Fermented Deglycyrrhizinated Licorice [FDGL] Improves Symptoms of Diabetic Neuropathy

Written by Chrystal Moulton. After 3 months, researchers observed a significant improvement in MCV (P<0.001), CMAP (P=0.025), SCV (P<0.001), VPT (P<0.001), and serum amylase (P<0.001) in the treatment group compared to placebo.

hands massaging footAmylase is an enzyme created by the exocrine pancreas which digests starch. This enzyme is essential to glycolysis and the tricarboxylic acid cycle and respiratory chain.1 Serum amylase deficiency was correlated to diabetic complications in several studies.2-4 Insulin resistance and insulin deficiency have long been identified as a key issue leading to diabetic complications.5,6 Fermented deglycyrrhizinated licorice [FDGL] is a compound that is rich in alpha amylase enzymes.6 Understanding the importance of hypoinsulinemia and amylase deficiency in exacerbating complications in diabetic patients, researchers in the current study investigated the effects of fermented deglycyrrhizinated licorice [FDGL]  supplementation in the treatment of diabetic complications.6

Fermented deglycyrrhizinated licorice [FDGL] utilized for this study was formulated specifically for this trial with 2500 IU/g powder containing naturally occurring flavonoids found in licorice root. Participants for this trial were recruited from a diabetic clinic in Cairo, Egypt. A total of 120 patients were chosen from 269 patients with either type I or type II diabetes. Patients were chosen based on these inclusion requirements:

  • Age: 15-65 years old
  • BMI: <30 kg/m2
  • HBA1C: <9%
  • Serum amylase: <45 IU/L
  • Vibration perception threshold: >15V
  • Diabetes duration: 1-5 years

Participants had to be clinically asymptomatic but exhibited early-stage diabetic polyneuropathy and were not being treated with sympathomimetic or anti-epileptic agents, tricyclic antidepressants, neurotoxic drugs, and any other medications that could influence nerve function. Furthermore, patients with disorders that could cause neuropathy such as chronic alcohol consumption, B12 deficiency, autoimmune/ connective-tissue diseases or hypothyroidism were excluded from this trial. Eligible patients were randomly assigned to receive the treatment or placebo in a 1:1 ratio. The study was designed as a randomized double-blind placebo-controlled trial. Participants in the treatment group were required to take 500mg fermented deglycyrrhizinated licorice [FDGL] capsules twice daily one hour before meals along with their prescribed diabetes medication. Each capsule contained approximately 1250 IU of alpha-amylase. Patients in the placebo group were given capsules that contained 500mg non-fermented deglycyrrhizinated licorice, which they were also required to take twice daily 1 hour before meals along with their prescribed medication. A control group consisting of 20 healthy participants served as a baseline for analysis. Participants in the control group did not undergo follow-up assessments (at 3 or 6 months) nor received any treatment/placebo medication.  Serum glucose was checked 2 hours after initial intake of the assigned protocol twice daily for 3 days and diabetic medication was adjusted to ensure appropriate glycemic control throughout the study. Study duration was 6 months.

At baseline, researchers conducted clinical laboratory tests (comprehensive blood tests including serum amylase measurement), neurological assessments (testing sensitivity to pain, temperature, and touch), and blood pressure readings. Further neurophysiological assessments included a series of tests measuring nerve conduction. This included motor and sensory nerve conduction velocity [MCV, measured at the peroneal nerve / SCV, measured at the sural nerve], sensory nerve action potential [SNAP, measured at the sural nerve], compound muscle action potential amplitude [CMAP, measured at the peroneal nerve] and vibration perception threshold [VPT, at six points on the sole of each foot].  Electrocardiogram was also performed as part of a routine assessment. Researchers repeated these assessments after 3 months and 6 months following baseline for patients in the treatment and placebo groups.  T-tests were used for statistical analysis.

A total of 102 patients consented and 83 successfully completed the trial at 6 months. The average age of participants was 44.63 ±7.07 yrs and 45.35 ±8.29 yrs in the treatment and placebo group, respectively. Average BMI was 28.09 ±6.04 and 26.97 ±5.25 in the treatment and placebo groups, respectively. No statistically significant differences were observed between the treatment and placebo group in either clinical or demographic parameters. In both the placebo and treatment groups, HbA1C was significantly higher than the control group (P<0.001) and serum alpha-amylase was significantly lower than the healthy controls (P<0.001). Furthermore, in both the treatment and placebo groups, baseline values of MCV, SCV, and VPT were significantly different compared to healthy controls (P<0.001). This indicated a significant deficit in nerve and sensory function in the patients across the placebo and treatment groups.  After 3 months, researchers observed a significant improvement in MCV (P<0.001), CMAP (P=0.025), SCV (P<0.001), VPT (P<0.001), and serum amylase (P<0.001) in the treatment group compared to placebo. After 6 months, significant improvement was maintained in MCV, SCV, VPT, and serum amylase (P<0.001) in the treatment group. Researchers also observed significant improvements in HbA1C (P=0.027) after 6 months in the treatment group. Further analysis showed that type 1 diabetes patients had sustained significant improvement in CMAP, SCV, and serum amylase throughout the duration of the study (P<0.05). Meanwhile, type 2 diabetes patients experienced sustained improvement in MCV, CMAP, SCV, and serum amylase throughout the trial (P<0.05). Researchers also conducted modeling and least squares analysis to evaluate the strength of their findings. In both analyses, serum alpha-amylase, SCV, and VPT were significantly improved when associated with FDGL intake (P<0.05). Additionally, sensitivity analysis showed that diabetes type had no effect on MCV, CMAP, SCV, SNAP, VPT, and serum amylase at either 3 or 6 months.

Results from this trial showed that 6 months treatment with FDGL significantly improved nerve conductivity in type 1 and 2 diabetic patients with early-stage diabetic polyneuropathy. According to researchers, in 6 months, 99% of the deficit in SCV and 83.6% of the deficit in VPT compared to control was restored in the intervention group. Implications of these findings are promising and warrant additional investigation to confirm these results.

Source: Massoud, Ahmad Mohamed Ali, Hoda Mohamed Ali Massoud, Ahmed Abdel-Aala El-Shawarby, and Mahmoud Ibrahim Elseidy. “Randomized Double-blind Placebo-controlled study to evaluate the efficacy of fermented deglycyrrhizinated licorice for treatment of diabetic polyneuropathy.” Endocrine 91, no. 1 (2026): 51.

© The Author(s) 2026

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Posted May 18, 2026.

Chrystal is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Chicago.

References:

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  3. Lee JG, Park SW, Cho BM, et al. Serum amylase and risk of the metabolic syndrome in Korean adults. Clinica chimica acta; international journal of clinical chemistry. Sep 18 2011;412(19-20):1848–53. doi:10.1016/j.cca.2011.06.023
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  5. Chandana G, Veigas NM, Raghavendra D. Association of serum amylase with insufficient insulin action in type I and type II diabetes mellitus and metabolic syndrome. International Journal of Clinical Biochemistry and Research. 2016;3(4):421–425.
  6. Massoud AMA, Massoud HMA, El-Shawarby AA, Elseidy MI. Randomized Double-blind Placebo-controlled study to evaluate the efficacy of fermented deglycyrrhizinated licorice for treatment of diabetic polyneuropathy. Endocrine. Feb 2 2026;91(1):51. doi:10.1007/s12020-025-04476-5

 

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