Top Cognitive Enhancements Continued - #1: How To Actually "Rewire" Your Brain!

As I scroll social (ad) platform feeds and web search results the number of times ads and articles say “rewire your brain” is surprising to me. The implication being, people think or feel their brain is not “wired” correctly. And should be “rewired” to conform with “normal” or ideal wiring.

It’s just an analogy for neuroplasticity, you say? Absolutely right. But it hits a little soft spot in me anyway. One that would prefer we accept ourselves as mother nature made us, first, then employ the self-efficacy that affords us in our quest for self-improvement.

There are of course clinical diagnoses with correlated (not always causal) relationships to physical or biochemical brain damage. And other “wiring” that can cause psychosis. But that’s not who these articles and ads are targeting. They’re targeting healthy, generally successful adults with brains that are wired exactly as “designed” by evolution for self-protection. For survival.

Among them, beautiful “neurodivergent” brains with dyslexia, ADHD, and autism. Deviations that appear to be more common now than ever. And have even become sought after in the tech sector, for Neurodiversity as a Competitive Advantage.

As someone with some subjectively high-functioning ADHD myself, the pivotal idea that transformed my relationship to it, from a negative, self-destructive one, to a positive and self-constructive one, was flipping the assumed direction of adaptation.

The direction of adaptation between an individual and an institution is typically defined by a power asymmetry. Traditionally, the larger the institution, the greater its authority to define normality by its own code of norms. The “abnormal” individual is assigned that label by the institution as a relative value judgement. Not as an absolute, objective condition.

To be sure, your brain is wired perfectly for change, adaptation, and self-improvement. Neuroplasticity is the label but our brains are not moldable like plastic in the hands of an expert "neuroscientist" sculptor.

Neural pathways change (neuro-plastically) with concerted effort, repetition, and simple positive reinforcement. But there’s no one magic wand or silver bullet. The best results come from combining novel physical movement with new information and dietary reinforcement drive a flywheel of progressive momentum.

Even before the literature backed my own experience, “rewiring” my brain (changing my mind from self-destructive to self-affirming identity and though habits), has always begun with changing my whole body biochemistry, through diet and exercise first and foremost. The positive psychological dominos fall in succession with far less effort after our body’s house is in biological order.

In any case, the “circuit” being exploited by using a wiring analogy to promote neuroplasticity, or sell a book or course purporting to “rewire your brain”, doesn’t require a PhD in neuroscience to understand. It’s a device used to manipulate people since abstract thought emerged: weaponized metaphor.

Neuroplasticity is changing your neural connections. Neurogenesis is building new neurons. They can be paired to work together to “rewire” our brains. And ostensibly, then change our mind ~ the real goal.

New cells built by neurogenesis usually die within a few weeks if no new demand, novel challenges, put them to work. One animal study showed how physical demand helped produce neuronal cells, and cognitive demand kept them alive and active^[21].

BDNF (brain-derived neurotrophic factor) is what connects neurogenesis and neuroplasticity. It’s why “rewiring” our brain (creating new neuronal pathways) begins with changing our whole body’s biochemistry through diet and physical movement. Consistent movement over time, plus new, novel movement involving coordination.

Acetylcholine is the transmitter the hippocampus requires for learning new information. Alpha-GPC is a nutritional supplement and precursor to acetylcholine.

In animal research, taking alpha-GPC after high neuronal demand raised choline acetyltransferase and BDNF (acetylcholine precursors) compared to control subjects^[14].

The process is simple:

This is why athletic and scholastic challenges together are such a powerful engine of self-improvement. Leaving us nostalgic for our alma mater later in life. As often the case, we knew it intuitively long before evidence told us why.

Alpha-GPC is a cholinergic precursor. Cholinergic precursors supply choline for acetylcholine, the learning and attention neurotransmitter.

Alpha-GPC is about 41% choline, making it the more concentrated form^[1].

Citicoline is about 18.5% choline, but it also supplies cytidine, which is converted to uridine, which in turn supports phosphatidylcholine in synaptic membranes^[2].

Both raise brain choline availability because they readily cross the blood-brain barrier to synthesize acetylcholine, the learning neurotransmitter.

The difference is action. Alpha-GPC can quickly increase acetylcholine levels. While citicoline supports longer-term brain health and neuroprotection.

Prescribed by a doctor, alpha-GPC is a medical intervention against cognitive decline. Sold by a sports nutrition retailer, it’s an athletic performance support. Both are one and the same compound proving again the complexity of our biochemistry.

Biochemists identified alpha-GPC around 1950^[3]. By 1985, Italian regulators authorized it as a prescription drug for dementia^[4] and doctors prescribed it to treat severe cognitive decline. Some European nations and S. Korea still prescribe alpha-GPC for cognitive impairment.

On the North American side it was simply classified as an unrestricted supplement.

Citicoline specifically provides cytidine, which converts to uridine to support synaptic structures^[2], while alpha-GPC shows additional activity by increasing brain-derived neurotrophic factor and modulating microglial inflammation^[6].

Mechanistic proof comes primarily from preclinical models. Human evidence relies on downstream measurements e.g. plasma choline levels^[7], and cognitive test scores.

Alpha-GPC has clear role in reducing cognitive decline. In 100 patients with mild cognitive impairment, 600 mg daily for 12 weeks beat placebo on cognitive tests^[8].

Citicoline holds the strongest long-term memory trial in the category. 100 healthy older adults with memory complaints, 500 mg daily, 12 weeks: episodic and composite memory both improved^[10]. Industry-funded, and still the best evidence we have for a choline compound in people without a diagnosis.

Twenty resistance-trained men took 315 or 630 mg of alpha-GPC. An hour later they scored better on the Stroop task, a standard measure of cognitive control^[11].

Another trial found increased jump force^[7] and motivation^[12]. Long-term cognitive benefit stays unmeasured.

In animal trials, alpha-GPC reduced neuronal death after severe seizures^[13] and increased brain-derived neurotrophic factor (BDNF) during periods of intense stress^[14]. But there’s no human evidence of these effects in healthy adults. The neuroprotection claim on our bottle is hypothesis.

Alpha-GPC is a chemically isolated derivative of soy lecithin^[15]. Citicoline is fermented into a stable salt.

Pure alpha-GPC is a viscous liquid that pulls moisture and degrades in capsules, so manufacturers bind it to a carrier.

The powder form is typically 50% bioactive compound, yet some manufactures produce 98% bioactive. 600 mg of 50% bioactive compound delivers 300 mg to the consumer. How a brand discloses this is unregulated, and brands often fail to disclose the details.

The MCI trial used 600 mg daily for twelve weeks^[8]. Acute cognitive benefit needed at least 315 mg an hour before the task^[11]. Citicoline memory work used 500 mg daily^[10]. The gap between the shelf and the science is the quiet scandal of this category.

Alpha-GPC is water-soluble and raises plasma choline without food or digesting fats^[7]. for it.

Trials dose timing about 60 minutes before a demanding activity, be it cognitive, physical or both.

Seven days of 300 mg alpha-GPC with BCAAs (branched chain amino acids) and L-citrulline raised peak power 11% and time to fatigue 36% in trained cyclists^[26].

The clearest synergy is clinical. Alpha-GPC added to the Alzheimer’s drug donepezil improved ADAS-Cog 18.5% at 24 weeks^[9].

For building synaptic membrane rather than acute focus, the pairing with a real mechanism is choline plus uridine plus omega-3 DHA.

Those are the three rate-limiting inputs neurons use to make phosphatidylcholine, the main material of a synapse.

Citicoline delivers two of the three by itself, choline and uridine^[2]. Alpha-GPC delivers choline only, so pair it with omega-3 DHA and an uridine source.

This pathway builds over weeks. Taken as a single pre-workout dose it does nothing^[25], so run it daily on a monthly scale. To meet spikes of demand, an intensive presentation at work or heavy training or competition day of cardio, keep the ~315 mg pre-activity dose separate.

Two observational studies from the same Korean database don’t quite align. One found rising stroke risk after cumulative alpha-GPC use^[17]. Another found lower stroke risk and delayed dementia^[18]. Neither can separate the compound from the vascular disease its users already had. That’s the scientific method at work.

With some years of daily use, take your blood pressure, lipids, and family stroke history to a physician.

Next week: We’ve completed our top ten cognitive enhancers series so the way forward widens open. I’m as excited to learn what next week brings as I hope you are!

Sunday inspo: Rewiring our neural pathways isn't a purchase. It's an interdisciplinary commitment be your true self, as nature and evolution (not modern society) made you.

Until next time, eat fresh foods and stay active Beautiful Self-aware Brain!
🫶🏽

[1] Li, J., et al. (2025). L-Alpha-Glycerylphosphorylcholine (L-α-GPC): A comprehensive review of its preparation techniques and versatile biological effects. Journal of Food Science.

[2] Świątkiewicz, M., & Grieb, P. (2022). Citicoline for supporting memory in aging humans. Aging and Disease.

[3] Alzheimer's Drug Discovery Foundation. Alpha-GPC (choline alfoscerate) Cognitive Vitality report. [VERIFY BEFORE PUBLICATION - web source]

[4] Sagaro, G. G., et al. (2023). Activity of choline alphoscerate on adult-onset cognitive dysfunctions: A systematic review and meta-analysis. Journal of Alzheimer's Disease.

[5] Gatti, G., et al. (1992). A comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphorylcholine and citicoline in normal volunteers. Int J Clin Pharmacol Ther Toxicol.

[6] Che, X., et al. (2025). Unlocking the potential of l-α-glycerylphosphorylcholine: From metabolic pathways to therapeutic applications. Nutrition Reviews.

[7] Marcus, L., et al. (2017). Evaluation of the effects of two doses of alpha glycerylphosphorylcholine on physical and psychomotor performance. Journal of the International Society of Sports Nutrition, 14, 39.

[8] Jeon, J., et al. (2024). Efficacy and safety of choline alphoscerate for amnestic mild cognitive impairment: A randomized double-blind placebo-controlled trial. BMC Geriatrics, 24.

[9] Sagaro, G. G., et al. (2023), ibid.; and Comparative study of choline alfoscerate as a combination therapy with donepezil (2024). Medicine.

[10] Nakazaki, E., et al. (2021). Citicoline and memory function in healthy older adults: A randomized, double-blind, placebo-controlled clinical trial. The Journal of Nutrition, 151(8), 2153-2160.

[11] Kerksick, C. (2024). Acute alpha-glycerylphosphorylcholine supplementation enhances cognitive performance in healthy men. Nutrients, 16(23), 4240.

[12] Tamura, Y., et al. (2021). Alpha-glycerylphosphorylcholine increases motivation in healthy volunteers: A single-blind, randomized, placebo-controlled human study. Nutrients, 13(6), 2091.

[13] Lee, S., et al. (2016). Late treatment with choline alfoscerate increases hippocampal neurogenesis and provides protection against seizure-induced neuronal death and cognitive impairment. Brain Research, 1654, 66-76.

[14] Yu, H. J., et al. (2022). The effect of choline alphoscerate on non-spatial memory and neuronal differentiation in a rat model of dual stress. Brain Research, 1786.

[15] Turck, D., et al. (2026). Safety of L-alpha-glycerylphosphorylcholine from soya phospholipids (lecithin) as a novel food. EFSA Journal.

[16] Kansakar, U., et al. (2023). Choline supplements: An update. Frontiers in Endocrinology, 14.

[17] Lee, G., et al. (2021). Association of L-α glycerylphosphorylcholine with subsequent stroke risk after 10 years. JAMA Network Open, 4(11).

[18] Kim, H.-K., et al. (2025). Association between L-α glycerylphosphorylcholine use and delayed dementia conversion: A nationwide longitudinal study in South Korea. The Journal of Prevention of Alzheimer's Disease.

[19] Cho, H. J., & Kim, Y. J. (2009). Efficacy and safety of oral citicoline in acute ischemic stroke: Drug surveillance study in 4,191 cases. Methods Find Exp Clin Pharmacol, 31(3), 171-176.

[20] Turck, D., et al. (2024). 'Citicoline' and support of the memory function: Evaluation of a health claim pursuant to Article 13(5). EFSA Journal, 22.

[21] Kempermann, G., Kuhn, H. G., & Gage, F. H. (1997). More hippocampal neurons in adult mice living in an enriched environment. Nature, 386, 493-495; and van Praag, H., et al. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature Neuroscience, 2(3), 266-270. [VERIFY BEFORE PUBLICATION]

[22] Erickson, K. I., et al. (2011). Exercise training increases size of hippocampus and improves memory. PNAS, 108(7), 3017-3022. [VERIFY BEFORE PUBLICATION]

[23] Rehfeld, K., et al. (2017). Dancing or fitness sport? The effects of two training programs on hippocampal plasticity and balance abilities in healthy seniors. Frontiers in Human Neuroscience, 11, 305; and Rehfeld, K., et al. (2018). Dance training is superior to repetitive physical exercise in inducing brain plasticity in the elderly. PLOS ONE, 13(7). [VERIFY BEFORE PUBLICATION]

[24] Draganski, B., et al. (2004). Changes in grey matter induced by training. Nature, 427, 311-312. [VERIFY BEFORE PUBLICATION]

[25] Bunn, J., Crossley, A., & Timiney, M. D. (2018). Acute ingestion of neuromuscular enhancement supplements do not improve power output, work capacity, and cognition. Journal of Sports Medicine and Physical Fitness, 58(7-8), 974-979.

[26] Harrington, R. (2023). Effects of branched chain amino acids, l-citrulline, and alpha-glycerylphosphorylcholine supplementation on exercise performance in trained cyclists: A randomized crossover trial. Journal of the International Society of Sports Nutrition, 20.

[27] Baumel, B., Doraiswamy, P. M., Sabbagh, M., & Wurtman, R. (2020). Potential neuroregenerative and neuroprotective effects of uridine/choline-enriched multinutrient dietary intervention for mild cognitive impairment: A narrative review. Neurology and Therapy, 10, 43-60.