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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, cross-over clinical trial

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Abstract

Purpose

Despite the lack of evidence, a growing number of people are using herbal medicine to attenuate the burden of diabetes. There is an urgent need to investigate the clinical potential of herbs. Preliminary observations suggest that American ginseng (Panax quinquefolius [AG]) may reduce postprandial glycemia. Thus, we aimed to evaluate the efficacy and safety of AG as an add-on therapy in individuals with type 2 diabetes (T2DM) controlled by conventional treatment.

Methods

24 individuals living with T2DM completed the study (F:M = 11:13; age = 64 ± 7 year; BMI = 27.8 ± 4.6 kg/m2; HbA1c = 7.1 ± 1.2%). Utilizing a double-blind, cross-over design, the participants were randomized to receive either 1 g/meal (3 g/day) of AG extract or placebo for 8 weeks while maintaining their original treatment. Following a ≥ 4-week washout period, the participants were crossed over to the opposite 8-week treatment arm. The primary objective was HbA1c, and secondary endpoints included fasting blood glucose and insulin, blood pressure, plasma lipids, serum nitrates/nitrites (NOx), and plasominogen-activating factor-1 (PAI-1). Safety parameters included liver and kidney function.

Results

Compared to placebo, AG significantly reduced HbA1c (− 0.29%; p = 0.041) and fasting blood glucose (− 0.71 mmol/L; p = 0.008). Furthermore, AG lowered systolic blood pressure (− 5.6 ± 2.7 mmHg; p < 0.001), increased NOx (+ 1.85 ± 2.13 µmol/L; p < 0.03), and produced a mean percent end-difference of − 12.3 ± 3.9% in LDL-C and − 13.9 ± 5.8% in LDL-C/HDL. The safety profiles were unaffected.

Conclusions

AG extract added to conventional treatment provided an effective and safe adjunct in the management of T2DM. Larger studies using physiologically standardized ginseng preparations are warranted to substantiate the present findings and to demonstrate therapeutic effectiveness of AG.

ClinicalTrials.gov Identifier

NCT02923453.

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Acknowledgements

This study was financially supported by the Ontario Ministry of Agriculture, Food and Rural Affairs, Agriculture and Agri-Food Canada (Ontario Tobacco Diversification Program) with 50% of funding, and the rest was provided by Chai-Na-Ta Corp. Langley, BC, Canada, which also provided the study materials, CNT 2000 ginseng extract and placebo capsules. Chai-Na-Ta Corp. was dissolved in July 9, 2012 and since then appears to have ceased to carry out any operations. The PI has made efforts and attempts to contact the private Chai-Na-Ta but got no response. Hence, Chai-Na-Ta Corp. did not have the opportunity to provide comments on the final manuscript as per the research agreement clause. JLS is funded by a PSI Graham Farquharson Knowledge Translation Fellowship, Canadian Diabetes Association (CDA) Clinician Scientist award, CIHR INMD/CNS New Investigator Partnership Prize, and Banting & Best Diabetes Centre Sun Life Financial New Investigator Award. We wish to acknowledge a research fellow Ryon Bateman from University of Western Ontario who performed a nitric oxide analysis for the purpose of the present study.

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Authors and Affiliations

  1. Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, Toronto, ON, Canada

    Vladimir Vuksan, Zenith Zheng Xu, Elena Jovanovski, Alexandra L. Jenkins, Uljana Beljan-Zdravkovic, John L. Sievenpiper, P. Mark Stavro & Andreea Zurbau

  2. Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada

    Vladimir Vuksan & John L. Sievenpiper

  3. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Vladimir Vuksan, Zenith Zheng Xu, Elena Jovanovski, John L. Sievenpiper, P. Mark Stavro & Andreea Zurbau

  4. Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Vladimir Vuksan

  5. Division of Endocrinology & Metabolism, St. Michael’s Hospital, Toronto, ON, Canada

    Vladimir Vuksan & John L. Sievenpiper

  6. Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases—UH Merkur, School of Medicine, University of Zagreb, Zagreb, Croatia

    Lea Duvnjak

  7. Chai-Na-Ta Corp., Langley, BC, Canada

    Michael Z. C. Li

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  1. Vladimir Vuksan
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  2. Zenith Zheng Xu
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  3. Elena Jovanovski
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  4. Alexandra L. Jenkins
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  5. Uljana Beljan-Zdravkovic
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  6. John L. Sievenpiper
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  7. P. Mark Stavro
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  8. Andreea Zurbau
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  9. Lea Duvnjak
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  10. Michael Z. C. Li
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Corresponding author

Correspondence to Vladimir Vuksan.

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Confllict of interest

VV currently holds grant support for ginseng research from the Canadian Institutes of Health Research, Canadian Diabetes Association (CDA), Canada and the National Institute of Horticultural & Herbal Science, RDA, Korea. He also received a donation from BTGin co. Daejeon, Korea for a research on their proprietary Rg3 Korean red ginseng in diabetes. VV is holder of an American (No. 7,326,404 B2) and Canadian (No. 2,410,556) patent for use of viscous fibre blend in diabetes, metabolic syndrome and cholesterol lowering. At the time of the study, VV was a partial owner of Glycemic Index Laboratories (Toronto, ON, Canada) and has since retired from the organization (April, 2015). ALJ is part owner and Director of Research at GI Labs, a clinical research organization. JLS has received research support from the Canadian Institutes of health Research (CIHR), Diabetes Canada, PSI Foundation, Banting and Best Diabetes Centre (BBDC), Canadian Nutrition Society (CNS), American Society for Nutrition (ASN), Calorie Control Council, INC International Nut and Dried Fruit Council Foundation, National Dried Fruit Trade Association, The Tate and Lyle Nutritional Research Fund at the University of Toronto, and The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers). He has received speaker fees and/or honoraria from Diabetes Canada, Canadian Nutrition Society (CNS), Dr. Pepper Snapple Group, Dairy Farmers of Canada, Sprim Brasil, WhiteWave Foods, Rippe Lifestyle, mdBriefcase, Alberta Milk, FoodMinds LLC, Memac Ogilvy & Mather LLC, PepsiCo, The Ginger Network LLC, International Sweeteners Association, Nestlé Nutrition Institute, Pulse Canada, Canadian Society for Endocrinology and Metabolism (CSEM), and GI Foundation. He has ad hoc consulting arrangements with Winston & Strawn LLP, Perkins Coie LLP, and Tate & Lyle. He is a member of the European Fruit Juice Association Scientific Expert Panel. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes (EASD), and Canadian Cardiovascular Society (CCS), as well as an expert writing panel of the American Society for Nutrition (ASN). He serves as an unpaid scientific advisor for the Food, Nutrition, and Safety Program (FNSP) and the Technical Committee on Carbohydrates of the International Life Science Institute (ILSI) North America. He is a member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His wife is an employee of Unilever Canada. LD serves as a speaker or advisory Board member of NovoNordisk, Boehringer, Astra Zaneca, Eli Lilly, Sanofi, Takeda, MSD, Merck, Amgen, Sandoz. ML was formerly employed at Chai-Na-Ta Corp. He is presently with Wellgenex Sciences Inc., Richmond, BC, Canada. None of the sponsors mentioned above had a role in any aspect of the present study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, approval of the manuscript or decision to publish. ZX is presently with Pharma Medica Research Inc. EJ, UBZ, MS, and AZ have no declared conflicts of interest related to this paper.

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Uljana Beljan-Zdravkovic is sadly deceased. This article is in memory of Uljana whose expertise made a great contribution to the design of this study.

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Vuksan, V., Xu, Z.Z., Jovanovski, E. et al. 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, cross-over clinical trial. Eur J Nutr 58, 1237–1245 (2019). https://doi.org/10.1007/s00394-018-1642-0

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