Randomized Double-blind Placebo-controlled study to evaluate the efficacy of fermented deglycyrrhizinated licorice for treatment of diabetic polyneuropathy

To evaluate the efficacy of α-amylase enzyme prepared from fermented deglycyrrhizinated licorice root extract (FDGL) in treating early-stage diabetic polyneuropathy (DPN). A double-blind, placebo-controlled randomized trial involving 83 type 1 and II diabetic patients aged 15–65 years with diabetes duration ≤ 5 years, serum amylase < 45 IU/L. Patients were not complaining of clinical diabetic polyneuropathy (DPN), yet they showed demonstrable electrophysiological changes (vibration perception threshold [VPT] > 15 V), low nerve conduction velocity (NCV), and low serum amylase levels. Patients were randomized to receive either FDGL capsules (gp A; 0.5 gm twice daily containing 1250 IU of α-amylase) or a matched placebo (gp B) for 6 months. For comparison, 20 healthy volunteers matched for age, sex, and body constitution were recruited (control gp). Primary outcomes were the changes in motor nerve conduction velocity (MCV) and vibration perception threshold (VPT) from baseline. Secondary outcomes included changes in sensory nerve conduction velocity (SCV), serum amylase levels, and HbA1C. Outcomes were assessed at baseline, after 3, and 6 months. The study was registered on ClinicalTrials.gov (NCT07148804). A total of 83 diabetic patients were analyzed. Compared to placebo, patients who received FDGL (GpA) demonstrated a significant increase in MCV, SCV, and serum amylase with a reduction in VPT at 3 and 6-month follow-up (p < 0.001 for all outcomes). Compared to the control group, this corresponds to a restoration of 32% and 99% of the neurological deficits of MCV and SCV, respectively. HBA1C remained around the baseline values at the end of the study with no significant difference between the groups. Oral administration of α-amylase enzyme in FDGL significantly improved nerve conduction and restored serum amylase levels in both type I and II diabetic patients. Further studies are needed to verify its effect on other complications. This study was registered at ClinicalTrials.gov (NCT07148804).