Ginkgo biloba: what it is and how it works

Ginkgo biloba is one of the oldest plants on Earth and at the same time one of the most popular plant extracts in the world. It is sold as a remedy for memory, circulation and concentration, and in sports nutrition as a component of "cognitive" and pre-workout complexes. The editorial team explains what exactly ginkgo leaves contain, which mechanisms of action are described in the scientific literature and where the line runs between pharmacology and marketing.

A "living fossil" plant

The two-lobed ginkgo (Ginkgo biloba) is the only surviving species of an entire class of gymnosperm plants that grew back in the time of the dinosaurs. Because of this, botanists often call it a "living fossil". The tree originates from China, lives for hundreds of years, and is resistant to air pollution and pests, so it is readily planted in cities, including in Ukraine.

For medical and food purposes, mainly the leaves are used. Ginkgo seeds are traditionally eaten in Chinese cuisine, but they contain ginkgotoxin — a vitamin B6 derivative that in larger amounts can cause seizures. That is why quality products are made specifically from the leaves rather than the seeds, and this is an important distinction to keep in mind.

In modern phytopharmacology, ginkgo has taken a special place thanks to German research of the 1960s–1990s. It was then that the standardized extract EGb 761 was developed, which still remains the "gold standard": most large clinical trials have been conducted with it. Results obtained for EGb 761 cannot be automatically transferred to an arbitrary leaf powder.

In the European Union, dry ginkgo leaf extract has the status of a herbal medicinal product with "well-established use" for improving age-related cognitive impairment. At the same time, in many countries, as in Ukraine, ginkgo is also sold as a dietary supplement, with varying quality and content of active substances.

Composition of the standardized extract

Ginkgo leaves contain hundreds of compounds, but two groups are considered pharmacologically significant. The first is flavonols in the form of glycosides (derivatives of quercetin, kaempferol and isorhamnetin). The second is terpene lactones: ginkgolides A, B, C, J and bilobalide, which occur only in this plant.

The standardized extract EGb 761 is obtained through a complex multi-stage process. During it, the concentration of beneficial substances is increased, while the undesirable ones — ginkgolic acids, which have allergenic and potentially toxic properties — are almost completely removed. That is why standardization matters not only for efficacy but also for safety.

These parameters are enshrined in the European Pharmacopoeia and the monograph of the European Medicines Agency. When a supplement label states "24/6", it refers precisely to the proportion of flavonoids and terpene lactones, close to this standard.

The extraction ratio (usually around 35–67:1) means that only 1 g of extract is obtained from several dozen grams of dry leaves. So 120 mg of standardized extract and 120 mg of ground leaves are completely different things in terms of content.

Mechanisms of action

Unlike a synthetic drug with a single target, ginkgo extract acts through several mechanisms at once. Most of them have been described in laboratory and animal models, so they should be transferred to humans with caution. Nevertheless, the general picture looks as follows.

• Microcirculation.The extract reduces blood viscosity and promotes the dilation of small vessels, partly through the nitric oxide system.
• Platelets.Ginkgolide B blocks the platelet-activating factor receptor, which theoretically reduces their aggregation.
• Antioxidant protection.Flavonols neutralize free radicals and protect cell membranes from lipid peroxidation.
• Neurotransmitters.In animals, effects on cholinergic, dopaminergic and serotonergic transmission have been described.
• Mitochondria.In preclinical models, bilobalide supports the energy metabolism of neurons under conditions of oxygen deficiency.

It is important that none of these mechanisms alone is "strong". Ginkgo's effects are mild and cumulative, and in clinical trials they often barely differ from placebo. That is why we always consider the mechanism and the clinical outcome separately.

For athletes, the appeal is most often to the effect on circulation: supposedly, better microcirculation means better oxygen delivery to the muscles. However, ginkgo's vascular effects concern primarily small vessels and patients with disorders of them, rather than healthy trained people.

Pharmacokinetics: how the substances enter the blood

Terpene lactones are well absorbed after oral intake: the bioavailability of ginkgolides A and B and bilobalide in human studies is assessed as high. Their maximum plasma concentration is reached approximately 1–2 hours later, and the half-life is several hours, so in clinical protocols the daily dose is usually divided into two intakes.

Flavonols behave differently. They enter the blood mainly in the form of conjugates (glucuronides and sulfates) after the glycosides are broken down in the intestine. Their concentrations are much lower and individual variability is higher, which partly explains the heterogeneity of clinical results.

Taking the extract with food somewhat slows absorption but does not significantly change the total amount of substances absorbed. Therefore, in the instructions for registered products, the timing of intake relative to food is usually not critical.

In laboratory studies, ginkgo extract affects liver enzymes of the cytochrome P450 family and transport proteins. Clinically significant interactions have not been described for all drugs, but caution is mandatory with anticoagulants, antiplatelet agents and some other medications.

What is confirmed and what is not

The most research on ginkgo has been conducted in elderly people with cognitive impairment. Systematic reviews, including the Cochrane review, concluded that the results are inconsistent: some studies show a small benefit, others do not. In the large American GEM trial (more than 3000 participants, 240 mg per day, average follow-up of about 6 years), the extract did not reduce the incidence of dementia.

The European GuidAge study with five years of intake also found no statistically significant reduction in the risk of Alzheimer's disease. For healthy young people there are short-term studies with acute doses in which individual improvements in attention were recorded, but they are small and were not always reproduced.

As for sport, the data are even more modest. Several small studies examined the effect of ginkgo on aerobic performance and altitude sickness. In the classic PHAIT study among trekkers in the Himalayas, ginkgo did not prevent mountain sickness, whereas acetazolamide was effective.

Thus, ginkgo is a substance with interesting pharmacology but a moderate, often contradictory clinical evidence base. It is neither a "brain stimulant" nor a means of directly improving athletic performance.

Editorial conclusions

Ginkgo biloba is a unique plant whose standardized leaf extract contains flavonol glycosides and terpene lactones. It is the composition of the extract, not the name of the plant on the label, that determines whether a product can be compared with clinical studies.

The mechanisms of action of ginkgo are multifaceted — from antioxidant protection to effects on platelets and microcirculation — but mostly mild. Large multi-year trials have not confirmed the extract's ability to prevent dementia.

For an athlete, ginkgo can at most be an auxiliary component, not the basis of a program. Before taking it, one should consider the risk of interactions with medications that affect blood clotting.

The editorial team also recommends reading our materials "The benefits of Ginkgo biloba for athletes: the evidence base", "Side effects of Ginkgo biloba" and "Bacopa monnieri: what it is and how it works".

References

1. European Medicines Agency, Committee on Herbal Medicinal Products (HMPC). European Union herbal monograph on Ginkgo biloba L., folium. London: EMA; 2015.
2. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 2009;(1):CD003120.
3. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA. 2008;300(19):2253–2262.
4. Vellas B, Coley N, Ousset PJ, et al. Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol. 2012;11(10):851–859.
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6. Gertsch JH, Basnyat B, Johnson EW, Onopa J, Holck PS. Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT). BMJ. 2004;328(7443):797.
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