Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Current Clinical Evidence for Korean Red Ginseng in Management of Diabetes and Vascular Disease: A Toronto's Ginseng Clinical Testing Program

  • Vuksan, Vladimir (Clinical Nutrition Risk Factor Modification Center, St. Michael's Hospital) ;
  • Sievenpipper, John (Clinical Nutrition Risk Factor Modification Center, St. Michael's Hospital) ;
  • Jovanovski, Elena (Clinical Nutrition Risk Factor Modification Center, St. Michael's Hospital) ;
  • Jenkins, Alexandra L. (Clinical Nutrition Risk Factor Modification Center, St. Michael's Hospital)
  • Received : 2010.11.30
  • Accepted : 2010.12.16
  • Published : 2010.12.29
Download PDF
⟨ Previous Next ⟩

Abstract

While ginseng is reported to have a wide array of applications, there is growing evidence for its indications in diabetes and vascular disease. A clear connection, however, has not been established between ginseng's composition, dose and its targeted efficacy in humans. We therefore developed and initiated the Korean Red Ginseng Clinical Testing Program for diabetes and vascular function which is an efficacy and safety-based clinical screening model for ginseng. The most efficacious sources, ginsenoside profiles, doses, and modes of administration were examined in sequential, acute, followed by long term, randomized-controlled trials to investigate the efficacy and safety profiles. This review discusses the current state of the clinical research of Korean red ginseng program conducted in Toronto, paving the way for the use of clinically selected ginseng and its ginsenoside fractions in the management of diabetes and vascular diseases.

Keywords

References

  1. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414-1431. https://doi.org/10.2337/diacare.21.9.1414
  2. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-2559. https://doi.org/10.1056/NEJMoa0802743
  3. ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560-2572. https://doi.org/10.1056/NEJMoa0802987
  4. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999;281:2005-2012. https://doi.org/10.1001/jama.281.21.2005
  5. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457-2471. https://doi.org/10.1056/NEJMoa072761
  6. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-139. https://doi.org/10.1056/NEJMoa0808431
  7. Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care 1995;18:1373-1375. https://doi.org/10.2337/diacare.18.10.1373
  8. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. Variable effects of American ginseng: a batch of American ginseng (Panax quinquefolius L.) with a depressed ginsenoside profile does not affect postprandial glycemia. Eur J Clin Nutr 2003;57:243-248. https://doi.org/10.1038/sj.ejcn.1601550
  9. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. Decreasing, null and increasing effects of eight popular types of ginseng on acute postprandial glycemic indices in healthy humans: the role of ginsenosides. J Am Coll Nutr 2004;23:248-258. https://doi.org/10.1080/07315724.2004.10719368
  10. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. Null and opposing effects of Asian ginseng (Panax ginseng C.A. Meyer) on acute glycemia: results of two acute dose escalation studies. J Am Coll Nutr 2003;22:524-532. https://doi.org/10.1080/07315724.2003.10719331
  11. Sievenpiper JL, Arnason JT, Vidgen E, Leiter LA, Vuksan V. A systematic quantitative analysis of the literature of the high variability in ginseng (Panax spp.): should ginseng be trusted in diabetes? Diabetes Care 2004;27:839-840. https://doi.org/10.2337/diacare.27.3.839
  12. Pasupuleti VK, Anderson JW. Ginseng in type 2 diabetes mellitus: A review of the evidence in humans. Nutraceuticals, glycemic health and type 2 diabetes. 1st ed. Ames: Wiley-Blackwell/IFT Press, 2008.
  13. Vuksan V, Sievenpiper JL. Herbal remedies in the management of diabetes: lessons learned from the study of ginseng. Nutr Metab Cardiovasc Dis 2005;15:149-160. https://doi.org/10.1016/j.numecd.2005.05.001
  14. Vuksan V, Sievenpiper JL, Koo VY, Francis T, Beljan-Zdravkovic U, Xu Z, Vidgen E. American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med 2000;160:1009-1013. https://doi.org/10.1001/archinte.160.7.1009
  15. Vuksan V, Sievenpiper JL, Wong J, Xu Z, Beljan-Zdravkovic U, Arnason JT, Assinewe V, Stavro MP, Jenkins AL, Leiter LA, al. American ginseng (Panax quinquefolius L.) attenuates postprandial glycemia in a time-dependent but not dose-dependent manner in healthy individuals. Am J Clin Nutr 2001;73:753-758. https://doi.org/10.1093/ajcn/73.4.753
  16. Vuksan V, Stavro MP, Sievenpiper JL, Beljan-Zdravkovic U, Leiter LA, Josse RG, Xu Z. Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes. Diabetes Care 2000;23:1221-1226. https://doi.org/10.2337/diacare.23.9.1221
  17. Vuksan V, Stavro MP, Sievenpiper JL, Koo VY, Wong E, Beljan-Zdravkovic U, Francis T, Jenkins AL, Leiter LA, Josse RG, et al. American ginseng improves glycemia in individuals with normal glucose tolerance: effect of dose and time escalation. J Am Coll Nutr 2000;19:738-744. https://doi.org/10.1080/07315724.2000.10718073
  18. Vuksan V, Sievenpiper JL, Xu Z, Wong EY, Jenkins AL, Beljan-Zdravkovic U, Leiter LA, Josse RG, Stavro MP. Konjac-Mannan and American ginsing: emerging alternative therapies for type 2 diabetes mellitus. J Am Coll Nutr 2001;20(5 Suppl):370S-380S. https://doi.org/10.1080/07315724.2001.10719170
  19. Stavro PM, Woo M, Heim TF, Leiter LA, Vuksan V. North American ginseng exerts a neutral effect on blood pressure in individuals with hypertension. Hypertension 2005;46:406-411. https://doi.org/10.1161/01.HYP.0000173424.77483.1e
  20. Stavro PM, Woo M, Leiter LA, Heim TF, Sievenpiper JL, Vuksan V. Long-term intake of North American ginseng has no effect on 24-hour blood pressure and renal function. Hypertension 2006;47:791-796. https://doi.org/10.1161/01.HYP.0000205150.43169.2c
  21. Tetsutani T, Yamamura M, Yamaguchi T, Onoyama O, Kono M. Can red ginseng control blood glucose in diabetic patients. Ginseng Rev 2000;28:44-47.
  22. Sievenpiper JL, Sung MK, Di Buono M, Seung-Lee K, Nam KY, Arnason JT, Leiter LA, Vuksan V. Korean red ginseng rootlets decrease acute postprandial glycemia: results from sequential preparation- and dose-finding studies. J Am Coll Nutr 2006;25:100-107. https://doi.org/10.1080/07315724.2006.10719519
  23. Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, Di Buono M, Lee KS, Leiter LA, Nam KY, Arnason JT, et al. Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis 2008;18:46-56. https://doi.org/10.1016/j.numecd.2006.04.003
  24. Zhou W, Chai H, Lin PH, Lumsden AB, Yao Q, Chen CJ. Molecular mechanisms and clinical applications of ginseng root for cardiovascular disease. Med Sci Monit 2004;10:RA187-RA192.
  25. Yun TK. Brief introduction of Panax ginseng C.A. Meyer. J Korean Med Sci 2001;16 Suppl:S3-S5. https://doi.org/10.3346/jkms.2001.16.S.S3
  26. Kang SY, Kim SH, Schini VB, Kim ND. Dietary ginsenosides improve endothelium-dependent relaxation in the thoracic aorta of hypercholesterolemic rabbit. Gen Pharmacol 1995;26:483-487. https://doi.org/10.1016/0306-3623(95)94002-X
  27. Kang SY, Schini-Kerth VB, Kim ND. Ginsenosides of the protopanaxatriol group cause endothelium-dependent relaxation in the rat aorta. Life Sci 1995;56:1577-1586. https://doi.org/10.1016/0024-3205(95)00124-O
  28. Kim ND, Kang SY, Kim MJ, Park JH, Schini-Kerth VB. The ginsenoside $Rg_3$ evokes endothelium-independent relaxation in rat aortic rings: role of K+ channels. Eur J Pharmacol 1999;367:51-57. https://doi.org/10.1016/S0014-2999(98)00899-1
  29. Kim ND, Kang SY, Park JH, Schini-Kerth VB. Ginsenoside $Rg_3$ mediates endothelium-dependent relaxation in response to ginsenosides in rat aorta: role of K+ channels. Eur J Pharmacol 1999;367:41-49. https://doi.org/10.1016/S0014-2999(98)00898-X
  30. Kim ND, Kang SY, Schini VB. Ginsenosides evoke endothelium-dependent vascular relaxation in rat aorta. Gen Pharmacol 1994;25:1071-1077. https://doi.org/10.1016/0306-3623(94)90121-X
  31. Kim ND, Kim EM, Kang KW, Cho MK, Choi SY, Kim SG. Ginsenoside $Rg_3$ inhibits phenylephrine-induced vascular contraction through induction of nitric oxide synthase. Br J Pharmacol 2003;140:661-670. https://doi.org/10.1038/sj.bjp.0705490
  32. Sung J, Han KH, Zo JH, Park HJ, Kim CH, Oh BH. Effects of red ginseng upon vascular endothelial function in patients with essential hypertension. Am J Chin Med 2000;28:205-216. https://doi.org/10.1142/S0192415X00000258
  33. Park KM, Kim YS, Jeong TC, Joe CO, Shin HJ, Lee YH, Nam KY, Park JD. Nitric oxide is involved in the immunomodulating activities of acidic polysaccharide from Panax ginseng. Planta Med 2001;67:122-126. https://doi.org/10.1055/s-2001-11508
  34. Shin JY, Song JY, Yun YS, Yang HO, Rhee DK, Pyo S. Immunostimulating effects of acidic polysaccharides extract of Panax ginseng on macrophage function. Immunopharmacol Immunotoxicol 2002;24:469-482. https://doi.org/10.1081/IPH-120014730
  35. Han K, Shin IC, Choi KJ, Yun YP, Hong JT, Oh KW. Korea red ginseng water extract increases nitric oxide concentrations in exhaled breath. Nitric Oxide 2005;12:159-162. https://doi.org/10.1016/j.niox.2005.02.001
  36. Han KH, Choe SC, Kim HS, Sohn DW, Nam KY, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, et al. Effect of red ginseng on blood pressure in patients with essential hypertension and white coat hypertension. Am J Chin Med 1998;26:199-209. https://doi.org/10.1142/S0192415X98000257
  37. Caron MF, Hotsko AL, Robertson S, Mandybur L, Kluger J, White CM. Electrocardiographic and hemodynamic effects of Panax ginseng. Ann Pharmacother 2002;36:758-763. https://doi.org/10.1345/aph.1A411
  38. Nichols WW, Edwards DG. Arterial elastance and wave reflection augmentation of systolic blood pressure: deleterious effects and implications for therapy. J Cardiovasc Pharmacol Ther 2001;6:5-21. https://doi.org/10.1177/107424840100600102
  39. Nichols WW, Singh BM. Augmentation index as a measure of peripheral vascular disease state. Curr Opin Cardiol 2002;17:543-551. https://doi.org/10.1097/00001573-200209000-00016
  40. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, Ducimetiere P, Benetos A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001;37:1236-1241. https://doi.org/10.1161/01.HYP.37.5.1236
  41. Felmeden DC, Spencer CG, Blann AD, Beevers DG, Lip GY. Low-density lipoprotein subfractions and cardiovascular risk in hypertension: relationship to endothelial dysfunction and effects of treatment. Hypertension 2003;41:528-533. https://doi.org/10.1161/01.HYP.0000056997.40992.41
  42. Stavro PM, Woo M, Vuksan V. Korean red ginseng lowers blood pressure in individuals with hypertension. Am J Hypertens 2004;17:33A.
  43. Stavro PM, Hana AK, Vuksan V. The effect of Korean red ginseng extracts with escalating levels of ginsenoside $Rg_3$ on blood pressure in individuals with high normal blood pressure or hypertension. Am J Hypertens 2002;15:34A.
  44. Jovanovski E, DeSouza L, Ezatagha A, Lee AS, Jenkins AL, Dias A, Vuksan V. The Influence of Korean red ginseng (Panax ginseng C. A. Mayer) root and its derived fractions, ginsenosides and polysaccharides on endothelial function: an acute double blind, crossover randomized controlled trial in healthy individuals. In: Natural Health Product Research Society of Canada. Proceeding of the 5th annual natural health products research conference and trade show: science across borders, global natural health products research; 2008 Mar 26-29; Toronto, ON, Canada. March 29th Oral Presentation.

Cited by

  1. Inhibition of TNF-α-Mediated NF-κB Transcriptional Activity by Dammarane-Type Ginsenosides from Steamed Flower Buds of Panax ginseng in HepG2 and SK-Hep1 Cells vol.22, pp.1, 2014, https://doi.org/10.4062/biomolther.2013.096
  2. Effects of Korean White Ginseng (Panax Ginseng C.A. Meyer) on Vascular and Glycemic Health in Type 2 Diabetes: Results of a Randomized, Double Blind, Placebo-controlled, Multiple-crossover, Acute Dose Escalation Trial vol.3, pp.2, 2014, https://doi.org/10.7762/cnr.2014.3.2.89
  3. The amelioration of plasma lipids by Korean traditional confectionery in middle-aged women: A cross-over study with western cookie vol.10, pp.6, 2016, https://doi.org/10.4162/nrp.2016.10.6.590
  4. Effects of dietary fermented red ginseng marc and red ginseng extract on growth performance, nutrient digestibility, blood profile, fecal microbial, and noxious gas emission in weanling pigs vol.46, pp.1, 2018, https://doi.org/10.1080/09712119.2018.1466708
  5. Fungal Endophytes from Three Cultivars of Panax ginseng Meyer Cultivated in Korea vol.36, pp.1, 2010, https://doi.org/10.5142/jgr.2012.36.1.107
  6. Inhibition of TNF-α-mediated NF-κB Transcriptional Activity in HepG2 Cells by Dammarane-type Saponins from Panax ginseng Leaves vol.36, pp.2, 2012, https://doi.org/10.5142/jgr.2012.36.2.146
  7. Increase in the Contents of Ginsenosides in Raw Ginseng Roots in Response to Exposure to 450 and 470 nm Light from Light-Emitting Diodes vol.36, pp.2, 2010, https://doi.org/10.5142/jgr.2012.36.2.198
  8. Diversity of Fungal Endophytes in Various Tissues of Panax ginseng Meyer Cultivated in Korea vol.36, pp.2, 2012, https://doi.org/10.5142/jgr.2012.36.2.211
  9. Morphological Characteristics of Korean Dried Ginseng Products vol.36, pp.3, 2010, https://doi.org/10.5142/jgr.2012.36.3.314
  10. Efficacy of Korean Red Ginseng in the Treatment of Alopecia Areata vol.36, pp.4, 2010, https://doi.org/10.5142/jgr.2012.36.4.391
  11. Effects of Natural Bioactive Products on the Growth and Ginsenoside Contents of Panax ginseng Cultured in an Aeroponic System vol.36, pp.4, 2010, https://doi.org/10.5142/jgr.2012.36.4.430
  12. Rg3-enriched Korean Red Ginseng enhances blood pressure stability in spontaneously hypertensive rats vol.5, pp.3, 2016, https://doi.org/10.1016/j.imr.2016.05.006
  13. Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection vol.40, pp.4, 2010, https://doi.org/10.1016/j.jgr.2015.09.002
  14. Protective roles of ginseng against bacterial infection vol.5, pp.11, 2010, https://doi.org/10.15698/mic2018.11.654
  15. Co-immunomodulatory Activities of Anionic Macromolecules Extracted from Codium fragile with Red Ginseng Extract on Peritoneal Macrophage of Immune-Suppressed Mice vol.30, pp.3, 2020, https://doi.org/10.4014/jmb.1909.09062