Which randomized controlled trials have directly compared Ginkgo biloba extract (EGb 761) versus placebo for tinnitus and what were their outcomes?
Executive summary
Randomized, double‑blind, placebo‑controlled trials directly testing the standardized Ginkgo biloba extract EGb 761® for tinnitus exist and have been synthesized in systematic reviews and meta‑analyses that largely report small but statistically significant benefits for EGb 761 versus placebo in selected trials and populations [1] [2]. However, appraisal of the literature reveals heterogeneity in trial quality, populations (primary tinnitus vs dementia cohorts with neurosensory symptoms), and in conclusions across reviewers — some meta‑analyses find superiority [1] [3] while other independent reviews and large trials report little or no clinically meaningful benefit [4] [5].
1. The RCT landscape: how many placebo‑controlled trials tested EGb 761 and where they sit in the evidence base
Systematic searches that focus specifically on the standardized extract EGb 761® identify eight randomized, placebo‑controlled clinical trials addressing tinnitus or neurosensory symptoms that included tinnitus outcomes, and reviews focused on EGb 761 report that those trials showed statistically significant superiority of active treatment over placebo in many endpoints (change in tinnitus volume/intensity in three studies; overall severity in six, significant in five) [1] [6]. In contrast, broader reviews and meta‑analyses that pooled different ginkgo preparations or applied stricter selection criteria have reached less positive conclusions, highlighting that the apparent effect is concentrated in trials of the EGb 761 formulation rather than all ginkgo products [4] [5].
2. Representative trials: designs and headline outcomes
Several individual randomized trials are repeatedly cited: a double‑blind outpatient study that randomized 60 chronic tinnitus patients to oral EGb 761 (2 × 80 mg/day) versus placebo after a 10‑day EGb 761 infusion found significant superiority of EGb 761 for the primary outcome (change in tinnitus volume) at 4, 8 and 12 weeks in the intention‑to‑treat analyses, though absolute differences were described as moderate and data completeness declined over time [7]. Older randomized trials such as Meyer and Morgenstern & Biermann are cited in reviews and reported variously as showing benefit on severity or loudness measures, but reporting detail and methodological clarity vary across those reports [5] [8].
3. Meta‑analyses and pooled signals: when EGb 761 looks favorable
Meta‑analytic work that restricts analysis to EGb 761 trials — notably a dementia‑focused meta‑analysis that examined neurosensory symptoms including tinnitus at a 240 mg daily dose — reported that EGb 761 was superior to placebo for tinnitus with a weighted mean difference favoring treatment (−1.06 on an 11‑point scale; p = 0.003), concluding an overall benefit in those trial sets [3] [2]. Systematic reviews focused on EGb 761 similarly conclude evidence of efficacy in several controlled studies, particularly when trials enrolled patients whose primary complaint included tinnitus [1] [9].
4. Conflicting reviews, methodological caveats and clinical significance
Not all syntheses agree: Cochrane‑style and other broader reviews that included non‑EGb 761 products or judged trial quality differently have concluded that evidence is insufficient or that Ginkgo biloba does not clearly benefit tinnitus patients, with pooled responder rates sometimes only marginally better than placebo (for example, 21.6% vs 18.4% in one meta‑analysis noted by reviewers) and concerns about flawed trials and heterogeneity in extract composition undermining certainty [4] [5]. Trial limitations cited across reviews include small sample sizes, variable outcome measures, short follow‑up, differing dosing regimens, and mixed patient populations (primary tinnitus vs dementia cohorts with incidental tinnitus) — all of which temper claims about robust clinical benefit [7] [5] [2].
5. Bottom line for clinicians and researchers
When the evidence is limited to randomized, placebo‑controlled trials of the standardized EGb 761® extract, several trials and meta‑analyses report statistically significant improvements in tinnitus measures versus placebo, particularly in certain patient groups or dosing regimens [1] [7] [3]. Yet broader syntheses and critiques emphasize modest absolute effects, heterogeneity across studies, and methodological weaknesses that leave clinical relevance uncertain and warrant cautious interpretation and further high‑quality RCTs with standardized endpoints [4] [5] [2].