What is alpha-GPC?
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.[1]
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.[2]
What are alpha-GPC's main benefits?
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).[3][1] 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.[3]
Athletes are another population that may benefit from alpha-GPC supplementation. Preliminary evidence suggests that alpha-GPC increases vertical jump power.[4][5] Additionally, a pilot study reported that alpha-GPC increased peak bench press force, but not peak power or rate of force development.[5] Whether alpha-GPC increases isometric strength is currently unclear.[5][7]
What are alpha-GPC's main drawbacks?
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.[8] 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.[9]
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.[10] Moreover, a 2021 mouse study found that alpha-GPC supplementation promoted atherosclerosis.[11]
However, the currently available evidence is preliminary in nature, so randomized controlled trials and large cohort studies are needed to confirm these findings.
How does alpha-GPC work?
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.[12][13][14][15]
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.
