title: Zinc supplementation for tinnitus.
abstract: Tinnitus is the perception of sound without external acoustic stimuli. Patients with severe tinnitus may have physical and psychological complaints and their tinnitus can cause deterioration in their quality of life. At present no specific therapy for tinnitus has been found to be satisfactory in all patients. In recent decades, a number of reports have suggested that oral zinc supplementation may be effective in the management of tinnitus. Since zinc has a role in cochlear physiology and in the synapses of the auditory system, there is a plausible mechanism of action for this treatment.
  
  
  
  To evaluate the effectiveness and safety of oral zinc supplementation in the management of patients with tinnitus.
  
  
  
  The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 6); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 July 2016.
  
  
  
  Randomised controlled trials comparing zinc supplementation versus placebo in adults (18 years and over) with tinnitus.
  
  
  
  We used the standard methodological procedures recommended by Cochrane. Our primary outcome measures were improvement in tinnitus severity and disability, measured by a validated tinnitus-specific questionnaire, and adverse effects. Secondary outcomes were quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters, change in tinnitus loudness, change in overall severity of tinnitus and change in thresholds on pure tone audiometry. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
  
  
  
  We included three trials involving a total of 209 participants. The studies were at moderate to high risk of bias. All included studies had differences in participant selection criteria, length of follow-up and outcome measurement, precluding a meta-analysis. The participants were all adults over 18 years with subjective tinnitus, but one study conducted in 2013 (n = 109) included only elderly patients. Improvement in tinnitus severity and disabilityOnly the study in elderly patients used a validated instrument (Tinnitus Handicap Questionnaire) for this primary outcome. The authors of this cross-over study did not report the results of the two phases separately and found no significant differences in the proportion of patients reporting tinnitus improvement at four months of follow-up: 5% (5/93) versus 2% (2/94) in the zinc and placebo groups, respectively (risk ratio (RR) 2.53, 95% confidence interval (CI) 0.50 to 12.70; very low-quality evidence).None of the included studies reported any significant adverse effects. Secondary outcomesFor the secondary outcome change in tinnitus loudness, one study reported no significant difference between the zinc and placebo groups after eight weeks: mean difference in tinnitus loudness -9.71 dB (95% CI -25.53 to 6.11; very low-quality evidence). Another study also measured tinnitus loudness but used a 0- to 100-point scale. The authors of this second study reported no significant difference between the zinc and placebo groups after four months: mean difference in tinnitus loudness rating scores 0.50 (95% CI -5.08 to 6.08; very low-quality evidence).Two studies used unvalidated instruments to assess tinnitus severity. One (with 50 participants) reported the severity of tinnitus using a non-validated scale (0 to 7 points) and found no significant difference in subjective tinnitus scores between the zinc and placebo groups at the end of eight weeks of follow-up (mean difference (MD) -1.41, 95% CI -2.97 to 0.15; very low-quality evidence). A third trial (n = 50) also evaluated the improvement of tinnitus using a non-validated instrument (a 0 to 10 scale: 10 = severe and unbearable tinnitus). In this study, after eight weeks there was no difference in the proportion of patients with improvement in their tinnitus, 8.7% (2/23) treated with zinc versus 8% (2/25) of those who received a placebo (RR 1.09, 95% CI 0.17 to 7.10, very low-quality evidence).None of the included studies reported any of our other secondary outcomes (quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters or change in thresholds on pure tone audiometry).
  
  
  
  We found no evidence that the use of oral zinc supplementation improves symptoms in adults with tinnitus.
authors.affiliation: Medicina, Medical School, Universidade Federal de São Paulo, Rua Pedro de Toledo, 598, São Paulo, São Paulo, Brazil, 04039-001.
authors.forename: Osmar C
authors.initials: OC
authors.lastname: Person
authors.forename: Maria Es
authors.initials: ME
authors.lastname: Puga
authors.forename: Edina Mk
authors.initials: EM
authors.lastname: da Silva
authors.forename: Maria R
authors.initials: MR
authors.lastname: Torloni
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D011795:Surveys and Questionnaires; D014012:Tinnitus / Q000628:therapy*; D016896:Treatment Outcome; D015032:Zinc / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D015032:Zinc