Which clinical trials have tested phosphatidylserine or Bacopa monnieri for age‑related memory decline?

1. Phosphatidylserine’s most cited randomized trial: the 1991 Neurology study

The landmark randomized, double‑blind, placebo‑controlled trial treated 149 subjects meeting criteria for age‑associated memory impairment (AAMI) with phosphatidylserine 100 mg three times daily or placebo for 12 weeks and reported improvement on learning and memory performance and on global clinical ratings in the treated group, with the largest benefits seen in participants with lower baseline performance ^[1].

2. Follow‑up PS trials and variations in source and formulation

Subsequent clinical work explored soy‑derived PS and PS combined with other nutrients in elderly cohorts: trials have tested soy‑origin PS in age‑related memory complaints and PS formulations containing omega‑3s in double‑blind trials that suggested potential memory benefits in non‑demented elderly with complaints, though these studies vary by dose, duration, and endpoints ^[2]. Early positive trials used bovine‑brain PS which raised safety concerns and were removed from market sources, prompting development of soy and sunflower PS products ^{[6] [1]}.

3. Bacopa monnieri trials in older adults and mixed populations

Randomized, placebo‑controlled trials of Bacopa include studies in older adults with age‑associated memory impairment such as Raghav et al. (Indian J Psychiatry, 2006) and Calabrese et al. that tested standardized Bacopa extracts in elderly samples and reported improvements on certain cognitive measures after weeks to months of treatment ^{[2] [7] [8]}. Additional randomized trials have evaluated Bacopa in healthy middle‑aged and older adults and in other populations (children with attention symptoms, subjects with hypertension), producing a mixed but overall suggestive signal for modest cognitive benefits ^{[4] [3]}.

4. Combination trials that blur attribution: Bacopa plus phosphatidylserine and other nutraceuticals

At least one prospective, multicenter, noncomparative exploratory clinical study tested a commercial combination (Illumina) containing Bacopa extract, astaxanthin, soy‑derived phosphatidylserine, and vitamin E in subjects with mild cognitive impairment (MCI) for 60 days and reported improved cognitive and mnemonic scores, but the noncomparative design prevents attributing effects to any single ingredient ^{[9] [5] [10]}. Other trials referenced in reviews similarly used multi‑ingredient supplements, complicating causal inference about Bacopa or PS alone ^{[5] [11]}.

5. Systematic reviews and the balance of evidence

Systematic reviews and meta‑analyses conclude Bacopa has “promising” cognitive‑enhancing effects across heterogeneous trials, and that phosphatidylserine has shown benefit in some randomized trials for age‑related memory impairment, but both literatures suffer from small sample sizes, short durations, variable extracts/formulations, and inconsistent endpoints, leaving prevention of dementia unproven ^{[3] [4] [6]}. The 2012 Pase et al. review and later meta‑analyses synthesize RCTs but emphasize the need for higher‑quality, longer‑term, adequately powered trials ^{[9] [3]}.

6. Limitations, conflicts of interest, and open questions

Interpretation is constrained by frequent use of proprietary extracts, variable dosing regimens, short follow‑up, and studies that are industry‑sponsored or test commercial combination products — factors that can bias outcomes and obscure which ingredient drives any effect ^{[5] [11]}. Crucially, no trial identified in these sources demonstrates that Bacopa or PS prevents progression to dementia; most show modest, domain‑specific cognitive changes over weeks to months in selected samples ^{[4] [3]}.