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http://dx.doi.org/10.1016/j.jgr.2019.11.005

Effect of coadministration of enriched Korean Red Ginseng (Panax ginseng) and American ginseng (Panax quinquefolius L) on cardiometabolic outcomes in type-2 diabetes: A randomized controlled trial  

Jovanovski, Elena (Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital)
Smircic-Duvnjak, Lea (School of Medicine University of Zagreb, University Clinic for Diabetes, Endocrinology and Metabolic Diseases)
Komishon, Allison (Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital)
Au-Yeung, Fei (Rodney) (Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital)
Sievenpiper, John L. (Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital)
Zurbau, Andreea (Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital)
Jenkins, Alexandra L. (Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital)
Sung, Mi-Kyung (Department of Food and Nutrition, Sookmyung Women's University)
Josse, Robert (Division of Endocrinology & Metabolism, St. Michael's Hospital)
Li, Dandan (Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital)
Vuksan, Vladimir (Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital)
Publication Information
Journal of Ginseng Research / v.45, no.5, 2021 , pp. 546-554 More about this Journal
Abstract
Background: Diabetes mellitus and hypertension often occur together, amplifying cardiovascular disease (CVD) risk and emphasizing the need for a multitargeted treatment approach. American ginseng (AG) and Korean Red Ginseng (KRG) species could improve glycemic control via complementary mechanisms. Additionally, a KRG-inherent component, ginsenoside Rg3, may moderate blood pressure (BP). Our objective was to investigate the therapeutic potential of coadministration of Rg3-enriched Korean Red Ginseng (Rg3-KRG) and AG, added to standard of care therapy, in the management of hypertension and cardiometabolic risk factors in type-2 diabetes. Methods: Within a randomized controlled, parallel design of 80 participants with type-2 diabetes (HbA1c: 6.5-8%) and hypertension (systolic BP: 140-160 mmHg or treated), supplementation with either 2.25 g/day of combined Rg3-KRG + AG or wheat-bran control was assessed over a 12-wk intervention period. The primary endpoint was ambulatory 24-h systolic BP. Additional endpoints included further hemodynamic assessment, glycemic control, plasma lipids and safety monitoring. Results: Combined ginseng intervention generated a mean ± SE decrease in primary endpoint of 24-h systolic BP (-3.98 ± 2.0 mmHg, p = 0.04). Additionally, there was a greater reduction in HbA1c (-0.35 ± 0.1% [-3.8 ± 1.1 mmol/mol], p = 0.02), and change in blood lipids: total cholesterol (-0.50 ± 0.2 mmol/l, p = 0.01), non-HDL-C (-0.54 ± 0.2 mmol/l, p = 0.01), triglycerides (-0.40 ± 0.2 mmol/l, p = 0.02) and LDL-C (-0.35 ± 0.2 mmol/l, p = 0.06) at 12 wks, relative to control. No adverse safety outcomes were observed. Conclusion: Coadministration of Rg3-KRG + AG is an effective addon for improving BP along with attaining favorable cardiometabolic outcomes in individuals with type 2 diabetes. Ginseng derivatives may offer clinical utility when included in the polypharmacy and lifestyle treatment of diabetes. Clinical trial registration: Clinicaltrials.gov identifier, NCT01578837;
Keywords
Ginseng; Hypertension; Randomized controlled trial; Type-2 diabetes;
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1 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 Sep;23(9):1221-6.   DOI
2 Vuksan V, Sievenpiper J, Xu Z, Beljian-Zdravkovic JA, Arnason J, Bateman R, Leiter L, Josse RG, Francais T, Stavro M. Ginseng and diabetes: a new way to use an old medicine. C J D C 2001;25(2):111-20.
3 Nagar H, Choi S, Jung SB, Jeon BH, Kim CS. Rg3-enriched Korean Red Ginseng enhances blood pressure stability in spontaneously hypertensive rats. Integr Med Res 2016 Sep;5(3):223-9.   DOI
4 Food and Drug Administration. Guidance for industry. Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and Prevention.
5 Hong SJ, Fong JC, Hwang JH. Effects of crude drugs on glucose uptake in 3T3-L1 adipocytes. Kaohsiung J Med Sci 2000 Sep;16(9):445-51.
6 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 Oct;20(5 Suppl). 370S-80S.   DOI
7 Li GD, Lu ZQ. [Effect of ginseng saponins on insulin release from isolated pancreatic islets in the rat]. Zhong Xi Yi Jie He Za Zhi 1987 Jun;7(6):357-9. 326.
8 Shishtar E, Sievenpiper JL, Djedovic V, Cozma AI, Ha V, Jayalath VH, Jenkins DJ, Meija SB, DeSouza RJ, Jovanovski E, et al. The effect of ginseng (the genus panax) on glycemic control: a systematic review and meta-analysis of randomized controlled clinical trials. PLoS One 2014;9(9):e107391.   DOI
9 Ketema EB, Kibret KT. Correlation of fasting and postprandial plasma glucose with HbA1c in assessing glycemic control; systematic review and meta-analysis. Arch Public Health 2015;73:43.   DOI
10 Catapano AL, Graham I, De BG, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2016 Oct 14;37(39):2999-3058.   DOI
11 Gui QF, Xu ZR, Xu KY, Yang YM. The efficacy of ginseng-related therapies in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Medicine (Baltimore) 2016 Feb;95(6):e2584.   DOI
12 Lee KH, Bae IY, Park SI, Park JD, Lee HG. Antihypertensive effect of Korean Red Ginseng by enrichment of ginsenoside Rg3 and arginine-fructose. J Ginseng Res 2016 Jul;40(3):237-44.   DOI
13 Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, DiBuono 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 Jan;18(1):46-56.   DOI
14 Jeon BH, Kim CS, Kim HS, Park JB, Nam KY, Chang SJ. Effect of Korean red ginseng on blood pressure and nitric oxide production. Acta Pharmacol Sin 2000 Dec;21(12):1095-100.
15 Sattar N. Revisiting the links between glycaemia, diabetes and cardiovascular disease. Diabetologia 2013 Apr;56(4):686-95.   DOI
16 Ham W, Kim WT, Lee JS, Ju HJ, Kang SJ, Oh JH, Her Y, Chung JY, Park K, Choi YD. Efficacy and safety of red ginseng extract powder in patients with erectile dysfunction. Korean J Urol 2009;50(2):159-64.   DOI
17 Song YB, An YR, Kim SJ, Park HW, Jung JW, Kyung JS, Hwang SY, Kim YS. Lipid metabolic effect of Korean red ginseng extract in mice fed on a high-fat diet. J Sci Food Agric 2012 Jan 30;92(2):388-96.   DOI
18 Chung SH, Choi CG, Park SH. Comparisons between white ginseng radix and rootlet for antidiabetic activity and mechanism in KKAy mice. Arch Pharm Res 2001 Jun;24(3):214-8.   DOI
19 Aa J, Wang G, Hao H, Huang Q, Lu Y, Yan B, Zha WB, Liu LS, Kang A. Differential regulations of blood pressure and perturbed metabolism by total ginsenosides and conventional antihypertensive agents in spontaneously hypertensive rats. Acta Pharmacol Sin 2010 Aug;31(8):930-7.   DOI
20 Zafari N, Asgari S, Lotfaliany M, Hadaegh A, Azizi F, Hadaegh F. Impact of hypertension versus diabetes on cardiovascular and all-cause mortality in Iranian older adults: results of 14 Years of follow-up. Sci Rep 2017 Oct 27;7(1):14220.   DOI
21 Kim SH, Park KS. Effects of Panax ginseng extract on lipid metabolism in humans. Pharmacol Res 2003 Nov;48(5):511-3.   DOI
22 Mucalo I, Jovanovski E, Vuksan V, Bozikov V, Romic Z, Rahelic D. American ginseng extract (panax quinquefolius L.) is safe in long-term use in type 2 diabetic patients. Evid Based Complement Alternat Med 2014;2014:969168.
23 Kim YS, Woo JY, Han CK, Chang IM. Safety analysis of panax ginseng in randomized clinical trials: a systematic review. Medicines 2015 Jun;2(2):106-26.   DOI
24 Whelton PK, Carey RM, Aronow WS, Casey Jr DE, Collins KJ, Dennison HC, DePalma SM, Gidding S, Jamerson KA, Jones D, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American college of cardiology/American heart association task force on clinical Practice guidelines. Hypertension 2017 Nov 13.
25 Vuksan V, Xu ZZ, Jovanovski E, Jenkins AL, Beljan-Zdravkovic U, Sievenpiper J, Stavro PM, Zurbau A, Duvnjak L, Li MZC. Efficacy and safety of American ginseng (panax quinquefolius L) extract on glycemic control and cardiovascular risk factors in individuals with type 2 diabetes: a double-blind, randomized, crossover clinical trial. Eur J Nutr 2018.
26 Sen S, Querques MA, Chakrabarti S. North American Ginseng (Panax quinquefolius) prevents hyperglycemia and associated pancreatic abnormalities in diabetes. J Med Food 2013 Jul;16(7):587-92.   DOI
27 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 Mar;27(3):839-40.
28 Stravo PM, Vuksan V. Effect of fermented Korean ginseng fortified with ginsenoside Rg3 on blood pressure in individuals with high normal blood pressure or hypertension. In: Proceedings of the 8th intern symposium on ginseng; Oct28-31 2002. p. 416-23. South Korea.
29 Jeong D, Irfan M, Kim SD, Kim S, Oh JH, Park CK, Kim HK, Rhee MH. Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in vivo thrombus formation. J Ginseng Res 2017 Jan 13.
30 Prasad K, Sharma V, Lackore K, Jenkins SM, Prasad A, Sood A. Use of complementary therapies in cardiovascular disease. Am J Cardiol 2013 Feb 1;111(3):339-45.   DOI
31 Kim ND, Kang SY, Kim MJ, Park JH, Schini-Kerth VB. The ginsenoside Rg3 evokes endothelium-independent relaxation in rat aortic rings: role of K+ channels. Eur J Pharmacol 1999 Feb 12;367(1):51-7.   DOI
32 Vuksan V, Stavro MP, Sievenpiper JL, Koo VY, Wong E, Beljan-Zdravkovic U, Francais 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 Nov;19(6):738-44.   DOI
33 Sievenpiper JL, Sung MK, Di BM, 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 Apr;25(2):100-7.   DOI
34 Jeon BH, Kim CS, Park KS, Lee JW, Park JB, Kim KJ, Kim SH, Chang SJ, Nam KY. Effect of Korea red ginseng on the blood pressure in conscious hypertensive rats. Gen Pharmacol 2000 Sep;35(3):135-41.   DOI
35 Jovanovski E, Bateman EA, Bhardwaj J, Fairgrieve C, Mucalo I, Jenkins AL, Vuksan V. Effect of Rg3-enriched Korean red ginseng (Panax ginseng) on arterial stiffness and blood pressure in healthy individuals: a randomized controlled trial. J Am Soc Hypertens 2014 Aug;8(8):537-41.   DOI
36 Brunstrom M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ 2016 Feb 24;352. i717.   DOI
37 Pickering TG, Shimbo D, Haas D. Ambulatory blood-pressure monitoring. N Engl J Med 2006 Jun 1;354(22):2368-74.   DOI
38 Reboldi G, Gentile G, Angeli F, Ambrosio G, Mancia G, Verdecchia P. Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients. J Hypertens 2011 Jul;29(7):1253-69.   DOI
39 Pang H, Wang HL, Fu L, Su CY. [Pharmacokinetic studies of 20(R)-ginsenoside RG3 in human volunteers]. Yao Xue Xue Bao 2001 Mar;36(3):170-3.