Alpha-GPC and Cognition in Sport

Supplement labels and websites communicate with their buyers why XYZ supplement could be beneficial for consumption (a.k.a., label claims). Companies are mandated by the US Food and Drug Administration to include a disclaimer that a supplement's label claims have not been validated by the FDA. (1) What’s often missing is context for those claims. For instance, are these claims based on healthy versus diseased research populations? Was the dose used in the studies comparable to what the supplement label is recommending?

One supplement continuing to gain traction in baseball is alpha-GPC for its apparent cognitive enhancements.

In this blog, I’ll review:

• What alpha-GPC and choline are.

• The proposed benefits in sport.

• How researchers evaluate cognition.

• Available research in older adults with mild cognitive decline, dementia, and Alzheimer’s disease.

• Available research in athletes.

For brevity’s sake, I’ll refer to alpha-GPC moving forward as GPC. Other names it goes by are L-alpha-GPC, choline alfoscerate, and alpha-glycerophosphorylcholine.

GPC supplement bottle example pulled from the National Institutes of Health Dietary Supplement Label Database.

What is GPC (and Choline)?

Choline

Choline is an essential vitamin-like nutrient that humans can produce, but not in large enough quantities to meet our daily needs. (2-3) The adequate intake (AI) levels for choline in those 19 years and older are 550 mg for men and 425 mg for women. During pregnancy, choline further increases up to 450 mg per day and then 550 mg during lactation. (4) Sources of dietary choline include:

• 441 mg for three large eggs.

• 230 mg for 6 oz. top round beef.

• 144 mg for 6 oz. roasted chicken breast.

• 115 mg 2 cups 1% cow’s milk.

• 107 mg for ½ cup roasted soybeans. (4)

Choline can cross through the blood-brain barrier (BBB) and is required for the production of the neurotransmitter acetylcholine, lipoproteins, phospholipids, cell-membrane signaling phospholipids, phosphatidycholine, and sphingomyelin. (5) The latter two “are essential for membrane synthesis and synaptic function”, plus cell membrane integrity. (6) During pregnancy, choline is beneficial for fetal memory development and mitigates risk of neural tube defects (hence the higher AI levels).

In post-mortem brain assessments of those having Alzheimer’s disease and when compared to age-matched controls, choline and phospholipids were decreased and the phospholipid catabolite GPC increased. Tayebati et al. (2013) wrote that “cellular membrane breakdown is a typical feature of neuronal degeneration in acute (stroke) and chronic (dementia) disorders.” (5)

Already, it seems plausible that choline is necessary for the brain, fetal development, and has a role in the development and presence of cognitive decline.

GPC

Like choline, GPC is a precursor to phosphatidylcholine and acetylcholine. It can also cross the BBB. (2) What’s nice about GPC as a supplement is that it’s odorless, tasteless, and can dissolve evenly in water—making its addition to any supplement concoction seamless. By weight, GPC is 41% choline (2,7)

Choline and its derivatives. Source: Oregon State University Linus Pauling Institute (3).

My hand-drawn simplified choline pathway. Info from Oregon State University Linus Pauling Institute (3) and Chen et al. 2024 (16).

Why Alpha-GPC in Sport?

A few of the consistent claims for GPC in sport include its role as a cognitive enhancer and how it lacks the jitteriness that caffeine can present in certain individuals.

But First: How do Researchers Evaluate Cognition?

There is no standard or agreement throughout the literature on how “cognition” is measured. It may include tests to evaluate reaction time, mental fatigue (e.g., the Stroop Test), cognitive impairment in the Elderly or after a concussion (e.g., the Mini-Mental State Examination [MMSE], SCAT 6), memory recall, simple math equations, or even subjective assessments of fatigue, energy, alertness, and focus. (8,9) The tool used can be specific to a disease state or diagnosis, or the type of cognitive variable of interest.

Understanding how a research group defined cognition may affect what you as the practitioner value from the results.

GPC Research in Older Adults and Cognitive Health

The common themes across the vast majority of studies evaluating GPC and cognitive health include:

• Outcomes evaluating GPC intake and either the risk of developing or the prevalence of Alzheimer’s disease, dementia, or mild cognitive decline (a precursor of dementia). (6,10)

• Participants being quite older than the typical college or professional athlete.

It makes sense to target older populations, as brain acetylcholine levels decline with age and it’s thought that this contributes to the development of those cognitive concerns listed. (11) In the aging brain, GPC intake has shown to increase acetylcholine levels. (10)

Yet using studies in older populations with cognitive impairments to justify supplementation in younger, healthy adults isn’t appropriate. Translating available evidence is meant to translate data from similar groups—not from a disease state to a healthy group of participants.

For instance, let’s say a study was done on improving mobility in athletes in the week after an ACL reconstruction, where the athletes needed to wear a brace on their affected knee. The brace greatly limited their mobility and researchers wanted a safe solution. Let’s say they measure how quickly the athletes can move across a room. Wearing a brace, that may mean slowly hopping or limping. Then, the researchers intervene with crutches or a wheelchair. Now, the athletes can move across the room quickly. What dietitians would not take from this study is that either the use of crutches or wheelchairs would help all non-surgical athletes move faster. With cognitive health, it’s important to recognize a disease or disabled state—even if we cannot see the injury.

A summary of a few studies in older populations:

• Niu et al. (2025) found that combined dietary and supplemental choline in healthy adults with an average age of 56.1 years resulted in the lowest hazard ratio for developing dementia (353.9 mg/day) or Alzheimer’s disease (337.7 mg/day). (6) These intakes are less than the 425-550 mg adequate intakes set for choline in older adults.

• The consumption of egg yolks have shown benefit in reducing the risk of dementia and improving cognitive tests in those with mild cognitive decline and dementia. (12)

• The systematic review and meta-analysis by Sagaro et al. (2023) found that in patients with cognitive impairment, GPC supplementation only sometimes improved cognition compared to other medications (either meds on their own or paired with GPC) or placebo groups. The common daily dose across studies was 1,200 mg GPC ranging from 3 months to 2 years. (10)

GPC Research in Athletes and Cognitive Health

Two consistently-cited studies for GPC, cognitive support, and athletes are poster presentations from conferences.

Poster presentations are helpful, as they’re necessary for research exploration, learning, fine-tuning an experimental process, and creating data for grant proposals (research is expensive!). However, they lack the rigor of the peer-review process needed for journal publication. Posters are also succinct in their details (you can only fit so much text on a poster), so they lack the details needed for a reader to fully digest the experiment. Reasonably, they shouldn't be used as references.

Regarding those two conference posters:

• Parker et al. (2015) concluded their submission with “acute supplementation with caffeine or Alpha-GPC had no statistically significant beneficial effect on measures of mood, cognitive function, or physiological performance.” Doses in this crossover study included 200 mg GPC, 400 mg GPC, 200 mg caffeine, or a placebo. (13)

• Shields et al. (2014) evaluated five college-aged males in a cross-over design, evaluating supplement intake and visual reaction, mental aptitude, and power output measurements. The three arms of the trial included a placebo, caffeine*, and a supplement called MindSet by Haleo Inc.** Results did not include p-values, but the researchers wrote that MindSet was “as effective as” caffeine in improving cognitive function. (14)

For published studies:

• Thomas et al. (2019) had nine elite e-sport players undergo cognitive and physical testing prior to consuming a placebo or AI Reload energy drink. Thirty minutes later, participants played three League of League games, each followed by additional testing. The energy drink was listed to have contained 150 mg caffeine along with a proprietary blend of L-theanine, GPC, phosphatidylserline, and nicotinamide adenine dinucleotide*. The placebo did not contain caffeine. Ultimately, there was no significant difference between the treatment and control group for mental or physical improvement in performance. (15)

• In the Hoffman et al. (2010) study, researchers evaluated the CRAM supplement. Each daily dose contained a mixture of 150 mg GPC, 125 mg choline bitartrate, 60 mg caffeine, phosphatidylserine, and other B vitamins. Both the treatment and control groups underwent reaction tests before and after exhaustive exercise on days one and 28 of the study. Comparing groups, the only significant post-exercise cognitive benefit was in the treatment group on the first day of the study. Yet four weeks of daily supplementation thereafter did not provide benefits. (8)

• Marcus et al. (2017) split a group of healthy, recreationally-active, college-aged men into four groups to evaluate if 200 mg caffeine, 250 mg or 500 mg GPC, or a placebo taken daily for seven days would affect various cognitive and performance metrics. Across all groups, by the end of the trial there were no cognitive differences. A quote from the researchers: "It is more likely that a study would demonstrate change in cognition with a cognitively compromised population as compared to healthy young adults." (17)

What’s difficult to parse from the available research in athletes includes (a) missing information, as posters lack the detail of published studies, and (b) supplement blends that make it difficult to parse out dosing, if GPC specifically resulted in improvement, and/or if there’s a benefit from ingredients interacting.

*Dosing was not listed.

**I could not locate this supplement, but the authors noted it included tyrosine, acetyl-L-carnitine, GPC, Gingko Biloba, blueberry extract, and L-theanine. No doses were listed.

Key Takeaways

So, when you read the claims of GPC for cognitive health, know that the available research is referring to choline in these scenarios:

• GPC/choline reduce the risk of various forms of cognitive impairment in older populations.

• Those with a low choline intake seemingly have a higher prevalence of impairment.

• When adding GPC/choline in those with cognitive impairments, improvements occur.

Research in cognitive impairment in the Elderly is a great starting point for what research could be done in athletes for a potential cognitive edge. Unfortunately, the research doesn’t currently reflect that.

As always—and for all nutrients—if someone has an inadequate diet deplete in certain nutrients then yes, increasing dietary and/or supplemental levels is of course warranted. A quick note:

• Choline is not a standard addition to multivitamins, so double-check your pills.

• If using GPC supplements, GPC is 41% choline by weight. If aiming for a 550-mg choline dose to meet the AI then the GPC supplement would need to be 1,341 mg GPC (or 550 mg divided by 0.41). I've noticed GPC supplement labels recommending one dose (~500 mg) three times daily, probably for this reason.

References

(1) U.S. Food & Drug Administration. (2024, March 28). Label claims for conventional foods and dietary supplements. https://www.fda.gov/food/nutrition-food-labeling-and-critical-foods/label-claims-conventional-foods-and-dietary-supplements

(2) Kansakar, U., Trimarco, V., Mone, P., Varzideh, F., Lombardi, A., & Santulli, G. (2023). Choline supplements: an update. Front Endocrinol (Lausanne),14:1148166. https://pubmed.ncbi.nlm.nih.gov/36950691/)

(3) Higdon, J. (2000). Choline. Oregon State University Linus Pauling Institute Micronutrient Information Center. https://lpi.oregonstate.edu/mic/other-nutrients/choline

(4) National Institutes of Health Office of Dietary Supplements. (2022, June 2). Choline fact sheet for health professionals. https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/

(5) Tayebati, S.K., & Amenta, F. (2013). Choline-containing phospholipids: relevance to brain functional pathways. Clin Chem Lab Med,51(3):513-21. https://pubmed.ncbi.nlm.nih.gov/23314552/

(6) Niu, Y.-Y., Yan, H.-Y., Zhong, J.-F., Diao, Z.-q., Li, J., … & Liu, D. (2025). Association of dietary choline intake with incidence of dementia, Alzheimer disease, and mild cognitive impairment: a large population-based prospective cohort study. Am J Clin Nutr,121(1):5-13. https://pubmed.ncbi.nlm.nih.gov/39521435/

(7) Li, J., Zhang, J., Wang, Y., Yang, Y., Su, Y., … & Chang, C. (2025). L-alpha glycerylphosphorylcholine (L-a-GPC): a comprehensive review of its preparation techniques and versatile biological effects. J Food Sci,90(6):e70338. https://pubmed.ncbi.nlm.nih.gov/40556032/

(8) Hoffman, J.R., Ratamess, N.A., Gonzalez, A., Beller, N.A., Hoffman, M.W., … & Jäger, R. (2010). The effects of acute and prolonged CRAM supplementation on reaction time and subjective measures of focus and alertness in healthy college students. J Int Soc Sports Nutr,7:39. https://pubmed.ncbi.nlm.nih.gov/21156078/

(9) Raja, A., & Shah, D. (2025, December 8). 189. creatine as medicine: brain health, bone, & longevity, Darren Candow, PhD [Audio podcast]. Medicine Redefined Podcast. https://www.medicineredefined.com/189-creatine-as-medicine-brain-health-bone-longevity-darren-candow-phd/

(10) Sagaro, G.G., Traini, E., & Amenta, F. (2023). Activity of choline alphoscerate on adult-onset cognitive dysfunctions: a systematic review and meta-analysis. J Alzheimers Dis,92(1):59-70. https://pubmed.ncbi.nlm.nih.gov/36683513/

(11) Yamashita, S., Kawada, N., Wang, W., Susaki, K., Takeda, Y., … & Matsuoka, R. (2023). Effewcts of egg yolk choline intake on cognitive functions and plasma choline levels in healthy middle-aged and older Japanese: a randomized double-blinded placebo-controlled parallel-group study. Lipids Health Dis,22(1):75. https://pubmed.ncbi.nlm.nih.gov/37340479/

(12) Ylilauri, M.P.T., Voutilainen, S., Lönnroos, E., Virtanen, H.E.K., Tuomainen, T.-P., … & Virtanen, J.K. (2019). Associations of dietary choline intake with risk of incident dementia and with cognitive performance: the Kuopio ischemic heart disease risk factor study. Am J Clin Nutr,110(6):1416-23. https://pubmed.ncbi.nlm.nih.gov/31360988/

(13) Parker, A.G., Byars, A., Purpura, M., & Jager, R. (2015). The effects of alpha-glycerylphosphorylcholine, caffeine or placebo on markers of mood, cognitive function, power, speed, and agility. J Int Soc Sports Nutr,12(Suppl 1):P41. https://pmc.ncbi.nlm.nih.gov/articles/PMC4595381/

(14) Shields, K.A., Silva, J.E., Rauch, J.T., Lowery, R.P., Ormes, J.A., … & Wilson, J.M. (2014). The effects of a multi-ingredient cognitive formula on alertness, focus, motivation, calmness and psychomotor performance in comparison to caffeine and placebo. J Int Soc Sports Nutr,11(Suppl 1):P45. https://pmc.ncbi.nlm.nih.gov/articles/PMC4271648/

(15) Thomas, C.J., Rothschild, J., Earnest, C.P., & Blaisdell, A. (2019). The effects of energy drink consumption on cognitive and physical performance in elite League of League players. Sports (Basel),7(9):196. https://pubmed.ncbi.nlm.nih.gov/31443435/

(16) Chen, S., Inui, S., Aisyah, R., Nakashima, R., Kawaguchi, T., ... & Yanaka, N. (2024). Role of Gpcd1 in intestinal alpha-glycerophosphocholine metabolism and trimethylamine N-oxide production. J Biol Chem,300(12):107965. https://pubmed.ncbi.nlm.nih.gov/39510189/

(17) Marcus, L., Soileau, J., Judge, L.W., & Bellar, D. (2017). Evaluation of the effects of two doses of alpha glycerlphosphorylcholine on physical and psychomotor performance. J Int Soc Sports Nutr,14:39 https://pubmed.ncbi.nlm.nih.gov/29042830/