A 12-week, randomized, double-blind study to evaluate the efficacy and safety of liver function after using fermented ginseng powder (GBCK25)

  • Su-Jin Jung Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Republic of Korea; and Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea https://orcid.org/0000-0003-1103-7477
  • Ji-Hyun Hwang Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Republic of Korea
  • Soo-Hyun Park Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Republic of Korea
  • Eun-Kyung Choi Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Republic of Korea; and Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea
  • Ki-Chan Ha Healthcare Claims & Management Incorporation, Jeonju, Republic of Korea
  • Hyang-Im Baek Healthcare Claims & Management Incorporation, Jeonju, Republic of Korea
  • Dong-Gue Shin Research & Development Center of GENERAL BIO Co., Ltd, Namwon, Jeollabuk-Do, Republic of Korea
  • Jeong-Hun Seo Research & Development Center of GENERAL BIO Co., Ltd, Namwon, Jeollabuk-Do, Republic of Korea
  • Soo-Wan Chae Department of Pharmacology, Chonbuk National University, Medical School, Jeonju, Republic of Korea https://orcid.org/0000-0003-3660-8272
DOI: https://doi.org/10.29219/fnr.v64.3517
Keywords: fermented ginseng, liver function, gamma-glutamyl transferase, hs-CRP, anti-fatigue

Abstract

Popular scientific summary
  • We confirmed significant decreases in GGT and hs-CRP levels in male subjects suspected of non-alcoholic liver disease as a result of supplementation with 125 mg of GBCK25 (low dose).
  • We found significant improvements in fatigue score with intake of 500 mg of GBCK25 (high dose).
  • GBCK25 supplementation has beneficial effects on liver function.
 

Background: Recently, clinical research has suggested that red ginseng components play a role in liver protection and combating fatigue. However, fermented ginseng has not been analyzed for liver-protective or anti-fatigue effects.

Objective: This study evaluates the positive effects of fermented ginseng powder (GBCK25) on liver function.

Methods: Ninety participants with elevated alanine aminotransferase levels (35 ≤ ALT ≤1 05 IU/L) were randomized to one of three groups. The participants were treated with GBCK25 tablets at a dose of 500 mg/day (high dose), 125 mg/day (low dose), or placebo group daily for 12 weeks. The primary outcomes included changes in ALT and gamma-glutamyl transferase (GGT) levels. The secondary outcomes included changes in aspartate amino-transferase (AST), high-sensitivity C-reactive protein (hs-CRP), multidimensional fatigue scale, lipid profile, and antioxidant markers.

Results: In male subjects, after 12 weeks of low-dose GBCK25 (125 mg) supplementation, the GGT (P = 0.036) and hs-CRP (P = 0.021) levels decreased significantly more than those in the placebo group. High-dose GBCK25 (500 mg) supplementation significantly decreased the fatigue score compared with the placebo group. There were no clinically significant differences between the groups when studying any safety parameter.

Conclusion: Our results suggest that GBCK25 supplementation has beneficial effects on liver function.

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References


  1. Review T, LaBrecque DR, Abbas Z, Anania F, Ferenci P, Khan AG, et al. World Gastroenterology Organisation global guidelines: nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol 2014; 48(6): 467–73. doi: 10.1097/MCG.0000000000000116

  2. Caballeria L, Arteaga I, Pera G, Rodriguez L, Aluma A, Auladell MA, et al. [Risk factors associated with non-alcoholic fatty liver disease: a case-control study]. Med Clin (Barc) 2013; 141(6): 233–9. doi: 10.1016/j.medcli.2012.11.034. Epub 2013 Apr 17.

  3. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003; 37(5): 1202–19. doi: 10.1053/jhep.2003.50193

  4. Zhu H, Li YR. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med (Maywood) 2012; 237(5): 474–80. doi: 10.1258/ebm.2011.011358

  5. Kim HS, Park SI, Choi SH, Song CH, Park SJ, Shin YK, et al. Single oral dose toxicity test of blue honeysuckle concentrate in mice. Toxicol Res 2015; 31(1): 61–8. doi: 10.5487/TR.2015.31.1.061

  6. Lu Y, Hu D, Ma S, Zhao X, Wang S, Wei G, et al. Protective effect of wedelolactone against CCl4-induced acute liver injury in mice. Int Immunopharmacol 2016; 34: 44–52. doi: 10.1002/jat.2550120613

  7. Muriel P, Garciapina T, Perez-Alvarez V, Mourelle M. Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J Appl Toxicol 1992; 12(6): 439–42. doi: 10.1002/jat.2550120613

  8. Wellington K, Jarvis B. SilymarIn: a review of its clinical properties in the management of hepatic disorders. Bio Drugs 2001; 15(7): 465–89. doi: 10.2165/00063030-200115070-00005

  9. Fried MW, Navarro VJ, Afdhal N, Belle SH, Wahed AS, Hawke RL, et al. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA 2012; 308(3): 274–82. doi: 10.1001/jama.2012.8265

  10. Chang IM. Liver-protective activities of aucubin derived from traditional oriental medicine. Res Commun Mol Path 1998; 102(2): 189–204.

  11. Lu JM, Yao QZ, Chen CY. Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr Vasc Pharmacol 2009; 7(3): 293–302. doi: 10.1177/1534735403256419

  12. Zeng XL, Tu ZG. [Induction of differentiation by ginsenoside Rh2 in hepatocarcinoma cell SMMC-7721]. Ai Zheng 2004; 23(8): 879–84.

  13. Cui Y, Shu XO, Gao YT, Cai H, Tao MH, Zheng W. Association of ginseng use with survival and quality of life among breast cancer patients. Am J Epidemiol 2006; 163(7): 645–53. doi: 10.1093/aje/kwj087

  14. Block KI, Mead MN. Immune system effects of echinacea, ginseng, and astragalus: a review. Integr Cancer Ther 2003; 2(3): 247–67. doi: 10.1177/1534735403256419

  15. Park EK, Shin YW, Lee HU, Kim SS, Lee YC, Lee BY, et al. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide. Biol Pharm Bull 2005; 28(4): 652–6. doi: 10.1248/bpb.28.652

  16. Zhang YG, Liu TP. Influences of ginsenosides Rb1 and Rg1 on reversible focal brain ischemia in rats. Zhongguo Yao Li Xue Bao 1996; 17(1): 44–8.

  17. Martinez-Mir I, Rubio E, Morales-Olivas FJ, Palop-Larrea V. Transient ischemic attack secondary to hypertensive crisis related to Panax ginseng. Ann Pharmacother 2004; 38(11): 1970. doi: 10.1345/aph.1E213

  18. Huong NTT, Murakami Y, Tohda M, Watanabe H, Matsumoto K. Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin. Biol Pharm Bull 2005; 28(8): 1389–93. doi: 10.1248/bpb.28.1389

  19. Kim HG, Cho JH, Yoo SR, Lee JS, Han JM, Lee NH, et al. Antifatigue effects of Panax ginseng C.A. Meyer: a randomised, double-blind, placebo-controlled trial. PLoS One 2013; 8(4): e61271. doi: 10.1371/journal.pone.0061271

  20. Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V. Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain. Neurochem Int 1997; 30(2): 181–90. doi: 10.1016/S0197-0186(96)00025-3

  21. Ji YC, Kim YB, Park SW, Hwang SN, Min BK, Hong HJ, et al. Neuroprotective effect of ginseng total saponins in experimental traumatic brain injury. J Korean Med Sci 2005; 20(2): 291–6. doi: 10.3346/jkms.2005.20.2.291

  22. Lee S-T, Chu K, Sim J-Y, Heo J-H, Kim MJAd, Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis Assoc Disord 2008;22(3):222–6. doi: 10.1097/WAD.0b013e31816c92e6

  23. Park H-J, Son C-GJTJoKM. Systematic analysis of Ginseng-focused Research Worldwide. The Journal of Korean Medicine 2008; 29(1): 60–6.

  24. Hong M, Lee YH, Kim S, Suk KT, Bang CS, Yoon JH, et al. Anti-inflammatory and antifatigue effect of Korean Red Ginseng in patients with nonalcoholic fatty liver disease. J Ginseng Res 2016; 40(3): 203–10. doi: 10.1016/j.jgr.2015.07.006

  25. Choi N, Kim JW, Jeong H, Shin DG, Seo JH, Kim JH, et al. Fermented ginseng, GBCK25, ameliorates steatosis and inflammation in nonalcoholic steatohepatitis model. J Ginseng Res 2019; 43(2): 196–208. doi: 10.1016/j.jgr.2017.10.002

  26. Aravinthan A, Antonisamy P, Kim B, Kim NS, Shin DG, Seo JH, et al. Fermented ginseng, GBCK25, ameliorates hemodynamic function on experimentally induced myocardial injury. J Ginseng Res 2016; 40(4): 462–5. doi: 10.1016/j.jgr.2016.07.002

  27. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18(6): 499–502. doi: 10.1093/clinchem/18.6.499

  28. Schwartz JE, Jandorf L, Krupp LB. The measurement of fatigue: a new instrument. J Psychosom Res 1993; 37(7): 753–62. doi: 10.1016/0022-3999(93)90104-N

  29. Kim B-G, Choi S-Y, Kim M-R, Suh HJ, Park HJJPB. Changes of ginsenosides in Korean red ginseng (Panax ginseng) fermented by Lactobacillus plantarum M1. Process Biochem 2010; 45(8): 1319–24. doi: 10.1016/j.procbio.2010.04.026

  30. Igami K, Shimojo Y, Ito H, Miyazaki T, Kashiwada Y. Hepatoprotective effect of fermented ginseng and its major constituent compound K in a rat model of paracetamol (acetaminophen)-induced liver injury. J Pharm Pharmacol 2015; 67(4): 565–72. doi: 10.1111/jphp.12342

  31. Kim OK, Nam DE, Jun W, Lee J. Cudrania tricuspidata water extract improved obesity-induced hepatic insulin resistance in db/db mice by suppressing ER stress and inflammation. Food Nutr Res 2015; 59: 29165. doi: 10.3402/fnr.v59.29165

  32. Pleiner J, Mittermayer F, Schaller G, Marsik C, MacAllister RJ, Wolzt M. Inflammation-induced vasoconstrictor hyporeactivity is caused by oxidative stress. J Am Coll Cardiol 2003; 42(9): 1656–62. doi: 10.1016/j.jacc.2003.06.002

  33. Lee DH, Blomhoff R, Jacobs DR. Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radical Res 2004; 38(6): 535–9. doi: 10.1080/10715760410001694026

  34. Lee DH, Ha MH, Kim JR, Gross M, Jacobs DR. Gamma-glutamyltransferase, alcohol, and blood pressure: a four year follow-up study. Ann Epidemiol 2002; 12(2): 90–6. doi: 10.1016/S1047-2797(01)00252-6

  35. Turgut O, Yilmaz A, Yalta K, Karadas F, Yilmaz MB. gamma-Glutamyltransferase is a promising biomarker for cardiovascular risk. Med Hypotheses 2006; 67(5): 1060–4. doi: 10.1016/j.mehy.2006.04.010

  36. Lee DH, Jacobs DR, Gross M, Kiefe CI, Roseman J, Lewis CE, et al. gamma-glutamyltransferase is a predictor of incident diabetes and hypertension: The coronary artery risk development in young adults (CARDIA) study. Clin Chem 2003; 49(8): 1358–66. doi: 10.1373/49.8.1358

  37. Lim JS, Kim YJ, Chun BY, Yang JH, Lee DH, Kam S. [The association between serum GGT level within normal range and risk factors of cardiovascular diseases]. J Prev Med Public Health 2005; 38(1): 101–6.

  38. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50(8): 1844–50. doi: 10.2337/diabetes.50.8.1844

  39. Pagano G, Pacini G, Musso G, Gambino R, Mecca F, Depetris N, et al. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology 2002; 35(2): 367–72. doi: 10.1053/jhep.2002.30690

  40. Dixon JB, Bhathal PS, O’Brien PE. Weight loss and non-alcoholic fatty liver disease: falls in gamma-glutamyl transferase concentrations are associated with histologic improvement. Obes Surg 2006; 16(10): 1278–86. doi: 10.1381/096089206778663805

  41. Taki K, Nishio K, Hamajima N, Niwa T. Metabolic syndrome defined by new criteria in Japanese is associated with increased liver enzymes and C-reactive protein. Nagoya J Med Sci 2008; 70(1–2): 1–9.

  42. Bo S, Gambino R, Durazzo M, Guidi S, Tiozzo E, Ghione F, et al. Associations between gamma-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: a possible implication for oxidative stress. World J Gastroenterol 2005; 11(45): 7109–17. doi: 10.3748/wjg.v11.i45.7109

  43. Kerner A, Avizohar O, Sella R, Bartha P, Zinder O, Markiewicz W, et al. Association between elevated liver enzymes and C-reactive protein – possible hepatic contribution to systemic inflammation in the metabolic syndrome. Arterioscl Throm Vas 2005; 25(1): 193–7. doi: 10.1161/01.ATV.0000148324.63685.6a

  44. Lee DC, Lau AS. Effects of Panax ginseng on tumor necrosis factor-alpha-mediated inflammation: a mini-review. Molecules 2011; 16(4): 2802–16. doi: 10.3390/molecules16042802

  45. Yoneda M, Mawatari H, Fujita K, Iida H, Yonemitsu K, Kato S, et al. High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH. J Gastroenterol 2007; 42(7): 573–82. doi: 10.1007/s00535-007-2060-x

  46. Swain MG. Fatigue in liver disease: pathophysiology and clinical management. Can J Gastroenterol 2006; 20(3): 181–8. doi: 10.1155/2006/624832

  47. Kim HG, Yoo SR, Park HJ, Lee NH, Shin JW, Sathyanath R, et al. Antioxidant effects of Panax ginseng C.A. Meyer in healthy subjects: a randomized, placebo-controlled clinical trial. Food Chem Toxicol 2011; 49(9): 2229–35. doi: 10.1016/j.fct.2011.06.020

Published
2020-04-06
How to Cite
Jung S.-J., Hwang J.-H., Park S.-H., Choi E.-K., Ha K.-C., Baek H.-I., Shin D.-G., Seo J.-H., & Chae S.-W. (2020). A 12-week, randomized, double-blind study to evaluate the efficacy and safety of liver function after using fermented ginseng powder (GBCK25). Food & Nutrition Research, 64. https://doi.org/10.29219/fnr.v64.3517
Issue
Vol 64 (2020)
Section
Original Articles

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