Ginkgo Biloba Extract : Herbal Preparation

The Ginkgo biloba tree is believed to be the oldest living tree species.

Fossils of ginkgo leaves date back more than 200 million years. During prehistoric times, ginkgo trees were common in North America and Europe but were threatened with extinction during the ice age.

The tree managed to survive in only one region of the world - southeastern China.

The first European to discover and catalog ginkgo biloba was Engelbert Kaempfer, a German physician and botanist, over 300 years ago.

The ginkgo tree was introduced to the Americas in 1784 by William Hamilton and was planted in Philadelphia.

Since then, trees have been planted in the U.S. and Canada along city streets and parks due to the tree's ability to withstand insects, disease, and urban pollution; it can live a thousand years and grow to a height of 100 to 125 feet.

As a testimony to its hardiness, a solitary ginkgo tree is reported to have survived the atomic blast in Hiroshima after its trunk was completely destroyed.[1]

The oldest Chinese materia medica, the Pen Tsau Ching (2800 B.C), recommended ginkgo leaves to "benefit the brain," and for asthma, swelling of the hands and feet as a result of cold, coughs, filariasis, and vascular disorder of aging.

Although the fruits and seeds of this tree have been used in China for nearly 5,000 years, its use in Western medicine did not begin until the 1950s.

The German health authorities declared GBE to be effective for symptomatic treatment of conditions caused by cerebral insufficiency or dementia syndromes that result in symptoms of disturbances in concentration, vertigo, tinnitus, weakened memory and mood swings accompanied by anxiety, and as adjunctive therapy for intermittent claudication.[2]

Ginkgo is probably the most studied herb in the world with nearly 300 published papers and the most widely used herb in Europe, accounting for over 10 million prescriptions each year and over $500 million in sales.

Herbal ginkgo preparations are rarely used in crude form. Instead, they are sold as concentrated extracts; 50 pounds of ginkgo leaves are required to make one pound of Ginkgo Biloba extract(GBE).[3]

Standardized GBE is one of the most popular prescriptions written in German and France, accounting for 1 to 1.5% of all prescriptions. In the U.S., where ginkgo is available only as a dietary supplement and not on prescription, sales in food, drug and mass merchandise outlets nearly tripled to $90.2 million in 1997 compared to 1996.[4]

To keep up with demand worldwide, plantations have been developed in South Carolina (USA) and near the Atlantic coast of France which contain over 25 million trees. Other plantations are located in Japan, South Korea and, of course, China.[1]

GBE contains flavone glycosides (usually standardized to 24% of the extract), including bioflavanoids quercitin, kaempferol, and isorhamnetin.

The flavanoid components are responsible for the herb's antioxidant and some of the platelet aggregation inhibiting effects. GBE also contains terpene lactones (usually 6% of the extract) which are a group of compounds unique to the herb.

One such group known as ginkgolides is responsible for improving circulation and inhibiting platelet aggregation factor.

Another terpene lactone, bilobalide, has shown neuroprotective activity in animal studies and the ability to stimulate regeneration of damaged nerve cells.

GBE improves micro-circulation by decreasing blood viscosity, erythrocyte aggregation,leukocyte rigidity, and increasing erythrocyte flexibility.[3]

GBE also exerts anti-ischemic action and relieves arteriolar spasm, allows better glucoseand oxygen uptake under ischemic conditions, and stimulates aerobic glycolysis and lactate clearance.[5]

Other effects include free radical scavenging, inhibition of platelet activating factor, beneficial effects on neurotransmitters and neuroreceptors, and anti-infective activity.[1]

Clinical Studies:

Numerous trials describe the peripheral effects of GBE.

In one randomized, placebo-controlled crossover study conducted in 10 volunteers, a significant decrease in erythrocyte aggregation (-15.6%) was noted during the GBE phase and blood flow through nail capillaries improved by 57%.[6]

In 60 patients with arterial erection dysfunction refractory to papaverine, after 6 months of GBE 50% of patients became potent, 20% were responsive to papaverine, 25% had inflow improvement but were unresponsive to papaverine, and 5% were unchanged.[7]

In another trial in patients with claudicating atherosclerotic arterial disease, ischemic areas decreased by 38% in those who received GBE compared with an increase of 5% in patients who received placebo.[8]

In a 3-year study in patients with peripheral arterial occlusive disease, GBE quadrupled the maximum walking distance after exercise.[9]

A meta-analysis, published in Lancet, indicated that GBE had a highly significant beneficial effect on walking distance in patients with intermittent claudication.[10]

Other studies involving GBE demonstrated efficacy in visual problems such as diabetic retinopathy, retinal insufficiency, and macular degeneration.[3]

More than 40 controlled clinical trials, published between 1975 and 1997 involving approximately 2500 patients, evaluated the effects of GBE in cerebral vascular disorders.

A meta-analysis of these studies concluded that GBE was useful for concentration and memory difficulty, tiredness, headache, tinnitus, confusion, lack of energy, depressed mood, dizziness and decreased performance.[11]

A recent study by Le Bars involving 309 patients with mild to moderately severe Alzheimers or multi-infarct dementia who received GBE 120mg per day.

Three scales were used to evaluate efficacy:

1) the cognitive subscale of the Alzhiemer's Disease Assessment Scale (ADAS-Cog), a performance based cognitive test that objectively measures memory, language, and orientation;

2) the Geriatric Evaluation by Relatives's Rating Instrument (GERRI), a rating survey completed by caregivers as a measure of daily living and social behavior; and

3) the Clinical Global Impression of Change (CGIC), an interview-based global assessment as determined by the clinician.

In the group receiving GBE, 27% of patients achieved a 4-point improvement in performance-based cognitive test scores vs 14% of placebo-patients. Considering the groups as a whole, there was no significant change in the average score of GBE-patients, whereas the mean score continued to deteriorate in the placebo group over the 2-year study period.

Similar changes were noted by subjective assessment of caregivers in the GERRI, in which 37% of the GBE group were considered improved vs 23% in the placebo group. No significant differences between the groups were noted by the CGIC.

In clinical terms, as assessed by the ADAS-Cog, cognitive improvement may be equivalent to a 6-month delay in the progression of the disease, which compares favorably to tacrine, the first drug approved by the FDA for the treatment of Alzheimers.

There were no differences in side effects between the two groups.[12]

1. Chavez ML. Hospital Pharmacy 1998;33:658-72 , 2. German Commission E Monographs, 1994. , 3. Ogletree RL. The Top 10 Scientifically Proven Natural Products. Natural Source Digest. 1997 , 4. Weekly Pharmacy Reports. March 23, 1998 , 5. Foster S. NARD J 1996;Oct:127-41 , 6. Jung F. Arzneim-Forsch 1990;40:589-93 , 7. Sikoria R. J Urol 1989;141:188A , 8. Mouren X. Angiology 1994;45:413-17 , 9. Bauer U. Vasa 1986;Supl 15:26 , 10. Kleijnen J. Lancet 1992;340:1136-39 , 11. Kleijnen J. Br J Clin Pharmacol1992;34:352-5 , 12. Le Bars PL. JAMA 1997;278:1327-32