Alpha-GPC (alpha-glycerophosphocholine or choline alphoscerate) is a choline-containing phospholipid. When ingested, alpha-GPC 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.
Alpha-GPC appears to easily cross the blood-brain barrier and is rapidly absorbed. It is currently the best cholinergic for increasing plasma and brain choline levels.
Oral supplementation of alpha-GPC is primarily of interest for nootropic or cognitive-enhancement purposes. There are a number of rodent studies that support this effect, but it has yet to be shown in otherwise 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). Alpha-GPC may also improve the effectiveness of acetylcholinesterase inhibitors (i.e., drugs that increase acetylcholine availability by slowing down its breakdown), which are used for treating Alzheimer’s disease.
Athletes are another population that may benefit from alpha-GPC supplementation. Preliminary evidence suggests that alpha-GPC increases vertical jump power. Additionally, a pilot study reported that alpha-GPC increased peak bench press force, but not peak power or rate of force development. Whether alpha-GPC increases isometric strength is currently unclear.
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. The No Observed Adverse Effect Level 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), and TMAO is associated with adverse cardiovascular outcomes in people with CVD and in mechanistic studies.
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. Moreover, a 2021 mouse study found that alpha-GPC supplementation promoted atherosclerosis.
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.
Acetylcholine is also responsible for the action potential that stimulates muscles to contract. Therefore, it’s theorized that increased acetylcholine levels lead to a stronger signal for muscle contraction and, consequently, increased force production.