What is Ginkgo biloba?

Thanks to the University of North Carolina School of Pharmacy for the use of this article!

Stew Eckard and Mike Darnofall

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Family: Ginkgoaceae

Plant: Ginkgo Tree, Maidenhair Tree

Trade Names: Tebonin, Tankan, and Rokan

General Description:

A) Deciduous tree that grows 100 to 200 feet high with trunk diameter of 3 to 4 feet
B) Lives as long as 1000 years

• -has survived for over 250 million years ("Living Fossil")
• -only tree to survive atomic blast in Hiroshima
• - grown in cities because of resistance to insects, bacteria, viruses, pollution and age

C) Common in North America, Europe, and China
D) Short horizontal branches with fan-shaped leaves ~5-10 cm across
E) Leaves and seeds used for medicinal purposes
F) Foul smelling fruit that is inedible
G) Ivory colored seed that is edible

Chemical Composition:

A) 24% Flavonoid Glycosides: Kaempferol, Quercetin, Isohamnetine
B) 6% Terpine molecules: diterpine gincolides (A, B, and C), sesquiterpine bilobalides
C) Organic Acids: hydroxykinurenic, kinurenic, protocatechic, vanillic, etc.
      -help make flavonoid and terpine molecules water-soluble

History and Folk Use:

A) Valued for medicinal properties in China for thousands of years ~2800 BC

• -ability to "benefit the brain"
• -relieves symptoms of asthma and cough

1) Ate ginkgo nuts for good taste, strengthening, and tonic properties

• Used as a kidney yang tonic for increased sexual energy, restoring hearing loss, soothing bladder irritation, and to stop bed wetting
• Made into a tea for congestion
• eaten regularly for control of yeast infections, frequent urination, cloudy urine, and  excess mucous in urinary tract
• cooked as a remedy for intestinal worms, cancer, gonorrhea, leukorrhea, and some antibiotic activity

2) Used the leaves to treat chilblains (symptoms of frostbite)
3) Made leaves into a tea which was sprayed into the throat for asthma

B) Late 17th century - Engelbert Kaempfer was the 1st European to discover and catalog the tree
C) 1771 - Linnaeus named the tree Ginkgo Biloba
     Ginkgo = Silver plume (Japanese)
     Biloba = Two lobes

D) 1784 - Brought to America to the garden of William Hamilton near Philadelphia

Pharmacology:

A) Total extract more active than isolated compounds suggesting synergism
B) Ginkgo Biloba Extract (GBE) has three main effects on the body

1) Improves circulation to all vital organs

• stimulates greater venous tone which helps clear toxic metabolites that accumulate during ischemia
• balanced action on arterial and venous systems
  • tonic effects during vasomotor paralysis
  • relaxant effects during vasomotor spasm

• dual action important because single action drugs, i.e. Vasodilators can aggravate ischemic conditions by deflecting blood and oxygen away from ischemic areas via dilation of healthy areas

• enhances oxygen utilization and glucose uptake in the brain

2) Stops damage by free radical oxidation

• inhibits lipid peroxidation of membranes
• isolation of Superoxide Dismutase from GBE (SOD is a potent antioxidant enzyme that is normally found in the body but in levels that decrease with age)

3) Blocks Platelet Activating Factor (PAF)

• prevents neutrophil activation, increased vascular permeability, smooth muscle contraction (bronchoconstriction), and decreased coronary flow associated with PAF
• Ginkgolide B is most effective

Clinical Applications:

A) Intermittent Claudication and Arterial Insufficiency
B) Cerebral Vascular Insufficiency and Impaired Mental Performance
C) Alzheimer's
D) Asthma
E) Others: Alertness, allergies, blood clotting, depression, hearing problems (tinnitus), heart disease, impotence, Parkinson's, Retinal Damage, Stroke, and Vertigo

Toxicity:

A) GBE

• no significant ADR's
• rarely with increased doses = mild GI upset and headache

B) Fruit

• contact with pulp causes severe allergic reactions, i.e. erythema, edema, and severe itching

Drug/Disease Interactions:

A) Cross reactivity between Ginkgo fruit and poison Ivy/Oak/Sumac Family
B) Vaso-active drugs: ACE Inhibitors, Calcium Channel Blockers, Beta-Blockers, et.al
C) Anticoagulants: Warfarin, Heparin
D) Insulin?

Dosage:

A) General/Daily use: 40 mg TID
B) Alzheimer's: occasionally up to 80 mg TID

**Products should be standardized as 24% flavonoid glycosides**

Clinical Trials:

I. Peripheral Arterial Insufficiency (U. Bauer)

• 79 patients with pain free claudication < 200 meters (Fontaine stage 2b)
• 6 month parallel double blinded randomized clinical trial comparing GBE to placebo
• 44 patients took GBE (3x40 mg/day) and 35 patients took placebo
• Both groups were comparable (age, weight, height, gender, risk factors) although the ginkgo group appeared worse off initially
• Assessments made by both physicians and patients at 0, 6, 12, 24 weeks demonstrated ginkgo to be active and superior to placebo:

• Pain free walking distance (120 m (+100%), GBE; 100 m (+33%), placebo)
• Maximum walking distance: (70% showed > 30% improvement and 6% showed > 100% improvement, placebo)
• Plethysmography (measures in blood flow on affected side): (48% increase in peak blood flow, GBE; slight decrease in blood flow, placebo)

Conclusion: GBE showed significant benefit in walking distance and improvement in limb perfusion. GBE was also well-tolerated with no significant side effects.

II. Vigilance (Alertness) / Mental Performance (Gebner et al)

• 60 patients (57-77 yo) with mental deterioration
• Randomly divided into three groups and double blinded (12 week trial):

• 20 received GBE (3x40 mg/day)
• 20 received nicergoline (5 mg/day)
• 20 received placebo

• Extensive examinations (EEG, psychophysiological measurements, patient interviews) at 0, 4, 8, 12 weeks
• Theta wave / alpha wave ratio on resting EEG was the best indicator of vigilance (high ratio = low vigilance)

• Significant decrease in ratio GBE relative to the other two groups

• Reaction time to a light signal was the best indicator of mental performance

• RT was 20 msec faster with GBE relative to the other two groups

• Subjective efficacy and tolerance

• GBE was judged effective by 3/4 of patients and 3/4 of investigators
• No concrete evidence of drug-induced side effects/intolerance

Conclusion: GBE induces a restoration of vigilance (alertness, adaptability to change) towards normal levels especially in patients with significant initial mental deterioration. The findings at the behavioral level correlate with EEG findings.

III. Acute Mountain Sickness (AMS)/Vascular Reactivity to Cold (Roncin et al)

• 44 healthy subjects who had previously experienced AMS (minimum score of 2 on AMS questionnaire)
• Randomized parallel study of preventive effect of GBE on AMS and vasomotor changes of the extremities during a 30-day Himalayan trip (altitude at the base camp was 4900 meters)
• One group (22) received GBE (2x80 mg/day) while the other group (22) received a placebo
• Principle assessment criterion was score on Environmental Symptoms Questionnaire (ESQ) comprising 67 items each scored on a 6-point scale
• Symptoms on the ESQ include:

• aching in legs, feet, shoulders, arms, hands
• coldness in hands/feet
• numbness in a body part
• "feeling sick"
• decreased diuresis
• headache, insomnia, vertigo, nausea (cerebral AMS)
• dyspnea on exertion/at rest (respiratory AMS)

• Questionnaires were filled out daily during ascent to base camp (8 days) and for 3 days following; then on days 17, 20, 21, 23
• Results from principle assessment (ESQ):

• Zero (GBE); 41% (placebo) developed cerebral AMS
• 14% (GBE); 82% (placebo) developed respiratory AMS

• Secondary assessment criteria were based on:

• functional disability (six point scale assessing parasthesia, pain, numbness, stiffness, swelling of hands)
• peripheral vasomotor reactions measured by plethysmography (days 0,15-17, 28-30)
  • digital systolic pressure (DSP) at room temperature
  • DSP after 3 minutes at 10 degrees C
  • Difference between 1 and 2 is the cold gradient

• Results from plethysmography measurements:

• 23% improvement (decrease) in cold gradient (GBE)
• 104% deterioration (increase) in cold gradient (placebo)

Conclusion: GBE appears to be a useful treatment for the prevention of AMS. It is well tolerated with no particular adverse effects. Its efficacy vs. placebo has been demonstrated on both cerebral and respiratory components of AMS. It also decreases vasomotor disorders of the extremities, as demonstrated by plethysmography and a specific functional disability questionnaire.

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References:

Bauer U:  6 Month Double-Blind Randomized Clinical Trial of Ginkgo Biloba Extract vs Placebo in Two Parallel Groups in Patients Suffering From Peripheral Arterial Insufficiency.  Arzeneimittel-Forsch 34, 716-721, 1984.

Gessner B, Voelp A, and Klasser M:  Study of the Long-term Action of a Ginkgo Biloba Extract on Vigilance and mental Performance as Determined by Means of Quantitative Pharmaco-EEG and Psychometric Measurements.  Arzeneimittel-Forsch  35, 1459-1465, 1985.

Kleijnen J and Knipschild P:  Gingko Biloba.  Lancet 340, 1136-1139, 1992.

Murray M:  The Healing Power of Herbs.  Prima Publishing.  Rockland, CA.  1995.  pp. 143-161.

Murray M, Pizzorno:  A Textbook of Natural Medicine.  Bastyr University Publication, 1996.

Oberpichler H, Beck T, and Abdel-Rahman M:  Effects of Gingko Biloba Constituents Related to Protection Against Brain Damage Caused by Hypoxia.  Pharmacological Research Communication 20, 349-368, 1988.

Roncin J, Schwartz F, D'Arbigny P:  EGB 761 in control of Acute Mountain Sickness and Vascular Reactivity to Cold Exposure.  Aviation, Space, and Environmental Medicine 67, 445-452, 1996.

Web Sites as Follows:

http://www2.shore.net/~spectrum/ginko.html

http://www.televar.com/alpha/elixer.html

http://www.excite.com/xdr/Health_and_Fitness/Alternative_Medicine/

http://www.netspace.net.au/~michaelm/

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