Phosphatidylserine

Phosphatidylserine has a long history but a modest evidence base. The original cognitive trials in the late 1980s and early 1990s used bovine cortex PS (BC-PS), which is no longer sold over the counter in the US after BSE concerns shifted the entire market to soy-derived and sunflower-derived plant PS. The plant-PS trials are smaller and the effect sizes are softer than the original BC-PS work. The FDA reviewed the evidence in 2003 and allowed a qualified health claim that PS "may reduce the risk of dementia and cognitive dysfunction in the elderly," with the explicit caveat that the supporting evidence is "limited and inconclusive." That phrasing is the honest summary.

The cognitive case rests on a handful of trials. Crook 1991 (Neurology) treated 149 adults with age-associated memory impairment for 12 weeks with 100mg BC-PS three times daily and found improvements on learning and daily-life memory tasks, particularly in the lowest-baseline subgroup. The plant-PS replications are weaker. Kato-Kataoka 2010 ran a 6-month double-blind RCT in 78 elderly Japanese adults with memory complaints at 100mg or 300mg/day of soy-PS and saw delayed verbal recall improve in the lowest-baseline subgroup, with no clear dose-response. Vakhapova 2010 used a PS-DHA conjugate (not plain PS) in 157 non-demented elderly adults for 15 weeks and reported significant improvement in immediate verbal recall, mostly in the higher-functioning subgroup. None of these trials show large effects, and the post-hoc subgroup analyses do most of the work.

The exercise-cortisol story is separate and uses higher doses. Monteleone 1992 gave healthy men 800mg/day of BC-PS for 10 days and saw blunted ACTH and cortisol responses to a cycling stress test. Starks 2008 gave trained males 600mg/day of soy-PS for 10 days and reported a 39% reduction in peak cortisol and a higher testosterone-to-cortisol ratio after moderate cycling. The mechanism is plausible but the trials are small (n under 10 in each), short, and have not been replicated at scale. This is an early signal in athletes, not a settled finding for general stress.

The pediatric ADHD signal is also early. Hirayama 2014 randomized 36 unmedicated children 4-14 years old to 200mg/day of soy-PS or placebo for 2 months and reported improvements in ADHD symptoms and short-term auditory memory. A 2021 systematic review and meta-analysis (Bruton et al.) pooled three trials (216 children) and found a statistically significant effect on inattention but not on overall ADHD or hyperactivity-impulsivity, with low overall evidence quality. PS is not a substitute for first-line ADHD treatment, but the inattention signal is real enough to warrant follow-up trials.

What this all adds up to: PS is reasonable to try for age-related memory complaints in older adults at the standard 100mg three times daily, with the understanding that benefits are modest and largest in those with lower baseline performance. It is reasonable to try at 600-800mg/day for athletes specifically targeting the cortisol response to high-volume training, with no strong general-population stress evidence. Choose Sharp-PS (soy) or Sharp-PS GREEN (sunflower) for the standardized form behind the modern trials. Plain "phosphatidylserine complex" without a branded extract identifier is harder to evaluate.