of the twelve (12) brain health nutrient compounds that should first be supplied by the MIND diet, only three (3) provide direct cognitive enhancement:
Choline (related variations: Alpha-GPC or Citicoline/CDP-Choline)
Creatine
L-Tyrosine
In other words, though we should first obtain our brain health nutrients from whole food sources, augmenting them with supplements is justified by the limited dosage that whole foods alone typically provide.
So let’s now build on last week’s Top Cognitive Enhancement Supplements Recommended Online, surveyed for consensus across fourteen of the best known, well qualified health influencers.
Below are the nutritional compounds that rise to the top based on research1. They belong in two functional enhancement supplement categories, direct and indirect. Here’s an easy way to distinguish them:
Direct
Positive and fast acting effects on cognitive function.Indirect
Regulating or mitigating potentially negative effects. Sometimes slightly slower-acting. Functional benefits are secondary.
Direct Cognitive Enhancers
Alpha-GPC (L-alpha-glycerylphosphorylcholine)
Phosphatidylserine (PS)
Ginkgo Biloba
L-Theanine
Bacopa Monnieri
Huperzine A - separated for deserved elaboration next Sunday
I’ve omitted caffeine from the direct cognitive enhancers, when it’s often included, because most of us already consume enough, or more than enough, in its natural forms, coffee or tea.
And I’m setting Huperzine A aside for today, because it’s a potent acetylcholinesterase (uh·see·tuhl·kow·luh·neh·str·ays) inhibitor with special complications and risks that deserve special attention.
Indirect Cognitive Enhancers
Ashwagandha
Ginseng
Acetyl-L-Carnitine (ALCAR)
Rhodiola Rosea
Back to the top five in bold, above. These can safely be consumed together (“stacked”), in conventional dosages by a healthy adult with no interacting prescription medications.
But let’s get real. There’s little or no improvement above a certain level to be gained by consuming more than four or five of these. If we add more we’re really reconfiguring the whole stack, for some reason. And we’ll explore those reasons in an upcoming edition.
Today, let’s un-pack and prioritize the top five by functional benefits.
Anecdotally, I frequently take the first four of these top five in the morning, depending on my day’s planned activities. Only Bacopa Monnieri is not included in my personal ADHD optimization stack. I’ll explain why in an upcoming edition.
Top Three Reasons Behind Each of The Top Five Cognitive Enhancement Supplements
What are the top four reasons Alpha-GPC is among the most consistently recommended direct cognitive enhancement supplements?
What are the top three reasons Phosphatidylserine (PS) is among the most consistently recommended direct cognitive enhancement supplements?
Highly consistent human evidence. Multiple double-blind trials showing benefits esp. age-related memory support.2a,b,c
Neuronal membrane function. Directly tied to attention, learning, and memory.2d,e,f
Stress resilience. Multiple trials indicate cortisol/ACTH (stress, intense exercise) response mitigation, improved recovery.2g,h
What are the top three reasons Ginkgo Biloba is among the most consistently recommended direct cognitive enhancement supplements?
Ginkgo has one of the largest bodies of double-blind human research evidence for mitigating cognitive decline. Memory, attention, and general cognitive function improvements.3a,c
Cerebral microcirculation and vascular function, delivery of oxygen and nutrients to brain tissue are mechanisms of its effects on attention and cognitive performance.3a,c
Antioxidant and neuroprotective attributes support long-term brain health and resilience against oxidative stress.3a,c
What are the top three reasons L-Theanine is among the most consistently recommended direct cognitive enhancement supplements?
Multiple placebo-controlled human studies show L-theanine with caffeine improves attention, task switching, reaction time, executive function, reduced distraction.4a,b,c
Consistently demonstrates improved relaxed alertness and cognitive performance under stress.4d,e,f
Human EEG research shows L-theanine increase alpha-wave activity, associated with relaxed wakefulness, attentional readiness, and reduced mental fatigue, sustained concentration and cognitive endurance.4g,h
What are the top three reasons Bacopa Monnieri is among the most consistently recommended direct cognitive enhancement supplements?
Strong, double-blind, placebo-controlled human study evidence of memory improvements, information processing, and learning rate.5a,b,c
Unlike stimulants, benefits of attention, processing speed, and cognitive performance.5a,d
Neuroprotective adaptations protect against oxidative stress for healthier neurotransmitters, supporting learning, memory, and cognitive resilience.5e,f,g
How To Take Them For +Bioavailability?
Best consumed with fatty foods i.e. eggs, salmon, avocado, olive oil, nuts and such:
Phosphatidylserine (PS)
Ginkgo Biloba
Bacopa Monnieri
The remainder are well absorbed with or without food. Those with sensitive digestion can take them with meals for GI comfort.
Alpha-GPC
Ginkgo Biloba
L-Theanine (Personally, I prefer without food for faster absorption - let me know your input in web post’s comments)
Timing & Stacking Recommendations For Activity Preparation?
30–60 minutes before cognitively demanding work, concentration, meetings/presentations with rapid attention switching
Alpha-GPC
L-Theanine
Ginkgo Biloba (optional)
Functional benefits:
Attention
Focus
Working memory
Information processing
Mental fatigue resistance
30–90 minutes before intensive learning, studying, skill acquisition, or memory-heavy work
Bacopa Monnieri
Phosphatidylserine (PS)
Ginkgo Biloba
Alpha-GPC (optional but recommended)
Functional benefits:
Memory formation
Memory retention
Learning/Info encoding
Next week we’ll unpack and prioritize the remaining cognitive enhancement supplements recommended by the top fourteen websites and YouTube channels. And I have a few to add, as well.
Huperzine A
Ashwagandha
Ginseng
Acetyl-L-Carnitine (ALCAR)
Rhodiola rosea
??
Please share what you take that’s not listed here, in the comments
Until next week, stay active, Beautiful Self-aware Brain!
🫶🏽
PS. I’m not an affiliate, or monetizing in any way yet, but when you shop for supplements, I recommend The Natural.
Footnotes:
Alpha-GPC:
a) Acute Alpha-Glycerylphosphorylcholine Supplementation Enhances Cognitive Performance in Healthy Men (2024)
https://pmc.ncbi.nlm.nih.gov/articles/PMC11644786
b) Tamura Y, et al. Alpha-Glycerylphosphorylcholine Increases Motivation in Healthy Volunteers: A Single-Blind, Randomized, Placebo-Controlled Human Study. Nutrients. (2021)
https://www.mdpi.com/2072-6643/13/6/2091
c) Alpha-GPC - Uses, Side Effects, and More
https://www.webmd.com/vitamins-supplements/alpha-gpcPS:
a) Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991.
https://pubmed.ncbi.nlm.nih.gov/2027477/
b) Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging Clin Exp Res. 1993.
https://pubmed.ncbi.nlm.nih.gov/8323999/
c) Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. J Clin Biochem Nutr. 2010.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2966935/
d) Influence of phosphatidylserine on Na+/K+-stimulated ATPase and acetylcholinesterase activity. Biochem J. 1984.
https://pmc.ncbi.nlm.nih.gov/articles/PMC1153623/
e) Phosphatidylserine reverses the age-dependent decrease in cortical acetylcholine release: a microdialysis study. Eur J Pharmacol. 1991.
https://pubmed.ncbi.nlm.nih.gov/2060587/f) Phosphatidylserine increases hippocampal synaptic efficacy. 1993.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2503954/g) The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr. 2008.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2503954/h) Effects of phosphatidic acid and phosphatidylserine complex on the endocrine stress response. Lipids Health Dis. 2014.
https://link.springer.com/article/10.1186/1476-511X-13-121Ginkgo Biloba:
a) A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. JAMA. 1997.
https://pubmed.ncbi.nlm.nih.gov/9351013/
b) Proof of efficacy of the special extract EGb 761 in outpatients with mild to moderate primary degenerative dementia. Pharmacopsychiatry. 1996.
https://pubmed.ncbi.nlm.nih.gov/8850435/c) Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features. Arzneimittelforschung. 2007.
https://pubmed.ncbi.nlm.nih.gov/17966121/
d) Effect of Ginkgo biloba on blood fluidity and microcirculation in volunteers. Arzneimittelforschung. 1990.
https://pubmed.ncbi.nlm.nih.gov/2090360/
e) Effects of Ginkgo biloba extract on cerebral blood flow and endothelial function. Clin Hemorheol Microcirc. 1999.
https://pubmed.ncbi.nlm.nih.gov/10568244/f) Effects of EGb 761 on mitochondrial function and oxidative stress. Pharmacopsychiatry. 2003.
https://pubmed.ncbi.nlm.nih.gov/13130389/g) Stabilization of mitochondrial function by Ginkgo biloba extract. Neurobiology of Aging. 2007.
https://pubmed.ncbi.nlm.nih.gov/16797786/h) Neuroprotective effects of Ginkgo biloba extract. Cellular and Molecular Life Sciences. 2003. https://pubmed.ncbi.nlm.nih.gov/14523549/
L-Theanine:
a) The effects of L-theanine, caffeine and their combination on cognition and mood. Biological Psychology. 2008.
https://pubmed.ncbi.nlm.nih.gov/18006208/b) The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutritional Neuroscience. 2008.
https://pubmed.ncbi.nlm.nih.gov/18681988/c) The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutritional Neuroscience. 2010.
https://pubmed.ncbi.nlm.nih.gov/21040626/d) L-Theanine reduces psychological and physiological stress responses. Biological Psychology. 2007.
https://pubmed.ncbi.nlm.nih.gov/16930802/e) Ingestion of theanine reduces stress-related symptoms and improves cognitive function under stress. Pharmacology Biochemistry and Behavior. 2013.
https://pubmed.ncbi.nlm.nih.gov/23415724/f) The acute effects of L-theanine on stress and anxiety in healthy adults. Nutrients. 2021.
https://pubmed.ncbi.nlm.nih.gov/33467349/g) L-Theanine, a unique amino acid of green tea and its relaxation effect in humans. Trends in Food Science & Technology. 1999. (Reviews and discusses original EEG findings.) https://pubmed.ncbi.nlm.nih.gov/20394401/
h) Effects of L-theanine on resting-state alpha brain wave activity in humans. Original EEG research demonstrating increased alpha activity.
https://pubmed.ncbi.nlm.nih.gov/11388472/Bacopa Monnieri:
a) The chronic effects of an extract of Bacopa monnieri (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berlin). 2001. https://pubmed.ncbi.nlm.nih.gov/11713615/
b) Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology. 2002.
https://pubmed.ncbi.nlm.nih.gov/12093601/
c) Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. Journal of Alternative and Complementary Medicine. 2010.
https://pubmed.ncbi.nlm.nih.gov/20642252/
d) Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly. Journal of Alternative and Complementary Medicine. 2008. https://pubmed.ncbi.nlm.nih.gov/18611150/
e) Antioxidant activity of Bacopa monnieri in rat frontal cortex, striatum and hippocampus. Phytotherapy Research. 2000.
https://pubmed.ncbi.nlm.nih.gov/10705656/f) Russo A, Borrelli F. Bacopa monniera, a reputed nootropic plant: an overview. Phytomedicine. 2005.
https://pubmed.ncbi.nlm.nih.gov/15898707/g) Effect of Bacopa monniera on stress-induced changes in brain neurotransmitters and oxidative stress markers. Phytotherapy Research. 2005.
https://pubmed.ncbi.nlm.nih.gov/16177979/