Which dietary supplements have reliable clinical trial evidence for cognitive benefits, if any?

1. Multivitamins: the clearest randomized‑trial signal, but still modest

Large randomized cohorts from the COSMOS program and a combined meta‑analysis found consistent, statistically significant but modest improvements in global cognition and episodic memory for older adults taking a daily multivitamin‑mineral versus placebo over two to three years, an effect that investigators interpreted as roughly a two‑year slowing of cognitive aging in the studied populations ^{[1] [2]}. While these are among the strongest clinical findings available, authors and commentators note that the trials do not identify which specific micronutrients drive the benefit and that effects may vary by baseline nutrition and individual factors, limiting broad prescriptions for everyone ^[2].

2. Omega‑3 fatty acids: biologically plausible but inconsistent RCT outcomes

Omega‑3 fatty acids remain biologically plausible for brain health, yet randomized controlled trials produce mixed results: some find no benefit in mild‑to‑moderate Alzheimer’s disease or in healthy young adults, and systematic reviews conclude there is little firm evidence that omega‑3 supplements reliably enhance cognition across populations ^{[3] [4]}. Consequently, omega‑3s cannot be claimed as a proven cognitive enhancer based on current RCT data, although subgroup effects and methodological heterogeneity leave open the possibility of benefit in particular settings or dosages ^{[4] [3]}.

3. Ginkgo, curcumin and many botanicals: promising anecdotes, failed large trials or limited data

Ginkgo biloba has a long observational history but a large, placebo‑controlled randomized trial (EGb‑761) in more than 3,000 older adults found no reduction in overall incidence of dementia, and reviewers conclude there is no conclusive evidence that ginkgo prevents or slows dementia ^[5]. Curcumin shows positive preclinical signals and small human trials suggest potential for preventing decline in some healthy samples, but clinical trials are limited, inconsistent, and hampered by bioavailability issues, so evidence remains inconclusive ^[5]. Other botanicals such as Bacopa monnieri have several small RCTs and meta‑analytic signals indicating modest cognitive benefits in certain measures, yet heterogeneity of extracts, short durations, and small sample sizes make the evidence suggestive rather than definitive ^{[7] [8] [9]}.

4. B vitamins, phosphatidylserine, berry extracts and combined formulas: mixed signals and variable quality

B vitamins are mechanistically plausible for homocysteine‑related pathways and have supportive mechanistic literature, but clinical trials have not consistently shown prevention of cognitive decline, and evidence is nuanced by baseline deficiency and trial design ^{[10] [11]}. Phosphatidylserine and berry‑based foods or concentrates show some positive small trials or observational associations—berries in whole‑food trials and some exploratory supplement studies—but the evidence base is not robust or uniform enough for firm clinical recommendations ^{[12] [13] [14]}. Multi‑ingredient “cocktails” appear in exploratory studies but their composite designs make it impossible to attribute effects to individual ingredients ^[14].

5. The meta‑message: most supplements lack reliable, generalizable RCT proof and carry regulatory and quality caveats

Comprehensive narrative and systematic reviews emphasize that while a minority of supplements and multi‑nutrient strategies show modest, replicated signals (notably multivitamins in older adults), the majority of the 72 commonly marketed ingredients lack high‑quality RCT evidence; many trials are small, short, heterogeneous, or industry‑driven, and supplement labeling and safety are not regulated like drugs, which raises potential for variability and interaction risks ^{[6] [11] [3]}. Readers and clinicians must weigh modest benefits against uncertain long‑term safety, individual nutritional status, and realistic expectations.

6. What reliable conclusions can be drawn now—and what remains to test

The clearest, pragmatic takeaway from randomized trials is that a daily multivitamin‑mineral showed modest cognitive benefit in older adults in COSMOS and pooled analyses, while single‑agent supplements such as omega‑3s, ginkgo, and curcumin have mixed or insufficient clinical trial support; numerous herbal extracts (e.g., Bacopa) and food‑based interventions (berries) are promising but need larger, longer, standardized RCTs to be considered proven therapies ^{[1] [2] [3] [4] [5] [7] [13]}. Where reporting is silent or inconsistent about specific populations, dosages, or long‑term harms, definitive claims cannot be made without further high‑quality randomized evidence ^{[6] [11]}.