Alpha-lipoic acid does not improve olfactory training results in olfactory loss due to COVID-19: a double-blind randomized trial

Abstract

Objectives: Olfactory loss is a recognized long-term dysfunction after Coronavirus Disease 2019 (COVID-19) infection. This investigation aimed to assess the effect of alpha-lipoic acid as an adjuvant treatment of olfactory training on the improvement of smell loss in post-COVID-19 patients.

Methods: This randomized controlled trial included 128 adult outpatients who had persistent smell loss for more than 3-months after COVID-19 infection. The participants were randomly allocated into two groups: the intervention treatment group, which received alpha-lipoic acid associated to olfactory training, and comparison treatment group, which received placebo pills associated to olfactory training. The participants were followed-up for 12-weeks. Olfactory dysfunction was assessed in terms of Visual Analog Scale (VAS), and the Connecticut Chemosensory Clinical Research Center (CCCRC) test for the Brazilian population.

Results: A total of 100 participants completed the follow-up period and were analyzed in this study. Both groups have improved CCCRC score (p = 0.000), olfactory threshold (p = 0.000), identification score (p = 0.000) and VAS score (p = 0.000) after 12-weeks follow-up. No significant differences were determined between the intervention and comparison treatment groups in CCCRC score (p = 0.63), olfactory threshold (p = 0.50), identification score (p = 0.96) and VAS score (p = 0.97). In all these criteria, comparison treatment group went slightly worse. At the endpoint of the study, the frequency of anosmia reduced to 2% in the intervention treatment group and to 7.8% in the comparison treatment group. Also, 16.8% of the intervention group' subjects, and 15.7% of comparison treatment group's patients reached normosmia.

Conclusions: Overall, there was a strongly significant difference in olfactory function between baseline and endpoint for both groups. However, based on the lack of significant difference between the intervention treatment and the comparison treatment groups in terms of olfactory changes, our study appoints that the alpha-lipoic acid is not better than olfactory training alone to treat olfactory loss after COVID-19.

Level of evidence: Level 2.

Keywords: Alpha-lipoic acid; COVID-19; Olfactory dysfunction; Olfactory test; Post acute COVID-19 syndrome.