By David Kiefer, MD, Editor

Synopsis: Panax quinquefolius has the potential to become commonplace in the treatment of cancer-related fatigue.

Source:Barton DL, et al. Wisconsin ginseng (Panax quinquefolius) to improve cancer-related fatigue: A randomized, double-blind trial, N07C2. J Nat Cancer Inst 2013;Jul 13; [Epub ahead of print]

The authors of this study were following upon two preclinical pilot studies showing some benefit in cancer-related fatigue with two doses (1000 mg and 2000 mg daily) of Panax quinquefolius, also known as American or Wisconsin ginseng.

The researchers randomized 364 people with cancer (except brain or CNS lymphoma) diagnosed in the last 2 years to either 2000 mg of P. quinquefolius (dried, powdered root in 500 mg capsules, containing 3% ginsenosides) daily or placebo. Participants also needed to have a score of 4 or more on the 11-point cancer-related fatigue scale. Patients were excluded if they had pain or insomnia
(> 4 on an 11-point scale), used systemic steroids or opioids, used ginseng in the past or currently, or changed cancer-treatment status during the 8-week study period.

The primary endpoint was the Multidimensional Fatigue Symptom Inventory Short Form (MFSISF), which measures the subjective experience of fatigue. There are six items, each of which are rated from 0 (not at all) to 5 (extremely); overall the MFSISF ranges from 0 (no fatigue) to 30 (extreme fatigue for each descriptor). Several other subscales provided secondary endpoints. Data were collected at time 0 (before the intervention), 4 weeks, and 8 weeks.

Of the 364 patients who underwent randomization, 80 withdrew (mostly for adverse effects and a variety of other reasons) before the completion of the treatment protocol; there were no significant demographic differences between the treatment and placebo groups at baseline or in the subjects who withdrew early. However, of the 80 patients who withdrew early, 39 were still included in the primary endpoint analysis; a total of 147 in the ginseng group and 153 in the placebo group were analyzed. This partial inclusion was not obviously done according to an intention-to-treat analysis, compromising the rigor of the methodology and believability of the final results. That said, the researchers reported that the MFSISF changed 14.4 in the ginseng group and 8.2 in the placebo group from baseline to 4 weeks (P = 0.07), but 20 (ginseng) and 10 (placebo) at 8 weeks (P = 0.003). For a subgroup analysis on people currently undergoing chemotherapy (vs those who had completed therapy), the ginseng group at both the 4- and 8-week time points displayed statistically significant changes in the MFSISF when compared to placebo.

The secondary endpoints, using a variety of other fatigue and physical symptom scales, showed a range of results from statistically significant improvements with the ginseng group to no difference between ginseng and placebo. With respect to adverse effects, nausea, vomiting, insomnia, anxiety, and agitation were reported by study participants at equivalent frequencies in the placebo and ginseng groups.

Commentary

The authors of this article make a compelling case for why treatments for cancer-related fatigue are desperately needed. More than half of people undergoing chemotherapy or radiation experience cancer-related fatigue, and fatigue is a major factor affecting quality of life in this population. In addition, there are few, if any, viable treatments for this condition. In steps P. quinquefolius.

P. quinquefolius, or American ginseng, is known not only in North America. It has a spectacular reputation in Asia, home of Asian, or Korean, ginseng (Panax ginseng), as being either better, stronger, or different from the more well-known P. ginseng. It is different in the sense that, simply put, P. ginseng is known to be more "yang," or elevating and heating, whereas P. quinquefolius is generally more "yin," or cooling and calming. There are phytochemical differences that could account for these clinical nuances, as well as varying animal and human research results documenting specific effects.¹ The authors refer to the plant as "Wisconsin ginseng," a "type" of P. quinquefolius. Technically, this plant is likely similar to other "types" of P. quinquefolius; "type" is neither a botanical term nor an herbal medicine term, but is merely referring to the geographic source of the herbal product for this study. The mention of a "Wisconsin" ginseng is a testament to the booming industry in Wisconsin as much as it illustrates the difficulty in relying on common plant names to concretely communicate about the topic. Also, while threatened in the wild, it is being extensively cultivated in northern climates such as Wisconsin.

There seems to be a mechanistic connection to the use of P. quinquefolius in this context. Many of these adaptogenic plants have an effect on the hypothalamus-pituitary-adrenal axis, which could alter a global symptom such as fatigue. The authors point out connections in the research literature between cancer-related fatigue and an elevated inflammatory state, and anti-inflammatory effects are another in vitro, and presumably in vivo, effect of the various ginseng species.

Thankfully, the authors of this study mention one of our greatest concerns in the use of dietary supplements during chemotherapy or radiation, namely that these products would counteract the effectiveness of the allopathic intervention. The medical literature is frustratingly mute about ginseng and such interactions. The cause for concern is that ginsenosides can have antioxidant effects, but in vitro and some in vivo studies mostly on Asian ginseng (P. ginseng), also show antitumor effects, as well as the potentiation of chemotherapeutic agents.² Hopefully, future studies will bring more clarification to the safety and efficacy of the different species of ginseng in this regard.

There are some concerns with the methodology in this study. The issue of the handling of the dropouts and the lack of an intention-to-treat analysis could have compromised the study’s results, especially given the large number of people (n = 80) who didn’t complete the study. Also, the exclusion criteria of significant pain or insomnia may have eliminated some of a patient pool that would have otherwise made these results more generalizable. Nonetheless, these are important results and another example of an integrative therapeutic that fills a niche otherwise unoccupied by conventional treatment modalities. Provided the research community can convince clinicians of the safety of P. quinquefolius during cancer treatment, this important herb may become commonplace in the treatment of cancer-related fatigue.

References

1. Kiefer D, Pantuso T. Herbal medicines: Panax ginseng. Am Fam Physician 2003;68:1539-1542.
2. Stargrove MB. Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies. Mosby Elsevier; St. Louis: 2008.