American Ginseng (Panax quinquefolius) for Upper Respiratory Tract Infections

By Tiffany Segre, MD, and Craig Schneider, MD, Dr. Schneider is Director of Integrative Medicine, Department of Family Medicine, Maine Medical Center in Portland. Dr. Segre is a Fellow in the Integrative Family Medicine Program at Maine Medical Center and University of Arizona (Tucson); they report no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.

Herbal remedies known as ginseng are based on the roots of several distinct species of plants, mainly Korean or Asian ginseng (Panax ginseng), American ginseng (Panax quinquefolius), and Siberian ginseng (Eleutherococcus senticosus). Each of these species is part of the Araliaceae family of plants: however, although American ginseng is closely related to Panax ginseng, neither should be confused with Siberian ginseng, which is actually an unrelated plant.

American ginseng has a long history of traditional use by Native Americans. Extensive cultivation now occurs in the American Midwest and Canada, and, unfortunately, it is becoming endangered in the wild due to over-harvesting and habitat loss. These supply and demand forces have led to several other plants being marketed as ginseng, but enactment of the Farm Security and Rural Investment Act in 2002 now permits only roots of Panax species to be labeled as ginseng.1

Ginsengs have traditionally been utilized as "adaptogens," or substances that help an organism respond to stress in the environment. Although there is abundant research on Asian ginseng, American ginseng has only recently been subjected to clinical investigation, and there is emerging evidence that it may reduce postprandial glucose levels in patients with Type 2 diabetes2 as well as protect individuals from upper respiratory tract infections (URTIs).

This article will focus on the use of a specific American ginseng extract, CVT-E002 (COLD-fX®, CV Technologies Inc., Edmonton, Alberta, Canada), which has been studied in the prevention of URTIs.

COLD-fX

CVT-E002 is a proprietary botanical extract of North American ginseng root (Panax quinquefolius) standardized to contain 80% polysaccharides and oligosaccharides (poly-furanosyl-pyranosyl-saccharides) and 10% protein. Batch-to-batch consistency is certified using ChemBioPrint® Technology.3 Most studies have used a freeze-dried extract encapsulated to contain 200 mg per capsule.

Readers may be familiar with CVT-E002 from COLD-fX advertisements distributed in popular magazines featuring testimonial from hockey star Mark Messier.

Mechanism of Action/Laboratory Studies

American ginseng root contains triterpene saponins commonly known as ginsenosides. At least 30 ginsenosides have been reported to exist in the various ginseng species.4 Individual ginsenosides are known to have distinct effects, with some opposing the actions of others. American ginseng also contains polysaccharides. There appear to be differences in ginsenoside content between wild and cultivated American ginseng, as well as between batches, plant parts, and preparation methods utilized.5 CV Technologies claims that CVT-E002 differs from other Asian and American ginseng products in content of polysaccharides and ginsenosides.

Polysaccharides and oligosaccharides from ginseng are believed to be responsible for its immunomodulating activity.6 Pre-clinical studies of American ginseng have reported activation of monocytes, induction of tumor necrosis factor-α and interferon-γ, as well as stimulation of natural killer cell activity and interleukin-2 (IL-2) production.7,8 Stimulation of B-lymphocyte proliferation, serum immunoglobulin production, and macrophage production of IL-1 and IL-6 in vitro have also been reported.6

It remains unclear just how American ginseng impacts the development of URTIs or their course, as some of the effects described above would seem to be associated with improvements (e.g., increased γ-interferon production), while others might be expected to lead to worsening of symptoms (e.g., increased production of inflammatory cytokines).9,10

Clinical Evidence

There have been three randomized, double-blind, placebo-controlled trials recently published addressing the efficacy of American ginseng for the prevention of URTIs.

McElhaney et al published a small randomized, double-blind trial in 2006 evaluating the efficacy of CVT-E002 (400 mg/d) in reducing the incidence and duration of respiratory symptoms in healthy community-dwelling seniors older than age 65.11 This placebo-controlled study included 43 volunteers from Edmonton, Canada, over a four-month period beginning in September 1998. Subjects received the influenza vaccine one month into the study. They were asked to self-assess and document the presence and duration of cold symptoms, any additional cold medications taken, and adverse effects experienced.

In the first eight weeks of the study, the number of acute respiratory infection (ARI) symptoms was similar in both groups. However, during the last two months of the study, significantly fewer subjects in the ginseng group reported ARI symptoms compared to placebo (32% vs. 62%, P = 0.05). The ginseng group reported 55% fewer days of ARI symptoms than did the placebo group. Incidence of adverse effects was similar in the two groups. The authors concluded that CVT-E002 could be effective in reducing the frequency as well as the duration of ARI symptoms in healthy community-dwelling seniors; however, the small sample size and lack of a validated instrument for evaluating ARI symptoms limit the impact of the author's conclusions. Of note, there was no influenza circulating in the community during the period in which the study was conducted.

Predy et al conducted a larger randomized, double-blind study during influenza season in the Edmonton area comparing CVT-E002 (400 mg/d) to placebo for the prevention of URTIs in healthy community-dwelling adults ages 18-65.12 The primary endpoint of this 2005 study was the number URTIs, and secondary endpoints included the severity and duration of URTI symptoms. Subjects (130 in the ginseng group and 149 in the placebo group) were asked to complete a daily log of their cold symptoms, severity, and duration. They contacted an investigator as soon as cold symptoms started and colds were verified per modified Jackson criteria (two-day symptom scores >14).

The mean number of colds verified was lower in the ginseng group, but this difference was not significant. However, the ginseng group did have a significantly reduced rate of recurrent colds (10% in the ginseng group vs. 22.8% in the placebo). There was also a significant decrease in the total number of cold symptoms experienced (31% lower) and their overall duration (34.5% less days). The incidence of adverse effects was similar for the two groups. The investigators concluded that in a healthy adult population, CVT-E002 could safely reduce the risk of recurrent colds as well as the number of colds per person and their duration. This study was well designed, attending to adherence with study protocol and using standardized criteria to evaluate cold symptoms. Intention-to-treat analysis was used, and both study participants and statisticians remained blinded. Unlike the other CVT-E002 studies, participants were excluded from this study if they had received the influenza vaccine in the last six months.

In 2004, another group, also led by McElhaney, investigated whether taking CVT-E002 as prophylaxis in the influenza season decreased the incidence of ARI in institutionalized older adults.13 This study was originally designed as two randomized, double-blind trial arms testing CVT-E002 200 mg orally twice daily against placebo. The first trial lasted eight weeks, beginning in mid-February 2000 and included 89 mostly female subjects (average age 81 years) from three nursing home and assisted living facilities in Canada. The second study consisted of a similar participant profile and lasted 12 weeks, starting in late December 2000. About 90% of the subjects in both groups had been vaccinated for influenza. Clinical assessments for ARI occurred twice a week. ARI was defined as two respiratory symptoms or one respiratory symptom and one constitutional symptom. Symptomatic participants were cultured for influenza, respiratory syncytial virus (RSV), parainfluenza, and rhinovirus. Serology testing was also used to test for influenza. The primary outcome for the study was clinically confirmed ARI.

Results demonstrated no significant difference between the placebo and CVT-E002 groups for the number of clinical cases of ARI or the severity or duration of the symptoms in either of the two arms. The number of laboratory-confirmed ARI in each of the two trials alone was too low to detect meaningful differences. Therefore, the authors used a combined analysis (the Mantel-Haenszel odds ratio) to evaluate the endpoints. Once again, clinically symptomatic ARI was not significantly reduced in the treatment group. However, the authors point out that the incidence of laboratory-confirmed ARI due to influenza (odds ratio [OR] 0.14) as well as influenza and RSV (OR 0.11) was significantly higher in the placebo group. The number of adverse events was high, but similar in both the placebo and CVT-E002 groups.

The authors concluded that CVT-E002 may provide a safe option for preventing ARI in an institutional setting, even when people have been vaccinated. CVT-E002 may be helpful in decreasing laboratory-confirmed ARI; however, the trial was not statistically powered to evaluate this secondary endpoint. In addition, there were no significant differences in clinical symptom scores between the groups, so the clinical utility of laboratory-confirmed ARI is unclear. Altogether, though the results are suggestive of minimal benefit, it is difficult to draw definitive conclusions from this study.

Adverse Effects

In these studies, American ginseng was reported to cause adverse gastrointestinal effects (nausea, heartburn, diarrhea), dry mouth, myalgias, and arthralgias at rates similar to placebo.

Conclusion

CVT-E002 is a well standardized product with known phytochemical composition and limited lot-to-lot variability. It appears to be well tolerated and safe to use for up to 16 weeks. Data from three industry-sponsored studies (two by the same lead author) suggest that in healthy adults American ginseng in the form of CVT-E002 may be beneficial in decreasing the number of recurrent colds and the duration of symptoms if introduced early in the cold season. Further well-designed, non-industry sponsored studies would contribute greatly to revealing the true utility of American ginseng for prevention of upper respiratory tract illness.

Recommendation

CVT-E002 appears to be safe and well tolerated for use during cold and flu season. As preliminary evidence suggests it may reduce the frequency of recurrent colds and the duration of symptoms, a trial by well-informed and otherwise healthy adults is reasonable at 400 mg/d.

References

1. 107th Congress. Farm Security and Rural Investment Act of 2002. 107-171. Available at: www.ers.usda.gov/Features/farmbill/. Accessed Jan. 12, 2007.

2. Vuksan V, et al. American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med 2000;160:1009-1013.

3. Pang PKT, et al. Chemical and pharmacological standardization of herbal extracts. United States Patent #6,156,291. Dated: Dec. 5, 2000.

4. Wang A, et al. Determination of ginsenosides in plant extracts from Panax ginseng and Panax quinquefolius L. by LC/MS/MS. Anal Chem 1999;71:1579-1584.

5. Sievenpiper JL, et al. Decreasing, null and increasing effects of eight popular types of ginseng on acute postprandial glycemic indices in healthy humans: The role of ginsenosides. J Am Coll Nutr 2004;23:248-258.

6. Wang M, et al. Immunomodulating activity of CVT-E002, a proprietary extract from North American ginseng (Panax quinquefolium). J Pharm Pharmacol 2001;53:1515-1523.

7. Luo P, Wang L. Peripheral blood mononuclear cell production of TNF-alpha in response to North American ginseng stimulation (abstract). Altern Ther 2001;7:S21.

8. Wang, M, et al. A proprietary extract from North American ginseng (Panax quinquefolium) enhances IL-2 and IFN-gamma productions in murine spleen cells induced by Con-A. Int Immunopharmacol 2004;4:311-315.

9. Turner RB. Studies of "natural" remedies for the common cold: Pitfalls and pratfalls. CMAJ 2005;173:1051-1052.

10. Eccles R. Understanding the symptoms of the common cold and influenza. Lancet Infect Dis 2005;5:718-725.

11. McElhaney JE, et al. Efficacy of COLD-fX in the prevention of respiratory symptoms in community-dwelling adults: A randomized, double-blinded, placebo controlled trial. J Altern Complement Med 2006;12:153-157.

12. Predy GN, et al. Efficacy of an extract of North American ginseng containing poly-furanosyl-pyranosyl-saccharides for preventing upper respiratory tract infections: A randomized controlled trial. CMAJ 2005;173:1043-1048.

13. McElhaney JE, et al. A placebo-controlled trial of proprietary extract of North American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults. J Am Geriatr Soc 2004;52:13-19. Erratum in: J Am Geriatr Soc 2004;52:following 856.