What doses and formulations of phosphatidylserine were used in randomized trials showing cognitive benefit in MCI?

1. Historical dose pattern: 100 mg three times daily (≈300 mg/day) emerges repeatedly

Several of the older and larger randomized controlled trials that reported cognitive improvements used a regimen of 100 mg of phosphatidylserine taken three times per day (total ≈300 mg/day). A double‑blind trial in hospitalized demented patients described administration of “3 × 100 mg” tablets for weeks in the active arm (placebo‑controlled) ^[2], and safety/efficacy work on a PS‑DHA formulation randomized 157 non‑demented elderly to receive 300 mg PS per day versus placebo for 15 weeks, with reported cognitive gains in the active group ^[1]. Meta‑analytic and review sources also cite trials using 100 mg thrice daily when summarizing the clinical literature ^{[6] [3]}.

2. Formulations matter: PS combined with omega‑3 fatty acids (DHA, ALA) is common

A recurrent theme across trials with positive outcomes is that PS was not always a lone ingredient; several randomized studies tested PS formulated together with omega‑3 fatty acids. The PS‑DHA formulation (PS combined with docosahexaenoic acid) that showed improved immediate verbal memory in non‑demented elders is explicitly reported in the safety/efficacy trial (300 mg PS/day, PS‑DHA) ^[1], and other randomized work has tested PS together with omega‑3s such as α‑linolenic acid (ALA), with a recent Chinese randomized, double‑blind, placebo‑controlled trial finding some cognitive improvements using a food supplement containing PS plus ALA in older adults with MCI ^{[4] [7]}. Reviews and advocacy‑science summaries note that PS preparations have varied widely in fatty‑acid composition across trials, complicating interpretation ^[5].

3. Source of PS: animal‑derived, soy‑derived, and newer plant sources complicate comparison

Earlier PS supplements often derived from animal (brain or fish) sources; later products shifted to soy‑derived PS (Soy‑PS) and, more recently, sunflower‑derived PS used in pediatric or other trials ^{[8] [9] [10]}. Some randomized trials that failed to replicate benefits used soy‑derived PS, leading commentators to speculate that source and fatty‑acid composition might influence efficacy ^[11]. The Alzheimer’s Drug Discovery Foundation and other reviews explicitly call out the heterogeneity of PS chemical composition across studies as a barrier to direct comparison ^[5].

4. Recent MCI‑focused randomized trials: combination products and limited dose transparency

The most recent randomized trial specifically in Chinese older adults with MCI tested a “food supplement containing phosphatidylserine and α‑linolenic acid” and reported improvements in short‑term memory and biochemical markers, but the publicly available abstracts and database entries in the provided reporting do not state the exact PS milligram dose in the intervention arm, so dose‑level conclusions for that trial cannot be asserted from these sources alone ^{[7] [4]}. The pattern across multiple trials, however, still points toward multi‑hundred‑milligram daily exposure (≈300 mg/day) in positive studies, often as divided doses and frequently packaged with omega‑3s ^{[1] [2] [3]}.

5. Bottom line and research caveats

The pragmatic takeaway is that randomized trials reporting cognitive benefit in MCI and related memory‑complaint populations have most often used PS in the ~300 mg/day range, frequently split into three 100 mg doses, and frequently delivered as combined formulations with omega‑3 fatty acids such as DHA or ALA; nevertheless, heterogeneity in PS source (animal, soy, sunflower), fatty‑acid composition, trial populations, and incomplete reporting in some recent trials prevents a definitive single‑dose, single‑formulation prescription based solely on the supplied literature ^{[2] [1] [4] [5]}.