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Ginkgo appears to be relatively safe. Extremely high doses have been given to animals for long periods of time without serious consequences, and results from human trials are also generally reassuring. 1 2 Safety in young children, pregnant or nursing women, or those with severe liver or kidney disease, however, has not been established.
In all the clinical trials of ginkgo up through 1991 combined, involving a total of almost 10,000 participants, the incidence of side effects produced by ginkgo extract was extremely small. There were 21 cases of gastrointestinal discomfort, and even fewer cases of headaches, dizziness, and allergic skin reactions. 3 However, there are few potential problems. Perhaps the most serious have been the numerous case reports of internal bleeding associated with use of ginkgo (spontaneous as well as following surgery). 4 Based on these reports, as well as previous evidence that ginkgo inhibits platelet function, 5 studies have been performed to determine whether ginkgo significantly affects bleeding time or other measures of blood coagulation, with somewhat inconsistent results. 6 Prudence suggests that ginkgo should not be used by anyone during the periods before or after surgery or labor and delivery, or by those with bleeding problems such as hemophilia.
It also seems reasonable to hypothesize that ginkgo might interact with blood-thinning drugs, amplifying their effects on coagulation. However, two studies found no interaction between ginkgo and warfarin (Coumadin), 7 and another found no interaction with clopidogrel. (Although, it did find a slight interaction with the related drug cilostazol.) 8 While these findings are reassuring, prudence indicates physician supervision before combining ginkgo with blood-thinning drugs.
One study found that when high concentrations of ginkgo were placed in a test tube with hamster sperm and ova, the sperm were less able to penetrate the ova. 9 However, since we have no idea whether this much ginkgo can actually come into contact with sperm and ova when they are in the body rather than a test tube, these results may not be meaningful in real life.
The ginkgo extracts approved for use in Germany are processed to remove alkylphenols, including ginkgolic acids, which have been found to be toxic. 10 The same ginkgo extracts are available in the United States. However, other ginkgo extracts and whole ginkgo leaf might contain appreciable levels of these dangerous constituents.
Seizures have also been reported with the use of ginkgo leaf extract in people with previously well-controlled epilepsy; in one case, the seizures were fatal. 11 It has been suggested that ginkgo might interfere with the effectiveness of some antiseizure medications, specifically phenytoin and valproic acid . 12 Another possible explanation is contamination of ginkgo leaf products with ginkgo seeds, the seeds of the ginkgo plant contain a neurotoxic substance called 4-methoxypyridoxine (MPN). 13 Finally, the drug tacrine (also used to improve memory) has been associated with seizures, and ginkgo may affect the brain in ways similar to tacrine. 14 Regardless of the explanation, prudence suggests that people with epilepsy should avoid ginkgo.
According to a study in rats, ginkgo extract may cause the body to metabolize the drug nicardipine (a calcium channel blocker ) more rapidly, thereby decreasing its effects. 15 In addition, this finding also suggests potential interactions with numerous other drugs, although more research is needed to know for sure which ones might be affected.
Antibiotics in the aminoglycoside family can cause hearing loss by damaging the nerve carrying hearing sensation from the ear. One animal study evaluated the potential benefits of ginkgo for preventing hearing loss, and found instead that the herb increased damage to the nerve. 16 Based on this finding, individuals using aminoglycosides should avoid ginkgo.
It has been suggested that ginkgo might cause problems for people with type 2 diabetes both by altering blood levels of medications as well as by directly affecting the blood-sugar regulating system of the body. 17 However, the most recent and best designed studies have failed to find any such actions. 18 Nonetheless, until this situation is clarified, people with diabetes should use ginkgo only under physician supervision.
Interactions You Should Know About
If you are taking:
- Blood-thinning drugs, such as aspirin and other nonsteroidal anti-inflammatory drugs (eg, ibuprofen), cilostazol, clopidogrel (Plavix) , heparin , pentoxifylline (Trental) , ticlopidine (Ticlid) , and warfarin (Coumadin) : Simultaneous use of ginkgo could theoretically cause bleeding problems and should not be undertaken without physician supervision.
- Calcium channel blockers : Ginkgo might reduce their effectiveness.
- Antipsychotic medications in the phenothiazine family as well as atypical antipsychotic drugs (such as clozapine and olanzapene): Ginkgo might help them work better with fewer side effects.
- Aminoglycoside antibiotics: Use of ginkgo might increase risk of hearing loss.
- Medications to prevent seizures: Ginkgo might interfere with their effectiveness.
- DeFeudis FV. Ginkgo biloba Extract (EGb 761): Pharmacological Activities and Clinical Applications. Paris, France: Elsevier Science; 1991:143-146.
- Kalus JS, Piotrowski AA, Fortier CR, Liu X, Kluger J, White CM. Hemodynamic and electrocardiographic effects of short-term Ginkgo biloba. Ann Pharmacother. 37(3):345-9.
- DeFeudis FV. Ginkgo biloba Extract (EGb 761): Pharmacological Activities and Clinical Applications.Paris, France: Elsevier Science; 1991:143-146.
- Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med. 1997;336:1108.
- Chung KF, Dent G, McCusker M, Guinot P, Page CP, Barnes PJ. Effect of a ginkgolide mixture (BN 52063) in antagonising skin and platelet responses to platelet activating factor in man. Lancet. 1(8527):248-51.
- Kohler S, Funk P, Kieser M. Influence of a 7-day treatment with Ginkgo biloba special extract EGb 761 on bleeding time and coagulation: a randomized, placebo-controlled, double-blind study in healthy volunteers. Blood Coagul Fibrinolysis. 2004;15:303-309.
- Engelsen J, Nielsen JD, Winther K. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin-treated outpatients. A randomised, double-blind, placebo-crossover trial. Thromb Haemost. 2002;87:1075-1076.
- Aruna D, Naidu MU. Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol. 63(3):333-8.
- Ondrizek RR, Chan PJ, Patton WC, King A. An alternative medicine study of herbal effects on the penetration of zona-free hamster oocytes and the integrity of sperm deoxyribonucleic acid. Fertil Steril. 71(3):517-22.
- Siegers CP. Cytotoxicity of alkylphenols from Ginkgo biloba. Phytomedicine. 6(4):281-3.
- Granger AS. Ginkgo biloba precipitating epileptic seizures. Age Ageing. 30(6):523-5.
- Kupiec T, Raj V. Fatal seizures due to potential herb-drug interactions with Ginkgo biloba. J Anal Toxicol. 29(7):755-8.
- Kajiyama Y, Fujii K, Takeuchi H, Manabe Y. Ginkgo seed poisoning. Pediatrics. 109(2):325-7.
- Gregory PJ. Seizure associated with Ginkgo biloba? [letter]. Ann Intern Med. 2001;134:344.
- Shinozuka K, Umegaki K, Kubota Y, et al. Feeding of Ginkgo biloba extract (GBE) enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats. Life Sci. 2002;70:2783-2792.
- Miman MC, Ozturan O, Iraz M, Erdem T, Olmez E. Amikacin ototoxicity enhanced by Ginkgo biloba extract (EGb 761). Hear Res. 169(1-2):121-9.
- Kudolo GB. The effect of 3-month ingestion of Ginkgo biloba extract (EGb 761) on pancreatic beta-cell function in response to glucose loading in individuals with non-insulin-dependent diabetes mellitus. J Clin Pharmacol. 2001;41:600-611.
- Kudolo GB, Wang W, Elrod R, et al. Short-term ingestion of Ginkgo biloba extract does not alter whole body insulin sensitivity in non-diabetic, pre-diabetic or type 2 diabetic subjects-A randomized double-blind placebo-controlled crossover study. Clin Nutr. 2005 Nov 14. [Epub ahead of print]