International Journal of Chinese Medicine

Submit a Manuscript

Publishing with us to make your research visible to the widest possible audience.

Propose a Special Issue

Building a community of authors and readers to discuss the latest research and develop new ideas.

A Randomized, Double-Blind Clinical Trial for Effect of Wisconsin Ginseng (Panax quinquefolius) in Improvement of Rheumatoid Arthritis Associated Fatigue

Purpose: To observe and evaluate the clinical efficacy of the Wisconsin ginseng (Panax quinquefolius) herbal botanical adjunctive treatment to improve Rheumatoid Arthritis (RA) fatigue. A secondary aim was to observe RA related biomarkers and evaluate the safety of the treatment. Methods: Eligible adult patients with RA were enrolled between September 2019 and January 2020 at a multisite in a double-blind randomized trial with each intervention lasting 8 weeks with prescription medications, diet, and lifestyle kept constant. Interventions consisted of Wisconsin ginseng in doses of 3,000, or 6,000 mg/day or placebo given in twice daily dosing over 8 weeks. Primary endpoint outcome measures were changes from baseline at 4 and 8 weeks utilizing the Visual analogue scale to evaluate fatigue severity (VAS-F) and Disease activity score 28-joint count erythrocyte sedimentation rate & C-reactive protein (DAS28 ESR & CRP), secondary objectives included The health assessment questionnaire disability index (HAQ-DI), Cyclic adenosine monophosphate (cAMP), and Cyclic guanosine monophosphate (cGMP). Safety parameters included complete blood count (CBC), liver, kidney and function. Results: A total of 17 individuals with well-controlled RA that complained of fatigue completed the study. The safety profiles were unaffected. Kruskal-Wallis test was used to compare the efficacy at 4 weeks and 8 weeks after treatment, there was no significant difference in efficacy between the groups 4 weeks after treatment (Z=2.914, P=0.233). After 8 weeks of treatment, there was a significant difference in efficacy between the groups (Z=6.753, P=0.034). Further pair comparison showed that the effect of the high-dose 6,000 mg/day group demonstrated greater efficacy than the control group (Z=6.325, P=0.01). Conclusions: Addition of Wisconsin ginseng to conventional therapy in RA with fatigue, thus warrants further investigation to guide the role of Wisconsin ginseng to improve fatigue associated with autoimmune disorders as an adjunct treatment. Trial registration: Chinese Clinical Trials Registry. Identifier: ChiCTR1900026257; Registration Date: 2019-09-28.

Rheumatoid Arthritis, Fatigue, Panax quinquefolius, Wisconsin Ginseng, Complementary and Integrative Health

Vandenhouten Eric Eugene, Song Xinwei. (2020). A Randomized, Double-Blind Clinical Trial for Effect of Wisconsin Ginseng (Panax quinquefolius) in Improvement of Rheumatoid Arthritis Associated Fatigue. International Journal of Chinese Medicine, 4(4), 71-81.

Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Is the incidence of rheumatoid arthritis rising? Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. 6, s.l.: Arthritis Rheum, 2010, Vol. 62. 1576-1582.
2. Rheumatoid arthritis. Scott DL, Wolfe F, Huizinga TW. 9746, London, England: Lancet, 2010, Vol. 376.
3. The prevalence and meaning of fatigue in rheumatic disease.. Wolfe F, Hawley DJ, Wilson K. s.l.: J Rheumatol, 1996, Vol. 23.
4. Correlates of fatigue in older adults with rheumatoid arthritis. Belza BL, Henke CJ, Yelin EH, Epstein WV, Gilliss CL. 93-9, s.l.: Nurs Res, 1993, Vol. 42.
5. The assessment of fatigue. A practical guide for clinicians and researchers. Dittner AJ, Wessely SC, Brown RG. s.l.: J Psychosom Res, 2004, Vol. 56, pp. 157-70.
6. Genetics of rheumatoid arthritis susceptibility, severity, and treatment response. Viatte S, Barton A. 4, s.l.: Seminars in immunopathology, 2017, Vol. 39, pp. 395-408.
7. Four different patterns of fatigue in rheumatoid arthritis patients: results of a Q-sort study. Stephanie Nikolaus1, Christina Bode, Erik Taal and Mart A. F. J. van de Laar. s.l.: RHEUMATOLOGY, 2010, Vol. 49, pp. 2191-2199.
8. Pharmacological and Clinical Efficacy of American Ginseng (Panax Quinquefolius): A Mini Review. andenhouten Eric E., Li Yan, Ying Wang. 4, s.l.: International Journal of Chinese Medicine, 2019, Vol. 3, pp. 64-79. ISSN: 2578-9465 (Print); ISSN: 2578-9473 (Online).
9. National Institutes of Health (NIH). The National Center for Complementary and Integrative Health (NCCIH). National Institutes of Health (NIH). [Online] 09 26, 2020. [Cited: 09 26, 2020.]
10. Oriental medicine: an introduction. D., Ehling. 4, s.l.: Ther Health Med., 2001, Vol. 7, pp. 71-82.
11. Giovanni Maciocia. Diagnosis in Chinese Medicine A Comprehensive Guide. London: Elsevier, 2004. 0-4430-6448-2.
12. Professor Gao Mingli's clinical experience in treating rheumatoid arthritis with deficiency of qi and Yin. Wu Qihua, Gao Mingli. 1, Shenyang: Rheumatism and Arthritis, 2019, Vol. 8. ISSN: 2095-4174.
13. Gamble, Dan Bensky Steve Clavey Erich Stöger with Andrew. Chinese Herbal Medicine: Materia Medica (Portable 3rd Ed.). s.l.: Eastland Press, 2015. ISBN: 0-939-616-82-3 978-0-939616-82-4.
14. Ginseng as a Treatment for Fatigue: A Systematic Review. Noe l M. Arring, Denise Millstine, Lisa A. Marks, Lillian M. Nail. 00, s.l.: THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE, 2018, Vol. 00, pp. 1-10.
15. United States Department of Agriculture (USDA). Agriculture Marketing Service (USDA). United States Department of Agriculture (USDA). [Online] 08 31, 2020. [Cited: 08 31, 2020.]
16. GINSENG BOARD OF WISCONSIN, INC. Why Wisconsin Ginseng? [Online] GINSENG BOARD OF WISCONSIN, INC., 08 31, 2020. [Cited: 08 31, 2020.]
17. Validity and reliability of a scale to assess fatigue. K A Lee, G Hicks, and G Nino-Murcia. 3, s.l.: Psychiatry Res, 1990, Vol. 36.
18. Clinical measurement of disease activity in rheumatoid arthritis: why, how and utility of patient self-assessment. Peter P Cheung, & Laure Gossec. 3, s.l.: Int. J. Clin. Rheumatol., 2014, Vol. 9, pp. 327–339. ISSN 1758-4272.
19. The status and evaluation of the diagnostic and therapeutic criteria of traditional Chinese medicine for rheumatoid arthritis. Bing, Zhao Xinxiu and Qin. s.l.: CHINESE ARCHIVES OF TRADITIONAL CHINESE MEDICINE, 2009, Vol. 9, pp. 1879-1880. ISSN: 1673-7717.
20. Efficacy of medical ozone-majorautohaemotherapy combined with traditional Chinese medicine fumigation in the treatment of patients with rheumatoid arthritis. Li Shenghong, Chang Guangchi, Zhou Fang, Pang Yanli, Xiao Junzhou, Dong Qingpeng, Yun Xiawang [1]. 6, s.l.: Pain Clinic Journal, 2013, Vol. 9. ISSN: 1672-9633.
21. Determining rheumatologists' accuracy at assessing functional disability in rheumatoid arthritis patients using the Health Assessment Questionnaire-Disability Index. Carter JD, Lodhi AB, Nagda SR, et al. 5, 2007: J Rheumatol., Vol. 34, pp. 958-63.
22. Four different patterns of fatigue in rheumatoid arthritis patients: results of a Q-sort study. Nikolaus S, Bode C, Taal E, van de Laar MA. 11, s.l.: Rheumatology (Oxford)., 2010, Vol. 49, pp. 2191-2199.
23. Research on immunological regulation effect of Radix Panacis Quinquefolii and related preparation. Wang YH, Liu Zhong S, Guan F, Wang R. s.l.: Chin Arch Tradit Chin Med (Chin), 2004, Vol. 22, pp. 566-567.
24. Korean Red Ginseng exhibits no significant adverse effect on disease activity in patients with rheumatoid arthritis: a randomized, double-blind, crossover study. Cho SK, Kim D, Yoo D, Jang EJ, Jun JB, Sung YK. 2, s.l.: J Ginseng Res., 2018, Vol. 42, pp. 144-148.
25. Effect of Immune No. 2 on the immune reconstitution in patients with HIV/AIDS after highly active antiretroviral treatment: a randomized double blind placebo controlled clinical trial. Wang J, Li Y, Tang YL, Lin HS, Wu XF, Liu J. 5, s.l.: Chin J Integr Med., 2013, Vol. 19, pp. 340-346.
26. 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. Vuksan V, Xu ZZ, Jovanovski E, et al. 3, s.l.: Eur J Nutr., 2019, Vol. 58, pp. 1237-1245.
27. Pilot study of Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA. Barton DL, Soori GS, Bauer BA, et al. 2, s.l.: Support Care Cancer., 2010, Vol. 18, pp. 179-187.
28. Validity and reliability of a scale to assess fatigue. Lee KA, Hicks G, Nino-Murcia G. 3, s.l.: Psychiatry Res., 1991, Vol. 36, pp. 291-298.
29. Confirmation of the validity of the HAQ-DI in two populations living with chronic illnesses. Sousa KH, Kwok OM, Ryu E, Cook SW. 1, s.l.: J Nurs Meas., 2008, Vol. 16, pp. 31-42.
30. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. 1, s.l.: Arthritis Rheum., 1995, Vol. 38, pp. 44-48.
31. Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations. Roxas M, Jurenka J. 1, s.l.: Altern Med Rev, 2007, 2007, Vol. 12, pp. 25-48.
32. Ameliorative effects of ginseng and ginsenosides on rheumatic diseases. YS., Yi. 3, s.l.: J Ginseng Res., 2019, Vol. 43, pp. 335-341.
33. Regulatory effects of ginsenosides on lipid metabolism. LV Wen-shan, YANG Li-li, HUANG Hai-tao. 2, 2013: International Journal of Endocrinology and Metabolism (Chin), Vol. 33, pp. 115-117, 125.
34. STUDIES ON THE MECHANISMS OF IMMUNOREGULATORY EFFECTS OF GINSENOSIDE RG1 IN AGED RATS. Zhang, M Liu and JT. 2, s.l.: Acta Pharmaceutica Sinica, 1996, Vol. 31, pp. 95-100.
35. Effects of Panax ginseng root on the vertical and horizontal motor activities and on brain monoamine-related substances in mice. Itoh T, Zang YF, Murai S, Saito H. 5, s.l.: Planta Med., 1989, Vol. 55, pp. 429-433.
36. Degradation of ginsenosides in humans after oral administration. Tawab MA, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M. 8, s.l.: Drug Metab Dispos., 2003, Vol. 31, pp. 1065-1071.
37. Comparative analysis of the gut microbiota in people with different levels of ginsenoside Rb1 degradation to compound K. Kim KA, Jung IH, Park SH, Ahn YT, Huh CS, Kim DH. 4, s.l.: PLoS One., 2013, Vol. 8.
38. Screening of Drug Metabolizing Enzymes for the Ginsenoside Compound K In Vitro: An Efficient Anti-Cancer Substance Originating from Panax Ginseng. Xiao J, Chen D, Lin XX, et al. 2, s.l.: PLoS One., 2016, Vol. 11.
39. Anti-cancer effects of ginsenoside compound k on pediatric acute myeloid leukemia cells.. Chen Y, Xu Y, Zhu Y, Li X. 1, s.l.: Cancer Cell Int., 2013, Vol. 13.
40. Joint-protective effects of compound K, a major ginsenoside metabolite, in rheumatoid arthritis: in vitro evidence. Choi YS, Kang EH, Lee EY, et al. 8, s.l.: Rheumatol Int., 2013, Vol. 33, pp. 1981-1990.
41. Anti-arthritic effect of ginsenoside Rb1 on collagen induced arthritis in mice. Kim HA, Kim S, Chang SH, Hwang HJ, Choi YN. 10, s.l.: Int Immunopharmacol., 2007, Vol. 7, pp. 1286-1291.
42. Analysis of main chemical composition of Panax quinquefolium from different habitats. Haibo, Ma Jing and Rui. s.l.: Northwest Pharmaceutical Journal (Chin), 2019, Vol. 5, pp. 601-604.
43. Study on quality of Panax quinquefolius from different habitats. Tang Liyue, Chen Xiaorong, and Li Wengui. 001, s.l.: Chinese journal of Health Care Nutrition (Chin), 2018, Vol. 028.
44. Decreasing, null and increasing effects of eight popular types of ginseng on acute postprandial glycemic indices in healthy humans: the role of ginsenosides. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. 3, s.l.: J Am Coll Nutr., 2004, Vol. 23, pp. 248-258.