Effects of Bojungikgi-tang and its modifications for Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Mikyung Kim; Chang-ho Han; Kim, Mikyung; Han, Chang-ho

doi:10.13048/jkm.23024

JKM > Volume 44(2); 2023 > Article

Kim and Han: Effects of Bojungikgi-tang and its modifications for Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Review Article

The Journal of Korean Medicine 2023; 44(2): 181-200.

DOI: https://doi.org/10.13048/jkm.23024

Effects of Bojungikgi-tang and its modifications for Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Mikyung Kim¹

, Chang-ho Han²^{, *}

¹Department of Internal Medicine, College of Korean Medicine, Sangji University

²Department of Internal Medicine, College of Korean Medicine, Dongguk University

Correspondence to: Chang-ho Han 123, Dongdae-ro, Gyeongju-si, Gyeongsangbuk-do 38066, Dongguk University WISE campus Tel: +82-54-770-1260, E-mail: hani@dongguk.ac.kr

Received March 26, 2023 Revised April 26, 2023 Accepted May 10, 2023

Abstract

Objectives

This study aimed to evaluate the efficacy and safety of Bojungikgi-tang (BJIG) and its modifications for patients with anemia.

Methods

The subject of analysis of this study was a parallel design randomized controlled trial in which BJIG or its modifications was administered orally to patients who met the World Health Organization’s anemia criteria and the efficacy and safety were prospectively measured. Electronic databases were searched to retrieve eligible literature published from 1 January 2000 to 12 February 2023. A meta-analysis was conducted, and the risk of bias (RoB) and level of evidence of the included studies was assessed using the Cochrane RoB 2 tool and GRADE method, respectively.

Results

Five studies were included in the meta-analysis. When BJIG or its modifications was administered to anemia patients receiving conventional treatment, additional benefits compared to the non-administered group were found in terms of an increase in red blood cell count (mean difference (MD) 0.46 x 10¹²/L, 95% confidence interval (CI) 0.17 to 0.74), hemoglobin concentration (MD 9.28 g/L, 95% CI 6.06 to 12.51), hematocrit (MD 2.57%, 95% CI 1.76 to 3.38), total effective rate (odds ratio 5.29, 95% CI 2.05 to 13.68), and traditional Chinese medicine symptom scores (standardized MD −1.51, 95% CI −2.79 to −0.24).

Conclusions

This study demonstrated the clinical potential of BJIG and its modifications to provide additional benefits to patients with anemia receiving conventional treatment.

Keywords: anemia, Bojungikgi-tang, Buzhong yiqi-tang, Hochuekkito, systematic review

Fig. 1

Flowchart of study selection process

Fig. 2

Forest Plots (Bojungikgi-tang Plus Conventional Treatment Versus Conventional Treatment)

(A) Red blood cell count (x 10¹²/L)

(B) Hemoglobin concentration (g/L)

(D) Total effective rate

(E) Traditional Chinese Medicine symptom score

Fig. 3

Risk of Bias Summary

Table 1

Characteristics of Included Studies

Study ID	Age	No. of patients	Target patients			Intervention	Control	Formulation	Dose	Frequency	Duration
Study ID	TG/CG	TG(M)/CG(M)	Type of anemia (+ PI)	Baseline Hb (g/L)	Anemia severity	Intervention	Control	Formulation	Dose	Frequency	Duration
He 201318)	47.5±13.6/ 45.3±10.96	91(59)/57(34)	Renal anemia	TG: 63.23±3.17 CG: 64.31±3.02	Severe	mBJIG+Conv for anemia	Conv for anemia	decoction	1/2 pack*	2	8 wks
Li 200519)	25.6±13.2/ 27.33±11.8	60(49)/40(31)	Post op. hemorrhagic anemia + PI^†	TG: 73.4±4.3 CG: 74.6±3.8	Severe	mBJIG+Conv for op.	Conv for op.	decoction	1/2 pack	2	2 wks
Xu 202120)	74.57±6.6/ 75.68±8.58	30(13)/31(14)	Post op. hemorrhagic anemia	TG: 110.95±22.36 CG: 116.27±25.84	Mild	mBJIG+Conv for op.	Conv for op.	decoction	1/3 pack	3	Over 1 wk
Chen 202121)	35.53±7.84/ 35.67±9.29	30(15)/30(13)	Anemia with hemorrhoids+ PI^‡	TG: 86.03 ± 11.36 CG: 85.83 ± 9.61	Moderate	BJIG+mox	Mox	decoction	1/2 pack	2	1 mns
Zhou 201922)	28.6±6.4/ 29.2±6.1	60(0)/60(0)	Pregnant women with iron deficiency anemia	TG: 73.3±9.6 CG: 74.5±9.8	Moderate	BJIG+iron capsule	iron capsule	Granule	3 gram	3	4 wks

* Pack=貼,

PI^†: qi deficiency and blood stasis (氣虛血瘀),

PI^‡: spleen deficiency and sinking of qi (脾虛氣陷)

Abbrebiations: TG, treatment group; CG, control group; No., number; M, male; PI, pattern identification; Hb, hemoglobin; mBJIG, modified Bojungikgi-tang; Conv, conventional treatment; wks, weeks; op., operation; BJIG, Bojuingikgi-tang; mox, moxibustion; mns, months

Table 2

Prescription Composition of Bojungikgi-tang Used in Included Studies

Study ID/ingredients	Astragali Radix (黃芪)	Glycyrrhizae Radix (甘草)	Ginseng Radix (人蔘)	Angelicae Gigantis Radix (當歸)	Citri Pericarpium (陳皮)	Cimicifugae Rhizoma (升麻)	Bupleuri Radix (柴胡)	Atractylodis Macrocephalae Rhizoma (白朮)	Other ingredients
He 201318)	30		15*			10		12	Jujubae Fructus 15, Lycii Fructus (枸杞子) 15, Rhei Radix Et Rhizoma (大黃) 9, Poria (茯苓) 15, Dioscoreae Rhizoma (山藥) 15, Mori Fructus (桑椹子) 15, Oryzae Semen (生米仁) 30, Leonuri Herba (益母草) 30
Li 200519)	30	6	30*	6	6	6	10	15	Jujubae Fructus 30, Salviae Miltiorrhizae Radix (丹蔘) 30, Lonicerae Flos (金銀花) 30, Agrimoniae Herba (仙鶴草) 30, Notoginseng Radix (三七根) 15, Eupolyphaga (土鱉蟲) 15
Xu 202120)	30	10	10	15	10	10	10	10	Paeoniae Radix Alba (白芍藥) 15, Paeoniae Radix Rubra (赤芍藥) 10, Cinnamomi Ramulus (桂枝) 10, Cnidii Rhizoma (川芎) 10, Moutan Cortex (牧丹皮) 10
Chen 202121)	30	10	15	10	10	10	10	10	-
Zhou 201922)	DNR	DNR	DNR*	DNR	DNR	DNR	DNR	DNR	Jujubae Fructus (大棗), Zingiberis Rhizoma Crudus (生薑), dextrin

The number in the table represents the daily dose of each ingredient.

* Codonopsis Pilosulae Radix (黨參) was used instead of Panax ginseng C.A. Meyer. Abbreviation:DNR, dosage not reported.

Table 3

Summary of Findings

Outcome measures	No. of studies	No. of participants	Certainty of evidence
RBC	4	428	⊝⊝○○ Low^ac
Hb	5	489	⊝⊝○○ Low^ac
HCT	3	269	⊝⊝○○ Low^af
TER	4	341	⊝○○○ Very Low^bef
TCM	2	121	⊝○○○ Very Low^bdef

Superscripts: a, serious RoB; b, very serious RoB; c, serious inconsistency; d, very serious inconsistency; e, serious indirectness; f, serious imprecision Abbreviations: No, number; RBC, red blood cell; Hb, hemoglobin; HCT, hematocrit; TER, total effective rate; TCM, traditional Chinese medicine symptoms score

Appendices

Appendix I

Anemia Diagnosis and Severity Criteria

Population	Non-Anemia	Anemia

		Mild	Moderate	Severe
Men*	≥ 130	110–129	80–109	< 80
Women†	≥ 120	110–119	80–109	< 80
Pregnant women	≥ 110	100–119	70–99	< 70

Numbers in the table are hemoglobin concentrations (grams per liter)

* 15 years of age and above,

† non-pregnant women 15 years of age and above

Excerpts from: WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Geneva, World Health Organization, 2011 (WHO/NMH/NHD/MNM/11.1) (http://www.who.int/vmnis/indicators/haemoglobin.pdf).

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