Nov 24 2008

No Benefit from Gingko

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Gingko biloba is widely used as a supplement (even though it is really an herbal drug) to improve memory to help treat or prevent dementia. However, there are no quality trials showing that it is effective. This month in JAMA is published the results of a study that has been going on for the past 8 years looking at ginkgo in elderly patients. I have actually been waiting for these results for a while – a large and fairly definitive trial to end the debates about the significance of the preliminary data we have had so far.

The results did not surprise me – after following 3069 subjects for an average of 6.1 years, the study concluded:

In this study, G biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI. (MCI = minimal cognitive impairment)

Therefore the best data we have to date – the results of a very large, well controlled, and highly anticipated trial – gingko does not work. It is always interesting, once such trials have come to light, to then look back at the previous research to see how it compares. What we find is a pattern of suggestively positive studies. Basic science data, for example, showed that gingko extract may reduce amyloid precursor protein in mice – this is a protein that builds up in Alzheimer’s disease. Preliminary clinical trials were mixed but tended to be positive.

What this means is what John Ioannidis has been finding when looking at the clinical literature. Preliminary studies are usually wrong. We don’t really know if something works until we have seen large definitive clinical trials. Therefore, for all those other supplements and treatments where there is currently suggestive but preliminary data, but no high quality clinical data – claims made for them are probably wrong.

We are also seeing a pattern that very popular herbal remedies, sold as supplements in the US, are falling one by one as they are being subjected to definitive clinical trials. This is the one good outcome produced by the National Center for Complementary and Alternative Medicine (NCCAM). Generally, the NCCAM has funded more than a decade’s worth of worthless studies, ideologically conceived, poorly designed, and whose results have been largely ignored (especially when negative).

But former director Stephen Strauss wanted the NCCAM to have some legitiamte scientific successes – so he went after CAM’s scientifically low-hanging fruit – herbs. I agree with this assessment. If anything in CAM might work it is herbal drugs, because they are, after all, just pharmaceuticals in unpurified plant form. They are drugs. There is no reason why they cannot have a useful pharmacological effect. However, their active ingredients are not isolated, purified, and quantified, and probably exist in low doses.

Under Strauss the NCCAM funded several large clinical trials of popular herbs: St. John’s Wort was found to be ineffective for major depression of moderate severity.  (Although the data overall on St. John’s Wort is complex and more recent data suggests there may be a small effect in depression.) Echinacea is not effective in the treatment or prevention of colds in children or adults.

Rather than validating popular herbal remedies, the NCCAM has shown that they do not work. Echinacea and Gingko have failed sufficiently, in my opinion, that they should be abandoned as whole herb therapies. St. John’s Wort has mostly failed, and really only a small effect is possible given the research. But all of these herbs may contain chemicals that can be useful if isolated and studied.

There is a long list of other herbs still being promoted for clinical use by the supplement industry, but only at the preliminary or no research level. We have every reason to believe they will follow the same course as the herbs that came before them. The question is – is the public best served by spending billions of dollars every year on these herbs when so far the most definitive research shows they probably don’t work? Perhaps the research should come before the marketing.

But of course even after the most definitive research shows that an herb does not work for an indication for which it is being marketed, the supplement industry will not admit defeat. Why should they? Why should they abandon a lucrative market just because their product does not work? The regulations do not require them to.

The Natural Products Association’s response to the Gingko study is typical. In general the response of proponents and those who stand to make money from herbs (or any alternative treatment) to research is this: if it is positive (no matter how bad the study) that proves their treatment works. If it is negative (no matter how good the study) this just means that more research is needed.

CNN reports the NPA response to this gingko study:

The Natural Products Association (NPA), which represents ginkgo manufacturers, released a statement that said the new research can’t be used to make broad conclusions because the average age of the participants was nearly 80, and the findings may not apply to the general population.

“I still think there is great promise for ginkgo biloba,” says Daniel Fabricant, Ph.D., the vice president of scientific and regulatory affairs at the NPA.

Heads I win, tales you lose. The only herbal remedy that has been abandoned by proponents and marketers because evidence showed it was unsafe is ephedra – and that was only after the FDA banned it as unsafe. Proponents have never, to my knowledge, abandoned a claim or a product due to negative scientific data.

That is the bottom line. No industry or profession can claim to be evidence-based if they never stop using or selling a treatment because scientific evidence shows it does not work. We will see what happens to the gingko market. I predict nothing will happen. The NPA already has their spin.

As a thought experiment, imagine how you would react to a pharmaceutical company dismissing negative evidence about one of their drugs in the same way.

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