The Effectiveness of Bojungikgi-tang and its modifications on Chronic Fatigue Syndrome: A Systematic Review And Meta-analysis

Donghyun Nam; Nam, Donghyun

doi:10.13048/jkm.20007

JKM > Volume 41(1); 2020 > Article

Nam: The Effectiveness of Bojungikgi-tang and its modifications on Chronic Fatigue Syndrome: A Systematic Review And Meta-analysis

Review Article

The Journal of Korean Medicine 2019; 41(1): 93-106.

Published online: March 9, 2020

DOI: https://doi.org/10.13048/jkm.20007

The Effectiveness of Bojungikgi-tang and its modifications on Chronic Fatigue Syndrome: A Systematic Review And Meta-analysis

Donghyun Nam^*

Division of Horticulture & Medicinal Plant, Andong National Univ. Andong, Republic of Korea

Correspondence to: Donghyun Nam, Department of Biofunctional Medicine & Diagnostics, College of Korean Medicine, Sangji University, 83 Sangjidae-gil Wonju-si Gangwon-do, Republic of Korean, #26339, Tel: +82-33-738-7504, Fax: +82-33-730-0653, E-mail: omdnam@sangji.ac.kr

Received August 27, 2019 Revised November 26, 2019 Accepted December 10, 2019

Abstract

Objectives

The aim of this review is to ascertain whether Bojungikgi-tang and its modifications is more effective than non-specific management in chronic fatigue syndrome (CFS).

Methods

We collected clinical trials to investigate the effects of Bojungikgi-tang and non-specific management on general symptoms, fatigue, and sleep quality in CFS patients. The databases used for data retrieval were Pubmed, Central Cochrane, CNKI, VIP, CiNii, OASIS, RISS, and Koreamed. We performed selection/exclusion process from the found records according to prespecified criteria, and assessed the final included trials according to the Cochrane risk of bias tool. The included studies were classified on the basis of interventions in experimental group.

Results

Seven randomized controlled trials (476 participants) were eligible and their results were synthesized in the meta-analysis. The synthesis showed a substantial effect of Bojungikgi-tang (relative risk 0.20 [95% CI 0.13 to 0.31], Z=7.44, P<0.00001; I²=0%) and combination of Bojungikgi-tang and Sosiho-tang (relative risk 0.15 [95% CI 0.08 to 0.28], Z=5.85, P<0.00001; I²=0%) compared with non-specific management on improvement of general symptoms. However, we could not find sufficient clinical research records to determine their effects of improvement on fatigue and sleep quality.

Conclusions

Bojungikgi-tang and its modifications are more effective than non-specific management for improvement of general symptoms in CFS post-treatment.

Keywords: Bojungikgi-tang, chronic fatigue syndrome, meta-analysis, systematic review

Fig. 1

PRISMA chart. It presents the process for study selection

Fig. 2

Risk of bias summary (A) and its graph (B). Each risk of bias item for all included studies was shown.

Fig. 3

Forest plot for improvement of general symptoms.

Table 1

Summary Table of the Included Studies.

Author	Year	Diagnostic criteria	Pattern	No. of case (male : female) [experimental : control]	Intervention			Outcomes	Adverse event
Author	Year	Diagnostic criteria	Pattern	No. of case (male : female) [experimental : control]	Experimental	control	Duration	Outcomes	Adverse event
Shu YQ	1997	CDC 1988	-	58 (16:42) [30:28]	BIT a,b	Usual care	2 months	Effectiveness	N.A.E.
Yang SH	2004	CDC 1994	Liver depression and spleen deficiency	72 (35:37) [38:34]	BIT+SST c	Supplement	1 month	Effectiveness	N.R.
Jiang Q	2012	CDC 1994	Insufficiency of middle qi, Dual deficiency of the heart and spleen	70 (35:35) [35:35]	BIT+GBT a	Supplement + education	8 weeks	Effectiveness, IgA, IgG, IgM	N.A.E.
Tian H	2012	CDC 1994	-	64 (36:28) [32:32]	BIT a	Usual care	8 weeks	Effectiveness	N.R.
Wang H	2012	CDC 1988	Liver depression and spleen deficiency	84 (32:52) [42:42]	BIT+SST a	Supplement	4 weeks	Effectiveness, Symptom severity	N.R.
Teng FY	2014	CDC 1994	Insufficiency of middle qi	60 (23:37) [30:30]	BHT a,b	Supplement	8 weeks	Effectiveness	N.R.
Li YM	2015	CDC 1994	Liver depression and spleen deficiency	68 (37:31) [34:34]	BIT+SST a	Supplement	4 weeks	Effectiveness, Fatigue severity	N.R.

BIT means Bojungikgi-tang (補中益氣湯); SST, Sosiho-tang (小柴胡湯); GBT, Gwibi-tang (歸脾湯); BHT, Bojunghaepi-tang (補中解疲汤); N.A.E., no adverse event; N.R., not reported.

a liquid extracted by boiling the raw material;

b modification according to symptoms;

c extract granules.

Table 2

The Quality of Evidence.

Outcome	Certainty assessment						Summary of findings

	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Effect (95% CI)	Certainty
General status	Bojungikgi-tang (補中益氣湯) versus control: 7 studies

	RCT	Very seriousa	Not seriousb	Not seriousc	Not seriousd	Nonee	RR 0.20 (0.13 ~ 0.31)	⊕⊕○○LOW

	Bojungikgi-tang (補中益氣湯) versus control: 3 studies

	RCT	Very seriousa	Not seriousb	Not seriousc	Seriousf	Nonee	RR 0.27 (0.15 ~ 0.49)	⊕○○○ VERY LOW

	Bojungikgi-tang (補中益氣湯) + Sosiho-tang (小柴胡湯) versus control: 3 studies

	RCT	Very seriousa	Not seriousb	Not seriousc	Not seriousd	Nonee	RR 0.15 (0.08 ~ 0.28)	⊕⊕○○ LOW

	Bojungikgi-tang (補中益氣湯) + Gwibi-tang (歸脾湯) versus control: 1 study

	RCT	Very seriousa	Not seriousb	Not seriousc	Seriousf	Nonee	RR 0.13 (0.02 ~ 0.95)	⊕○○○ VERY LOW

Fatigue	Bojungikgi-tang (補中益氣湯) + Sosiho-tang (小柴胡湯) versus control: 1 study

	RCT	Very seriousa	Not seriousb	Not seriousc	Seriousg	Nonee	MD 2.24 (3.02 ~ 1.46)	⊕○○○ VERY LOW

RCT means randomized controlled trial; CI, confidence interval; RR, relative risk; MD, mean difference.

a the proportion of studies assessed as low risk of bias was less than 30%;

b I² was less than 50%;

c directness was undoubted;

d total sample size was more than 200, and 95% CI of RR did not cross 1;

e publication bias was not assessed;

f total sample size was less than 200, but 95% CI of RR did not cross 1;

g total sample size was less than 200, but 95% of MD did not cross zero.

참고문헌

1. Fukuda, K, Straus, SE, Hickie, I, Sharpe, MC, Dobbins, JG, & Komaroff, A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group [see comments]. Ann Intern Med, (1994). 121(12), 953-9.

2. Holmes, GP, Kaplan, JE, Gantz, NM, Komaroff, AL, Schonberger, LB, & Straus, SE, et al. Chronic fatigue syndrome: A working case definition. Ann Intern Med, (1988). 108(3), 387-9.

3. Meirleir, KL, De Peterson, DL, Klimas, NG, Lerner, aM, Bested, AC, & Sherkey, Ja, et al. Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. J Chronic Fatigue Syndr, (2003). 11(1), 7-97.

4. Sharpe, MC, Archard, LC, Banatvala, JE, Borysiewicz, LK, Clare, AW, & David, A, et al. A report - chronic fatigue syndrome: guidelines for research. J R Soc Med, (1991). 84(2), 118-21.

5. Jason, LA, Brown, A, Clyne, E, Bartgis, L, Evans, M, & Brown, M. Contrasting case definitions for chronic fatigue syndrome, Myalgic Encephalomyelitis/chronic fatigue syndrome and myalgic encephalomyelitis. Eval Health Prof, (2012). 35(3), 280-304.

6. Carruthers, BM, Sande, MI, van de Meirleir, KL, De Klimas, NG, Broderick, G, & Mitchell, T, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med, (2011). 270(4), 327-38.

7. Committee on the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Beyond myalgic encephalomyelitis/chronic fatigue syndrome. Washington, D.C. National Academies Press;(2015.

8. Kwak, K, Cho, J, & Son, C. Study on chronic fatigue syndrome from Oriental medicine point of view. Korean J Orient Intern Med, (2008). 29(4), 962-969.

9. Kim, JW, Kim, HJ, Jang, ES, Jung, H, Hwang, MW, & Nam, DH. Survey on pattern identification and treatment of chronic fatigue in Korea medicine. J Physiol Pathol Korean Med, (2018). 32(2), 126-33.

10. Reeves, WC, Wagner, D, Nisenbaum, R, Jones, JF, Gurbaxani, B, & Solomon, L, et al. Chronic fatigue syndrome - a clinically empirical approach to its definition and study. BMC Med, (2005). 3, 19.

11. Treatment of ME/CFS. Centers Dis Control Prev. 2018. https://www.cdc.gov/me-cfs/treatment/index.html

12. Hundertmark, JD, Hickie, IB, Beard, DD, Larkins, RG, & Molesworth, SR. Chronic fatigue syndrome clinical practice guidelines: Psychological factors. Med J Aust, (2002). 177(9), 525-7.

13. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management. Clinical guideline, (2007). CG53.

14. Chen, R, Moriya, J, Yamakawa, JI, Takahashi, T, & Kanda, T. Traditional chinese medicine for chronic fatigue syndrome. Evid Based Complement Alternat Med, (2010). 7(1), 3-10.

15. Adams, D, Wu, T, Yang, X, Tai, S, & Vohra, S. Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome. Cochrane database Syst Rev, (2009). (4), CD006348.

16. Adams, D, Wu, T, Yang, X, Tai, S, & Vohra, S. Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome. Cochrane Database Syst Rev, (2018.

17. Wang, YY, Li, XX, Liu, JP, Luo, H, Ma, LX, & Alraek, T. Traditional Chinese medicine for chronic fatigue syndrome: A systematic review of randomized clinical trials. Complement Ther Med, (2014). 22(4), 826-33.

18. Liu, Q. Discussion on the therapeutic effect of traditional Chinese medicine diagnosis and treatment of chronic fatigue syndrome. Foreign Med Sci, (1993). 15(6), 15.

19. Zheng YY. Guiding principles for clinical research of new drugs in traditional Chinese medicine. Beijing. China Medical Science and Technology Press;(2002.

20. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions ver 5.1.0. The cochrane collaboration;(2011.

21. Guyatt, GH, Oxman, AD, Vist, GE, Kunz, R, Falck-Ytter, Y, & Alonso-Coello, P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ, (2008). 336(7650), 924-6.

22. Kim S, Park J, Seo H, Lee Y, Jang B, Son H, et al. NECA’s guidance for undertaking systematic reviews and meta-analyses for intervention. National evidence-based healthcare collaborating agency;(2011.

23. Shu, Y, & Zhang, G. Treatment of 30 cases of chronic fatigue syndrome with buzhongyiqi decoction. J Anhui Tradit Chinese Med Coll, (1997). 16(5), 11.

24. Yang, S, Gao, M, Yang, X, & Chen, D. Clinical observation of the treatment of chronic fatigue syndrome by using buzhongyiqi decoction in combination with xiaochaihu decoction. J Beijing Univ Tradit Chinese Med, (2004). 27(2), 87-9.

25. Jiang, Q. Therapeutic effect of buzhongyiqi decoction and guipi decoction on chronic fatigue syndrome. Beijing J Tradit Chinese Med, (2012). 2(31), 121-2.

26. Tian, H, & Wang, S. Treatment of 32 cases of chronic fatigue syndrome with buzhongyiqi decoction. Jiangxi J Tradit Chinese Med, (2012). 43(8), 26-7.

27. Wang, H. Clinical study on buzhongyiqi decoction and xiaochaihu decoction in treating chronic fatigue syndrome. Asia-Pacific Tradit Med, (2012). 8(8), 67-8.

28. Teng, F, Jiang, Q, & Huang, Y. Therapeutic effect of buzhongjieliu decoction on chronic fatigue syndrome. Guid J Tradit Chinese Med Pharm, (2014). 20(4), 108-10.

29. Li, Y. Clinical observation on treatment of chronic fatigue syndrome with liver depression and spleen deficiency syndrome by buzhongyiqi decoction and xiaochaihu decoction. Asia-Pacific Tradit Med, (2015). 11(17), 124-5.

30. Vincent, A, Brimmer, DJ, Whipple, MO, Jones, JF, Boneva, R, & Lahr, BD, et al. Prevalence, incidence, and classification of chronic fatigue syndrome in Olmsted county, Minnesota, as estimated using the Rochester epidemiology project. Mayo Clin Proc, (2012). 87(12), 1145-52.

31. Kim, CH, Shin, HC, & Pak, YW. The prevalence of chronic fatigue and chronic fatigue syndrome: A hospital based study. J Korean Acad Fam Med, (2000). 21(10), 1288-98.

32. Ko, KM, Leon, TYY, Mak, DHF, Chiu, PY, Du, Y, & Poon, MKT. A characteristic pharmacological action of ‘Yang-invigorating’ Chinese tonifying herbs: enhancement of myocardial ATP-generation capacity. Phytomedicine, (2006). 13(9–10), 636-42.

33. Leong, PK, Wong, HS, Chen, J, & Ko, KM. Yang/Qi invigoration: An herbal therapy for chronic fatigue syndrome with yang deficiency? Evidence -based Complement Altern Med, (2015). 2015, 945901.

34. Leong, PK, Chen, N, & Ko, KM. Mitochondrial decay in ageing: ‘Qi-invigorating’ schisandrin B as a hormetic agent for mitigating age-related diseases. Clin Exp Pharmacol Physiol, (2012). 39(3), 256-64.