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No Benefit from Ginkgo biloba in MS

by Steven Novella, Sep 17 2012

One of the themes of this blog (and my other medical blog, science-based medicine) is that there is a structure and natural history to scientific (and specifically medical) research and in order to understand the answer to any specific scientific question one must look at the whole of the research, not just a single study.

Analyzing individual studies is important because they are the units of which the scientific literature is comprised. Further, some individual studies are large, rigorous, and fairly definitive – but it takes a long time to get there, and most of the scientific literature is comprised of less-than-definitive studies.

There are also recurring patterns in the research that help us put individual studies into context and better arrive at reliable conclusion, which is the whole point of research in the first place. For example, medical studies usually begin with pre-clinical basic science, then progress to pilot clinical studies. A pilot study is small and usually less rigorous in design. Such studies are exploratory – their purpose is to see if we should even bother, and if it will be safe, to do larger more difficult trials. Studies progress with larger or better designed studies until we get to fairly definitive trials. Then and only then do we have some idea if a treatment actually works and is safe.

It can often take 1-2 decades, however, to get to that point. Meanwhile a vast body of preliminary exploratory research may have been generated, with systematic reviews and meta-analysis to help us make sense of it all. The preliminary exploratory stage of scientific research is often little more than a Rorschach test – people see in it what they want.

In medical research there is a well-documented positive bias to preliminary research. There is researcher bias combined with researcher degrees of freedom (methods of subconsciously biasing a study to the desired outcome), placebo effects, and publication bias, all conspiring to make a treatment seem as if it works when it doesn’t.

The story of Ginkgo biloba fits into this general pattern – early weakly positive studies showing a potential benefit from Ginkgo for memory symptoms, and even dementia and Alzheimer’s disease. A 2009 large rigorous study, however, found no benefit at all. Since Ginkgo is a popular herbal remedy its use was based more on tradition (which sometimes means someone’s invented sales hype) rather than solid basic science. There never was much of a rationale for thinking Ginkgo would help in memory, beyond common use. In any case, the clinical evidence is ultimately what mattered, and it showed that Gingko has no benefit.

The same pattern has now been repeated with regard to Ginkgo and specifically the treatment of cognitive symptoms with multiple sclerosis (MS). A pilot study involving only 22 individuals (a good rule of thumb is that any study with less than 50 subjects should be considered preliminary) showed a possible benefit from Gingko in MS, specifically on reports of fatigue and functional performance. The study concluded:

This exploratory pilot study showed that no adverse events or side effects were reported and that ginkgo exerted modest beneficial effects on select functional measures (eg, fatigue) among some individuals with MS.

A second study involving 38 subjects found no statistically significant results, but did find a non-significant trend in improvement in the Stroop test.  The authors concluded that the data: “suggests that GB may have an effect on cognitive domains assessed by this test.”

The whole point of pilot studies, as I indicated above, is not as a basis for clinical treatment but as a guide to further research. The study provided some evidence that Gingko is at least safe and may have a benefit, so researcher performed a follow up study, which has now been published. This study involved 120 subjects divided into two groups, one receiving Ginkgo (120mg twice a day) and the other placebo. They used four measures of cognitive ability at baseline and after 12 weeks and found no statistically significant difference in any measure.

It’s hard to make a convincing trend from three studies, but they do mirror the pattern seen with Ginkgo studies in general – the larger the study the smaller the effect and the most rigorous studies show no effect. We also see the general trend of a positive bias among preliminary studies.

Ginkgo is still widely sold with claims that it improves cognition, despite the negative evidence. It’s hard to find exact figures without paying for market research, but I find estimates are all in the range of hundreds of millions of dollars annually in sales worldwide.

The story of Ginkgo is typical – early positive-biased research with later more rigorous studies finally giving us reliable information, in this case that Gingko is ineffective for the indication for which it is most commonly used.

8 Responses to “No Benefit from Ginkgo biloba in MS”

  1. d brown says:

    On the front page of the newspaper, is news of a new drugs study being ended because of killing people with hart attacks.

  2. MadScientist says:

    I think I was taking Gingko but I can’t remember why.

    Even in a botanic garden in Oslo I saw something that made me fume. There was a magnificent maidenhair tree standing there and an awful plaque that ruined the whole experience by claiming that Gingko has medicinal value. It’s a beautiful tree and is great for shade – why do people pretend it has magical powers?

    • Max says:

      Medicinal value = magical powers?

      • MadScientist says:

        No, but there was never any good evidence for any medicinal value whatsoever in Gingko – just more magical claims such as with most ‘traditional’ remedies. One of the telltale signs of magical claims is that Gingko reputably cures numerous ailments, just like every other snake oil. What Steven presents here is the refutation of a specific claim of medical efficacy – Gingko is claimed to have many other medical (magical) benefits. Of course some drugs do cure many ailments although those tend to be related (for example, antibiotics cure an incredible range of ailments but those are all related to bacterial infections). Acetylsalicylic acid is usually used for pain relief but it has some side-effects which are of value in the treatment regime for other unrelated conditions, so that is an example of a drug having multiple benefits for unrelated ailments. The difference with Ginkgo is that Ginkgo is touted as an actual cure for many unrelated things – a claim which is extremely unlikely to be true and for which the evidence contradicts the claims.

      • Max says:

        I thought Ginko was supposed to be a blood thinner, or is that considered its side effect?

  3. tmac57 says:

    Ginkgo Biloba…sounds like something from ‘The Lord of The Rings’,so it does resonate as ‘magical’ for some reason (or lack of reason I should say).

  4. Tony Zitzelberger says:

    This is a book to read The Eden Prescription Who did the study and how?

    When I mentioned my friends earlier you might have thought I was starting a bar joke, “A pharmacist, a lab tech, and a drug researcher walked into a bar…,” but I was serious. Here are a few tidbits about my friends that are relevant to The Eden Prescription.

    My friend who performs research on animals for a large drug company freely admits that it’s the drug company’s marketing department that twists research, creates new products from by-products of failed research, and then creates public demand for it through advertising.

    My friend who is a 25-year veteran cancer research lab tech has witnessed how foreign students perform lab work for cancer projects at universities for wages slightly above minimum wage. She has advised me on health and warns me about the sickcare industry (her words) like advising me NOT to get annual mammograms to prevent breast cancer; to avoid surgery and drugs whenever possible; to take vitamins and drink green tea; and that eating red meat is a known colon cancer risk.

    My friend, the pharmacist, also explores botany as a serious hobby. She taught me the meaning of the phrase, “research designed to fail.” It’s a phrase bantered around the holistic community that I didn’t implicitly understand. My friend explained there are two common methods to make research fail. First, study the non-healing part of a plant. For example if a plants’ roots contain its medicinal properties, then study the leaves instead. A second way is to dilute the common recommended dose for healing, to a mere fraction of itself. Then study the effectiveness of the highly diluted version. My friend says that most of the research paid for by drug companies on the healing abilities of herbs and plants are done in this manner – they are designed to fail.

    As for me, my “cancer incident” led me to look for natural cures everywhere. I found a Naturopathic Physician who suggested a protocol known to boost my immune system and help my body to heal itself of cancer. And that’s exactly what it did. Important component of that protocal are listed in this book. I also surrounded myself with supportive and hopeful books, videos and articles. It’s important to have faith, hope, and support when you choose a more natural cure for cancer. This book offers hope when others around you might fail at
    supporting you.

    What is also fantastic about this book is at the end, there is a chapter on all the tests that are going on to prove that things like Vitamin D, Vitamin C, Pomegranete and other natural ingredients do have an incredible effect on cancers. These are referenced for the reader to go and check out. There is also a book list that Ethan read to help him research for his book.