Ginkgo biloba

Background

Ginkgo biloba is regarded as a living fossil. It is the only living species of the ancient Ginkgoacae family. In evolutionary terms Ginkgo biloba is one of the oldest living species of trees — fossils related to present-day Ginkgo biloba date back 270 million years to the Permian period. The tree grows to about 30m tall and is reputed to survive for 1000 years. Ginkgo biloba is also known as the Maidenhair Tree, the Fossil Tree, and the Kew Tree. In Chinese it has several names including ying guo (silver fruit), bai guo (white fruit), and yingxing (silver apricot); in Japanese it is ginnan.

According to popular websites, Ginkgo biloba has been used in traditional Chinese medicine for 5000 years, for asthma, bronchitis, heart dysfunction and chilblains. The Schwabe Pharma website mentions that in 1965, Dr Schwabe introduced the first Ginkgo biloba extract into Germany. Today, Ginkgo biloba extract is apparently available on prescription in Germany and France for ‘cerebral insufficiency,’ including memory, confusion, depression, anxiety, dizziness, tinnitus, and headache. In other parts of Europe, the US and Canada, the extract is widely available as a supplement.
Large commercial plantations supply worldwide demand for Ginkgo biloba extract made from the leaf. (For convenience, in the rest of this article, Ginkgo biloba extract is abbreviated to GBE.)

Active Compounds

According to scientific studies, the active ingredients are flavonoids (flavonal glycosides), terpenoids, and terpene lactones (ginkgolides and bilobalide). Flavonoids and terpenoids are found in many plants. However, ginkgolides and bilobalide are unique to Ginkgo biloba.

A frequently used extract, known as EGb 761, is produced from the ground-up leaves of Ginkgo biloba and contains 24% w/w flavone glycosides and 6% w/w terpene lactones. It is marketed as Tanakan, Tebonin, and Rokan. Another extract, known as LI 1370 and marketed as Kaveri, is similar except that it contains 25% w/w glycosides.

Physiological Function

According to scientific studies, GBE increases cerebral blood flow and oxygen supply.
For example, in a clinical trial on patients undergoing cardiopulmonary bypass surgery, GBE was administered intravenously prior to surgery. After numerous blood tests, the authors concluded “Ginaton could improve cerebral oxygen supply, promote SOD [superoxide dismutase] activity to inhibit production of free radicals in patients undergoing CPB [cardiopulmonary bypass], and thus shows an evident protective effect in the brain.”

Deng, Y. K., F. Wei, and D. G. Zhang. ‘[Brain protective effects of ginkgo biloba leaf extract (ginaton) in patients undergoing hypothermic cardiopulmonary bypass].’ Chinese journal of integrated traditional and Western medicine, no. 9 (2006): 795-798.

Studies suggest that GBE may modulate the cholinergic system, with effects on choline uptake and acetylcholine (ACh) release, an inhibitory effect on acetylcholine esterase (AChE), and increases in cholinergic muscarinic receptors.

Scientific Literature

The Cochrane Library lists 482 clinical trials for Ginkgo biloba!

Clinical trials have mainly investigated the use of GBE as a treatment for cerebral dysfunction, including age-related cognitive decline, Alzheimer’s Disease, other dementias, and cerebrovascular disease. The results are mixed and show inconsistent effects, with some trials demonstrating significant benefits and others showing no benefit, compared to placebo. The reason for this inconsistency across a large number of trials has not been explained.

Clinical trials have also been conducted on GBE as a potential treatment for peripheral vascular disease (including intermittent claudication), premenstrual syndrome, schizophrenia, tinnitus, and vertigo. A small number of studies have investigated GBE for arteriosclerosis, asthma, cancer, diabetes (including diabetic nephropathy), sexual function, altitude sickness, age-related macular degeneration, and multiple sclerosis. The studies show mixed benefits for these interventions as well.

SUMMARY: Based on the evidence from a large number of trials, collectively involving 1000s of people, GBE has a beneficial effect on cognitive function in some healthy people and in some patients with cerebral dysfunction, but it does not benefit everyone.

Cognitive Effects in Healthy Subjects

A number of scientific studies suggest that GBE’s cognitive effects are most potent when combined with other herbal supplements.

Studies suggest that GBE combined with other supplements may lead to faster response time and improved accuracy.

In a double-blind, crossover study, 24 healthy adults (mean age 44 years) received placebo or a combined supplement 3x daily for 14 days, followed by the opposite treatment for 14 days. The supplement contained 40mg GBE (50ms for a measure of working memory and decreased the error rate on a test of delayed memory by 2%; these results were statistically significant compared to placebo. In their discussion the authors note “Ginkgo biloba significantly decreased RT for a measure of working memory. Test 6 can be considered a sensitive index of `working memory capacity’, since it requires that subjects maintain memory items, scan the contents of same to determine if a probe stimulus matches, and discriminate false probe items from the memory set. The test is demanding, and the >50 ms decrease in RT from the placebo to Ginkgo biloba nutrient conditions is robust and remarkable, especially given the application of substantial pre-nutrient task practice and completion of two trial block testing procedures. This approach was specifically adopted to minimize the variability attributable to time-on-task effects, which is often ignored or under-appreciated. The slight decrease in error rate for the `delayed memory’ task in Test 9 also supports the specific effects of Ginkgo biloba on memory. Thus, the present findings can be attributed to Ginkgo biloba compound effects on working memory capacity in normal adults rather than test-related parameters, although additional studies are needed to determine optimal dosage, the time course of the effects and the neurophysiological genesis of the mental improvement.”

Polich, J., and R. Gloria. ‘Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: Systematic assessment of perception, attention and memory.’ Human Psychopharmacology 16, no. 5 (2001): 409-416.

Note: VINCTO contains all of the ingredients used in the above study except for riboflavin, as well as additional ingredients.

A study suggests that GBE combined with phosphatidylserine may increase speed of memory and increase calmness.

In a double-blind crossover study, 28 healthy young volunteers received single doses of GBE 120mg alone, GBE 120mg complexed with phosphatidylserine, GBE 120mg complexed with phosphatidylcholine, and placebo, with 7 days washout in-between. Performance was tested on a computerised test battery and serial subtraction tasks prior to and up to 6h after drug administration. All three treatments were associated with increased calmness. GBE alone was not associated with markedly improved performance. “However, administration of GBE complexed with phosphatidylserine resulted both in improved secondary memory performance and significantly increased speed of memory task performance across all of the post-dose testing sessions. Enhancement following GBE complexed with phosphatidylcholine was restricted to a modest improvement in secondary memory performance which was restricted to one post-dose time point.”

Kennedy, David O., C. F. Haskell, P. L. Mauri, and A. B. Scholey. ‘Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine.’ Human Psychopharmacology, no. 4 (2007): 199-210.

Note: VINCTO contains both GBE and phosphatidylserine.

A study suggests that GBE combined with ginseng may improve wellbeing.

In a crossover study of EEG in 10 healthy male volunteers, ingestion of a drink containing ginseng 0.232g and “ginkgo extract” 2g resulted in “an attenuation of circadian induced electrical delta power decreases” with eyes open and closed, and “absolute increases of delta power” during a reading test. These changes were statistically significant 2h after the drink, which the authors “interpreted to indicate a higher degree of emotional well-being”.

Dimpfel, W., A. Kler, E. Kriesl, R. Lehnfeld, and I. K. Keplinger-Dimpfel. ‘Neurophysiological characterization of a functionally active drink containing extracts of ginkgo and ginseng by source density analysis of the human EEG.’ Nutritional Neuroscience, no. 5-6 (2006): 213-224.

Note: the above study by Dimpfel used an extremely high dose of GBE and we query its accuracy. NOTE: VINCTO contains a very low dose of GBE for safety reasons, however it does contain both GBE and ginseng.

Scientific studies show that GBE on its own exerts cognitive enhancement effects. For example, studies show that GBE may improve quality of memory at low doses

3 double-blind crossover studies of acute, single dose GBE 120mg and placebo (with 7 day washout period in-between), involved 78 healthy young volunteers. Performance was tested on a computerised cognitive assessment battery prior to and up to 6hr after administration. “The results showed that 120 mg of Ginkgo engendered a significant improvement on the ‘quality of memory’ factor that was most evident at 1 and 4 hr post-dose, but had a negative effect on performance on the ‘speed of attention‘ factor that was most evident at 1 and 6 hr post-dose. The current study confirmed the previous observation of modestly improved memory performance following 120 mg of GBE, but suggests that acute administration of this typical daily dose may have a detrimental effect on the speed of attention task performance which is opposite to that seen previously following higher doses.”

Kennedy, David O., P. A. Jackson, C. F. Haskell, and A. B. Scholey. ‘Modulation of cognitive performance following single doses of 120 mg Ginkgo biloba extract administered to healthy young volunteers.’ Human Psychopharmacology, no. 8 (2007): 559-566.

Note: VINCTO contains a low dose of GBE for safety reasons. The outcome of the above study by Kennedy suggests that consumers of low dose GBE are most likely to experience the improvement on ‘quality of memory’ factor. However, the negative effect on low dose GBE on the ‘speed of attention’ factor mentioned in the above study is counterbalanced in VINCTO’s formula by Bacopa monnieri.

Studies suggest that GBE may improve speed of attention at high doses.

In a crossover study, 20 healthy patients aged 19-24 years received acute doses of GBE (Pharmaton, GK501) 120mg, 240mg or 360mg, or placebo. At 240mg and 360mg, GBE produced a statistically significant, dose-dependent improvement of the ‘speed of attention’ factor on cognitive tests, evident at 2.5h and still present at 6h after drug administration. Performance on the ‘quality of memory’ factor of the cognitive tests was significantly enhanced for the 120mg dose at 1h and 4h.

Kennedy, David O., Andrew B. Scholey, and Keith A. Wesnes. ‘The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers.’ Psychopharmacology 151, no. 4 (2000): 416-423.

Note: This earlier study by Kennedy is the corollary to the low dose study mentioned above.

A study suggests that acute, low dose GBE may improve sustained attention and pattern recognition

52 healthy young volunteers received a single acute dose of GBE 120mg (n=26) or placebo and were tested 4h later. GBE significantly improved performance on the sustained attention task and pattern recognition memory task, but had no effect on working memory, planning, mental flexibility, or mood.

Elsabagh, Sarah, David E. Hartley, Osama Ali, Elizabeth M. Williamson, and Sandra E. File. ‘Differential cognitive effects of Ginkgo biloba after acute and chronic treatment in healthy young volunteers.’ Psychopharmacology 179, no. 2 (2005): 437-446.

Adverse Effects and Contraindications

Clinical trials have used daily doses of GBE ranging from 112mg/day to 480mg/day. 600mg single dose seems to be the largest standardized extract used. At high doses of 300mg and above, some studies reported adverse effects, including bleeding events, gastrointestinal disturbances, headaches, dizziness, nausea, and allergic skin reactions. NOTE: VINCTO contains a very low, safe dose of GBE.

There is a suggested link between GBE and bleeding events, although the association is not causally proven. Safety recommendations in relation to bleeding:

Pregnant women should not take GBE.
People about to have surgery or dental work should not take GBE prior to the procedure.
People with blood disorders such as bleeding diathesis should not take GBE without consulting a doctor.
People taking anticoagulant drugs (eg warfarin, heparin) or antiplatelet drugs (eg aspirin) should not take GBE due to possible potentiation effect without consulting a doctor.

People taking certain types of antidepressants should not take GBE without consulting a doctor. GBE may enhance the effects of monoamine oxidase inhibitors and selective serotonin reuptake inhibitors and there has been a report of an adverse interaction between ginkgo and trazodone. GBE may add to the effects of 5-HTP in inhibiting MAO.

High doses of GBE could decrease the effectiveness of anti-seizure medications, such as carbamazepine or valproic acid.

VINCTO contains a very low, safe dose of GBE. However if you are worried about any of the above, consult your doctor before using VINCTO.

These statements have not been evaluated by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat, cure, or prevent any disease.

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