Wednesday November 19 2008
The leaves of the ginkgo biloba tree used to make the extract
A study has found that “ginkgo biloba does not prevent dementia” according to The Daily Telegraph. The newspaper reports that thousands of elderly people taking the Chinese herbal supplement to ward off dementia may be “wasting their time”.
The well-conducted randomised controlled trial behind this story provides the best evidence to date on the use of ginkgo biloba supplements by healthy, elderly people to prevent dementia. The study, which followed up 3,000 people for an average of six years, has found no difference in the number of new dementia cases between groups taking a standard ginkgo supplement or a placebo.
Clinical symptoms of dementia are preceded, sometimes years before, by brain changes. To ensure that by looking simply at clinical dementia symptoms they haven’t missed an effect of ginkgo on the brain, the researchers intend to investigate a subgroup of participants using brain scans. This will show whether ginkgo is having any effect at this level.
Where did the story come from?
This study was conducted by Dr DeKosky and other investigators. It was funded and supported by the National Centre for Complementary and Alternative Medicine (NCCAM) and other national, charitable and academic institutions.
The ginkgo biloba tablets and identical placebos were donated by Schwabe Pharmaceuticals. The study was published in the peer-reviewed medical journal, JAMA.
What kind of scientific study was this?
The study behind this news report is a large randomised, double-blind, placebo-controlled trial in five academic medical centres across the United States. Researchers were exploring the use of ginkgo biloba to prevent dementia.
According to the researchers, ginko is prescribed in some countries for preservation of memory, and to date there has been no large, well-run study to investigate whether the supplement can in fact prevent the onset of dementia. Researchers set out to investigate whether 240mg of gingko could reduce the incidence of dementia due to any cause and in particular due to Alzheimer’s disease.
Between 2000 and 2002, people aged over 75 were contacted through details from voter registration and other mailing lists. They were asked to volunteer for this study and asked to also volunteer a person who would be willing to be interviewed every six months (a proxy).
Several exclusion criteria applied to people in this study, including current cases of dementia (a score of greater than 0.5 on the Clinical Dementia Rating Scale), people taking warfarin or drugs used to treat dementia, mental disorders (including depression and psychosis), history of bleeding disorders or Parkinson's disease, or other abnormal health markers.
Those who were not willing to discontinue over-the-counter ginkgo extract for the duration of the study, those taking large doses of vitamin E and those with a known allergy to ginkgo biloba were also excluded.
Overall 3,069 volunteers took part in this study. Most of them had normal cognition and 16% of them (482 people) had mild cognitive impairment. They were randomised to either ginkgo biloba or placebo at each medical site.
During the course of the study some people withdrew consent or were not available for follow up, so in the end 2,874 people were available for analysis. The people receiving treatments and the physicians giving them their treatments were not aware of whether they were using placebos or ginkgo (i.e. the study was double blind).
The researchers re-interviewed participants every six months for an average of six years, testing cognition and memory and undertaking a full battery of cognitive testing if either the participant or their proxy reported onset of a new cognitive or memory problem.
Those who met the criteria for new-onset dementia (depending on how many of the cognition/memory tests they failed) were sent for more specialist evaluation and brain scanning to confirm the diagnosis. This confirmed the diagnosis and determined which type it was.
Using statistical techniques, the researchers then compared the incidence (number of new cases) of dementia during the study between the ginkgo group and the placebo group.
What were the results of the study?
The average age of participants in this study was 79 years. 54% were men and 46% were women. During the course of the study, 246 people in the placebo group and 277 people in the ginkgo group were diagnosed with dementia. There was no difference in the rate of total dementia or Alzheimer’s between the two groups.
Of the total dementia cases, the majority (92%) were classified as having Alzheimer’s disease. Whether the person had normal cognition or mild cognitive impairment at the beginning of this study did not appear to affect these results.
There seemed to be a small protective effect on new cases of vascular dementia (dementia caused by damaged blood vessels in the brain), though the number of people in these groups was very small.
The researchers also conclude that the adverse events were similar between ginkgo and placebo. There were twice as many haemorrhagic strokes in the ginkgo group (16 vs 8), though the numbers were small and the difference was not statistically significant.
What interpretations did the researchers draw from these results?
The researchers concluded that the results did not show that ginkgo is effective in preventing or delaying the onset of dementia or Alzheimer’s disease in those aged over 75 years. The study used a standardised formulation of gingko biloba and given this, the researchers believe that their results are applicable to other formulations.
What does the NHS Knowledge Service make of this study?
This large, randomised, controlled trial provides good, robust evidence that ginkgo biloba supplements may be of limited use in preventing dementia in generally healthy elderly people.
The design and size of this study mean that confidence in the results is high and as such, this is the best evidence to date of how ginkgo performs when used to prevent dementia.
The one shortcoming that the researchers highlight is the follow up time of the study, as participants were followed for six years on average. Symptoms of dementia may take many years to become evident, meaning that ‘an effect of ginkgo biloba, positive or negative, may take many more years to manifest’.
The researchers say that further to this study they are planning to explore the brain function and possible brain changes using MRI scans in a subgroup of participants. This will explore whether or not ginkgo biloba is associated with changes preceding clinical symptoms of dementia.
The effects of ginkgo biloba at this level will not be known until the results of this further study are published.
Sir Muir Gray adds...
I never thought ginkgo did prevent dementia. In research negative findings are at least as important as positive ones.