Sep 17 2012

No Benefit from Ginkgo biloba in MS

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 conclusions, 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.

5 responses so far

5 thoughts on “No Benefit from Ginkgo biloba in MS”

  1. SARA says:

    Ginko is so much accepted in the culture as a memory aid, that it will be hard to overcome.

    I asked two friends at lunch today and both quickly agreed that it works – although they thought of it as a preventative for dementia. They both agreed that if they were offered a prescription for dementia, they would assume it worked better than Ginko.
    Both accepted without comment my info about Ginko but later said they would take it. It couldn’t hurt. “Science doesn’t understand everything.”

    I give up. Or at least today, I give up.

  2. Enzo says:

    The preliminary exploratory stage of scientific research is often little more than a Rorschach test – people see in it what they want.

    Really well put. I will be quoting that often.

    It’s really a shame that once a positive study is generated that the marketing machine is able to embed an idea so deeply into the culture. And then once better negative studies come out, they are ignored or completely missed. What’s more, somehow people will rationalize in defense of the products even though they probably don’t even know how they obtained the knowledge that “it works”.

    Really, it works? Where’d that information in your brain even come from? It’s amazing how promoters of this herbal market have managed to convince people.

  3. ksadrieh says:

    Its just hard to understand the “herbalist” mind set. Look, it usually doesn’t work. If it does work, we can stadardize the dose, regulate its safety, and maybe even get your insurance to cover it. Oh, but then it wouldn’t be “all-natural” anymore….

    Had a parent last week not give the vitamin D I prescribed but go to a natural product store and get natural vitamin D….

  4. SimonW says:

    Natural vitamin D, well Cod liver oil capsules at least, are cheaper here, and the sunlight is free, I’m guessing that thrift wasn’t her motivation.

  5. Raiden says:

    It’s worth pointing out that these large negative studies only show that taking Ginkgo Biloba at age 79 does not prevent progression to Alzheimers. They used EGB761 which is the highest quality extract.

    In fact, the 2012 study was funded by people who sell EGB761, and although they found no effect, they did find in another study a benefit in symptoms for those with Alzheimers or Vascular Dementia.

    It is also possible that since Alzheimers results largely from “rust” that builds up over a lifetime, 79 is simply too old to start taking Ginkgo Biloba, which is known to have antioxidant, and antiamyloidogenic properties. Maybe starting in your twenties would prevent Alzheimers.

    Does it improve memory? I think possibly. A meta-study finding no significant effect contained many studies, the most positive of which used EGB761. This is the high quality extract you would want.

    I don’t know what you mean “Ginkgo studies in general”. There are thousands of studies but there are not that many large human studies. They are mostly in vitro or in animals or are small. So there is nothing to “generalise”. The only big studies are on Alzheimers and they showed no preventative effect *in the elderly*, and a small positive effect in Alzheimers sufferers.

    Given the inneffectual nature of pharmaceutical drugs for cognitive decline in Alzheimers, it seems strange to single out Ginkgo Biloba as being worthy of disparagement.

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