Table 2.
Characteristics of Included Studies
| Study | Year/country | Primary disease | Fatigue subtype | Sample size | Age (years) | Interventions/dose/duration | Control | Primary outcome | Secondary outcome |
|---|---|---|---|---|---|---|---|---|---|
| Yagi et al45 | 2022/Japan | Gynecologic disease | Disease-related fatigue | E:15 C:15 |
E:45.1 ± 7.7 C:41.1 ± 8.3 |
NYT/7.5 g/10 days | Sodium ferrous citrate | CFS VAS-A |
AEsa |
| Lee et al41 | 2021/Korea | Malignant cancer | CRF | E:25 C:25 |
E:56.6 (11.6) C:58.7 (12.5) |
Sipjeondaebo-tang/9 g/3 weeks | Placebo | BFI | EORTC QLQ-C30 AEsb |
| Shin et al23 | 2021/Korea | Not limited | CFS | E:48 C:48 |
E:41.5 ± 8.2 C:40.6 ± 9.8 |
Sipjeondaebo-tang/9 g/8 weeks | Placebo | CIS VAS FSS ChFi |
EQ-5D-5L Safety assessmentc |
| Hong et al24 | 2020/Korea | NAFLD | Disease-related fatigue | E:48 C:46 |
E:50.0 ± 13.3 C:49.7 ± 13.2 |
KRG/2 g/4 weeks | Placebo | FSS | |
| Sung et al34 | 2020/Korea | Not limited | CF | E:25 C:25 |
E:49.000 ± 8.351 C:47.087 ± 10.795 |
KRG/3 g/6 weeks | Placebo | VAS FSS CFSQ |
EQ-5D-5L (Part 1 EQ-VAS) AEsd |
| Moon et al35 | 2020/Korea | Malignant tumor with insomnia | CRF | E:11 C:11 |
E:63.0 [53.0–71.0] C:63.0 [54.0–67.0] |
Cheonwangbosimdan/20 mL/4 weeks | CBT-I | BFI | EQ-5D-5L Safety assessment outcomes AEse |
| Kim et al25 | 2020/Korea | Colon cancer | CRF | E:219 C:219 |
E:60 (29–84) C:60 (27–86) |
KRG/2 g/16 weeks | Placebo | BFI FACIT-Fatigue survey |
AEsf |
| Jung et al36 | 2020/Korea | NAFLD | Disease-related fatigue | E:30; 30 C:30 |
E:42.83; 45.07 C:42.67 |
GBCK25/125 mg; 500 mg/12 weeks | Placebo | MFS | AEsg |
| Guglielmo et al22 | 2020/Italy | Head and neck cancer | CRF | E:17 C:15 |
E:58 [34–73] C:55 [35–79] |
American ginseng/1 g/8 weeks | Placebo | BFI | AEsh |
| Zhang et al43 | 2019/China | TCM asthenia syndrome | TCM asthenia syndrome | E:60; 60 C:60 |
E:34.88 ± 11.07; 35.8 ± 0.16 C:37.72 ± 10.88 |
KRG/1.8 g; 3.6 g/4 weeks | Placebo | Fatigue self-assessment scale | Safety assessmenti |
| Hamada et al44 | 2018/Japan | COPD | Disease-related fatigue | E:18 C:17 |
E:75.3 ± 6.1 C:74.7 ± 7.1 |
TJ-41/7.5 g/12 weeks | Untreated with TJ-41 | VAS | Acute exacerbationsj |
| Yennurajalingam et al46 | 2017/United States | Advanced cancer | CRF | E:63 C:64 |
E:61.0 (54.0–67.0) C:61.0 (53.3–66.8) |
PG/400 mg/28 days | Placebo | FACIT-Fatigue survey ESAS fatigue scale |
Toxicity and safetyk |
| Kim et al37 | 2017/Korea | EOC | CRF | E:15 C:15 |
E:55.9 ± 12.1 C:52.9 ± 10.1 |
Red ginseng/3 g/12 weeks | Placebo | BFI | EORTC QLQ-C30 AEsl |
| Hong et al38 | 2016/Korea | NAFLD | Disease-related fatigue | E:40 C:40 |
Not reported | KRG/3 g/3 weeks | Placebo | FSS | |
| Kim et al39 | 2013/Korea | Not limited | ICF | E:30; 30 C:30 |
E:39.5 (25, 57); 40.5 (22, 59) C:39.5 (24, 60) |
PG/1 g; 2 g/4 weeks | Placebo | CFSQ VAS |
AEsm |
| Etemadifar et al42 | 2013/Iran | RRMS | Disease-related fatigue | E:26 C:26 |
E:33.3 ± 7.5 C:34.5 ± 8.9 |
KRG/250 mg/12 weeks | Placebo | MFIS | MSQOL-54 AEsn |
| Barton et al47 | 2013/United States | All cancers, other than brain or CNS lymphoma | CRF | E:183 C:181 |
E:55.3 (12.7) C:55.9 (11.8) |
American ginseng/2 g/8 weeks | Placebo | MFSI-SF BFI POMS |
Side effectso |
| Jeong et al40 | 2010/Korea | Malignant cancer | CRF | E:20 C:20 |
E:49.4 (10.8) C:53.4 (8.0) |
TJ-41/7.5 g/2 weeks | Waiting list | VAS Trial Outcome Index–Fatigue |
FACT-General AEsp |
| Barton et al48 | 2010/United States | Cancer | CRF | E:70; 72; 71 C:69 |
E:58 (11); 60 (12); 62 (11) C:62 (13) |
American ginseng/750 mg; 1 g; 2 g/8 weeks | Placebo | BFI Vitality subscale of the SF-36 |
SF-36 Self-reported toxicities AEsq |
AEs include mild liver dysfunction in the E group.
AEs included dyspepsia in the E group and pruritus in the C group.
AEs include hot flashes, headache, heartburn, migraine, dermatitis, nausea, lower abdominal pain, dizziness, heavy stomach, loss of appetite, and muscle pain in both groups.
There were no AEs associated with intervention.
Not reported.
AEs included nausea in 128 patients (E group, 28%; C group, 32%), neutropenia in 62 subjects (E group, 19%; C group, 10%), hypertensive crises at high doses in the E group (G3, 3 cases, 1.40%), and C group (G2, 1 case, 0.47%). Neutropenia equal to and above grade 3 was more frequent in the E group than in the C group (13% vs. 7%). AEs resulting in trial product discontinuation occurred in nine patients (E group, 2%; C group, 2%). AEs resulting in death occurred in one patient in the C group.
No AEs were reported with the intervention.
Not reported.
No moderate or serious AEs were reported.
No patients experienced intervention-related AEs.
Grade 1 to 2 AEs included 27 patients in the E group and 24 patients in the C group; grade 3 to 5 AEs included 1 patient in the E group and 9 in the C group but without details.
Grade 1 AEs included nausea, insomnia, palpitation, headache, and urticaria in the E group and nausea, insomnia, headache, and urticaria in the C group.
AEs included systemic rash and pruritus.
AEs included constipation in the E group.
AEs included nausea, vomiting, insomnia, anxiety, and agitation in both groups.
AEs included increased blood urea nitrogen and creatinine level, flatulence, and dyspepsia but the specific group was not mentioned.
AEs included agitation, anxiety, insomnia, nausea, and vomiting in every group.
AEs, adverse events; BFI, Brief Fatigue Inventory; C, control; CBT-I, cognitive behavioral therapy for insomnia; CF, chronic fatigue; CFS, chronic fatigue syndrome; CFSQ, Chalder Fatigue Severity Questionnaire; ChFi, Chalder Fatigue Scale; CIS, Checklist Individual Strength; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; CRF, cancer-related fatigue; E, experimental group; EOC, epithelial ovarian cancer; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer QLQ-C30; EQ-5D-5L, European Quality of Life 5-dimension 5-level Questionnaire; ESAS, Edmonton Symptom Assessment System; FACIT, Functional Assessment of Chronic Illness Therapy; FACT, Functional Assessment of Cancer Therapy; FSS, Fatigue Severity Scale; GBCK25, fermented ginseng powder; ICF, idiopathic chronic fatigue; KRG, Korean red ginseng; MFIS, Modified Fatigue Impact Scale; MFS, Fatigue index based on the Multidimensional Fatigue Scale; MFSI-SF, Multidimensional Fatigue Symptom Inventory–Short Form; MSQOL-54, Multiple Sclerosis Quality of Life Questionnaire; NAFLD, nonalcoholic fatty liver disease; NYT, Ninjin'yoeito (Ren Shen Yang Rong Tang); PG, Panax ginseng; POMS, Profile of Mood States; RRMS, relapsing-remitting multiple sclerosis; SF-36, 36-Item Short Form Survey; Sipjeondaebo-tang, Juzentaihoto/shi quan da bu tang; TCM, traditional Chinese medicine; TJ-41, Bojungikki-tang (Hochuekkito/bu zhong yi qi tang); VAS, Visual Analog Scale.