Symptoms and Asymptote: Echinacea and Colds

Abstract & Commentary

By Russell H. Greenfield, MD, Editor

Synopsis: The results of this well-done study suggest that a specific formulation of echinacea may offer modest benefit to people with the common cold, but that such benefit is statistically, and likely clinically, insignificant. Data from the trial relating to physician-patient interaction and clinical response have yet to be published.

Source: Barrett B, et al. Echinacea for treating the common cold. Ann Intern Med 2010;153:769-777.

A respectable collection of research data exists regarding the effectiveness of echinacea against the common cold, yet a definitive recommendation remains elusive. Published results and conclusions vary widely, as do the methodologies employed. In part as an effort to remedy this situation, in part to further explore the therapeutic implications of the doctor–patient relationship, the authors of this study designed a 2-way factorial study in which subjects were randomized to 1) receive no, standard, or enhanced clinical interaction in one direction (33% chance), and 2) to receive no pills, placebo (blinded), echinacea (blinded), or open-label echinacea (unblinded) in the other direction (25% chance).

Subjects were recruited through advertisements and community events, and subsequently underwent screening via telephone interview. Subjects had to be 12 years of age or older with cold symptoms having developed within 36 hours. People with a history of allergic rhinitis and typical allergic symptoms, as well as those using antibiotics or decongestants, were excluded.

Each subject was assigned an envelope-within-an-envelope—this permitted group assignment to be revealed immediately after consent was obtained. A research assistant opened the larger envelope for group assignment and subjects then received and took their first dose of pills. The alkylamide-rich echinacea supplied to subjects contained the equivalent of 675 mg of E. purpurea root and 600 mg of E. angustofolia root, each standardized to 2.1 mg of alkylamides. Placebo pills were identical in appearance and similar pill bottles were used. Subjects received 2 tablets at enrollment, followed by 2-tablet doses 3 more times within 24 hours, and then 1 tablet 4 times a day for the next 4 days. Phytochemical analysis of the echinacea product was completed by an independent source at various times throughout the study and revealed stable constituent concentrations.

For the two-thirds of subjects who would be seeing a clinician, a second, smaller envelope was opened by the study clinician. This second envelope described allocation to standard or enhanced medical visit.

Symptoms were to be self-rated twice daily until they resolved, up to a maximum of 14 days. Nasal washings were collected at enrollment and 2 days later. These were analyzed for interleukin-8 levels and neutrophil counts.

The primary outcome of interest was the area under the curve for global symptom severity, with duration and severity assessed twice daily by self-report. Secondary outcomes of interest focused on measures of psychological and immunological impact. Tools employed included the Wisconsin Upper Respiratory Symptom Survey (short version), the Medical Outcomes Study Short Form-8 Scale, the Euro-Qol's feeling thermometer, the 4-item Cohen Perceived Stress Scale, the Ryff Personal Relationships Scale and the Life Orientation Test.

At trial's end, the average area under the curve for global severity and illness duration were lower in the blinded and open-label echinacea groups than in either the blinded placebo or no-pill groups. Mean global severity was 236, 258, 264, and 286 for the blinded echinacea group, the unblinded echinacea group, the blinded placebo group, and the no-pill group, respectively. Mean illness duration in the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, in comparison to 6.87 days in the blinded placebo group and 7.03 days in the no-pill group. An efficacy analysis that compared duration of illness in the two blinded groups (echinacea and placebo) yielded a mean difference of 0.53 day (Confidence Interval [CI], -1.25 to 0.19 days) and a T of 1.97 (P = 0.075). Subgroup analysis of 351 people identified with very early symptom onset revealed insignificantly reduced illness duration and global severity in those receiving echinacea compared with the no-pill or blinded placebo groups. No statistically significant differences were identified between the groups for secondary outcomes of interest. Incidence of adverse events was similar across all four groups.

The authors concluded that the pharmacologic activity of echinacea likely provides at best a modest benefit for people with the common cold.

Commentary

Viral respiratory infections are a major reason for missing school and work, and the study authors point out that billions of dollars are lost as a result, not to mention the dollars expended through doctor's visits. So it makes sense that investigation into safe means of preventing and treating upper respiratory infections needs to be supported. But perhaps only to a point, and with respect to echinacea it feels, at least to this reviewer, as though we may have reached that point.

These researchers are to be praised for their efforts—they developed and carried out a well-done trial, with additional results yet to be reported that promise to be compelling. There are shortcomings to make note of, including the perspective many hold that tincture of echinacea is more effective than pills. The authors themselves make clear that the results of but one of a wide variety of echinacea formulations being put to the test cannot rationally be used to judge the effectiveness of all such potential formulations. The authors also readily report that their trial may have been underpowered. The question of generalizability is legitimate if for no other reason than that the population in question is clearly unusual—out of the initial > 3,000 people screened for participation a total of 914 were already enrolled in another clinical study. In addition, retention was unusually high with approximately 98% of intended data collected, the largest data gap being for the nasal wash, where 33 subjects did not return within 24-72 hours after the first wash. Still, the results are meaningful and have clinical relevance—though the effect of echinacea in this setting was mild-to-moderate at best and did not achieve statistical significance, a half-day quicker to feeling better counts for something in the minds of some.

The authors point out that literally hundreds of studies examining the effectiveness of echinacea against the common cold have been published, including randomized trials. The array of results run the gamut from echinacea being dramatically effective, to its activity being equivalent in nature to placebo, and seemingly everything in between. Results of the current trial suggest that the specific formulation of echinacea studied may offer some benefit in the setting of an acute cold, but that the effects are statistically and, for many, clinically insignificant.

It may be that we are nearing the place of diminishing returns from this line of investigation. Though upper respiratory infection is a costly plague of mankind it is, nonetheless, a generally self-limited malady that many studies suggest might be avoided through general lifestyle measures such as getting adequate sleep; washing one's hands frequently; avoidance of touching the eyes, nose and mouth; managing stress in healthy ways; holding to a healthy diet and exercise regimen; and staying socially engaged even during cold season.

Beyond our moms' traditional advice, almost all cold remedies fail in providing their purported health benefits, yet some studies of specific formulations of echinacea suggest a potentially meaningful shortening of duration and lessening of severity of illness, and with a wide safety margin. Perhaps as medicine further embraces the individual nature of patients and their response to treatment, practitioners can find comfort in both the published science and the clinical experience that some people with upper respiratory infections do better with echinacea, some do not, but the remedy appears to be safe so it's worth a try.

The lines for treatment and symptom relief, though often approaching one another, do not always make for a clean and consistent intersection. In select clinical circumstances, such as the use of echinacea for the common cold, it's time to get comfortable with inconsistency.