Key messages

• Ginkgo biloba probably does not decrease severity of tinnitus.
• Ginkgo biloba does not reduce the intensity of tinnitus or improve quality of life.

What is the evidence.
See evidence matrix in Epistemonikos later

We found three systematic reviews [1],[2],[3] including four primary studies [4],[5],[6],[7], all corresponding to randomized trials. This table and the summary in general are based on the latter.

What types of patients were included*

All trials included adults whose reason for consultation was the presence of tinnitus.

What types of interventions were included*

All trials evaluated the use of Ginkgo biloba in the management of tinnitus: two used EGb761 extract, 160 mg/day [5] or 120 mg/day [6]; one used LI1370 extract, 150 mg/day [4]; and one did not mention the use of any specific extract, but it was administered in a dose of 120 mg/day [7].
All trials compared against placebo.

What types of outcomes
were measured

The different trials measured multiple outcomes, which were pooled by the systematic reviews as follow:

• Severity of tinnitus, through a subjective scale.
• Impact on the quality of life, through subjective scoring scales.
• Intensity of tinnitus, using audiometry in decibels (dB) and through subjective scoring scales.
• Presence of side effects to the use of Ginkgo biloba.

The average follow-up 12.5 weeks with a range between 12 and 14 weeks.

To whom this evidence does and does not apply

• These results are applicable to adults whose main symptom is tinnitus. Out of four trials, only one included patients with acute or subchronic tinnitus, with an average duration of 134 days [5], while the rest consider patients who report the symptom for a longer time: between 1-5 years of duration [4], average duration of 4.5 years [6] and an average persistence of the symptom of 4.8 years [7].
• It is relevant to mention that among the trials, two used the extract EGb761 of Ginkgo biloba [5],[6] and one the extract LI 1370 [4], which reflects a scarce standardization of the of the intervention, which may influence the lack of effect.
• These results are not applicable to patients who present another neurological comorbidity associated with tinnitus.

• The selected outcomes are those critical for decision-making according to the opinion of the authors and are in agreement, in general, with the systematic reviews identified. These are the outcomes related to the reduction of tinnitus, objectively or subjectively, in addition to the impact on the quality of life of the patients and the presence of side effects.
• Regarding the outcome severity of tinnitus, one trial [4] reported there was no difference between the experimental and control group, pre- and post-intervention, through a subjective scale of 0-19 points, whose name is not detailed.
• Regarding intensity of tinnitus, one trial [6] measured this outcome in decibels, using audiometry, noting that there was a non-significant reduction in the intervention group from 42.3 (36.6 to 48.1) to 39.0 (31.9 to 46.1), while the control group showed a non-significant increase from 44.1 (39.0 to 49.2) to 45.1 (39.1 to 51.2). Two other trials [4],[5] used unspecified subjective scales, where one [4] showed that the volume reduction was 13.6% in experimental patients versus 12.4% in the placebo group, and the other [5] noted that on a scale from 0 to 3 points, the difference between pre- and post-intervention in the experimental group was -1 point and -0.67 in the control group, both showing there was no difference between the experimental groups in terms of reducing the intensity of tinnitus.
• Regarding the outcome of quality of life, one trial [4] reported there was no difference between the experimental and placebo group, based on a subjective, unspecified scale, from 0 to 5 points pre and post-intervention. Another trial [7] did not show differences between both groups based on two surveys: the Tinnitus Handicap Inventory (the score difference between pre- and post-intervention was -4.7 points in the experimental group and -2.2 in the control group), and the Glasgow Health Status Inventory (the score difference before and after intervention was 1.94 in the experimental group and 2.52 in the control group). The third trial [5] did not report differences between groups, using a subjective scale (not specified), from 0 to 3 points, where the pre and post intervention difference in the experimental group was -0.84 and in the control group was - 0.59.
• Regarding adverse effects, one trial [4] showed no difference, reporting 10.6% of patients with side effects in the experimental group and 9.5% in the control group, where at least one third were gastrointestinal symptoms. The other trial [7] also showed no differences between the two groups, with 3% in the experimental group and 6% in the placebo group presenting diarrhea, and 3% in both groups had headache.

• The results of the systematic reviews were difficult to analyze, the measures of effect were not clear and there were no meta-analyses. Notwithstanding, the certainty of the evidence is moderate to high.
• Even though it is a safe intervention, it has no benefit, so, the balance between benefits and harms is not favorable.

• The reviews did not consider the costs associated with the use of Ginkgo biloba.
• Considering the absence of benefit), regardless of the cost, the balance between cost and benefits is not favorable.

• Faced with the evidence presented in this summary, most patients and doctors should lean against its use, considering Ginkgo biloba would have no effect on tinnitus.
• However, in the absence of alternative treatments for this condition, it is possible that some patients would choose to use treatments without adverse effects and low cost. It is particularly important to inform patients about the limitations of the evidence.

Differences between this summary and other sources

• The conclusions obtained in this summary agree with one of the systematic reviews identified [2]. However, two reviews [1], [3] suggest there may be a benefit, but the evidence base is limited. The discrepancy between these reviews and this summary is explained by the interpretation about the clinical relevance of the changes observed. The opinion of the authors of this summary is they are not relevant for patients.
• We did not identify international clinical guidelines about the management of tinnitus.

• The probability that future research changes the conclusions associated with the outcomes of this summary is low, considering the certainty of the existing evidence.
• We did not identify ongoing trials evaluating Ginkgo biloba for tinnitus in the International Clinical Trials Registry Platform (WHO) or ongoing systematic reviews in the Prospective Register of Systematic Reviews (PROSPERO).