Ginkgo (Ginkgo biloba L.)

Ginkgo (Ginkgo biloba L.)

Background

Ginkgo biloba has been used medicinally for thousands of years. Today, it is one of the top selling herbs in the United States, accounting for $140 million of sales in 1998.

Ginkgo is used for the treatment of numerous conditions, many which are under scientific investigation. Available evidence demonstrates ginkgo's efficacy in the management of intermittent claudication, Alzheimer's/multi-infarct dementia, and "cerebral insufficiency" (a syndrome thought to be secondary to atherosclerotic disease, characterized by impaired concentration, confusion, decreased physical performance, fatigue, headache, dizziness, depression, and anxiety).

Although not definitive, there is promising early evidence favoring use of ginkgo for memory enhancement in healthy subjects, altitude (mountain) sickness, symptoms of premenstrual syndrome (PMS), and reduction of chemotherapy-induced end-organ vascular damage.

Although still controversial, a recent large trial has shifted the evidence against the use of ginkgo for tinnitus.

The herb is generally well tolerated, but due to multiple case reports of bleeding, should be used cautiously in patients on anti-coagulant therapy, with known coagulopathy, or prior to some surgical or dental procedures.

Synonyms

Arbre aux quarante écus, adiantifolia, baiguo, bai guo ye, BN-52063, duck foot tree, Elefantenohr, EGb, EGb 761, Eun-haeng, facherblattbaum, Fossil tree, GBE, GBE 24, GBX, ginan, gin-nan, Ginkgoaceae (family) , ginkgo balm, ginkgoblätter, Ginkgo folium, Ginkgo biloba blätter, ginkgogink, ginkgold, ginkgopower, ginkyo, icho, ityo, Japanbaum, Japanese silver apricot, kew tree, kung sun shu, LI 1370, maidenhair tree, noyer du Japon, oriental plum tree, pei kuo, pei-wen, Pterophyllus, Pterophyllus salisburiensis, Rokan, salisburia, Salisburia adiantifolia , Salisburia macrophylla , sophium, silver apricot, tempeltrae, tanakan, tanakene, tebofortan, tebonin, temple balm, tramisal, valverde, vasan, vital, ya chio, yin-guo, yin-hsing.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*Claudication (painful legs from clogged arteries)
Numerous studies suggest that Ginkgo biloba taken by mouth causes small improvements in claudication symptoms (leg pain with exercise or at rest due to clogged arteries). However, ginkgo may not be as helpful for this condition as exercise therapy or prescription drugs. Preliminary research comparing ginkgo to pentoxifylline (Trental®) has not provided clear answers. Most studies have used 120 milligrams of gingko per day, divided into 2 to 3 doses, for up to six months. Additional evidence is needed from well-designed studies comparing or combining ginkgo with drug and exercise therapies.

A

Dementia (multi-infarct and Alzheimer's type)
Many human and laboratory studies have examined the use of ginkgo for dementia. Most research has not been well designed. Despite these deficiencies, the scientific literature overall does suggest that ginkgo (120 to 240 milligrams daily) benefits people with early stage Alzheimer's disease and multi-infarct dementia, and may be as helpful as acetylcholinesterase inhibitor drugs such as donepezil (Aricept®). Well-designed research comparing ginkgo to prescription drug therapies is needed.

A

Cerebral insufficiency
Multiple clinical trials have evaluated gingko for a syndrome called "cerebral insufficiency." This condition, more commonly diagnosed in Europe than the United States, may include poor concentration, confusion, absent-mindedness, decreased physical performance, fatigue, headache, dizziness, depression, and anxiety. It is believed that cerebral insufficiency is caused by decreased blood flow to the brain due to clogged blood vessels. Some research reports benefits of ginkgo in patients with these symptoms, but most have been poorly designed without reliable results. Better studies are needed before a strong recommendation can be made.

B

Age-associated memory impairment (AAMI)
Age-associated memory impairment (AAMI) is a non-specific syndrome, which may be caused by early Alzheimer's Disease or multi-infarct dementia (conditions for which ginkgo has been shown to have benefit). There is preliminary research showing small improvements in memory and other brain functions in patients with AAMI, although some studies disagree. Overall, there is currently not enough clear evidence to recommend for or against ginkgo for this condition.

C

Altitude (mountain) sickness
A small amount of poorly designed research reports benefits of ginkgo for the treatment of altitude (mountain) sickness. Additional study is needed before a recommendation can be made.

C

Chemotherapy side effects reduction
In limited human study, ginkgo has been examined in addition to 5-fluorouracil (5-FU) in the treatment of pancreatic and colorectal cancer, to measure possible benefits on side effects. At this time, there is not conclusive evidence in this area.

C

Decreased libido and erectile dysfunction (impotence)
Ginkgo has been used and studied for the treatment of sexual dysfunction in men and women. Ginkgo may be effective in the treatment of erectile dysfunction, based on human and animal studies that show blood vessel relaxant properties, which may improve blood flow in the penis to achieve an erection. Ginkgo has also been reported in limited human study to treat sexual dysfunction in men and women caused by antidepressant drugs, such as fluoxetine (Prozac®). In general, studies are small and not well designed. Additional research is needed before a recommendation can be made.

C

Depression and seasonal affective disorder (SAD)
Preliminary study of seasonal affective disorder (SAD) suggests that ginkgo is not effective in preventing the development of winter depression. Other research in elderly patients with depression shows possible minor benefits. Overall, there is not enough evidence to form a clear conclusion.

C

Glaucoma
Several small human studies report ginkgo may be associated with mild increases in blood flow to the eyes, vision and intraocular pressure. However, these studies are poorly designed and small in size. Additional well-designed research is needed before a recommendation can be made.

C

Macular degeneration
Preliminary research suggests that ginkgo may improve eye blood flow, although it remains unclear if macular degeneration is significantly affected by ginkgo. More research is needed in this area before a conclusion can be drawn.

C

Memory enhancement (in healthy people)
A recent well-designed study reports that ginkgo at a dose of 120 milligrams daily for six weeks did not improve memory or concentration in people older than 60 years. However, prior evidence from smaller, less rigorous studies suggests that ginkgo in doses greater than or equal to 240 milligrams daily may enhance memory in healthy individuals. Therefore, although it remains unclear if higher doses of ginkgo are effective, it seems unlikely that 120mg has significant benefits.

C

Multiple sclerosis
Based on laboratory study, it has been suggested that ginkgo may provide benefit in multiple sclerosis (MS). Human research is limited to several small studies, which have not found consistent benefit. Additional research is needed before a recommendation can be made.

C

Premenstrual syndrome (PMS)
Initial study in women with premenstrual syndrome or breast discomfort suggests that ginkgo may relieve symptoms including emotional upset. Further well-designed research is needed before a recommendation can be made.

C

Ringing in the ears (tinnitus)
There is conflicting research regarding the use of ginkgo for tinnitus. Traditional use and multiple small, poorly designed studies from the 1980s and 1990s report benefits. However, a well-designed recent study found no benefit. Additional well-designed research is needed in order to resolve this controversy.

C

Vertigo
A small amount of poorly designed research reports benefits of ginkgo for the treatment of vertigo. Additional study is needed before a recommendation can be made.

C

Vitiligo
One small study using oral ginkgo biloba extract 40mg three times daily reports that ginkgo appears to arrest the progression of this disease. Better-designed studies are needed to confirm these results.

C

Stroke
Laboratory studies suggest that ginkgo may be helpful immediately following strokes because of possible antioxidant or blood vessel effects. However, initial study of ginkgo in people having strokes found no benefits.

D

Cocaine dependence
One small study reports no benefit of ginkgo for cocaine independence.

D

* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).

Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Acidosis, aging, alcoholism, allergies, angina, anti-bacterial, anti-fungal, antioxidant, anti-parasitic, anxiety, atherosclerosis ("clogged" arteries), asthma, attention deficit hyperactivity disorder, blood vessel disorders, blood clots, breast disease, breast tenderness, bronchitis, cancer, cardiac rhythm abnormalities, chilblains (inflammation of toes, fingers, ears, or face with exposure to cold), chronic rhinitis, congestive heart failure, cough, deafness, dermatitis, diabetes, diabetic nerve damage (neuropathy), diabetic eye disease, digestion, dizziness, dysentery (bloody diarrhea), eczema, fatigue, filariasis, freckle-removing, gastric cancer, genitourinary disorders, hearing loss, heart disease, heart attack, headache, hepatitis B, high cholesterol, high blood pressure, hypoxia (lack of oxygen), insomnia, labor induction, menstrual pain, migraine, mood disturbances, Raynaud's phenomenon, respiratory tract illnesses, scabies (ginkgo cream), schizophrenia, sepsis, skin sores (ginkgo cream), swelling, traumatic brain injury, ulcerative colitis, varicose veins.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Standardization

Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. Ginkgo is available as ginkgo leaf, ginkgo leaf extract, and ginkgo seed. Ginkgo leaf extract is the most commonly used form. Products which use standardized extracts referred to as EGb 761 should contain 24% ginkgo flavone glycosides and 6% terpenoids. Products which use standardized extracts referred to as LI 1370 should contain 25% ginkgo flavone glycosides and 6% terpenoids.

Adults (18 years and older)

General : 80 to 240 milligrams of a 50:1 standardized leaf extract taken daily by mouth in 2 to 3 divided doses has been used and studied (standardized to 24% to 25% ginkgo flavone glycosides and 6% terpine lactones). Other forms used include tea (bags usually contain 30 milligrams of extract), 3 to 6 milliliters of 40 milligrams per milliliter extract daily in three divided doses, and "fortified" foods. Ginkgo seeds are potentially toxic and should be avoided. The German ginkgo product Tebonin®, given through veins (IV), was removed from the German market due to significant side effects.

Claudication (painful legs from clogged arteries) : 80 to 240 milligrams of a 50:1 standardized leaf extract taken daily by mouth in 2 to 3 divided doses has been studied. There is evidence that 240 milligrams daily may be more beneficial than 120 milligrams daily. 3 to 6 milliliters of a 40 milligram per milliliter extract taken daily by mouth in three divided doses has also been studied, with some evidence that 6 milliliters may be more effective than 3 milliliters per day. The ginkgo product Tanakan® has been studied at a dose of 100 milligrams in 500 milliliters of normal saline, given twice daily into a vein (IV) for blood vessel disease, although this type of dosing is not proven safe.

Cerebral insufficiency : Doses of 112 to 160 milligrams daily, divided into three doses for up to 12 weeks, have been used in studies.

Dementia : Doses of 120 to 240 milligrams daily in three divided doses have been studied.

Memory enhancement (in healthy people) : Doses of 240 to 360 milligrams daily in three divided doses have been studied.

Children (younger than 18 years)

There is not enough scientific evidence to recommend use of ginkgo in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Allergy/hypersensitivity to Ginkgo biloba or members of the Ginkgoaceae family may occur. There is a case report of a severe reaction called Stevens-Johnson syndrome, including skin blistering and sloughing-off, after use of the ginkgo product One-A-Day® Memory and Concentration, which contains 60 milligrams of ginkgo leaf extract as well as vitamins B6, B12, and choline bitartrate. There may be cross-sensitivity to ginkgo in people allergic to urusiols (mango rind, sumac, poison ivy, poison oak, cashews), and an allergic cross-reaction has been reported in a person allergic to poison ivy.

If administered into a vein (IV), gingko may cause a skin allergy, blood vessel irritation and damage. Ginkgo fruit or pulp has caused strong allergic reactions after skin contact, and severe skin reactions and intestinal spasms have occurred after direct contact with fleshy fruit pulp.

Side Effects and Warnings

Overall, ginkgo leaf extract (used in most commercial products) appears to be well tolerated in most healthy adults at recommended doses for up to six months. In several reviews, ginkgo was associated with similar rates of side effects as placebo (sugar pill). Minor symptoms including headache, nausea, and intestinal complaints have been reported.

Bleeding has been associated with the use of ginkgo taken by mouth, and caution is advised in patients with bleeding disorders or taking drugs/herbs/supplements that may increase the risk of bleeding. Dosing adjustments may be necessary. Ginkgo should be stopped prior to some surgical or dental procedures. Reports of bleeding range from nose bleeds to life-threatening bleeding in several case reports. In some of these reports, ginkgo has been used with other agents that may also cause bleeding. For example, spontaneous bleeding into the eye (hyphema) was reported in a 70-year-old man taking 80 milligrams per day of ginkgo for one week. This patient was also taking 325 milligrams of daily aspirin, which can also increase the risk of bleeding. Spontaneous bleeding into and around the brain has been reported in several cases: in a 33-year-old woman taking ginkgo 120 milligrams per day for two years with no other medications, in a 72-year-old woman (subdural bleeding), in a 61-year-old male taking ginkgo 120 to 160 milligrams per day for more than 6 months (subarachnoid hemorrhage), in a 56-year-old man who regularly used an herbal preparation including ginkgo, and in a 78-year-old woman taking ginkgo for two months in addition to the blood thinner warfarin (intracerebral bleeding). Excess bleeding has also been reported after gall bladder surgery (laparoscopic cholecystectomy).

Toxicity from eating ginkgo seeds is sometimes called "Gin-nan food poisoning," and is documented in as many as 70 case reports between 1930-1970, with the worst effects seen in infants. Eating the seeds is potentially deadly, due to risk of tonic-clonic seizures and loss of consciousness. There is a case report of two patients with well-controlled seizure disorder who had seizures after starting ginkgo. However, reports of seizure activity associated with use of ginkgo leaf extract are rare.

Based on human study, gingko may theoretically affect insulin and blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.

There have been uncommon reports of headache, dizziness, stomach upset, nausea, diarrhea, vomiting, muscle weakness, loss of muscle tone, restlessness, heart racing, rash, and irritation around the mouth with the use of ginkgo. There is a case report of "coma" in an elderly Alzheimer's patient taking trazodone and ginkgo, although it is not clear that ginkgo was the cause. Based on laboratory and human research, ginkgo may decrease blood pressure, although there is one report of ginkgo possibly raising blood pressure in a person taking a thiazide diuretic ("water pill"). Based on theory, high concentrations of ginkgo may reduce male and female fertility. Contamination with the drug colchicine has been found in commercial preparations of Ginkgo biloba.

Pregnancy and Breastfeeding

Use of gingko is not recommended during pregnancy and breastfeeding due to lack of reliable scientific study in this area. The risk of bleeding associated with ginkgo may be dangerous during pregnancy.

References

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January 01, 2004