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The Effect of Insamyangyeongtang on Anemia: A Systematic Review

Article information

J Korean Med. 2025;46(2):177-189
Publication date (electronic) : 2025 June 1
doi : https://doi.org/10.13048/jkm.25027
Seyeon Lee1,2orcid_icon, Changwoo Han1,2,orcid_icon
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 2025 April 17; Revised 2025 May 12; Accepted 2025 May 22.

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

General Characteristics of Included Trials

GRADE Summary of Findings

Herbal Composition of Insamyangyeongtang

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Article information Continued

Fig. 1

Fig. 1

Literature Search, Exclusion, and Selection

Fig. 2

Fig. 2

The Risk of Bias of the Included Randomized Controlled Trials

Fig. 3

Fig. 3

The Risk of Bias of the Included Non-randomized Studies

Fig. 4

Fig. 4

Comparison between Groups with and without Insamyangyeongtang across All Included trials

Fig. 5

Fig. 5

Comparison between Groups with and without Insamyangyeongtang across Randomized Controlled Trials

Fig. 6

Fig. 6

Funnel Plot

Fig. 7

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.