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.[1] 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.[2][3]
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.[4] Moreover, a 2021 mouse study found that alpha-GPC supplementation promoted atherosclerosis.[5]
However, the currently available evidence is preliminary in nature, so randomized controlled trials and large cohort studies are needed to confirm these findings.