Which clinical trials have tested combinations of phosphatidylserine, bacopa and lion's mane for memory in older adults?
Executive summary
No randomized clinical trial was identified in the provided reporting that tests a three-way combination of phosphatidylserine (PS), Bacopa monnieri (bacopa) and Hericium erinaceus (lion’s mane) specifically for memory in older adults; the clinical literature cited instead contains trials of PS alone, bacopa alone, lion’s mane alone, and at least one exploratory trial of a multi-ingredient product that paired bacopa with phosphatidylserine but did not include lion’s mane [1] [2] [3] [4].
1. Trials of phosphatidylserine in older adults — solid single‑ingredient evidence but not the trio
Phosphatidylserine has been tested in multiple randomized and controlled trials in older adults with memory complaints or age-associated memory impairment, including a double‑blind randomized study of soybean‑derived PS (100 mg or 300 mg/day for six months) in Japanese subjects aged 50–69 and earlier trials showing improvements in learning and memory tasks versus placebo [1] [5] [2]. A large 190‑participant randomized trial in China evaluated a food supplement containing PS (with α‑linolenic acid) and reported improvements in several cognitive domains, especially short‑term memory, in older adults with mild cognitive impairment (MCI), but this tested PS in combination with ALA rather than with bacopa or lion’s mane [6] [7].
2. Bacopa research in older adults — evidence of memory benefit, sometimes combined with other nutrients but rarely with fungi
Clinical trials and narrative reviews show bacopa improves memory acquisition, retention and attention when given as a standardized extract over weeks to months, and some studies included older adults and Alzheimer’s patients in polyherbal or combination formulas [5] [8]. One noncomparative, multicenter exploratory clinical study tested a dietary supplement that contained bacopa together with astaxanthin, phosphatidylserine and vitamin E in subjects with MCI and reported cognitive improvements, but that study was not randomized, placebo‑controlled and did not include lion’s mane [3]. Thus bacopa has been paired with PS in at least one exploratory human study, yet that test lacks the methodological strength of randomized trials and did not include lion’s mane [3].
3. Lion’s mane trials — small, promising studies but generally standalone or paired differently
Lion’s mane has been evaluated in small clinical trials for MCI and early/mild Alzheimer’s disease showing transient cognitive benefits in some measures and safety over months, but these trials have been stand‑alone or used lion’s mane‑enriched extracts rather than being combined with PS and bacopa together [4] [9]. Reported lion’s mane trials vary in dose and duration, with some 12–16 week studies in older adults with MCI noting improvements that faded after cessation, but none in the provided reporting test a three‑ingredient formulation including PS and bacopa [4] [9].
4. What exists on combinations — commercial blends and exploratory studies, not definitive clinical trials of the three together
Commercial supplements and marketing summaries frequently combine PS, bacopa and lion’s mane in formulations and claim synergistic effects, but the provided sources show these are product compositions rather than randomized clinical trials proving efficacy of the three‑way mix [10] [11]. The literature does document at least one exploratory study that combined bacopa with PS (plus astaxanthin and vitamin E) in MCI subjects, but that noncomparative trial cannot substitute for a randomized, placebo‑controlled clinical trial of PS + bacopa + lion’s mane in older adults [3].
5. Conclusion, caveats and research gaps — a clear absence and what would settle it
Based on the reporting provided, there is no documented randomized, placebo‑controlled clinical trial that specifically tests the combination of phosphatidylserine, Bacopa monnieri and lion’s mane for memory outcomes in older adults; existing high‑quality trials address PS, bacopa, and lion’s mane individually or test PS with other lipids or bacopa in a multi‑ingredient exploratory study that lacked randomization and did not include lion’s mane [1] [2] [6] [3] [4]. This gap leaves unanswered whether a three‑way combination is additive, synergistic, or redundant; the available evidence supports further randomized, well‑powered trials that explicitly test that specific combination and report standardized cognitive endpoints and safety in older populations. The reporting reviewed does not allow ruling out unpublished or more recent trials; these conclusions reflect only the sources provided (p1_s1–[5]5).