The Effect of <i>Insamyangyeongtang</i> on Anemia: A Systematic Review

Seyeon Lee; Changwoo Han; Lee, Seyeon; Han, Changwoo

doi:10.13048/jkm.25027

JKM > Volume 46(2); 2025 > Article

Lee and Han: The Effect of Insamyangyeongtang on Anemia: A Systematic Review

Review Article

The Journal of Korean Medicine 2025; 46(2): 177-189.

Published online: June 1, 2025

DOI: https://doi.org/10.13048/jkm.25027

The Effect of Insamyangyeongtang on Anemia: A Systematic Review

Seyeon Lee¹^{, 2}

, Changwoo Han¹^{, 2}^{, *}

¹Korean Medicine Hospital of Pusan National University

²School of Korean Medicine, Pusan National University

Correspondence to: Changwoo Han,Korean Medicine Hospital of Pusan National University, 20, Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, Republic of Korea, Tel: +82-55-360-5957, E-mail: hancw320@pusan.ac.kr

Received April 17, 2025 Revised May 12, 2025 Accepted May 22, 2025

Abstract

Objectives

This systematic review endeavors to scrutinize the clinical benefits of Insamyangyeongtang (ISYYT) in managing anemia. ISYYT has been traditionally used to improve fatigue and weakness, symptoms commonly observed in anemic patients. However, no systematic review has yet comprehensively analyzed its effects.

Methods

A systematic search was conducted in Embase, PubMed, Cochrane Library, ScienceON, CNKI, and CiNii databases up to November 15, 2024. Comparative clinical studies, including randomized controlled trials (RCTs), quasi-randomized controlled trials, cohort studies, and case-control studies, were included. The primary outcome was hemoglobin level changes. Meta-analysis was implemented employing a random-effects model. The evidence certainty was appraised as per the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method.

Results

An overall of 10 studies (5 RCTs, 1 quasi-RCT, 1 non-randomized controlled trial, and 3 retrospective comparative studies) were included, with sample sizes varying from 18 to 1,061 participants. The meta-analysis showed that ISYYT combined with conventional treatment significantly increased hemoglobin levels compared to conventional treatment alone (mean difference: 0.45 g/dL, 95% CI: 0.17–0.73, p < 0.01). The evidence certainty was assessed as ‘low’ to ‘very low’ based on the criteria of the GRADE framework.

Conclusions

ISYYT may have a beneficial effect on hemoglobin levels, particularly when used as an adjunct to conventional anemia treatments. However, due to the high heterogeneity and risk of bias in included studies, further high-quality RCTs are necessary to confirm its clinical efficacy and safety.

Keywords: Insamyangyeongtang, anemia, hemoglobin, systematic review

Fig. 1

Literature Search, Exclusion, and Selection

Fig. 2

The Risk of Bias of the Included Randomized Controlled Trials

Fig. 3

The Risk of Bias of the Included Non-randomized Studies

Fig. 4

Comparison between Groups with and without Insamyangyeongtang across All Included trials

Fig. 5

Comparison between Groups with and without Insamyangyeongtang across Randomized Controlled Trials

Fig. 6

Funnel Plot

Fig. 7

Comparison between Insamyangyeongtang and Iron Supplement

Table 1

General Characteristics of Included Trials

Study ID	Region	Study design	Participants	Intervention	Control
Ando 1999²⁴⁾	Japan	Retrospective Comparative Study	Iron deficiency anemia	ISYYT* + Iron supplement (45) OR ISYYT (12), for 6 weeks	Iron supplement, for 6 weeks (10)
Hayashi 2003²⁵⁾	Japan	Non-Randomized Controlled Trial	Postmenopausal women diagnosed with osteoporosis and anemia	ISYYT 7.5 g/day, + usual doses of vitamin K2, activated vitamin D3 preparation, and calcitonin preparation, for 12 months (23)	Usual doses of vitamin K2, activated vitamin D3 preparation, and calcitonin preparation, for 12 months (16)
Motoo 2005²⁶⁾	Japan	Non-blinded, randomized controlled trial	Anemia induced by ribavirin treatment	ISYYT 9 g/day + interferon alpha 2b c̄ribavirin, for 24 weeks (9)	Interferon alpha 2b c̄ribavirin, for 24 weeks (9)
Kato 2020²⁷⁾	Japan	Retrospective Comparative Study	Anemia in pregnant women	ISYYT 7.5 g/day + Iron supplement 100 mg/day, for 30 days (22)	Iron supplement 100 mg/day, for 30 days (25)
Li 2021²⁸⁾	China	Non-blinded, randomized controlled trial	Anemia of chronic kidney disease	ISYYT decoction 100ml/day + erythropoietin c̄general care for chronic kidney disease, for 8 weeks (30)	Erythropoietin c̄general care for chronic kidney disease, for 8 weeks (30)
Fukuda 2022²⁹⁾	Japan	Retrospective comparative study	Anemia in pregnant women planning for autologous blood storage	ISYYT 9.0 g/day + iron supplement 100 mg/day, for 7 days (27)	Iron supplement 100 mg/day, for 7 days (38)
Kawakami 2022³⁰⁾	Japan	Quasi-randomize d controlled trial	Postpartum anemia	ISYYT 7.5 g/day, for 4 weeks (529)	Iron supplement (ferrous fumarate) 100 mg/day, for 4 weeks (532)
Yagi 2022³¹⁾	Japan	Non-blinded, randomized controlled trial	Preoperative anemia before gynecological surgery	ISYYT 7.5 g/day + iron supplement 100 mg/day, for a minimum of 10 days prior to surgery (15)	Iron supplement 100 mg/day, for a minimum of 10 days prior to surgery (15)
Ren 2023³²⁾	China	Non-blinded, randomized controlled trial	Anemia of chronic kidney disease	ISYYT decoction 200 ml/day + erythropoietin with conventional treatment for chronic kidney disease, for 8 weeks (30)	Erythropoietin with conventional treatment for chronic kidney disease, for 8 weeks (30)
Sun 2023³³⁾	China	Non-blinded, randomized controlled trial	Anemia of chronic kidney disease	ISYYT decoction 150 ml twice a day + erythropoietin with conventional treatment for chronic kidney disease, for 8 weeks (35)	Erythropoietin with conventional treatment for chronic kidney disease, for 8 weeks (35)

* ISYYT: insamyangyeongtang

Table 2

GRADE Summary of Findings

Outcomes	Anticipated absolute effects (95% CI)	No. of Participants (Studies)	Certainty of Evidence (GRADE)	Explanation
Change in hemoglobin across all comparative clinical studies	higher by 0.45 g/dL in ISYYT group (range: 0.17 to 0.73)	444 (9 studies)	⊕⊝⊝⊝ very low	risk of bias (−2), Inconsistency (−1)
Change in hemoglobin across randomized controlled trials	higher by 0.70 g/dL in ISYYT group (range: 0.43 to 0.97)	238 (5 studies)	⊕⊕⊝⊝ low	risk of bias (−1), imprecision (−1)

Table 3

Herbal Composition of Insamyangyeongtang

ID	Region	Herbal composition	Formulation & usage instruction
Ando 1999	Japan	Rehmannia root, Angelica root, Atractylodes rhizome, Poria sclerotium, Ginseng, Cinnamon bark, Polygala root, Peony root, Citrus unshiu peel, Astragalus root, Glycyrrhiza, Schisandra fruit (No details on individual herb dosages).	No information
Hayashi 2003	Japan	Rehmannia root 4.0 g, Angelica root 4.0 g, Atractylodes rhizome 4.0 g, Poria sclerotium 4.0 g, Ginseng 3.0 g, Cinnamon bark 2.5 g, Polygala root 2.0 g, Peony root 2.0 g, Citrus unshiu peel 2.0 g, Astragalus root 1.5 g, Glycyrrhiza 1.0 g, Schisandra fruit 1.0 g (per 7.5g of extract)	Ninjinyoeito extract granules (Kracie Pharmaceutical Ltd., Tokyo, Japan, EK-108), 2.5g per dose, three times a day (7.5g/d)
Kato 2020, Kawakami 2022, Yagi 2022	Japan		Ninjinyoeito extract granules (Kracie Pharmaceutical Ltd., Tokyo, Japan, KB-108), 3.75g per dose, two times a day (7.5g/d)
Motoo 2005, Fukuda 2022	Japan	Rehmannia root 4.0 g, Angelica root 4.0 g, Atractylodes rhizome 4.0 g, Poria sclerotium 4.0 g, Ginseng 3.0 g, Cinnamon bark 2.5 g, Polygala root 2.0 g, Peony root 2.0 g, Citrus unshiu peel 2.0 g, Astragalus root 1.5 g, Glycyrrhiza 1.0 g, Schisandra fruit 1.0 g (per 9g of extract)	Ninjinyoeito extract granules (Tsumura Co., Tokyo, Japan, TJ-108), 9.0 g/day
Li 2021	China	Codonopsis pilosula 20g, Astragalus membranaceus 30g, Angelica sinensis 10g, Cinnamomum cassia 9g, Atractylodes macrocephala 15g, Citrus reticulata peel 10g, Paeonia lactiflora 15g, cooked Rehmannia glutinosa 30g, Schisandra chinensis 9g, Poria cocos 10g, Polygala tenuifolia 10g, prepared Glycyrrhiza uralensis 9g, fresh Zingiber officinale 3 slices, Ziziphus jujuba 5 dates, Dioscorea opposita 15g, Cornus officinalis 15g, Millettia dielsiana10g.	The prescription was decocted into a 100mL concentrate and administered in two divided doses throughout the day.
Ren 2023	China	Codonopsis pilosula 10g, Astragalus membranaceus 30g, raw Atractylodes macrocephala 9g, Poria cocos 9g, Paeonia lactiflora 10g, Angelica sinensis 12g, Polygala tenuifolia 12g, prepared Glycyrrhiza uralensis 9g, Cinnamomum cassia 12g, Schisandra chinensis 4g, cooked Rehmannia glutinosa 12g, and Citrus reticulata peel 12g (For poor appetite, add Crataegus pinnatifida 15g and Massa fermentata 10g; for severe edema, add Polyporus umbellatus 10g and Alisma plantago-aquatica 10g; for weakness in the lower back and knees, add Eucommia ulmoides 12g and Achyranthes bidentata 10g).	The prescription was decocted and packaged by the Liuan City Hospital Pharmacy and taken one dose (200ml) per day, split into doses for morning and evening.
Sun 2023	China	Cinnamomum cassia, prepared Glycyrrhiza uralensis, and Schisandra chinensis, 9g each; Angelica sinensis, Citrus reticulata peel, Poria cocos, Polygala tenuifolia, and Millettia dielsiana, 10g each; Dioscorea opposita, Paeonia lactiflora, Cornus officinalis, and Atractylodes macrocephala, 15g each; Codonopsis pilosula 20g; Astragalus membranaceus and cooked Rehmannia glutinosa, 30g each; fresh Zingiber officinale 3 slices; and Ziziphus jujuba 5 dates (For severe itching, add Bombyx batryticatus and Periostracum cicadae, 10g each; for dry stools, add Cannabis sativa seed 10g).	The prescription was decocted into pouches with a dosage of 150ml per time, taken twice daily.

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