Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years.
Level 3 - non-randomized controlled study
Retrospective matched cohort study using administrative health claims data
PubMed 34817582 · doi:10.1001/jamanetworkopen.2021.36008
What was done
A population-based retrospective cohort study using South Korea's National Health Insurance Service database evaluated 12,008,977 adults aged 50 years or older without prior stroke or Alzheimer disease. Participants prescribed L-α glycerylphosphorylcholine (α-GPC) between 2006 and 2008 (n = 108,877) were compared with nonusers (n = 11,900,100) and evaluated in a covariate-matched cohort. Exposure was categorized by prescription duration (<2, 2 to 6, 6 to 12, and >12 months). Adjusted hazard ratios (aHRs) for total, ischemic, and hemorrhagic stroke from 2009 to 2018 were calculated using multivariate Cox proportional hazards regression.
What was found
In the matched cohort, α-GPC users had a significantly higher risk of total stroke (aHR, 1.43; 95% CI, 1.41-1.46), ischemic stroke (aHR, 1.34; 95% CI, 1.31-1.37), and hemorrhagic stroke (aHR, 1.37; 95% CI, 1.29-1.46). In the unmatched sample, users similarly had higher risks of total stroke (aHR, 1.46; 95% CI, 1.43-1.48), ischemic stroke (aHR, 1.36; 95% CI, 1.33-1.39), and hemorrhagic stroke (aHR, 1.36; 95% CI, 1.28-1.44). Increasing prescription duration of α-GPC showed a dose-response association with higher total stroke risk.
Why it matters
α-GPC is widely used as a cognitive enhancer and supplement, but this study links its use to an increased long-term risk of both ischemic and hemorrhagic stroke.
Limits
As an observational claims-based study, there is substantial risk of confounding by indication because individuals prescribed α-GPC may have had unmeasured early cognitive or cerebrovascular decline. Over-the-counter supplement intake and dietary choline were not captured, the study was restricted to a South Korean population, and biological intermediates (such as TMAO) were not measured.
Cited by
- supports Regular, high-dose usage of Alpha-GPC over long periods is associated with an increased risk of stroke and other cardiovascular events.