Study: Ginseng as a cure for chemo fatigue

reference

Barton DL, Liu H, Dakhil SR, et al. Wisconsin ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial.J Natl Cancer Inst. Aug 21, 2013;105(16):1230-1238.

design

In a double-blind study, cancer patients were randomly assigned to receive 2,000 mgPanax quinquefolius(American ginseng or Wisconsin ginseng) compared to placebo for cancer-related fatigue (CRF).

Participant

Eligible participants were adult cancer patients who had undergone or completed curative treatment and experienced fatigue rated at least 4 on a numeric analog fatigue scale (1–10) for at least 1 month. Exclusion criteria included any brain malignancies, previous use of ginseng, or chronic use of systemic steroids or opioids. Other causes of fatigue, such as pain and insomnia, were also examined and ruled out. All participants were diagnosed within two years of study enrollment. Three hundred and sixty-four participants (183 in the ginseng group, 181 in the placebo group) were enrolled from 40 institutions, and 200 participants were available for the primary endpoint analysis (147 in the ginseng group, 153 in the placebo group).

Study medications and dosage

Participants took two 500 mg capsules of pure BIDPanax quinquefoliusground root from a production batch or a matching placebo with rice powder. The ginseng contained 3% ginsenoside and was assessed by an independent company for quality and effectiveness.

Target parameters

The primary endpoint was change in the general subscale of the Multidimensional Fatigue Symptom Inventory (MFSI) from baseline to 4 weeks. Other MFSI subscales and the fatigue-inertia subscale of the Profile of Mood States (POMS) were also analyzed. The data were converted to a scale of 0–100 and evaluated after 4 and 8 weeks. A subset analysis analyzed those who were currently in treatment versus those who were not. Toxicities were assessed by self-report and provider assessment using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).

Key findings

Overall, there was no statistically significant difference in MFSI scores at 4 weeks, but a statistically significant difference was observed at 8 weeks for the ginseng group (P=0.003). Participants who underwent active treatment experienced a statistically significant improvement in fatigueboth4 and 8 weeks. Self-reported and CTCAE grading toxicities did not differ significantly between arms.

Effects on practice

Interest in the use of ginseng for CKD has been increasing since this research was first presented at the American Society of Clinical Oncology Annual Meeting in 2012. This attention is warranted given the persistent and debilitating nature of CKD and the lack of effective pharmacological interventions available.

In accordance with the Tolle Causum (Latin for “remove the cause”), the uniqueness of CRF compared to ordinary fatigue should be clarified. CKD is not relieved by sleep or rest,¹and patients with CKD report feeling “unusually or overwhelmingly tired.”²Chronic fatigue after treatment tends to remain stable over time, whereas treatment-related fatigue tends to worsen during therapy and improve in one to two months after completion of therapy.³The prevalence of fatigue has been reported to range from 59% to 96% in patients undergoing chemotherapy, 65% to 100% in patients receiving radiation therapy, and 30% in long-term survivors.⁴Several pharmacological agents such as methylphenidate, corticosteroids, anabolic steroids, antidepressants and modafanil as well as L-carnitine and coenzyme Q10 are currently used as remedies. However, few of these agents have been studied in large, placebo-controlled trials, and based on preclinical data, none of the agents studied have been shown to be significantly helpful. Based on my experience in an integrative care setting, I largely agree that there is little to no change in energy with these treatments.

The positive results of this study are compelling, especially given the broad spectrum of cancer patients.

Complicating matters is that the etiology of CRF is multifactorial and widely misunderstood. Proposed mechanisms include pro-inflammatory cytokines,⁵Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis,⁶Desynchronization of the circadian rhythm,⁷skeletal muscle loss,⁸and genetic dysregulation.⁹The advantage of using botanicals for this type of symptoms is that they contain a variety of components with different effects, many such as:Panax spp, are immunomodulators. Therefore,P. quinquefoliusmay be able to positively influence individual cases of CKD with different combinations of causative factors. Much of the research usesPanax sppcites the total ginsenoside amount and the ginsenoside subtypes as important determinants of the outcome. The current study was designed to use 2,000 mg/day based on a 2010 pilot study for CRF that used escalating doses ofP. quinquefolius. In the pilot study (n=290), the crop used contained 5% ginsenoside, and both the 1,000 mg and 2,000 mg/day dosages showed significantly improved fatigue over 8 weeks compared to 750 mg/day.¹⁰In this study, 40% of the intervention group felt a moderate to “much better” benefit compared to 17% on placebo. In the study examined, the crop contained 3% ginsenoside.

The positive results of this study are compelling, particularly given the broad cross-section of participating cancer patients from 40 different sites, with 78% of participants completing all study interventions. What is particularly noteworthy is the finding that the patients on current treatment not only benefited from ginseng after 4 weeks, but continued to improve over the 8 week period. As previously mentioned, patients with CRF undergoing treatment typically experience worsening of this condition during therapy. Therefore, you could think about using itP. quinquefoliusat the beginning of therapy to prevent the appearance of the symptom or at least reduce its intensity.

This calls into question the safety of using American ginseng while treating patients. There is literature on the possible estrogen potentiating effects ofP. quinquefoliusThis leads to the spread of hormone-sensitive cancers.¹¹Whether this is a valid effect of P. quinquefolius is not clear. A study from 2006 explains this finding with how ginseng is obtained. The researchers found that ginseng products obtained not from methanol extraction processes but from water extraction or pure ground root have no estrogenic properties.¹²In addition, there are preclinical data demonstrating inhibition of breast cancer cell lines by water-extracted American ginseng in both estrogen-sensitive and insensitive cell lines.¹³

Another safety concern is how the herb is metabolized by the liver. We do not want an intervention to potentially decrease or increase the metabolic rate of a chemotherapy drug. To date, in vitro data suggest a non-inhibitory effect of American ginseng on CP450 3A4.¹⁴CYP2B1, CYP3A23 and CYP1A2 gene expression.¹⁵Of course, in vitro data is not the same as clinical data, and as long as there are no human data, there is a risk of under- or overdosing of drugs. This represents a significant risk as the therapeutic window of chemotherapy drugs tends to be very narrow.

As an herbalist at heart, I must give you the utmost respectP. quinquefoliusas a wild, native plant traditionally used by both the Eclectics and Native Americans as a tonic for the nervous system. It occurs wild from Canada to Georgia and is considered endangered.¹⁶The future viability of wild American ginseng is at risk for several reasons, including overharvesting, the fact that it takes at least five years for the roots to grow before they are harvested, and increased economic incentives as the price of wild roots continues to rise. As a result, commercial farms grow crops. In the future, researchers should always indicate the source of their crop and the specific subtypes of ginsenosides in the plant used, as there are differences between crops grown in different bioregions.¹⁷

The use of American ginseng as a potential prevention and treatment of CRF looks promising, but more research is needed as human studies demonstrate its safety with the use of various chemotherapy drugs. It would also be worthwhile to study the effectiveness of American ginseng in comparison to other adaptogenic plants, such as:Eleutherococcus(Siberian Ginseng) orPanax ginseng(Asian Ginseng) in separate arms to evaluate efficacy and safety in the treatment of patients with CKD.