Ginkgo herb in seizure warning

Behind the Headlines

Monday February 1 2010

Ginkgo biloba extracts are popular supplements

Extracts of the Ginkgo biloba plant may increase the risk of seizures in people with epilepsy, BBC News has reported. The scientists behind the news are reportedly convinced the herbal extract could have detrimental effects.

The news comes from a scientific report that says one of the herbal extract’s active ingredients has been linked to seizures and deaths in animal studies. Consumption of ginkgo seeds has also been implicated in lethal cases of food poisoning in humans. The researchers raise the possibility that some commercially available ginkgo preparations may contain the toxin behind these adverse effects, mentioning 10 cases of seizures thought to be linked to the use of ginkgo-based products. The authors say it is essential that people are aware of the risks, and for manufacturers to assess the levels of toxin in their products.

While there is no evidence suggesting that Ginkgo biloba can prevent or slow dementia or aid stroke recovery in humans, many people make the personal choice to use the supplement. However, when making this decision, the public should also consider that ginkgo might also have adverse effects.

 

Where did the story come from?

The report was written by Dr Eckhard Leistner and Christel Drewke from the Institute for Pharmaceutical Biology of Rheinischen, Friedrich-Wilhelms University of Bonn, Germany. The report  was supported by a grant from the Deutsche Forschungsgemeinschaft research foundation and published in the Journal of Natural Products.

The BBC News coverage highlights the early stage of this research and is generally balanced. While the study’s authors are reportedly convinced that the herb could have a detrimental effect, news coverage features the opposing views of Professor John Duncan from the National Society for Epilepsy. Professor Duncan said that, "some herbs, for example St John's wort, are linked to a higher risk of seizures, but there is still not a great deal of evidence about problems related to ginkgo”.

 

What kind of research was this?

This is a narrative discussion of the properties of the many extracts from the Ginkgo biloba plant. The plant contains a number active ingredients, such as the leaf extract EGb 761, which has been studied as a potential aid for patients suffering from or developing Alzheimer’s disease. Another substance found in ginkgo is ginkgotoxin, a toxin present in the outer skin of the fruit, seeds and leaves of the plant. In theory, ginkgotoxin should be removed before the herb is used in any preparations.

 

What did the research involve?

The authors discuss the different active ingredients that are in Ginkgo biloba, including ginkgotoxin. They discuss the structure, biosynthesis and toxicology of ginkgotoxin and the molecular basis for its actions, presenting results from various studies. Animal studies discussed have shown that the toxin causes seizures and vomiting.

The toxin is also linked to a type of food poisoning called "gin-an sitotoxism", a condition that derives its name from ‘gin-nan’, the Japanese name for biloba seeds. Between 1930 and 1996, gin-nan poisoning has been reported about 70 times, with around one-quarter of cases proving fatal. Animal studies confirm that the toxin causes seizures, unconsciousness and paralysis of the legs. In higher doses it causes death.

They say that the ginkgolide chemicals present in the Gingko biloba tree have been shown in animal studies to have an effect on blood flow, and this property may be responsible for the improvements seen in animal studies on blood flow and the prevention of neurodegeneration after experimental stroke.

The researchers discuss how in dietary supplements the concentrations of these active ingredients are limited, e.g. the concentration of EGb 761 is limited to 5 parts per million in Europe. Conversely Ginkgo biloba teas may contain a higher concentration of active substances. The researchers estimate that “the amount of ginkgolic acids in one cup may exceed the recommended upper limit by 80 times”. They note that it is very likely that ginkgo tea also contains ginkgotoxin.

The narrative review also discusses several cases of seizures following ingestion of ginkgotoxin. They describe two striking cases of the recurrence of well-controlled epilepsy in two elderly patients after they took Gingko biloba medications. In both cases no further epileptic convulsions were reported after the remedy was withdrawn. The authors also discuss seven cases of seizures related to Gingko biloba listed in the US Food and Drug Administration’s Special Nutritionals Adverse Event Monitoring System.

 

How did the researchers interpret the results?

The authors acknowledged that although other researchers have discussed the potential adverse effects of Gingko biloba, it has not yet been possible to establish it as a cause because only a few cases have been described. The researchers say that, contrary to their own previous assumptions, they are now “convinced […] that G. biloba medications and other products can have a detrimental effect on a person’s health”.

Conclusion

Ginkgo biloba is a controversial herbal extract and the evidence about its efficacy is contradictory. There have been a number of well-conducted systematic reviews such as two that have investigated the use of Gingko biloba after stroke and to prevent or slow cognitive impairment and dementia. Both conclude that there is no evidence of benefit with this herb. A large six-year trial in published in 2008 followed more than 3000 people and also showed gingko had no effect on new cases of dementia.

The discussion about the safety of this popular remedy is equally important, particularly as in some countries ginkgo is marketed and sold as a dietary supplement and is therefore not subject to the strict quality and safety scrutiny that drugs need before they can be sold to the public. Interactions with ginkgo can also be dangerous when using it alongside other medications. The US Food and Drug Administration also warns of harmful, even life-threatening results, when combining supplements with medications (both prescribed or over-the-counter), or substituting them in place of medicines prescribed by a doctor.

The authors’ conclusion is a sensible one. They say there is a need to fully investigate the potential harms associated with the use of this commercially available health product, as these preparations may carry a clear potential for adverse effects, particularly in susceptible individuals. A large number of people use ginkgo-based products for a range of conditions and it seems sensible that they consider potential dangers alongside any benefits they hope it will bring. Further research and clearly labelled information on ginkgo-based products are some of the measures that can help the public make informed decisions about the use of these preparations. Specific information that may be of use when deciding on a product could be the concentration of ginkgotoxin it contains.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Ginkgo biloba's epilepsy seizures warning. BBC News, January 30 2010

Links to the science

Leistner E, Drewke C. Ginkgo biloba and Ginkgotoxin. Journal of Natural Products, 2010, 73 (1), pp 86–92

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