Friday October 10 2008
Leaves of the Ginkgo biloba plant, used to make the extract
“Ginkgo herb supplement could guard against stroke,” reports The Daily Telegraph today. The newspaper said that a study has shown that Ginkgo supplements can prevent brain damage in mice. The Daily Mail highlighted results that mice fed Ginkgo then given an artificial stroke had 50% less brain damage, as well as reduced paralysis and limb weakness.
This was a laboratory in mice that found that a particular extract of Ginkgo biloba can both reduce damage caused by a stroke and treat existing stroke injury in mice. However, it is important to interpret this study in relation to existing evidence on human use of Ginkgo biloba. A 2005 Cochrane review of previous studies concluded that there was no convincing evidence to support the routine use of Ginkgo biloba in stroke recovery.
As this was a laboratory study in mice rather than humans, this new research adds little to that picture.
Where did the story come from?
Dr Sofiyan Saleem and colleagues from John Hopkins University in Baltimore and Ipsen in France carried out this study. Ipsen is the pharmaceutical company which manufactures the extract of Ginkgo biloba used in this study.
The research was funded by Ipsen and the National Institutes of Health, and published in the peer-reviewed medical journal, Stroke. One of the researchers was provided with a postdoctoral fellowship for this work.
What kind of scientific study was this?
This was a laboratory study in mice, in which the researchers were investigating in more detail the mechanisms by which Ginkgo biloba extracts can protect neurones in the brain from damage known as oxidative stress.
The researchers were particularly interested in the effects that Ginkgo had on a series of chemical reactions involving an enzyme called heme oxygenase (HO). HO exists in the brain in two forms, HO-1 and HO-2. The researchers had a theory that the protective effects of Ginkgo biloba were related to its enhancement of HO-1 production.
There were several parts to their study, all using a “well-recognised standardised extract” of Ginkgo biloba leaves – Egb761 (Tanakan). In the first part, mice were orally given a Ginkgo biloba extract before a stroke was induced by blocking a major artery in the brain. This caused subsequent paralysis and other effects on the opposite side of the body to the block. Researchers used this disease model to mimic the effects of a stroke in humans.
The block was then removed and blood allowed to flow again for 24 hours before researchers assessed the effects of treatment on neurological function and brain cells. In this experiment they used both normal mice and those with a mutation that produced a malfunctioning HO-1 system.
In the second part of their study, the researchers induced an MCAO in some mice and then gave them Ginkgo biloba at various times during their attempts to restore blood flow to the brain. The effects of Ginkgo biloba on neurological function (extent of paralysis) on blood flow to the brain was assessed, as was its effects on the degree of damage caused by interrupted circulation. Physiological parameters (temperature, blood pressure, blood gases, etc.) were also measured.
The researchers also carried out some experiments with cultured neurones (brain cells) from mouse embryos, looking at the effects of incubation with Ginkgo biloba. They exposed the cells to toxic hydrogen peroxide, assessing the protective effects of Ginkgo biloba on cell survival.
What were the results of the study?
Mice with the induced stroke were examined 24 hours after blood flow had been restored. Those pretreated with the highest dose of Ginkgo biloba had less severe outcomes (in terms of neurological function and degree of cell damage) than those pretreated with lower doses or placebo.
Treatment with Ginkgo biloba at both five minutes and 4.5 hours after restoration of blood flow (reperfusion) led to a significant improvement in neurological function compared with no treatment after 24 hours. However this difference was no longer evident 72 hours after treatment. While treatment with Ginkgo biloba five minutes after reperfusion meant a reduced area of brain damage from stroke at 24 and 72 hours, treatment with Ginkgo biloba 4.5 hours after reperfusion only had an effect on brain injury at 24 hours.
The researchers also found that mice pretreated with Ginkgo biloba before stroke induction had greater blood flow in particular regions of the brain than those pretreated with placebo.These protective effects were not found in mice that were unable to produce HO-1. Ginkgo biloba protected neurones from damage caused by hydrogen peroxide and increased production of HO-1 in cells, while having no effect on HO-2 levels.
What interpretations did the researchers draw from these results?
The researchers conclude that their study has found that treatment with Ginkgo biloba extract significantly improves the outcome in mice after stroke and after attempts to restore blood flow.
Neurological function is improved, and the degree of damage in the brain appears reduced while there is no effect on physiological parameters. The mechanism of protection, they say, is through HO-1. They say that EGb761 – the particular extract of Ginkgo biloba they used – “might be useful as a preventive therapy or a postischaemic [after stroke] treatment to reduce the damaging effects of stroke”.
What does the NHS Knowledge Service make of this study?
While researchers have found that pretreatment with oral extracts of Ginkgo biloba ultimately protects mice from the harmful effects of an artificially induced-stroke, the direct relevance of these findings to humans is not clear.
Human studies have previously been carried out to assess whether Ginkgo biloba can support recovery after stroke in humans. A well-conducted systematic review carried out in 2005 concluded that “there was no convincing evidence from trials of sufficient methodological quality to support the routine use of Ginkgo biloba extract to support recovery after stroke”.
This animal study has shed further light on the activity of Ginkgo biloba at complex cellular levels and finds that the Ginkgo biloba extract appeared to prevent stroke injury, albeit in the short term. This may warrant further exploration, such as larger animal studies with longer follow-up times. More importantly, trials are needed to assess any potential benefits or harm to humans.
Key points to note about this study and its relevance to humans include:
- The stroke model used in this study (inducing a block in the middle cerebral artery of the mouse brain) may not be exactly the same as the disease in humans.
- The metabolic responses to brain injury are likely to be different between mice and humans.
- Even if we could extrapolate the results from mice directly to humans, the beneficial effects are limited at best, as the improvements in neurological function and reduction in area of brain cell damage did not persist beyond 72 hours.
- After investigating whether pretreatment with Ginkgo biloba can protect against a later stroke, the researchers only report on 24-hour outcomes (where high dose Ginkgo biloba was protective). Without longer term results it is impossible to say whether these beneficial effects lasted.
- More research, such as larger animal trials and eventually human trials, is needed to assess the relevance of pretreatment with Ginkgo biloba as a method of limiting damage from a subsequent stroke.
- The study was small, with only five to 12 mice per study group across these experiments. Generally small sample sets are not large enough to exclude the possibility that results of this type may have occurred by chance.
The methods of this study mean its findings cannot be directly applied to humans. As such, it adds little to the current body of evidence from previous human studies, which suggests that Ginkgo biloba has little effect when used to treat stroke damage.