Dec 22 2010
Echinacea continues to be a popular herbal product, used primarily for treating and preventing colds and flus. Sales were estimated at $132 million in the US alone in 2009, an increase of 7% over the previous year. Reports of major negative clinical trials have had only a modest and temporary effect on the popularity and sale of this herb, contradicting claims that the utility of such research is to inform consumers.
In the current issue of the Annals of Internal Medicine there is a new study of Echinacea for the treatment of cold symptoms: Echinacea for Treating the Common Cold, A Randomized Trial. I won’t hold out the punchline – the study was completely negative. But let’s put the results of this study into the context of the history of echinacea and the clinical evidence.
History of Echinacea
Modern proponents of echinacea frequently cite as support the claim that this plant has been used for centuries by many Native American cultures. This much is well-documented, but what is not clear is what echinacea was used for. For this there is no clear answer, except that echinacea was used for 15-20 different and unrelated conditions, from fatigue to snake bites. Let us consider the value of the claim for traditional use of any treatment.
Native American cultures did not have a written language, nor a tradition of science, rigorous observation, or objective confirmation. This is not a criticism – the latter points are true of every human pre-scientific culture. This is perhaps exacerbated by the dependence upon oral tradition. Further, the concept of illness and of specific ailments was very different in ancient cultures than modern concepts of disease. Add to that the challenge of proper translation, and it is extremely difficult to correlate what echinacea was actually used for with any modern application. In addition, there is no clear record that echinacea was used to treat upper respiratory viral infections.
So the claim for traditional use is dubious, but even if it were demonstrably true that is still a very weak justification for any specific treatment. The traditional use claim is based upon the demonstrably false assumption that centuries of use of a treatment (without rigorous testing) is compelling evidence for its efficacy. This assumption is contradicted by history, one dramatic example of which is the use of blood-letting and purging as part of Galenic medicine (the balancing of the four humors) for not just centuries but over two millennia in Western culture. Antiquity is no guarantee of efficacy. Human nature can apparently perpetuate worthless treatments indefinitely.
The journey of echinacea from traditional use in the New World to its modern popularity as a cold remedy is a tortuous one. It was first popularized by a dubious physician and snake-oil salesman called H.C.F. Meyer. In the late 1800s he sold echinacea as a panacea, claiming it cured everything, including cancer. He also heavily marketed the Native American connection, which was popular at the time. Meyer was unable to convince mainstream doctors of the time of his product’s value, but he was able to convince an eclectic physician by the name of Dr. King. (Eclectic physicians followed a tradition that included heavy use of herbal remedies.) King was instrumental in the popularity of echinacea at this time and until about the 1930s.
The story of echinacea then resurfaces in Germany in the 1930s. A German doctor by the name of Gerhard Madaus became interested in echinacea. He was a proponent of unconventional medical treatments and a promoter of herbal medicine in Germany. He visited the US with the intention of bringing back seeds for Echinacea augustifolia (the variety used, apparently, by Native Americans) but instead brought back seeds for Echinacea purpurea – and for that reason the latter variety of echinacea became popular in Europe.
While there were and continue to be many studies of the basic science of echinacea, there were no rigorous clinical trials of its safety or efficacy. Modern claims that it “boosts” the immune system, or is useful for infections, are not based upon any solid clinical evidence. Given the history, there is also no particular reason to believe that echinacea might be useful for colds, versus any other medical ailment.
This latest study add to the prior clinical research for echinacea and cold symptoms, which is basically negative. Like any such clinical research, there are lots of small and poorly controlled studies, with mixed results. Even the larger and somewhat controlled studies have mixed results, but the largest and best controlled studies are all negative.
A 2006 Cochrane review found:
Sixteen trials including a total of 22 comparisons of Echinacea preparations and a control group (19 placebo, 2 no treatment, 1 another herbal preparation) met the inclusion criteria. All trials except one were double-blinded. The majority had reasonable to good methodological quality. Three comparisons investigated prevention; 19 comparisons investigated treatment of colds. A variety of different Echinacea preparations were used. None of the prevention trials showed an effect over placebo. Comparing an Echinacea preparation with placebo as treatment, a significant effect was reported in nine comparisons, a trend in one, and no difference in six. Evidence from more than one trial was available only for preparations based on the aerial parts of Echinacea purpurea (E. purpurea).
Echinacea preparations tested in clinical trials differ greatly. There is some evidence that preparations based on the aerial parts of E. purpurea might be effective for the early treatment of colds in adults but the results are not fully consistent. Beneficial effects of other Echinacea preparations, and Echinacea used for preventative purposes might exist but have not been shown in independently replicated, rigorous RCTs.
Basically – this is the random scatter of evidence that we typically find for an ineffective treatment. But I also think the reviewers are being too generous. There does seem to be a relationship between the quality of the study and the likelihood of negative results. In addition, there are further well-controlled clinical trials since this review that are also negative.
A 2008 study added to the evidence that echinacea is not useful for prevention of colds or flus. They found no difference in incidence of cold symptoms in 90 volunteers taking echinacea vs placebo.
Echinacea studies for colds are divided into prevention and symptomatic treatment. Treatment trials generally fall into two categories – testing a cold virus challenge (giving subjects the cold), and treating colds acquired out in the world. Well-designed studies for cold prevention are all negative, including the additional 2008 study. Now we have another study of echinacea for the treatment of symptoms. Patients were enrolled in the study within 24 hours of getting cold symptoms. They were treated either with echinacea blinded, placebo blinded, echinacea open-label, or nothing. Here are the results:
Of the 719 patients enrolled, 713 completed the protocol. Mean age was 33.7 years, 64% were female, and 88% were white. Mean global severity was 236 and 258 for the blinded and unblinded echinacea groups, respectively; 264 for the blinded placebo group; and 286 for the no-pill group. A comparison of the 2 blinded groups showed a 28-point trend (95% CI, −69 to 13 points) toward benefit for echinacea (P = 0.089). Mean illness duration in the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, compared with 6.87 days in the blinded placebo group and 7.03 days in the no-pill group. A comparison of the blinded groups showed a nonsignificant 0.53-day (CI, −1.25 to 0.19 days) benefit (P = 0.075). Median change in interleukin-8 levels and neutrophil counts were also not statistically significant (30 ng/L and 1 cell/high-power field [hpf] in the no-pill group, 39 ng/L and 1 cell/hpf in the blinded placebo group, 58 ng/L and 2 cells/hpf in the blinded echinacea group, and 70 ng/L and 1 cell/hpf in the open-label echinacea group).
Bottom line – no benefit from echinacea. In the discussion the authors desperately try to put a positive spin on the data, essentially making two points. One is that there was a non-statistical trend in the data towards a positive effect. Non-statistical trends are useless, however. There already is a fairly low bar for statistical significance in clinical trials, biasing them toward false positives. Lowering the bar further to talk up “trends” is disingenuous spin, in my opinion. Further, a close look at the randomization in this trial shows that 6 of the 10 pre-study conditions also deviated by an amount equal to or greater than the deviation in outcome. In other words, there was a random scatter in the randomization just as in the outcomes – but all of which fell below statistical significant and is therefore just noise.
Their second point is that the data do not rule out a clinically significant benefit. Again – this is just spin. Studies never rule out a benefit too small to be measured by the study. So you can say this about any negative study. This study was reasonably powered, but it was not a huge study with thousands of subjects, so if you take the entire range of possible statistical results, it’s within the realm of possibility that this study missed a clinically relevant effect. But that is not the same thing as there being evidence for such an effect, and it in no way changes the fact that this study is nothing but negative.
The lead author, Bruce Barrett, is quoted as saying:
“Adults who have found echinacea to be beneficial should not discontinue use based on the results of this trial, as there are no proven effective treatments and no side-effects were seen,” Barrett added in a release.
This seems like an attempt to downplay negative results. In the discussion the authors argue that this one study, given the positive results in the past, should not change our thinking on echinacea. But I disagree with their assessment of prior research. They reference mainly two meta-analyses, which I found to be very low quality. They also cite the 2006 Cochrane review, making it seem as if this review is positive, when in fact it in generally negative. Further there is an implied endorsement of anecdotal experience in that statement – a naive position for a researcher to take.
The prior plausibility for echinacea as a cold remedy is very low, but not zero. As an herbal product it can feasibly have biological activity. The claim that it “boosts the immune system” is not credible, as such a phenomenon is not generally accepted. Basic science research essentially finds that the immune system is activated by echinacea, but this has not been distinguished from a non-specific immune response to a foreign substance. In other words, stimulating the immune system non-specifically (I can do this by punching you in the arm) and “boosting” the immune system so that it functions more effectively against an infection, are not the same thing. Leaping to the latter conclusion is not justified by the evidence.
From an historical perspective, there is no particular reason to conclude that echinacea might be effective for the cold. Its traditional use by Native Americans was for many indications, possibly including cough, but not specifically the cold or flu. The great number of conditions for which it was used indicates that echinacea was treated as a panacea, which further indicates there was no particular evidence for its effectiveness as a cold remedy. And further, such evidence would only amount to anecdotal evidence – the fact that belief in echinacea became culturally embedded is not a reliable indicator of efficacy.
While herbs are drugs, and drugs can have biological effects, it is unlikely that any random drug would work for any particular clinical indication.
It is therefore no surprise that the clinical evidence shows that echinacea is not effective for the prevention or treatment of colds or cold symptoms. This latest study adds to the evidence for lack of efficacy.
The market for echinacea, however, endures, largely on a sea of anecdotes and marketing spin that is incongruous with the evidence.
Note: This post was written partly from material and analysis provided by Wallace Sampson.
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