Herbal medicines: where is the evidence?

Growing evidence of effectiveness is counterbalanced by inadequate regulation

Sales of herbal medicines are booming. This is particularly true in the United States, where the market for herbal supplements is now approach. ing $4bn a year. The fastest growth has been recorded for St John's wort, a herbal antidepressant whose sales increased in one year by 2800%.¹ Faced with such figures doctors are inclined to ask where the evidence is. Are there rigorous trials to show that herbal treatments work?

Single studies are unlikely to convince sceptics, but an increasing body of evidence is now emerging from systematic reviews and meta.analyses of randomised clinical trials. These suggest that some herbal medicines are efficacious. The increased demand for St John's wort, for instance, was triggered by press reports of a meta-analysis of 23 randomised trials of 1757 patients with mild or moderate depression. The authors concluded that extracts of hypericum were significantly more effective than placebo (odds ratio 2.67; 95% confidence interval 1.78 to 4.01) and as effective as conventional antidepressants (odds ratio 1.10; 93 to 1.31) in alleviating the symptoms of mild to moderate depression.² Since this article was published, at least nine further randomised trials have appeared, all of which confirm the efficacy of this herbal antidepressant.³

Systematic analyses of other herbal medicines followed and drew similarly positive conclusions. A review of all nine placebo controlled, double blind randomised trials of ginkgo biloba for dementia, covering 1497 patients, showed that ginkgo was more effective than placebo in delaying the clinical course of dementia.⁴ A meta.analysis of 18 randomised controlled trials (2939 patients) of saw palmetto as a symptomatic treatment for benign prostate hyperplasia showed that it improved urological symptoms and flow measures significantly more than placebo.⁵ Saw palmetto was as effective as finasteride and had fewer adverse effects. A systematic review of horse chestnut seed extracts for chronic venous insufficiency included eight placebo controlled and five comparative randomised trials with a total of 1083 patients.⁶ All placebo controlled trials were positive and all comparative trials indicated equivalence with other active therapies. The effects included a reduction in leg volume and leg circumference as well as symptomatic improvements. In all, about 40 systematic reviews or meta.analyses of herbal drugs are available today (a full list provided by the author is available on the BMJ 's website).

With many of these herbal medicines we do not fully understand how they work. Nor do we always know which component is pharmacologically active. For example, hypericin was originally thought to be the active ingredient in St John's wort, but evidence is now accumulating that hyperforin may be equally important.⁷ Similarly, we assumed until recently that its mode of action was that of a monoamine oxidase Ipecacuanha Senna Wintergreen inhibitor, but its actions may be due, at least partly, to serotonin uptake inhibition.³

Even though herbal remedies may be effective, do their benefits outweigh the risks? Most herbal remedies in the United Kingdom and United States are sold as food supplements. Thus they evade regulation of their quality and safety. The UK's minister for public health recently pointed out that "the regime for unlicensed medicines does not give systematic protection to the public against low quality and unsafe unlicensed herbal remedies."⁸ Two recent British cases of severe nephropathy caused by Chinese herbal tea administered to treat eczema⁹ illustrate this. Huge variations exist in the quality of herbal medicinal preparations. When, for example, German commercial products of devil's claw were tested, an unacceptable variability of quality was noted.¹⁰ Yet Germany is often praised for the exemplary standard of quality control of herbal medicines. A recent study of herbal creams in the United Kingdom showed that 8 of 11 preparations contained undeclared dexamethasone at a mean concentration of 456 mg/g.¹¹

The possibility of herb.drug interactions is a further important - and under-researched - issue. On its own, for instance, ginseng has few serious adverse effects. When combined with warfarin, its antiplatelet activity might cause overanticoagulation.¹² Many other interactions between herbal remedies and synthetic drugs are conceivable, even likely.¹³ This issue is destined to play an increasingly important part in the debate about the safety of phytomedicines.

With rationing looming in virtually all healthcare systems, the question whether herbal medicines can save money is important. Not all plant based medicines are cheap. A standard daily dose of St John's wort, for instance, will cost more than that of a tricyclic antidepressant. However, such comparisons are over. simplistic, particularly in view of the fact that St John's wort is associated with only about half the incidence of adverse effects of a conventional antidepressant.²

As more and more herbal medicines are being used by more and more people, doctors should consider changing their often negative attitude towards them. Doctors, pharmacists, and other healthcare professionals need to be knowledgeable to advise their patients responsibly, and there is an unquestionable need for reliable information on herbal medicines, a demand that must be met adequately by undergraduate and postgraduate education. Doctors also have to realise that detailed questions about use of herbal drugs form an essential part of taking a medical history. Finally, doctors should monitor the perceived benefits and adverse effects of self prescribed herbal treatments consumed by their patients and bear in mind the possibility of herb.drug interactions. The minister for public health has emphasised the need for better protection and information for the public on herbal medicines,"⁸ and doctors should take an active part in this process.

E Ernst, professor, Department of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter EX2 4NT
Email: E.Ernst@exeter.ac.uk


studentBMJ 2000;08:347-394 October ISSN 0966-6494

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