Supplementation with extract of Gynostemma pentaphyllum leaves reduces anxiety in healthy subjects with chronic psychological stress: A randomized, double-blind, placebo-controlled clinical trial

Phytomedicine. 2019 Jan:52:198-205. doi: 10.1016/j.phymed.2018.05.002. Epub 2018 May 8.


Background: The ethanol extract of Gynostemma pentaphyllum Makino leaves (EGP) has been reported recently to have anxiolytic effects on chronically stressed mice models.

Purpose: We aimed to investigate the efficacy and safety of EGP on anxiety level in healthy Korean subjects under chronic stressful conditions.

Study design: Double-blind, placebo-controlled trial.

Methods: This study was conducted with 72 healthy adults who had perceived chronic stress and anxiety with a score on the State-Trait Anxiety Inventory (STAI) from 40 to 60. Participants were randomly assigned to receive either EGP (200 mg, twice a day, N = 36) or placebo (N = 36). All participants were exposed to repetitive loads of stress by performing the serial subtraction task for 5 min every second day during the 8-week intervention. Primary outcome of Trait-STAI and secondary outcomes of State-STAI, total score of STAI, Hamilton Anxiety Inventory (HAM-A), Beck Anxiety Inventory (BAI), blood norepinephrine and adrenocorticotropic hormone (ACTH), salivary cortisol and alpha-amylase, cardiovascular autonomic nervous system (ANS) functional test, and heart rate variability (HRV) test were measured before and after intervention.

Results: After the 8-week intervention, the EGP significantly lowered the score of the Trait Anxiety Scale of the STAI (T-STAI) by 16.8% compared to the placebo (p = 0.041). The total score on the STAI decreased by 17.8% in the EGP group and tended to improve compared with that of the placebo group (p = 0.067). There were no significant differences in the changes in score of S-STAI, HAM-A, BAI, and other parameters from baseline between the two groups. There was no causal relationship between the ingestion of EGP and adverse drug reactions.

Conclusion: We found that supplementation with EGP reduced "anxiety proneness" in subjects under chronic psychological stress, as shown by a decrease in the score of T-STAI and the tendency for decrease in the total score of STAI. This result suggests that EGP supplementation can be used as a regimen to safely reduce stress and anxiety; however, more studies are needed to establish the long-term safety and effectiveness.

Keywords: Anxiety; Chronic stress; Gynostemma pentaphyllum; Psychological stress; State-Trait Anxiety Inventory.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Anti-Anxiety Agents / therapeutic use*
  • Anxiety / drug therapy*
  • Double-Blind Method
  • Female
  • Gynostemma / chemistry*
  • Healthy Volunteers
  • Heart Rate
  • Humans
  • Hydrocortisone / analysis
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Plant Extracts / therapeutic use*
  • Plant Leaves / chemistry
  • Stress, Psychological / drug therapy*
  • alpha-Amylases / analysis


  • Anti-Anxiety Agents
  • Plant Extracts
  • Adrenocorticotropic Hormone
  • alpha-Amylases
  • Hydrocortisone
  • Norepinephrine