Alpha-GPC (alpha-glycerophosphocholine or choline alphoscerate) is a choline-containing phospholipid. When ingested, alpha-GPC is rapidly absorbed and easily crosses the blood-brain barrier. It is metabolized into choline and glycerol-1-phosphate. Choline is a precursor of acetylcholine, a neurotransmitter involved in memory, attention, and skeletal muscle contraction. Glycerol-1-phosphate is used to support cellular membranes.^[1]

Oral supplementation of alpha-GPC is primarily of interest for nootropic or cognitive-enhancement purposes. While there are certain cases in which alpha-GPC seems to be beneficial, there isn’t any research in healthy humans that suggests it provides some general “cognitive enhancement”. There are a number of rodent studies that show an improvement in learning and memory in supplemented animals, but these effects have yet to be demonstrated in healthy humans. In older adults with mild to moderate dementia — which involves disrupted cholinergic neurotransmission — alpha-GPC improves cognitive symptoms (e.g., memory and attention impairment).^[2][1] Alpha-GPC may also help those with glioblastoma, a type of brain cancer that is very difficult to treat. A 2022 study found that the overall survival rate of people with glioblastoma improved when alpha-GPC was added to surgical and chemotherapeutic treatments.^[3] Alpha-GPC may also improve the effectiveness of acetylcholinesterase inhibitors (drugs that increase acetylcholine’s availability by slowing down its breakdown), which are used for treating Alzheimer’s disease.^[2][4] When Alpha-GPC is added to this standard Alzheimer’s treatment, it may improve behavioral symptoms, functional outcomes, and cognitive symptoms.^[5]

Athletes are another population that may benefit from alpha-GPC supplementation. Preliminary evidence suggests that alpha-GPC increases vertical jump power. In one study, both caffeine and alpha-GPC improved vertical jump power, with the greatest improvement in participants who took a 200 mg dose of alpha-GPC.^[6][7] Additionally, a pilot study reported that alpha-GPC increased peak bench press force, but not peak power or rate of force development.^[8] In one study done in trained cyclists, alpha-GPC improved peak power and time to fatigue when used with L-citrulline.^[9] Whether alpha-GPC increases isometric strength is currently unclear.^[7][10]

Alpha-GPC is generally well-tolerated. Serious side effects have not been reported in human trials at a dosage of 1,200 mg per day for six months.^[11] The no-observed-adverse-effect level (NOAEL) is 150 mg per kg of body weight per day.

Recently, concerns have been raised about the potential of alpha-GPC to increase the risk of cardiovascular disease (CVD) because it serves as a substrate for the synthesis of trimethylamine-N-oxide (TMAO) in the gut, and TMAO is associated with adverse cardiovascular outcomes in people with CVD and in mechanistic studies. While an association may exist here, the causative link between TMAO and CVD isn’t particularly strong. In healthy people this may not be something to worry about, but in people with a high risk of CVD it may be prudent to consider the added risk.^[12][13]

A 2021 cohort study of more than 12 million participants (at least 50 years old), including 108,877 alpha-GPC users, reported that alpha-GPC use for at least 12 months was associated with an increased risk of stroke over 10 years.^[14] Moreover, a 2021 mouse study found that alpha-GPC supplementation promoted atherosclerosis.^[15]

However, the currently available evidence is preliminary in nature, so randomized controlled trials and large cohort studies are needed to confirm these findings.

Mechanistic evidence suggests that alpha-GPC exerts its effects by increasing the synthesis and release of acetylcholine in the brain, where it is involved in memory, motivation, arousal, and attention.^{[16][17][18][19]}

Acetylcholine is also responsible for the action potentials that stimulate muscles to contract. Therefore, it’s theorized that increased acetylcholine levels lead to a stronger signal for muscle contraction and, consequently, to increased force production.