Reviewed: Barton DL, Liu H, Dakhil S, et al. Wisconsin ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst. August 2013;105(16):1230-1238.
Cancer-related fatigue (CRF) can severely disrupt the lives of both those recovering from cancer and patients currently receiving cancer treatment. Although standard medications such as psychostimulants have been studied for the treatment of CRF, clinical studies have not confirmed their efficacy. Both American ginseng (Panax quinquefolius, Araliaceae) and Asian ginseng (P. ginseng) have been used in Traditional Chinese Medicine as adaptogens, among other uses. Compounds known as ginsenosides, found in ginseng, are broadly bioactive.1 This randomized, double-blind, placebo-controlled study was based on a prior clinical pilot study of American ginseng for patients with CRF. In the pilot study, American ginseng with 5% ginsenoside content was given to participants in 750, 1000, or 2000 mg doses for eight weeks versus a placebo. The results from that trial showed that 1000 and 2000 mgs of < >P. quinquefolius were most efficacious at four and eight weeks compared to placebo.2 Based on these results, this larger study investigated the efficacy and tolerability of 2000 mg daily of American ginseng with a reported level of 3% ginsenosides in patients with CRF. (The ginseng root material was further assessed for “quality” and “potency” by an unnamed company.)
Enrolled patients were randomly assigned to either active treatment (2000 mg daily of ground American ginseng root commercially cultivated in Wisconsin) or a rice powder placebo for eight weeks, taken in the morning and noon. American ginseng and placebo were procured from the Ginseng Board of Wisconsin (Wausau, WI) and produced with good manufacturing practices (GMPs) by Beehive Botanicals in Hayward, WI.
Patients with CRF (having a score ≥ [greater than or equal to] four using a scale ranging from 0=no fatigue to 10=severe fatigue) present one month or more prior to the study were included as long as their cancer diagnosis was made within the preceding two years. Patients with brain tumors or central nervous system lymphoma and those with a score of four or higher for pain or insomnia using the scale above were excluded. Also excluded were those taking steroids, opioids, ginseng, or other treatments for fatigue. The randomization process controlled for baseline fatigue, recurrent fatigue, cancer treatment type and length, and tumor characteristics.
An impact score on the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at four weeks was the primary outcome. This scale rates fatigue from 0 (no fatigue) to four (extreme fatigue). Change in scores on the Profile of Mood States (POMS) fatigue-inertia and vigor-activity subscales and the Brief Fatigue Inventory (BFI) scale were secondary outcomes. These assessments were administered at baseline, four, and eight weeks into the study. Patients described the type and severity of adverse side effects at the study’s start and weekly thereafter. Study administrators also gauged adverse side effects during clinic visits. Scales from 0-10 were used to assess fatigue, pain, and sleep quality.
Initially, 364 patients were enrolled, with 133 patients in the treatment group and 128 patients in the placebo group completing the study (n=261). At the four-week primary endpoint analysis, 147 patients were in the treatment group, and 153 patients were in the placebo group (n=300). At baseline, no differences were observed between groups’ fatigue assessments or demographic measurements. At four weeks into the study, the change in the MFSI-SF in those in the treatment group was a non-significant difference of 14.4±27.1 as compared with 8.2±24.8 for those in the placebo group (P=0.07). The difference in score change at eight weeks, however, was significant (20±27 vs. 10.3±26.2, treatment group vs. control group, respectively; P=0.003).
After eight weeks of treatment, the MFSI-SF physical subscore change from baseline was significantly greater in those in the treatment group as compared to the placebo group (3.0±17.9 vs. -1.7±18.2, P=0.004). This also was observed with MFSI-SF total score change from baseline at the end of the study (6.7± 4.0 vs. 3.7±14.6, P=0.02). The change from baseline in POMS fatigue inertia scores after eight weeks of treatment also was significantly greater in the treatment group as compared to the placebo group (18.6±24.8 vs. 10.2±26.1, P=0.008).
While the BFI total score was not significantly different between groups, the subscores for “worst fatigue” and “fatigue now” after eight weeks of treatment in the ginseng group were significantly improved as compared to the placebo group (P value and data not reported). Additionally, when only those patients undergoing cancer treatment were compared in both groups, the percentage change in MFSI-SF score from baseline of those in the treatment group was significantly more than that of the placebo group after both four and eight weeks (P=0.02 and 0.01, respectively).
Adverse side effects that occurred more frequently than 1% included agitation, anxiety, insomnia, nausea, and vomiting, while nervousness, sleep disturbances, and loose stools were also noted. The adverse effects of greater frequency were not significantly different between groups, suggesting that American ginseng supplementation seems well tolerated but does not alleviate adverse side effects inherent to this population. Both loose stools and pain were worse after baseline but occurred only in the placebo group over the course of the study.
In conclusion, this study reports the safety and efficacy of eight weeks of American ginseng supplementation for the alleviation of CRF. The authors state that these results were “clinically meaningful” (more than 10 points difference using a scale from 0 to 100). Due to the significant improvement in fatigue in those undergoing current cancer treatment versus those who had completed chemotherapy, American ginseng may be a possible treatment for CRF. Stated strengths of the study include its randomized and double-blind design, and that fatigue was distinguished from sleep deficit or pain. The authors cited the study’s limited duration and general difficulty of measuring fatigue as weaknesses.
Variations among studies of efficacy measures — such as improvement of BFI — may be due to variable concentrations of ginsenosides, which can result from agricultural inconsistencies and lack of content standardization during processing. Ideally, future studies also should investigate potential herb-drug interactions with chemotherapy. In summary, this study suggests that American ginseng may be a well-tolerated treatment of CRF, particularly during cancer treatment, for which no other pharmacotherapy has shown significant clinical benefit.
—Amy C. Keller, PhD
1. Lewis WH, Elvin-Lewis MPF. Medical Botany: Plants Affecting Human Health, 2nd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2003.
2. Barton DL, Soori GS, Bauer BA, et al. Pilot study of < >Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA. Support Care Cancer. 2010;18(2):179-187.