Wisconsin Ginseng (Panax quinquefolius) to Improve Cancer-Related Fatigue

A Randomized, Double-Blind Trial, N07C2

Debra L. Barton; Heshan Liu; Shaker R. Dakhil; Breanna Linquist; Jeff A. Sloan; Craig R. Nichols; Travis W. McGinn; Philip J. Stella; Grant R. Seeger; Amit Sood; Charles L. Loprinzi


J Natl Cancer Inst. 2013;105(16):1230-1238. 

In This Article

Abstract and Introduction


Background Safe, effective interventions to improve cancer-related fatigue (CRF) are needed because it remains a prevalent, distressing, and activity-limiting symptom. Based on pilot data, a phase III trial was developed to evaluate the efficacy of American ginseng on CRF.

Methods A multisite, double-blind trial randomized fatigued cancer survivors to 2000mg of American ginseng vs a placebo for 8 weeks. The primary endpoint was the general subscale of the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) at 4 weeks. Changes from baseline at 4 and 8 weeks were evaluated between arms by a two-sided, two-sample t test. Toxicities were evaluated by self-report and the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) provider grading.

Results Three hundred sixty-four participants were enrolled from 40 institutions. Changes from baseline in the general subscale of the MFSI-SF were 14.4 (standard deviation [SD] = 27.1) in the ginseng arm vs 8.2 (SD = 24.8) in the placebo arm at 4 weeks (P = .07). A statistically significant difference was seen at 8 weeks with a change score of 20 (SD = 27) for the ginseng group and 10.3 (SD = 26.1) for the placebo group (P = .003). Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment. Toxicities per self-report and CTCAE grading did not differ statistically significantly between arms.

Conclusions Data support the benefit of American ginseng, 2000mg daily, on CRF over an 8-week period. There were no discernible toxicities associated with the treatment. Studies to increase knowledge to guide the role of ginseng to improve CRF are needed.


Effective and safe interventions to prevent and treat cancer-related fatigue (CRF) are needed because it remains one of the most prevalent, distressing, and activity-limiting symptoms survivors can experience, in both the short and long term.[1–6] The prevalence of fatigue in patients undergoing chemotherapy is reported to be between 59% and 96% and, in patients receiving radiation therapy, between 65% and 100%.[4,7] Fatigue can persist 5 to 10 years after diagnosis and treatment.[2,3] CRF profoundly and negatively affects patients' quality of life and interferes with routine daily functioning.[5,6] Furthermore, fatigue accounts for a substantial amount of the variance in overall quality of life, with over 40% of variance attributed to fatigue.[1]

There is a lack of evidence to support the efficacy of pharmacologic interventions. Psychostimulants have been the most commonly studied pharmacologic intervention for CRF. Eight placebo-controlled randomized trials evaluating methylphenidate or related agents have been completed with all but one trial[8] being negative.[9–15] Despite popularity, the newer psychostimulants, such as modafanil, have also not yet been found to be effective in randomized controlled trials.[16] In addition, other central nervous system agents (eg, donepezil, paroxetine) have had negative results to date.[17,18]

Dietary supplements are a popular self-administered remedy among patients for symptoms that have no known effective treatment; CRF is no exception. Coenzyme Q 10, L-Carnitine, guarana, and ginseng have been used for fatigue and subsequently studied. Based on their role in cellular energy production, both coenzyme Q 10 and L-Carnitine were evaluated in placebo-controlled trials for CRF; they were found to be no more helpful than placebos.[19,20] Guarana has supportive data from a phase II placebo-controlled trial,[21] warranting further research.

Although many herbs have been touted through folklore and through traditional use as remedies for fatigue, none has probably enjoyed as much worldwide reputation and interest as ginseng. Within the context of traditional Chinese medicine, ginseng is generally viewed as an "adaptogen," a substance that can help restore balance to the body by bringing it back to a point of homeostasis.[22] There are two major species of ginseng, Asian (Panax ginseng) and American (Panax quinquefolius).[22,23] Both have a common mixture of active ingredients, the most important being ginsensosides. Between species of ginseng, there are varying amounts, strengths, and varieties of ginsensosides.[22,24,25]

Substantial objective evidence supporting that ginseng may be helpful for fatigue comes from preclinical data. Specifically, in vitro data demonstrate anti-inflammatory and cortisol modulating effects[26–28] consistent with the currently established physiology of CRF. Animal studies have reported improved endurance and swimming duration time with ginseng, specifically ginsenosides Rb1 and Rg1, both of which are present in both Asian and American ginseng.[25,29–31]

Two pilot trials have been completed in cancer survivors. One small study, only published in abstract form to date, reported positive effects of Asian ginseng in patients receiving chemotherapy.[32] A subsequent larger pilot trial was conducted within the North Central Cancer Treatment Group, which randomized 290 patients, receiving or having completed cancer treatment, to one of three doses of American ginseng—750mg, 1000mg, and 2000 mg—vs a placebo for 8 weeks. The primary outcome was CRF as measured by the Brief Fatigue Inventory (BFI), with a secondary fatigue measure of the Vitality subscale of the SF-36. Area under the curve analysis for the summed six items of activity interference from the BFI (higher being better) was 460 units for placebo, 467 for 750mg of ginseng, 480 for 1000mg of ginseng, and 551 for 2000mg of ginseng at 8 weeks. Likewise, mean changes from baseline in the vitality subscale (higher being better) were 7.3 and 7.8 for placebo and the 750-mg dose of ginseng, respectively, versus 14.6 and 10.5 for the 1000- and 2000-mg doses of ginseng, respectively. The improvements in the 1000- and 2000-mg doses of ginseng were seen at 4 weeks and were maintained at 8 weeks. The two highest doses of ginseng (1000 and 2000mg/day) outperformed the 750mg/day dose and placebo in every one of the eight predetermined study endpoints.[33]

Based on these encouraging pilot data, the purpose of our trial was to evaluate, using a double-blind design, the efficacy of 2000mg/day of American ginseng (Panax quinquefolius) as therapy for CRF and to evaluate its toxicities.