Ginseng

STUDY PURPOSE: To investigate the effectiveness of ginseng supplements for reduction of fatigue and enhancement of physical performance

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 12, 4 on fatigue reduction and 8 for physical performance 
• TOTAL PATIENTS INCLUDED IN REVIEW = 458 for fatigue, 212 for performance
• SAMPLE RANGE ACROSS STUDIES: 19–271
• KEY SAMPLE CHARACTERISTICS: Most studies were of healthy adults. One study on cancer, one on multiple sclerosis, and one on chronic idiopathic fatigue

PHASE OF CARE: Not specified or not applicable

Ginseng supplements were associated with an overall standard mean difference of 0.34  (95% confidence interval [0.16, 0.52]) for fatigue reduction; however, duration of use was only six weeks or less, and doses of less than 1000 mg/day showed no effect. No effect was seen for physical performance.

Ginseng may be helpful for fatigue reduction; however, this analysis included few studies and only one study on individuals with cancer. This analysis provides insufficient evidence to draw firm conclusions.

• Limited number of studies included
• Low sample sizes
• Authors stated that numerous randomized, controlled trials were excluded because of insufficient data.

Limited evidence exists to show the efficacy of ginseng supplements overall for fatigue reduction, and evidence here does not show any improvement in physical performance with ginseng.

To evaluate the efficacy of Wisconsin ginseng on cancer-related fatigue (CRF).

2,000 mg of Wisconsin ginseng or placebo BID (breakfast and lunch) over eight weeks. The assessment conducted at baseline and at four and eight weeks.

• N = 364
• MEAN AGE = 55.3 years for the ginseng group, 55.9 for the placebo group
• MALES: 19% in ginseng group and 25% in placebo group, FEMALES: 81% in ginseng group and 75% in placebo group         
• KEY DISEASE CHARACTERISTICS: Primarily breast (64% in ginseng and 57% in placebo groups) but included colon, prostate, hematologic, gynecologic, and combination/unknown/other cancers having completed or receiving curative intent therapy within past two years and who scored a minimum of 4 on 11-point scale that was present at least a month prior to study entry.
• OTHER KEY SAMPLE CHARACTERISTICS: Some were on active treatment during the study and some were post-cancer treatment.

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Mostly community cancer centers; location not specified

• PHASE OF CARE: Multiple phases of care

• Randomized, double-blind trial

• Multidimensional Fatigue Symptom Inventory–Short Form (general subscale)
• Profile of Mood States (fatigue-inertia and vigor-activity subscales)
• Brief Fatigue Inventory
• CTCAE (version not specified)

Statistically significant changes in scores for MFSI-SF between ginseng and placebo groups at four and eight weeks was in favor of ginseng, but only among those in active treatment. No differences in BFI scores were noted. Greater benefit reported among patients receiving active cancer treatment versus those who had completed treatment.

The ginseng group had improvements in fatigue scores over four- and eight-week periods without significant toxicities. However, data lacking on selected drug-ginseng interactions.

• Selective outcomes reporting
• Subject withdrawals ≥ 10%

Supports use of (controlled, manufactured) Wisconsin ginseng to modify CRF; however, more research is needed to determine how to maximize positive effects. It appears that ginseng effects may only be seen during active treatment.

To determine whether any of three specific doses of American ginseng help cancer-related fatigue, as well as to evaluate toxicity.

Patients were randomized to receive ginseng doses of 750, 1,000, or 2,000 mg per day or placebo. Doses were given in twice daily dosing over eight weeks. The ginseng used was Wisconsin ginseng that met quality-control requirements for pesticides and contaminants. Specific description of ginsenosides content is described. 

Outcome measures were obtained at baseline, four weeks, and eight weeks. Patients were stratified according to stage of disease, gender, baseline fatigue score, and current treatment. Randomization assignments were computer-generated using a dynamic allocation procedure for distribution of stratification factors.

• In total, 175 patients (66% female) with a history of chronic fatigue completed the study. 
• Mean age across study groups ranged from 58 to 62 years (standard deviation [SD] = 12).
• Patient diagnoses were predominantly breast, colon, and lung cancer.
• Of the patients, 62% had stage III/IV disease.
• Of the patients, 71% had a baseline fatigue score of 4 to 7.
• Of the patients, 65% had previous chemotherapy.
• Of the patients, 57% were receiving current chemotherapy and 18% were receiving current radiotherapy.
• No significant differences existed between groups in demographic, disease, or treatment characteristics.

This was a multisite collaborative trial of the North Central Cancer Treatment group and the Mayo Clinic.

This was a randomized, double-blind, placebo-controlled study.

• Brief Fatigue Inventory (BFI)
• Vitality subscale of the Medical Outcome Scale (MOS) Short Form (SF-36)
• Global Impression of Benefit Scale
• Pittsburgh Sleep Quality Index (PSQI)
• Global Impression of Change
• Linear Analogue Scale
• Toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI CTCAE)
• Patients completed weekly self reports of toxicities in a symptom experience diary to rate side effects on a 0 to 10 scale, with higher scores indicating greater severity.

• Mean scores for the SF-36 subscale between collective ginseng arms and placebo were not significantly different. A trend was observed for greater positive effects at the highest ginseng dose.
• Analysis of change in fatigue showed a greater effect on fatigue with the highest two dose groups, but this was not statistically significant.
• A trend was observed for greatest effect on quality of life measures at the highest ginseng doses.
• The greatest PSQI improvement over time occurred in the placebo group.
• Patient subjective perception of benefits showed an overall trend of higher benefit in the two highest ginseng dosage groups.
• No significant toxicities were associated with the use of ginseng.

Findings suggest that ginseng at the dose of 750 mg per day did not provide any benefit over that of placebo. At the two highest doses of ginseng, a trend was observed of decreased fatigue compared to placebo.

• The study was powered as a pilot study to evaluate composite ginseng dose groups versus placebo, so dose-related findings were underpowered to show statistical significance. 
• A challenge in studying herbal supplements is the lack of standardization and variability in content affected by growing conditions, so the findings may not be generalizable to use of ginseng grown elsewhere or under different climactic conditions.

The preliminary evidence here suggests that the improvement in patient perception with ginseng versus placebo is that this effect may have broad benefit to patients, even if objective measures of outcomes are nonsignificant. It would be worthwhile to more clearly and definitively evaluate the benefits of ginseng in additional larger, more definitive clinical trials.

To assess the safety and efficacy of high-dose ginseng for cancer-related fatigue

Patients were given a supply of ginseng for 29 days and instructed to take two 400 mg tablets twice daily. Study measures were obtained at baseline, day 15, and day 29.

• N = 24
• MEDIAN AGE = 58 years (range = 48–68 years)
• MALES: 50%, FEMALES: 50%
• KEY DISEASE CHARACTERISTICS: Genitourinary cancers were most common
• OTHER KEY SAMPLE CHARACTERISTICS: 87% were currently receiving cancer treatment with either combination chemotherapy or targeted therapies; 33% also were receiving radiation therapy

• SITE: Single site  
• SETTING TYPE: Not specified  
• LOCATION: Texas

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care

Prospective observational

• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)
• Edmonton Symptom Assessment Scale (ESAS)
• Hospital Anxiety and Depression Scale (HADS)

There was an improvement in the FACIT fatigue subscale on day 15 (p = 0.004) and day 29 (p = 0.0006) although scores increased between day 15 and 29. Improvement was also seen in the ESAS fatigue scale at both time points (p < 0.001). Appetite improved on day 15 (p = 0.004) and day 29 (p = 0.0097). Sleep was improved on day 15 (p = 0.004) but not on day 29. ESAS scores for anxiety were improved on day 15 (p = 0.002). There were no significant adverse effects attributed to ginseng.

The findings of this study suggest that high-dose ginseng may be helpful in the management of multiple symptoms among patients with cancer.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Other limitations/explanation: Patients were included and considered evaluable if they took only one dose of ginseng. The number of doses actually taken was not stated, so there is no way to know if symptoms changed over time due to ginseng or not, or in how many patients. For several symptoms, though statistically significant, actual changes in score were very small.

Ginseng appears to be safe and may be helpful in the management of multiple symptoms among patients with cancer. This study had multiple design limitations. Additional well-designed studies with larger patient samples are needed to provide sufficient evidence for the meaningful evaluation of efficacy.