What peer‑reviewed clinical trials have tested natural formulas for mild cognitive impairment and what were their conflicts of interest?
Executive summary
Randomized, peer‑reviewed trials have tested a range of natural formulas and supplements in people with mild cognitive impairment (MCI) — including Ginkgo biloba, saffron, curcumin, blueberry and other botanical extracts, omega‑3s and combined “nutraceutical” formulas — but the literature is heterogeneous and the reporting of conflicts of interest (COIs) is inconsistent across studies and reviews [1] [2] [3] [4]. Systematic reviews conclude that some products show modest signals of benefit in selected trials (notably Ginkgo in meta‑analyses) while overall evidence quality is low and COI disclosures range from explicit “no competing interests” statements to author links with supplement companies or industry funding noted in review acknowledgements [4] [1] [5].
1. Which peer‑reviewed randomized trials have tested natural formulas in MCI and nearby populations
Systematic reviews and meta‑analyses catalog dozens of randomized controlled trials (RCTs) that evaluated botanical extracts or supplements in MCI or mild Alzheimer’s — examples repeatedly cited include trials of Ginkgo biloba with pooled analyses finding benefit at 22–26 weeks in some meta‑analyses [4] [2], randomized studies of saffron for mild‑to‑moderate AD and for multidomain MCI (noted across recent reviews) [3] [1], a six‑month randomized, placebo‑controlled pilot trial of curcumin in Alzheimer patients (often cited in supplement reviews) [3], RCTs of blueberry supplementation reporting enhanced neural activation in MCI [3], trials of wild green oat extract in older adults [2], and RCTs of vitamin/trace element interventions such as folic acid plus vitamin B12 or probiotic plus selenium in AD/MCI spectrum populations [6] [7].
2. What the systematic reviews report about effect sizes and quality
Authors of recent systematic reviews and meta‑analyses emphasize heterogeneity in design, dosing, duration and outcomes: some interventions (Ginkgo biloba, bacopa, certain polyphenol or omega‑3 formulations) show modest improvements on cognitive scales in selected trials, but the overall evidence base is judged low quality with high risk of bias in many studies and inconsistent replication across independent groups [2] [5] [8]. The Frontiers meta‑analysis that pooled extended supplementation trials required ≥6 weeks and found mixed results and cautioned about heterogeneity and study limitations [3] [1].
3. How conflicts of interest were reported in the literature
Reporting practices vary: some syntheses explicitly declare no commercial or financial relationships that could be construed as COIs (the Frontiers meta‑analysis authors stated an absence of commercial/financial relationships) [1], and the BMJ Open protocol for an NMA declared “none” for competing interests [7]. Conversely, individual authors and institutes are occasionally flagged as having industry links or scholarships — for example, the NICM‑affiliated review noted a PhD scholarship from FIT‑BioCeuticals to an author and described NICM’s involvement in trials with funder‑related disclosures referenced [5] [9]. Across reviews the transparency and granularity of COI declarations for the primary RCTs themselves are unevenly summarized, so reviewers sometimes note limited COI reporting in original trial papers [5] [8].
4. What that pattern implies about interpretation and hidden agendas
When modest trial signals coincide with industry ties or with sparse COI reporting, the risk of bias increases and raises the possibility that positive small trials may be amplified by supplement industry interests; several reviews explicitly advise caution and call for larger, independent, better‑reported RCTs before clinical adoption [2] [8]. At the same time, publicly funded or independently reported syntheses frequently conclude there may be real, limited benefits for specific extracts (e.g., Ginkgo in some meta‑analyses) but stress replication and standardized reporting of COIs and trial protocols [4] [1].
5. Bottom line for readers and researchers
Peer‑reviewed RCTs exist for many natural formulas and supplements in MCI and adjacent conditions and systematic reviews enumerate them, but the overall evidence is mixed and frequently limited by small sample sizes, heterogeneity and inconsistent COI transparency; where COIs are reported the picture is mixed — from explicit “no competing interests” declarations in some reviews to documented industry scholarships or trial support in other reports — underscoring the need to evaluate each trial’s funding and author disclosures directly rather than rely on headline efficacy claims [1] [5] [8].