Ginkgo biloba extract (GBE) is a complex pharmacologically-active substance.⁴ Manufacturers use an acetone-water process with multiple purification steps to prepare an extract with a 35-67:1 ratio of dried leaves to final extract.⁵ The product is standardized to 22-27% ginkgo flavonol glycosides (quercetin, kaempferol, and isorhamnetin) and 5-7% terpene lactones ( 2.8-3.4% ginkgolides A, B, C,M, and J) as well as sesquiterpene (2.6-3.2% bilobalide).⁶ The extraction processes reduce the components most likely to result in allergic reactions and other undesirable effects (ginkgolic acids, ginkgotoxin, and sterols).^1,3 The most widely investigated extract is EGb 761, manufactured in Germany by Wilma Schwabe (but available in the U.S. as Ginkgold) using a process protected by U.S. patents. 

Manufacturers test the quality and identification of the dried leaf; they check for characteristic odor and color, identify the leaf- through microscopic characteristics and thin-layer chromatographic analysis for the flavone and terpene constituents. Further tests ensure the exclusion/ minimization of bacterial elements, foreign organic matter, pesticide and radioactive residues, and heavy metals.²

GBE has been a subject of intense research for 20-30 years. Toxicologic studies are underway at the National Toxicology Program.⁷ Previous studies reported in the literature indicate little potential for acute toxicity: oral LD₅₀ in mice of 7.73 g/kg (1.9g/kg of flavone glycosides, 464 mg/kg of terpene glycosides), I.V. LD₅₀ 1.1g/kg.⁷ Evidence of mutagenicity and carcinogenicity of quercetin and kaempferol at high doses in some animal species are documented.⁷ In rats, radiolabled GBE was concentrated in glandular, neuronal, eye tissues; 38% exhaled, 22% excreted in urine, 29% in feces at 72 hours.⁸

Pharmacotherapeutic evaluation of ginkgo at 120 mg BID showed no significant effect on BP, HR, or EKG parameters over 7 days in a randomized, placebo-controlled, crossover study of healthy volunteers (n=15).⁹ After oral administration, the bioavailability of ginkgolide A was >80% (half-life 4 hours); 70% excreted unchanged in urine. The bioavailability of ginkgolide B was >80% (half-life 6 hours); 50% excreted unchanged in urine. Bilobalide was 70% bioavailable with a half-life of 3 hours after 120 mg GBE ingestion with 30% excretion in urine.⁷ GBE did not have any effect on digoxin pharmacokinetics in 8 healthy volunteers.¹⁰

Researchers incompletely understand the mechanisms of action of GBE. Studies do support the contention of herbalists that the constituents in the herbal product operate synergistically, at least in the case of GBE.³

Current ideas about GBE's actions include:

1)   Anti-oxidant: Protection from oxidative stress (especially neurons and retinal tissue)
2)   Inhibition of platelet activating factor (PAF), which reduces platelet aggregation, free radical production, and smooth muscle contraction among other beneficial anti-inflammatory effects
3)   Improvement in micro-circulation mediated by regulation of vascular tone and permeability and reduction in blood viscosity
4)   Regulation of cholinergic neurotransmitters
5)   Protection from beta-amyloid toxicity in AlzheimerÕs dementia
6)   Activity against certain microbes (e.g., Pneumocystis carinii)
7)   Possibly decreases hyperinsulinemia associated with hypertension8)   Reduces cytochrome P450 1A2 (CYP1A2) and CYP2D6 activity and may either inhibit or induce CYP3A4 activity, thereby affecting metabolism of certain pharmaceuticals.^3,11-13

The most recent in vitro and animal studies continue to validate protective effects of GBE:

1)     Rats fed 150 mg/kg of GBE (usual human dose 1.6 mg/kg) had less retinal ganglion loss in response to episcleral vessel cautery than a control group; ¹⁴
2)     200 mg/ml of GBE increased cell survival after exposed to staurosporine (induces cell death similar to apoptosis).¹⁵