USE OF GINKGO
BILOBA SUPPLEMENTATION TO POSSIBLY ENHANCE COGNITION
Patients looking for the Holy Grail for cognitive
improvement have been using Ginkgo biloba for many years to the tune of over a
billion dollars per year. What is the data to support this use? Welcome to
the clinician’s roundtable. I am Dr. Leslie Lundt, your host, and with me
today is Dr. Jeffrey Kaye. Dr. Kaye is Professor of Neurology and Biomedical
Engineering at Oregon Health and Science University. He also directs The
Layton Aging and Alzheimer’s Disease Center at Oregon Health and Science
University as well as being the Director of Geriatric Neurology at the Portland
VA Medical Center. One more job he has is to direct the Oregon Center for
Aging and Technology.
DR. LESLIE LUNDT:
Welcome to Reach MD, Dr. Kaye.
DR. JEFFREY KAYE:
Thank you very much.
DR. LESLIE LUNDT:
You're a busy guy?
DR. JEFFREY KAYE:
I enjoy what I do.
DR. LESLIE LUNDT:
That's great. Now, tell us about Ginkgo biloba. Why has it
been used over the years to help cognition?
DR. JEFFREY KAYE:
Well, I think there are number of reasons. First of all,
there are no really good treatments for Alzheimer’s disease or dementias, and
people are in some ways, I think a little bit desperate sometimes to find
something that will help. I think there are a lot of people who fear getting
dementia and so even a lot of normal elderly will, or not even elderly people, day
bloomers will take supplements of various kinds in hopes that they would ward
off dementia at some later day.
DR. LESLIE LUNDT:
So the lack of reasonable alternatives and everybody is
afraid.
DR. JEFFREY KAYE:
I believe that is the reason that the public in general is
taking these (01:30) various compounds, in particular Ginkgo, but I also think
that there has been probably a little more scientific background to at least
suggest that there might be some benefit to Ginkgo.
DR. LESLIE LUNDT:
Tell us about your work in this area.
DR. JEFFREY KAYE:
Well, I've been very interested in Alzheimer’s disease and
actually brain aging for many years. I have been spending a lot of time in my
career looking at mechanisms for why people actually don't get demented, what
protects them from getting demented, and so along the way, I have been very
interested in treatments or other passways that might lead us to not years to
life, but life to years.
DR. LESLIE LUNDT:
So, you recently published a review of the Ginkgo research.
What did you find?
DR. JEFFREY KAYE:
Well, actually several years ago, with a colleague of mine
in OHSU, Dr. Barry Oken, we reviewed the literature on this; the randomized
controlled trials that had been performed, and there was a handful of that at
that time that met a reasonable criteria were well-conducted studies, and there
was a suggestion in fact that maybe on balance, there might be some positive
effect, but all the studies unless they had certain limitations. So, realizing
that, and a growing interest in alternative medicines, particularly even the
NIH, which in the last decade has established this, actually a National Center
for Complimentary and Alternative Medicine. We applied at NIH that we try to
begin to do a study (03:00) of Ginkgo biloba as a preventative for dementia.
So, just to highlight, we were really trying to set the stage for how this
compound or extract really because it is not a pure drug, might prevent the
onset of cognitive decline, not actually use it for people who already had
manifested dementia or Alzheimer’s disease. So in order to begin to do that,
one of the great interests was to try to shorten the development cycle if you
will because fortunately as it turns out for normal elderly, the rate of
developing cognitive impairment is not terribly high, that is particularly if
you are 65 or 70, only may be 1% to 2% at most of the population will develop
cognitive impairment or dementia in a given year. So you can imagine if you wanted
to look at individuals who would be prevented from progressing, you would have
to have thousands of individuals in order to change that very small conversion
rate over time, and so one mechanism for trying to overcome that, if you will,
low conversion rate for the purposes of proving that a treatment such as Ginkgo
might work as a preventative, was to raise the age at which we followed
people. So, the incidence of dementia essentially doubles with each successive
decade and so by focussing on people 85 and older, we reason that we might
actually be able to increase the rate of potential conversions of dementia
(04:30) within a grand cycle as funded by the NIH. So, with that sort of
concept in mind, we designed what we called a Proof Of Concept Clinical Trial
for the prevention, and enrolled 134 people who were randomized to a Ginkgo
treatment or a placebo and then they were followed for 36 months to see in fact
whether we had more people who converted to the cognitive impaired group or not
over that time.
DR. LESLIE LUNDT:
So, quite a long time, 36 months.
DR. JEFFREY KAYE:
Actually, it was 42 months. If I said 32, it was actually
42 months, in fact even longer. This was considered at the time truly prove
the concept because maybe would say, first of all no one had ever done a
clinical trial that was focused on the so-called oldest old, people 85 and
older; and furthermore could you actually consistently follow a group of people
in that age group over 42 months. And, so the first answer was in fact, we
definitely could and we did, and we had very a little dropout over that time
period. Interestingly, one of the things that we found was that many of these
older people that we approached to into the trial would say things like
"Sure, we're happy to help. No one thinks we can do anything at our
age."
DR. LESLIE LUNDT:
Hmm.
DR. JEFFREY KAYE:
And then, over time, they were very committed people to
staying in the project if they were able to.
DR. LESLIE LUNDT:
And what's the downside of using Ginkgo in terms of side
effects?
DR. JEFFREY KAYE:
Well, as in any clinical trial, we were particularly
interested in monitoring for side effects. One of the most important side
effects (06:00) that has been around and publicized was a potential concern about
bleeding risks or hemorrhagic side effects, and this is basically, I think
based on a number of case reports that had appeared in the literature that were
of concern, although collectively if one looks at the clinical trial that had
been done using Ginkgo extracts over many years, I do not really think there
has ever been a real excessive bleeding risks clearly found in those trials.
Nevertheless, this was of great concern and we took this very seriously. As it
turned out in our trial, we had an excess of strokes, but these were not
hemorrhagic or bleeding kinds of strokes. These were actually ischemic
strokes. There was one hemorrhagic stroke, but all the others were of the
ischemic variety. So, we honestly don't know what to make of that. It was not
an expected outcome, but it is something that we certainly, in the course of
our studies, observed and noted in our publication.
DR. LESLIE LUNDT:
If
you are joining us, you are listening to the clinician’s roundtable on ReachMD
XM 157, the channel for medical professionals. I am Dr. Leslie Lundt, your
host and with me today is Dr. Jeffrey Kaye. Dr. Kaye’s research program has
focused over the past 2 decades on the question of why some individuals remain protected
from dementia at advanced stages while others succumb at much earlier times.
We are discussing his research looking into Ginkgo biloba and cognition.
(07:30)
So, Dr. Kay, what did you find out of?
DR. JEFFREY KAYE:
Well, what we found was, in what is the standard of analysis
in randomized clinical trials and intense treatment analysis, there was no
reduced risk of progression to cognitive impairment whether somebody had been
randomized to Ginkgo or not. However, the thing that was tantalizing about
this trial, which was known to be under powered to start with because it was a
proof of concept trial and not a definitive trial, was that in a secondary
analysis when we controlled for the level of medication adherence among the
group, that is, the number of people who had remembered to take the medicine
properly based on the first 6 months of the trial, there was a significant
difference and this is I think is an extremely important principle that should
not be lost in the sort of technical jargon of analysis of the trial, and why I
think this is very important is that all of the cognitive prevention trials
that are ongoing or planned really need to take this into account prior to
analyzing their data. So if you think about it, in a prevention trial for
dementia, you are basically enrolling people who are normal. You do not have a
collateral informant and somebody who is following along with you as you would
have in a dementia trial. You have the person themselves reporting on how they
are doing. They are also themselves reporting on how well they are taking
medications. If their memory is declining as they progress through the trial,
their ability to report their level of adherence to the medication regimen is
going to be impaired progressively. (09:00) If you don't take that into
account in the analysis as the trial progresses, you can falsely believe that
in fact there was no effect because the person is saying, "Oh, I'm fine,
I'm taking all the medication" when in fact, they are not. The other
thing that I think is <_____> again not to get into the weeds of
statistical analysis, but this study only randomized 134 individuals and
actually 118 were actually completed this study. And, although statistically
not significant, if you look at the number of people who converted to cognitive
impairment over the 42 months who were taking Ginkgo, there were 7
individuals. Among the placebo group, there were 14. So, I think what that
tells you is that technically there was a 50% reduction in the incidence of
dementia if you will or cognitive impairment over the course of the study, but
we did not have the statistical power to really prove that. What this really
helps us with though is that as a statistician, one can do the math and in fact
we now know, based on this study, that one would need about 300 people in a
similar trial to definitively prove or not whether this actually is a treatment
that could prevent the rate of cognitive decline in the elderly.
DR. LESLIE LUNDT:
What do you currently recommend to your patients who are
anxious to help their cognition?
DR. JEFFREY KAYE:
Well, it is a very difficult science I think. If you have a
strict interpretation list, then you would say based on this trial, there is
not definitive evidence. (01:30) I think if you look out across all of the
trials out there, there is some evidence to suggest that there is a positive
effect, and I think that this is one of those areas where based on the person’s
health, their financial situation, because people can actually spend hundreds
of dollars on alternative medicines, one can suggest if you think this is
something you want to do, it is probably reasonable, although again we feel
obligated to say in this one study, we did find more strokes in the treatment
group. Again, going back to the issue of statistical power, if we had one
stroke in the placebo group, there would have been no statistically significant
difference in the two groups. So, again we are talking about issues where we
are trying to give advice based on data that is not definitive yet. I should
say, and I think that listeners really need to know, that there are currently
two very large or large studies that are houred in the 100s that should give us
a more definitive result. One is called the GEM study, which is being
conducted in The United States; and the other is called GuidAge Study, which is
a European study, and these are both randomized controlled trials. They are
being done in younger patients, or younger people. In one group, there are over
70; in the other there are over 75, and there will be potentially some
differences in the dosing, but at least we are very hopeful that these trials
may give us some other direction as to how to advice our patients.
DR. LESLIE LUNDT:
(12:00) So hopefully, we will know more by the time I'm 70.
DR. JEFFREY KAYE:
Well, I certainly hope we all do.
DR. LESLIE LUNDT:
Great, thanks for being on the show today.
DR. JEFFREY KAYE:
I really appreciate it. Thank you.
DR. LESLIE LUNDT:
We have been discussing the use of Ginkgo biloba
supplementation to possibly enhance cognition with Dr. Jeffrey Kaye.
I
am Dr. Leslie Lundt. You have been listening to the clinician’s roundtable on
Reach MD at XM 157, the channel for medical professionals. To listen to our
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Thank you for listening.
