Echinacea for Colds and the Flu

28Dec10
From flickr user tranchis

There's no persuasive evidence Flu Shield, or other echinacea products, can prevents colds or the flu, or lessen their symptoms or severity.

Colds and the flu (influenza) are among the most frequent and universal illnesses we all experience. Yet we don’t have any truly effective treatments for them. Sure, there are plenty of products available to treat the symptoms. And there are vaccines and some prescription treatments for influenza, which have modest effects.  But it would be nice if there was something that reliably protected us from getting sick at all, or could speed up recovery if we catch something.

We all have our own approaches for dealing with colds. Given that most infections are mild, differ in their symptoms, and will generally resolve on their own, it’s difficult to distinguish if any treatment is actually doing anything. Sure we felt better, but did the Tylenol take the headache away, or did it go away on its own? Would you have coughed as much if you didn’t take that cough suppressant? And did that chicken soup really make the cold go away sooner?

Variation in symptoms means our own observations can fool us. It also means a lot of anecdotes and testimonials about what actually works. To sort this out, we need some scientific tools: study a treatment, make observations, and evaluate their effects. But that’s hard to do when there’s only one subject, and nothing to compare with. So we turn to clinical trials that compare treatments with placebos, in larger groups, and we look for some sort of group effect.

An approach to herbal remedies

When we’re looking at different treatments, we need to thing about plausibility - is a treatment option something that might work, based on what we already know about the illness? If something is highly implausible, we would want some very impressive evidence to demonstrate a treatment works. Echinacea is a popular treatment for colds. But what are the odds that eating parts of a plant might help prevent or treat viral infections? Well, plants are natural chemical factories, and many plants have been found to produce medicinal effects when consumed. So without knowing anything more, it’s fair to say that echinacea could plausibly have some effect. But why would we expect it to have an effect on colds or the flu? Why echinacea, among all the species of plants?

Echinacea has a history of use by indigenous cultures for the treatment of a diversity of conditions. In the 19th century, echinacea was held out as a panacea-like “blood purifier” for an array of illnesses. And in the 1950′s, it started to be identified as a cold remedy. Since that time, hundreds of clinical trials have been conducted on the different species and parts of the plant, trying to evaluate if echinacea can prevent colds or influenza.

Chemical constituents of echinacea include polysaccharides (e.g., heteroxylan and arabinogalactan) and compounds like alkylamides, chicoric acid and echinacosides, all of which may induce immune responses. What’s not clear is if this actually means anything when consumed.

Beyond the basic science that has identified very general immune responses, there are a number of clinical trials that have been conducted on echinacea.  Many are small and not well designed, leading to a greater chance of bias, and therefore positive results. The best approach in this situation is a systematic review – a structured analysis of all of the evidence, with appropriate stratification and ranking based on the quality of that evidence. Looking at the evidence in a systematic way means less chance of “cherry picking” the studies that fit our hypothesis. Nicely, this type of review of echinacea has been conducted – by the Cochrane Collaboration.

The systematic review, entitled Echinacea for preventing and treating the common cold evaluated the best sixteen trials that studied echinacea. The authors’ conclusions?

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. [Randomized Controlled Trials]

So again, while the authors don’t rule out the possibility that there might be some sort an effect, there’s no persuasive evidence that demonstrates echinacea is effective. Importantly, none of the prevention trials showed an improvement over placebo. And the treatment trials showed inconsistent effects, which, if real, seem to be limited to the E. purpurea strain. So the research continues. But now there’s new evidence to add to this review.

The Newest Trial

Let’s take a quick look at the most recent trial, the one that’s been in the headlines recently. Does it give us more information about echinacea’s effectiveness?

The paper, Echinacea for Treating the Common Cold, appears in this month’s Annals of Internal Medicine, and is from Barrett et al. The study enrolled patients aged 12-80 with new colds (onset within the past 36 hours).  Participants were randomly allocated to one of four groups: no pills, placebo pills (blinded), echinacea pills (blinded), or echinacea pills (unblinded and open label). Echinacea tablets contained the equivalent of 675 mg of Echinacea purpurea root and 600 mg of Echinacea angustifolia root. There was a high dose for the first 24 hours, then one tablet four times a day for four days. The echinacea was well tolerated, with no significant adverse effects. The result?

Illness duration and severity were not statistically significant with echinacea compared with placebo. These results do not support the ability of this dose of the echinacea formulation to substantively change the course of the common cold.

No effect was noted. But the authors try hard to describe the negative results in a positive way, arguing that their trial does not rule out a meaningful effect. While statistically possible, that’s also the case with every negative study. We need to consider this from the perspective of prior plausibility (possible, but remote, based on other data), and the totality of the evidence, which has been unimpressive. And when this study is eventually incorporated into an updated of the Cochrane systematic review, it will add to the evidence that echinacea seems to have no meaningful effect on the treatments of colds.

Does Flu Shield Prevent Colds or the Flu?

A new product, widely advertised in Canada is an echinacea-based supplement called Flu Shield. It’s approved by Health Canada’s Natural Health Products Directorate with the following recommend use (search product 80005695 here):

Acts as supportive therapy in the treatment of colds, flus, upper respiratory infections and urinary infections. Traditionally used to fight off colds, flus and infections and traditionally used for the relief of sore throats due to colds.

The ingredient is Echinacea angustifolia, 200mg.

The manufacturer’s “monograph” for Flu Shield makes the following statement:

Jamieson FluShieldTM is clinically proven to fight the flu virus and boost immunity. FluShieldTM is the only flu defence product formulated with LPx3. More than 10 years in the making, LPx3 is a patented extract of selectively bred premium Echinacea angustifolia. The vital compounds in this unique formula are the most potent and concentrated of any echinacea. They have been scientifically tested for their biochemical activity and have been clinically proven to fight the onset and symptoms of flu, colds and upper respiratory infections.1,2,3,4

Having now looked at the overall evidence for echinacea, these statements are surprising. What’s the evidence provided?  References 2, 3, and 4 are not clinical trials, and provide no information to demonstrate that echinacea can treat or prevent colds or the flu. Furthermore, reference 4 looked at a different species of echinacea than the one in Flu Shield, so its relevance is unclear.

Reference 1, Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis by Shah et al. is the only citation that contains data on echinacea for preventing and treating colds (but not influenza). It’s a meta-analysis, or compilation, of 14 other studies that looked at different formulations of echinacea. (A meta-analysis differs from a systematic review in that there is a greater risk of bias.) The final conclusion of the meta-analysis is that echinacea effectively reduces the incidence and duration of colds – a much more definitive statement than the Cochrane review. But given what the Cochrane review concluded, we should probably look closer. A single well-conducted, rigorous study is more likely to be accurate than a collection of weak, underpowered studies. And that could be the case with this meta-analysis. It’s also unclear if different species, preparations, and sources of echinacea can even be pooled, given that the active ingredient isn’t known.

There is only one trial of the 14 in the Shah meta-analysis that actually studies Echinacea angustifolia, the species of echinacea that is in Flu Shield. The trial, by Turner et al., appeared in the New England Journal of Medicine in 2005, entitled An Evaluation of Echinacea angustifolia in Experimental Rhinovirus Infections. Not only did this trial consider the same species as in Flu Shield, it even looked at the same part of the plant: the root. This trial was well designed and well conducted: Subjects were randomized and treated in a double-blind fashion, actually physically inoculated with colds, and then isolated for days and observed for symptoms. The result? Echinacea had no significant effect. The authors concluded:

The results of this study indicate that extracts of E. angustifolia root, either alone or in combination, do not have clinically significant effects on infection with a rhinovirus or on the clinical illness that results from it.

Based on an analysis of the information provided by the manufacturer, the Cochrane systematic review, the Barrett paper, and then the Turner paper, there’s no available evidence that demonstrates the ingredient in Flu Shield has meaningful effects on treating colds. Rather, there’s fairly good evidence to suggest that Echinacea angustifolia is ineffective. There’s no evidence to suggest any species of echinacea can prevent colds. And there’s no evidence to show that echinacea has any meaningful effect against influenza infections.

Safety

It’s not enough to be effective. A treatment also needs to have a safety profile that’s acceptable. There seems to be little evidence to suggest echinacea is effective. But can it be taken safely? Answering this question is challenged by the variation in the different products and formulations available. On balance, echinacea seems to be well tolerated, and adverse effects seem to be mild. There’s less information in children, as well as pregnant and breastfeeding women, and is probably best avoided. There’s some question of whether echinacea can be linked with the stimulation of autoimmune diseases. For that reason it’s probably avoided by anyone with conditions such as rheumatoid arthritis.

Conclusion

When relying on anecdotes, or our own observations, it’s easy make the wrong inferences. Given what we know about colds and the flu, it’s only rigorous evaluation that can help us sort out what works from what doesn’t. Advocates of different echinacea products will inevitably spin the results from the most recent negative trial, claiming  their own version of echinacea product works because of some difference in formulation. Those differences in formulation might be real. But the onus is firmly on the purveyor to demonstrate that their echinacea product works. Because the scientific evidence, on balance, is not impressive: There’s no persuasive evidence that’s available to suggest that echinacea has any meaningful effects to prevent or treat colds or the flu.

Given there are really no well documented strategies to shorten the duration of a cold or the flu, we should focus on avoiding them. Thankfully, there are effective strategies to reduce our risk. Get a flu shot. And wash your hands frequently. Both strategies are backed up by good evidence.

Reference

ResearchBlogging.orgBarrett B, Brown R, Rakel D, Mundt M, Bone K, Barlow S, & Ewers T (2010). Echinacea for treating the common cold: a randomized trial. Annals of internal medicine, 153 (12), 769-77 PMID: 21173411

Echinacea. In: Natural Medicines Comprehensive Database. www.naturaldatabase.com Stockton CA: Therapeutic Research Faculty; accessed on 12/26/10.

Linde K, Barrett B, Bauer R, Melchart D, Woelkart K. Echinacea for preventing and treating the common cold. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD000530. DOI: 10.1002/14651858.CD000530.pub2

Saper RB. Clinical use of echinacea. In: UpToDate, Eamramond P (Ed), UpToDate, Waltham, MA, 2010. [Subscription required to view; patient excerpt here]

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