Alpha-GPC vs Citicoline: Which Choline Supplement Is Better?

Short answer: Neither has been shown to improve cognition reliably in healthy people. Citicoline has more trials, mostly small and in older people with cognitive impairment, and failed in a large stroke trial. Alpha-GPC has one positive Alzheimer’s trial, and in 12 million South Koreans it was linked to a 43 percent higher stroke rate. Ask a doctor before taking either.

There is no clear winner, because neither supplement has good evidence in healthy people and no trial has compared them directly. The evidence for both is preliminary: alpha-GPC rests on one positive trial in Alzheimer’s disease, and citicoline on small, short, often industry-linked trials.

If you are weighing them, two facts matter most. Citicoline has more trial data. Alpha-GPC carries a stroke signal from a very large observational study, with no comparable data for citicoline. For why choline matters in the first place and how to get it from food, see our article on choline as a brain nutrient.

Alpha-GPC vs citicoline at a glance

How each one works

Alpha-GPC occurs naturally in small amounts in the brain and in foods such as dairy, organ meats and soy. After you swallow it, it supplies choline for making acetylcholine, the messenger involved in memory, attention and learning.

Animal studies suggest it can raise brain acetylcholine; comparable human data are lacking. Its backbone can also go into phosphatidylcholine, the main fat in nerve cell membranes, though how much this happens is less clear.

Citicoline is broken down in the gut wall and liver into choline and cytidine. In humans, oral citicoline raises blood choline and uridine, while cytidine itself is barely detectable in blood (Wurtman 2000).

In a small study of 12 adults, single doses raised plasma uridine by 70–90 percent (500 mg) and 100–120 percent (2,000 mg) for 5–6 hours. In animal and cell studies, uridine boosts the making of membrane fats and synaptic proteins (Wurtman 2009). Whether this matters at supplement doses in people is not known.

Wurtman’s group at MIT found that giving animals uridine, DHA and choline together increased brain membrane fats and synaptic proteins (Wurtman 2009). This is the theory behind pairing citicoline with omega-3s, but the combination has not been shown to improve cognition in human trials.

Because citicoline is only about 18 percent choline, any effects it has may not be due to choline alone.

The evidence for alpha-GPC

Alzheimer’s disease. The main trial (De Jesus Moreno Moreno 2003) was multicenter, double-blind and placebo-controlled, in 261 people with mild to moderate Alzheimer’s disease. Those taking 1,200 mg a day for 180 days did clearly better than placebo on several cognitive and global scales, including the ADAS-Cog and MMSE. It is a single trial, and alpha-GPC is not an approved Alzheimer’s treatment in the US or Europe.

Vascular cognitive impairment. A review of choline-based supplements for cognitive problems caused by blood vessel disease (Parnetti 2007) found no clear benefit from lecithin. Alpha-GPC and citicoline had positive results, but in too few patients to generalize.

Healthy adults. A study often cited for alpha-GPC (Hoffman 2010) gave 19 college students a product that also contained caffeine, tyrosine, B vitamins and other ingredients. It cannot show an effect of alpha-GPC alone. There is no good evidence that alpha-GPC improves cognition in healthy people.

Exercise. A conference abstract (Ziegenfuss 2008) reported on 7 resistance-trained men. A single 600 mg dose 90 minutes before exercise raised peak growth hormone and bench press force; an alpha-GPC supplier funded it. In a crossover trial of 13 college-aged men (Bellar 2015), 600 mg a day for six days increased lower-body but not upper-body force. These studies are very small and short.

The evidence for citicoline

Older adults with cognitive problems. A Cochrane review of 14 short, varied trials (Fioravanti and Yanagi 2005) covered older people with chronic brain disorders. It found some evidence of benefit on memory and behavior in the short to medium term, but none on attention.

Healthy older adults. A randomized trial enrolled 100 healthy adults aged 50 to 85 with age-related memory complaints (Nakazaki 2021). Taking 500 mg a day of citicoline for 12 weeks improved episodic and composite memory compared with placebo. These were secondary outcomes, and two authors worked for the manufacturer.

Healthy women. McGlade (2012) studied 60 healthy women aged 40 to 60. After 28 days, 250 mg a day reduced both omission and commission errors on an attention test compared with placebo; 500 mg reduced commission errors. Several authors worked for the manufacturer. A citicoline-and-caffeine drink improved reaction time and attention in 60 healthy adults (Bruce 2014), but the caffeine makes it impossible to credit citicoline.

Stroke. In an open-label study without placebo (Alvarez-Sabín 2013), 347 people six weeks after a first ischemic stroke took 1,000 mg a day of citicoline or usual care for 12 months. The citicoline group had better attention, executive function and orientation at 6 and 12 months; other areas and day-to-day function did not differ clearly.

For acute stroke, Dávalos (2002) pooled four placebo-controlled trials in 1,372 patients. Complete recovery at three months was 25.2 percent on citicoline against 20.2 percent on placebo. Only one of the four trials had been positive on its own. The larger ICTUS trial (Dávalos 2012) randomized 2,298 patients and was stopped early because recovery was the same on citicoline and placebo.

These are mostly small, short, industry-linked studies. They suggest citicoline may have modest effects in healthy older adults, but this needs independent confirmation.

Safety: the alpha-GPC stroke signal

In trials, both supplements were generally well tolerated. Side effects, when they occur, are usually mild stomach upsets such as nausea or diarrhea, and are more likely at higher doses.

The Korean cohort. Lee (2021) used South Korean national health insurance data on 12,008,977 people aged 50 and over with no prior stroke or Alzheimer’s disease. People prescribed alpha-GPC had a 43 percent higher rate of stroke over about 10 years than matched non-users, and risk rose with longer use.

It is observational, so confounding cannot be ruled out; for example, early memory problems that prompted the prescription might raise stroke risk themselves. But it is a large and consistent signal.

TMAO. Gut bacteria turn choline from any source into trimethylamine, which the liver converts to TMAO. In mice, dietary choline and TMAO promoted hardening of the arteries (Wang 2011). Tang (2013) followed 4,007 patients having coronary angiography for three years.

Those with the highest TMAO levels had about 2.5 times the rate of heart attack, stroke or death as those with the lowest. These studies do not show that choline supplements cause heart disease in people. Eggs and meat also produce TMAO, and whether TMAO explains the alpha-GPC stroke signal is unknown.

Citicoline. There are no comparable large cohort studies of citicoline, and no studies comparing TMAO from the two supplements, so the absence of a signal does not show citicoline is safer. In ICTUS, safety outcomes and adverse events were the same on citicoline and placebo, and the Cochrane review found it well tolerated.

Interactions. In theory, both could add to the effects of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) used for Alzheimer’s disease. Do not combine them without your doctor’s guidance. Ask a doctor or pharmacist before starting either, especially if you have heart or stroke risk factors, are pregnant or breastfeeding, take medication or have a health condition.

Doses used in studies

These are the doses tested, not recommendations.

• Alpha-GPC: 1,200 mg a day as three 400 mg doses (Alzheimer’s trial); 600 mg as a single dose or daily for six days (exercise studies). At 40 percent choline, 600 mg provides about 240 mg of choline.
• Citicoline: 250–500 mg a day (healthy adults); 1,000 mg a day (after stroke); 500–2,000 mg a day (acute stroke trials). At 18 percent choline, 500 mg provides about 90 mg of choline.

Food counts too: two eggs provide about 290 mg of choline. See our eggs page and the choline article for food sources and intake targets.

Cost, and how they compare with choline bitartrate

Alpha-GPC is generally cheaper than citicoline per serving, and much cheaper per milligram of choline. Branded citicoline (Cognizin) usually costs more than generic.

Choline bitartrate is the cheapest choline source by far and is about 41 percent choline, slightly more than alpha-GPC. It raises blood choline and can make up for low dietary intake. But it has very little research on cognition, so it is not known whether it differs from the other two for the brain.

What the evidence can and cannot tell you

• Healthy adults: Citicoline has a few small, industry-linked trials with modest positive results; alpha-GPC has essentially none on cognition.
• Older adults with memory complaints or cognitive impairment: Citicoline has more trials, but they are small and short. Talk to your doctor about memory problems rather than self-treating.
• Stroke: Citicoline did not help in the large ICTUS trial for acute stroke; one open-label study suggests benefit for thinking after stroke. Stroke recovery should be managed by your medical team.
• Heart and stroke risk: Alpha-GPC has been linked to higher stroke risk in a large cohort; discuss this with your doctor.
• Athletes: Alpha-GPC has two very small exercise studies.
• Choline per dollar: Alpha-GPC delivers more than twice the choline per gram and costs less.

Frequently Asked Questions

Can I take alpha-GPC and citicoline together?

No studies have tested the combination, so there is no evidence of benefit or safety. If you consider it, ask a doctor or pharmacist, count total choline from all sources, and stay well below the Tolerable Upper Intake Level of 3,500 mg a day.

Which one raises acetylcholine more?

This has not been measured in head-to-head human studies. Alpha-GPC delivers more choline per gram, but that does not show it raises brain acetylcholine more.

Are there food sources of alpha-GPC or citicoline?

Both occur naturally in small amounts in food. Alpha-GPC is found in dairy, organ meats and soy lecithin. Food amounts are far below supplement doses.

Sources

• De Jesus Moreno Moreno, M. (2003). Cognitive improvement in mild to moderate Alzheimer’s dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clinical Therapeutics, 25(1), 178–193. doi:10.1016/s0149-2918(03)90023-3

• McGlade, E., Locatelli, A., Hardy, J., Kamiya, T., Morita, M., Morishita, K., Sugimura, Y., & Yurgelun-Todd, D. (2012). Improved attentional performance following citicoline administration in healthy adult women. Food and Nutrition Sciences, 3(6), 769–773. doi:10.4236/fns.2012.36103

• Alvarez-Sabín, J., Ortega, G., Jacas, C., Santamarina, E., Maisterra, O., Ribo, M., Molina, C., Quintana, M., & Román, G. C. (2013). Long-term treatment with citicoline may improve poststroke vascular cognitive impairment. Cerebrovascular Diseases, 35(2), 146–154. doi:10.1159/000346602

• Fioravanti, M., & Yanagi, M. (2005). Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database of Systematic Reviews, (2), CD000269. doi:10.1002/14651858.CD000269.pub3

• Dávalos, A., Castillo, J., Alvarez-Sabín, J., Secades, J. J., Mercadal, J., López, S., Cobo, E., Warach, S., Sherman, D., Clark, W. M., & Lozano, R. (2002). Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke, 33(12), 2850–2857. doi:10.1161/01.str.0000038691.03334.71

• Dávalos, A., Alvarez-Sabín, J., Castillo, J., et al. (2012). Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). The Lancet, 380(9839), 349–357. doi:10.1016/S0140-6736(12)60813-7

• Nakazaki, E., Mah, E., Sanoshy, K., Citrolo, D., & Watanabe, F. (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. doi:10.1093/jn/nxab119

• Bruce, S. E., Werner, K. B., Preston, B. F., & Baker, L. M. (2014). Improvements in concentration, working memory and sustained attention following consumption of a natural citicoline-caffeine beverage. International Journal of Food Sciences and Nutrition, 65(8), 1003–1007. doi:10.3109/09637486.2014.940286

• Ziegenfuss, T., Landis, J., & Hofheins, J. (2008). Acute supplementation with alpha-glycerylphosphorylcholine augments growth hormone response to, and peak force production during, resistance exercise (conference abstract). Journal of the International Society of Sports Nutrition, 5(Suppl 1), P15. doi:10.1186/1550-2783-5-S1-P15

• Bellar, D., LeBlanc, N. R., & Campbell, B. (2015). The effect of 6 days of alpha glycerylphosphorylcholine on isometric strength. Journal of the International Society of Sports Nutrition, 12, 42. doi:10.1186/s12970-015-0103-x

• Hoffman, J. R., Ratamess, N. A., Gonzalez, A., Beller, N. A., Hoffman, M. W., Olson, M., Purpura, M., & 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. Journal of the International Society of Sports Nutrition, 7, 39. doi:10.1186/1550-2783-7-39

• Parnetti, L., Mignini, F., Tomassoni, D., Traini, E., & Amenta, F. (2007). Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation? Journal of the Neurological Sciences, 257(1–2), 264–269. doi:10.1016/j.jns.2007.01.043

• Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., … & Hazen, S. L. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57–63. doi:10.1038/nature09922

• Tang, W. H., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013). Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. The New England Journal of Medicine, 368(17), 1575–1584. doi:10.1056/NEJMoa1109400

• Lee, G., Choi, S., Chang, J., Choi, D., Son, J. S., Kim, K., Kim, S. M., Jeong, S., & Park, S. M. (2021). Association of L-α glycerylphosphorylcholine with subsequent stroke risk after 10 years. JAMA Network Open, 4(11), e2136008. doi:10.1001/jamanetworkopen.2021.36008

• Wurtman, R. J., Regan, M., Ulus, I., & Yu, L. (2000). Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochemical Pharmacology, 60(7), 989–992. doi:10.1016/s0006-2952(00)00436-6

• Wurtman, R. J., Cansev, M., Sakamoto, T., & Ulus, I. H. (2009). Use of phosphatide precursors to promote synaptogenesis. Annual Review of Nutrition, 29, 59–87. doi:10.1146/annurev-nutr-080508-141059