Creatine and Alpha-GPC for Cognitive Enhancement  by Jeffrey Dach MD

The question frequently comes up, Doctor, how can I increase my energy, and improve my brain function? We deal with this issue in the office on a regular basis.

Creatine Supplementation

Creatine increases energy by increasing mitochondrial ATP production benefiting muscle and brain which have high energy demands. Alpha-GPC increases brain acetylcholine enhancing cognitive performance. The combination of the two has synergy with greater benefits when used together.

In 2025, Dr. Aleksandra Tomczyk points out the many health benefits of creatine, and writes:

Creatine augments intramuscular phosphocreatine stores, thereby optimising ATP resynthesis during high-intensity exercise and promoting anabolic adaptations. Neuroprotective mechanisms involve mitochondrial stabilisation, antioxidant activity, and modulation of neurotransmitter systems. These effects are mediated by systemic and cellular alterations in energy metabolism, hormone profiles, and inflammatory pathways

Clinical trials demonstrate significant improvements in muscular performance parameters, cognitive processing
speed, depressive symptomatology, and markers of muscle damage and regenerative capacity….The collective evidence supports creatine as a pleiotropic agent with potential applications extending beyond traditional sports nutrition into therapeutic domains addressing neurodegeneration, mood disorders, and post-viral fatigue syndromes. Given its broad applicability and favorable safety profile, creatine may hold value as a low-cost, scalable intervention in public health strategies aimed at promoting healthy aging, physical resilience, and cognitive well-being. Reference: Tomczyk, Aleksandra, et al. “From strength to cognition: The expanding role of creatine supplementation in health and disease.” Polish Journal of Public Health 135 (2025): 35-41.

Other Mitochondrial Nutrients:

Other mitochondrial nutrients add additional synergy, CoQ10, L-carnitine, D-ribose, Alpha lipoic acid, benfotiamine, Cordyceps and Ginseng.

Caffeine in Coffee

Of course, caffeine in coffee is probably the most widely used for added energy and cognitive enhancement

Link to Buy Thorne Supplement: Creatine+Alpha-GPC Combination

Articles with related interest:

Cordyceps Super Energy Food

Making Coffee Out of this World

Header Image: This is an animated gif of MRI images of a human head and brain. This image came from an MRI performed on me last year at Stony Brook University Medical Center. Author: Dwayne Reed (talk). CC 3.0 Courtesy of wikimedia commons.

Jeffrey Dach MD
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my blog: www.jeffreydachmd.com 

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References:

Gutiérrez-Hellín, Jorge, et al. “Creatine supplementation beyond athletics: benefits of different types of creatine for women, vegans, and clinical populations—a narrative review.” Nutrients 17.1 (2025): 95.
Creatine monohydrate supplementation is widely used by athletes in high-intensity, power-based sports due to its ability to enhance short-term performance by increasing intramuscular phosphocreatine (PCr) stores, which aid in ATP resynthesis during intense muscle contractions. However, emerging evidence suggests that creatine monohydrate offers benefits beyond athletic performance. This narrative review explores the literature supporting the advantages of creatine supplementation in women, vegans, and clinical populations. In women, who typically have lower baseline intramuscular creatine levels, supplementation may help alleviate fatigue-related symptoms associated with the menstrual cycle, particularly during the early follicular and luteal phases. For vegans and vegetarians, who often have reduced creatine stores due to the absence of creatine-rich animal products in their diet, supplementation can improve both physical and cognitive performance while supporting adherence to plant-based diets. Additionally, creatine supplementation holds potential for various clinical populations. It may mitigate muscle wasting in conditions such as sarcopenia and cachexia, support neuroprotection in neurodegenerative diseases such as Parkinson’s and Huntington’s, improve exercise capacity in cardiovascular diseases, and enhance energy metabolism in chronic fatigue syndrome. Creatine may also aid recovery from traumatic brain injury by promoting brain energy metabolism and reducing neuronal damage. In conclusion, creatine monohydrate supplementation can enhance physical performance, cognitive function, and overall health in women, vegans, and clinical populations by addressing creatine deficiencies, improving energy metabolism, and supporting recovery from physical and neurological challenges. Most available evidence supports the effectiveness of creatine monohydrate, which should be considered the preferred form of creatine supplementation over other variants. Additionally, proper creatine dosing is essential to maximize benefits and minimize potential adverse effects that may arise from chronic ingestion of excessively high doses.

Ważny, Maria, et al. “The Impact of Creatine Supplementation on Physical Function and Brain Health in the Aging Population: A Review Article.” Quality in Sport 49 (2026): 67815-67815.
Creatine supplementation improves both physical and mental health in older adults. It aids in the prevention of sarcopenia, the maintenance of muscle mass and strength, may positively influence bone health, and reduces the risk of falls. Additionally, it has a positive impact on cognitive functions, specifically improving memory and mental processing. Conclusions. Creatine should be considered a key part of nutrition for the geriatric population to support healthy aging. Because it helps both the body and the brain, it is an important tool for improving quality of life.

Tomczyk, Aleksandra, et al. “From strength to cognition: The expanding role of creatine supplementation in health and disease.” Polish Journal of Public Health 135 (2025): 35-41.
Creatine augments intramuscular phosphocreatine stores, thereby optimising ATP resynthesis during high-intensity exercise and promoting anabolic adaptations. Neuroprotective mechanisms involve mitochondrial stabilisation, antioxidant activity, and modulation of neurotransmitter systems. These effects are mediated by systemic and cellular alterations in energy metabolism, hormone profiles, and inflammatory pathways

Clinical trials demonstrate significant improvements in muscular performance parameters, cognitive processing
speed, depressive symptomatology, and markers of muscle damage andregenerative capacity. . The collective evidence supports creatine as a pleiotropic agent with potential applications extending beyond traditional sports nutrition into therapeutic domains addressing neurodegeneration, mood disorders, and post-viral fatigue syndromes. Given its broad applicability and favorable safety profile, creatine may hold value as a low-cost, scalable intervention in public health strategies aimed at promoting healthy aging, physical resilience, and cognitive well-being.

Gordji-Nejad, Ali, et al. “Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation.” Scientific reports 14.1 (2024): 4937.
Our results show that creatine induces changes in PCr/Pi, ATP, tCr/tNAA, prevents a drop in pH level, and improves cognitive performance and processing speed. These outcomes suggest that a high single dose of creatine can partially reverse metabolic alterations and fatigue‑related cognitive deterioration.

Post, Adrian, Dimitrios Tsikas, and Stephan JL Bakker. “Creatine is a conditionally essential nutrient in chronic kidney disease: a hypothesis and narrative literature review.” Nutrients 11.5 (2019): 1044.
Recent findings strongly suggest that the capacity of renal AGAT, and thus endogenous creatine production, progressively decreases with the increasing degree of CKD, to become absent or virtually absent in dialysis patients. We hypothesize that with increasing degree of CKD, creatine coming from meat and dairy in food increasingly becomes an essential nutrient. This phenomenon will likely be present in patients with CKD stages 3, 4 and 5, but will likely be most pronouncedly present in patients with dialysis-dependent CKD, because of the combination of lowest endogenous production of creatine and unopposed losses of creatine into the dialysate. It is likely that these increased demands for dietary creatine are not sufficiently met.

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Kerksick, Chad M. “Acute alpha-glycerylphosphorylcholine supplementation enhances cognitive performance in healthy men.” Nutrients 16.23 (2024): 4240.
hese results offer unique insight into the potential for A-GPC to acutely increase cognition in a group of young, healthy males. While previous research has indicated potential for A-GPC to acutely improve cognition in clinical populations, extending these outcomes to healthy individuals can be potentially meaningful for a wide variety of populations such as athletes, race car drivers, military operators, and other non-athletic populations who desire and have a need to improve their mental performance.

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Creatine 101. Which is Better? Creatine Monohydrate or Micronized Creatine?

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Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
my blog: www.jeffreydachmd.com 
Bioidentical Hormones 101 Second Edition
Menopausal Hormone Replacement, Health Benefits
Natural Thyroid Toolkit by Jeffrey Dach MD
Cracking Cancer Toolkit ebook
Cracking Cancer Toolkit print version
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Published on February 18th, 2026 by Jeffrey Dach MD