What randomized controlled trials have tested magnesium, zinc, or melatonin specifically for tinnitus and what were their outcomes?
Executive summary
Randomized controlled trial (RCT) evidence testing tinnitus-treatments-safety">magnesium, zinc, and melatonin for tinnitus is limited, mixed, and generally does not support routine use of these supplements to eliminate tinnitus; some trials show modest benefits on sleep or subgroup improvements but not consistent, clinically robust reductions in tinnitus severity versus placebo [1] [2] [3]. Clinical guidelines therefore do not recommend ginkgo, melatonin, zinc, or other dietary supplements as standard treatment for persistent bothersome tinnitus, though investigators note possible benefit in particular subgroups [1] [2].
1. Magnesium — suggestive preclinical signals but few definitive RCTs
Magnesium has biological plausibility—lower serum magnesium has been associated with tinnitus and animal models suggest post‑trauma magnesium may protect auditory function—but high‑quality randomized trials isolating magnesium for tinnitus are sparse and the systematic reporting concludes dietary supplements overall are ineffective for most patients [4] [5] [6] [2]. Commercial combination formulations that include magnesium (for example MEMOTIN® and Tinnitan Duo®) have been studied in clinic settings or small interventional cohorts, but these are not blinded, randomized trials of magnesium alone and thus cannot establish magnesium’s independent efficacy [5] [7]. The American Tinnitus Association and related reviews therefore treat magnesium evidence as preliminary and inconclusive [4] [1].
2. Zinc — randomized trials show inconsistent, largely negative results with a possible subgroup signal
Several randomized, placebo‑controlled trials have tested oral zinc for tinnitus; one cited randomized double‑blind study in elderly patients found zinc was no more effective than placebo, and Cochrane‑style systematic reviews compiled multiple RCTs finding no clear overall benefit for zinc on validated tinnitus severity outcomes [8] [3]. A single randomized, prospective, placebo‑controlled trial reported clinically favorable progress in 46.4% of zinc‑treated patients and large subjective reductions in severity in those receiving zinc, but that trial’s primary improvement did not reach statistical significance and subgroup analyses suggested benefit might concentrate in patients with baseline zinc deficiency [9]. Overall, the balance of randomized evidence does not support zinc as a broadly effective treatment, though clinicians and researchers note a plausible targeted role when deficiency is documented [3] [1].
3. Melatonin — the strongest RCT signal is for sleep; tinnitus intensity results are mixed but promising in some trials
Randomized, double‑blind trials of melatonin have repeatedly shown improvements in sleep quality for tinnitus sufferers and at least a few RCTs found statistically significant decreases in tinnitus measures compared with placebo or comparator therapy: a crossover RCT of 61 subjects reported significantly greater decreases in tinnitus matching and self‑rated tinnitus after melatonin versus placebo, and broader meta‑analyses and network meta‑analyses identify melatonin (sometimes combined with intratympanic steroid) among interventions associated with superior improvement versus control [10] [11] [12]. Systematic survey data also indicate melatonin commonly helps tinnitus patients’ sleep and emotional reaction even when its effect on core tinnitus loudness is inconsistent [2] [13]. In short, melatonin has the most reproducible randomized‑trial effect on sleep and some trials report parallel reductions in tinnitus metrics, but results are not uniform enough to form a blanket recommendation [10] [11].
4. Combination supplements, commercial studies, and methodological caveats
Many studies cited by manufacturers test multi‑ingredient supplements that include magnesium, zinc, and melatonin alongside Ginkgo, B vitamins, and other compounds; these trials sometimes report short‑term decreases in tinnitus loudness or improved PROMs but are often open‑label, small, or not isolating a single ingredient, making causal attribution impossible [5] [7] [12]. Systematic reviews emphasize heterogeneity in dosing, duration, outcome measures, and risk of bias across trials—which inflates the chance that small positive trials reflect placebo response or selective reporting rather than reproducible pharmacologic effects [3] [2].
5. Guidelines, practical takeaway, and research gaps
Major specialty guidance advises clinicians not to recommend ginkgo, melatonin, zinc, or other dietary supplements for persistent bothersome tinnitus because randomized evidence is inconsistent and overall effect sizes are modest; guidelines and surveys nonetheless acknowledge that some patients—especially those with sleep disturbance or documented nutrient deficiency—may derive subjective benefit [1] [2]. The research agenda is clear: larger, well‑powered RCTs that test single agents at standardized doses, prospectively stratify for deficiency or comorbidity (for example insomnia), and use validated tinnitus‑specific outcome measures are needed to move beyond suggestive subgroup signals to definitive clinical recommendations [3] [11].