Safety Profile
There is general agreement of a low risk associated with Ginkgo extract products. Possible serious side effects have rarely been noted in any of the numerous clinical trials on Ginkgo extract, and those that were noted were not significantly different from those experienced with placebo (e.g., Kanowski et al., 1996). In some clinical trials, the adverse effects reported by the placebo group were significantly higher than the group taking Ginkgo extract (Kleijnen and Knipschild, 1992).
There is one case report of a patient who developed bilateral subdermal hematomas following ingestion of 120 mg Ginkgo biloba extract daily. Whether the hematomas were caused by the Ginkgo extract remains unknown, but the bleeding time prolonged at 15 minutes and 9.5 minutes (normal range = 3.0-9.0 minutes) during self-administration of the extract improved to within normal ranges (to 6.5 minutes and 6.5 minutes) 35 days after discontinuation. Due to the demonstrated PAF-inhibiting ability of a Ginkgo extract, the authors suggested further investigation of possibly clinically relevant antiplatelet effects of Ginkgo extract, especially for longer duration treatments beyond normal clinical trial times (Rowin and Lewis, 1996). In a letter, Skogh (1998) expresses doubts about this association, noting that no inhibition of platelet aggregation is found from the "usual dose" of Ginkgo biloba extract. In reply, Vale (1998) summarily dismissed these doubts, quoting others who admitted that while the case did not prove a causal association with Ginkgo, warned to carefully monitor herbal extracts to "prevent rare but potential disastrous results" (Skogh, 1998).
Ginkgo biloba products are contraindicated in individuals with hypersensitivity to the plant or its products (Blumenthal, 1997).
One report of a possible association of Ginkgo extract with subarachnoid hemorrhage was reported in an elderly man taking 120-160 mg/day who already had shown a slightly increased bleeding time (Vale, 1998).
Whether Ginkgo extract may potentiate or have additive effects when combined with sedative medications is not known with certainty. However, Schulz et al. (1998), in a double-blind, placebo-controlled, randomized crossover trial in 12 women reported that a single dose of Ginkgo extract (LI 1370, 150 mg) produced an increase in subjective tiredness (measured with a visual analogue scale). However, Marcilhac et al. (1998) found no effect on plasma levels of corticosterone and ACTH in stressed rats chronically administered EGb 761 at a dosage of 50 mg/kg p.o. for 14 days.
Ginkgo extract (EGb, 180 to 240 mg/day x two weeks) was used in treatment of Fluoxetine-induced anesthesia of the genitals in a 37-year-old woman who was unresponsive to repeated attempts at amelioration with cyproheptadine (4 mg) and yohimbine (5.4 mg) one hour prior to sexual activity. The symptoms were relieved by the extract despite her continued intake of a selective serotonin re-uptake inhibitor (SSRI) antidepressant (fluoxetine, 60 mg/day), an antihistamine (cetirizine, 10 mg/day), and birth control pills (Tri-Levelen 28). Improvements were found in a reversal of delayed orgasms, a greater level of sexual desire, and restoration of clitoral, vulval, and vaginal sensation to previous levels. Ellison and DeLuca (1998) reported that the patient improved "spontaneously" and called for controlled double-blind studies to investigate the possibility of using EGb in the treatment of antidepressant-induced sexual dysfunctions since they interfere with treatment compliance and impair the quality of life of depressives. The authors noted that their patient continued to take Ginkgo extract.
An elderly patient taking SSRI medication for major depression reported improved libido and erections after taking Ginkgo to enhance his memory. When he went off the Ginkgo his sexual difficulties returned, and when he began taking Ginkgo again they went into remission (Cohen and Bartlik, 1998). Based on these observations, and the fact that no consistently effective pharmacological agent has been found that reliably treats SSRI-induced sexual dysfunction, Cohen and Bartlik conducted an open trial of Ginkgo (form not stated) in depressive men and women suffering from the same side effect. The patients were being treated with various kinds of antidepressants (bupropion, venlafaxine, nefazodone, fluoxetine, phenelzine, sertaline, vivactil, and paroxetine), the majority receiving SSRIs. Decreased libido was experienced by 76%, inhibited or delayed orgasm by 54%, and for 19% there were difficulties with erections. Various pharmacological means were attempted without satisfactory results, including yohimbine, buspirone, lower dosages of the antidepressants, and amantadine. Maintaining their antidepressant medications, 63 patients received Ginkgo extract at an average dosage of 207 mg/day for 28 days (60 mg 4 X/day to 120 mg 3 X/day). Cohen and Bartlik reported that 84% of the patients found relief from their antidepressant-induced sexual dysfunction, with more female patients (30/33) finding relief than males (23/30). No side effects or drug interactions from the Ginkgo treatment were reported.
German authorities report no interactions with other drugs. It is important to note that no definite drug interactions have been reported, even though those taking Ginkgo extract are often taking many other drugs simultaneously (Chang and Chang, 1997; Kleijnen and Knipschild, 1992).
German authorities report no precautions for the use of Ginkgo extract in pregnant or lactating women (Chang and Chang, 1997; Blumenthal et al., 1998).
In rare cases, mild gastrointestinal complaints, headache, and allergic skin reactions have been reported (Blumenthal et al. 1998; Kleijnen and Knipschild, 1992). A recent clinical study on Ginkgo was conducted in 241 institutionalized elderly men and women (ages 55-86). One hundred and 9inety-seven patients completed the trial; a total of 25 subjects dropped out due to side effects, including 9 from the placebo group and 8 each in the high-dose and low-dose Ginkgo groups (80 or 40 mg 3 X/day for 3 months, respectively). These side effects were largely dizziness and gastrointestinal complaints. However, no differences in the number of gastrointestinal complaints were found between the placebo group and the Ginkgo group. One patient in the high-dose group dropped out due to facial nerve pain and two in the high-dose group dropped out because of "mild gastric bleeding" (Brautigam et al., 1998).
The raw fruits have been reported toxic (especially to children) and have caused at least one fatality. However, this is of limited importance since the medicine is usually only prepared from the leaves or the cooked or processed fruits (Hobbs, 1991). Ginkgotoxin (4’-O-methylpyridoxine), a neurotoxin with antivitamin B6 activity, occurs in both the leaves and boiled seeds of G. biloba; however, the amounts detected were found to be so low as to not present a problem of toxicity, whether one ingests the boiled seeds or leaf-based medications (Arenz et al., 1996).
In traditional Chinese medicine, use of Ginkgo is contraindicated in "excess" conditions where there is acute infection with fever. Ginkgo extract is not recommended for continuous use. It should be taken for 10 days on, 3 days off, for up to several months (Hobbs, 1991), after which the benefits should be qualified (Blumenthal et al., 1998).