Risk Factor: C
Fetal Risk Summary
Ginkgo biloba (scientific name) is a popular herbal preparation. The dioecious ginkgo tree may live as long as several hundred to a thousand years. It is the sole survivor of the family Ginkgoaceae that dates back more than 200 million years. The tree, which may grow to a height of 30 to 40 meters (approximately 98 to 131 feet), has fan-shaped leaves and is indigenous to China, Japan, and Korea (1,2 and 3). Commercial plantations of ginkgo trees in the United States, however, are pruned to shrub height to allow mechanical picking of the leaves (4).
The medicinal parts of ginkgo are the fresh and dried leaves, and the seeds separated from their fleshy outer layer (2). Ginkgo leaf extract, however, is the most commonly used form of this herb (3). Numerous uses have been recommended for the various IV (not available in United States) and oral preparations of ginkgo leaf extract, some of which are: symptomatic relief of organic brain syndrome (e.g., cerebral insufficiency, anxiety and stress, memory impairment, headache, dementias, etc), intermittent claudication and other circulatory disorders, asthma, and vertigo and tinnitus of vascular origin (1,2,3,4 and 5).
Ginkgo seed, although not commercially available in the United States, is used orally as an antitussive and expectorant, as an aid for digestion, to prevent drunkenness, in asthma and bronchitis, and for genitourinary complaints (3). Topical uses include scabies and skin sores. Roasted seeds with the pulp removed are eaten for food in Japan and China (3).
The content of active compounds in ginkgo leaves may vary widely depending upon the season (1,6). Seasonal and other factors, such as location and method of harvest, may result in a variance as much as 300% in the concentrations of active compounds (6). Ginkgo leaf extract is prepared using an acetone-water extraction process and subsequent purification steps without adding concentrates or isolated ingredients (2,3,4 and 5). A number of chemical constituents have been identified in the extract (percentages refer to German Commission E standards): 22%27% flavanone glycosides (flavonoids consisting of monosides, biosides, and triosides of quercetin, kaempferol, isorhamnetins, and 3′-O-methylmyristicins); 5%7% terpene lactones (terpenoids) (2.8%3.4% ginkgolides A, B, C, and M [trilactonic diterpenes], 2.6%3.2% bilobalide [trilactone sesquiterpene]); and less than 5 ppm of ginkgolic acids (1,2,3,4 and 5). Other chemical constituents found in the leaf before processing, in addition to those identified in the extract, include amino acid 6-hydroxykynurenic acid, bioflavonoids (dimeric bioflavones: amentoflavone, bilobetin, ginkgetin, isoginkgetin, 5- methoxybilobetin, sciadopitysin) (about 40 different bioflavonoids have been identified), terpene lactone (ginkgolide J), steroids (sitosterol, stigmasterol), polyprenols, organic acids (shikimic, vanillic, ascorbic, p-coumaric), benzoic acid derivatives, carbohydrates, straight chain hydrocarbons, alcohol, ketones, and 2-hexenol (1). A 1993 Reference detailed the chemical structures of the active ingredients (flavonoids and terpene lactones) (7).
The seed contains 38% carbohydrate, 4% protein, and less than 2% fat (1). This part of the tree is not marketed in the United States, but may contaminate other ginkgo products (8). Chemicals found in the seed are alkaloids (e.g., ginkgotoxin), amino acids, cyanogenetic glycosides, and long-chain phenols (e.g., anacaric acid, bilobol, and cardanol) (1).
Reproduction studies in animals have revealed no mutagenic or teratogenic effects (1). No teratogenicity was observed in pregnant rats given oral doses up to 1600 mg/kg/day (1).
In a sperm penetration assay, zona-free hamster oocytes were incubated for 1 hour with two concentrations of ginkgo biloba, 0.1 mg/mL and 1.0 mg/mL, dissolved in HEPES-buffered synthetic human tubal fluid (modified HTF) (9). Fresh human donor sperm was suspended in the modified HTF and then mixed with the oocytes for 3 hours. Modified HTF served as the control. At the 0.1 mg/mL concentration, three of nine oocytes were penetrated, whereas at 1.0 mg/mL, zero (0 of 8) penetration occurred. The decrease in penetration was not associated with a decrease in sperm motility (9). In the second part of the study, sperm were incubated with the herbal solutions for 7 days (9). Neither concentration caused significant sperm DNA denaturation or mutation of a selected sperm sentinel gene (BRCA1 exon 11 gene), but the higher concentration reduced sperm viability compared with controls. Extrapolation of these data to the reproductive risk of ginkgo biloba in males is difficult, in part because the concentration of the herb in semen or sperm has not been studied (9). Moreover, although the doses used in this study are small fractions of the actual recommended human dose, usually expressed in milligrams of ginkgo, there is no published evidence that the adverse effects observed have occurred in vivo.
Although some ginkgo preparations may be standardized, the standardization of any herbal product as to its constituents, concentrations, and the presence of contaminants is generally lacking. Consumption of these products during pregnancy may result in fetal exposure to unintended chemicals and doses.
In summary, no reports describing the use of ginkgo biloba during human pregnancy have been located. No mutagenicity in animals or human sperm was observed and no teratogenicity occurred in one animal species, but the data and details of the animal studies are very limited. Moreover, a large number of chemicals have been identified from this herb and none have undergone rigorous reproductive testing. However, because ginkgo is an ancient herb and its use is widespread, it is doubtful that a major teratogenic effect or other significant reproductive toxicity would have escaped notice. More subtle or low-incidence effects, however, including structural and behavioral teratogenicity, the induction of abortions, and infertility may have escaped detection, and further study is required before human reproductive risk or safety can be assessed.
Because of the uncertainties described above, various sources can be found that either state there are no restrictions against its use in pregnancy (5), or that the herb is contraindicated during gestation (1,3,10). The safest course is to avoid ginkgo products during pregnancy.
Breast Feeding Summary
No reports describing the use of ginkgo biloba during lactation have been located. Although one source states that there are no restrictions to its use during lactation (5), other sources consider the use of the herb during lactation to be contraindicated (1,3,10). The latter course is the safest because of the large number of chemical compounds in the herb and the complete lack of information on the effects of exposure to these substances in a nursing infant.
- Ginkgo. The Review of Natural Products. St. Louis, MO:Facts and Comparisons. March, 1998.
- Ginkgo Biloba. PDR for Herbal Medicines. Montvale, NJ:Medical Economics. 1998:8713.
- Ginkgo Leaf, Ginkgo Leaf Extract, Ginkgo Seed. Natural Medicines Comprehensive Database. Stockton, CA:Therapeutic Research Faculty. 1999:37781.
- Robbers JE, Tyler VE. Tyler’s Herbs of Choice. The Therapeutic Use of Phytomedicinals. Binghamton, NY:Haworth Press. 2000:1416.
- Ginkgo Biloba Leaf Extract. Blumenthal M, Senior Editor. The Complete German Commission E Monographs. Therapeutic Guide to Herbal Medicines. Austin, TX:American Botanical Council. 1998:1368.
- Product information. BioGinkgo 27/7. Pharmanex, 1998.
- Sticher O. Quality of Ginkgo preparations. Planta Medica 1993;59:211.
- Boullata JI, Nace AM. Safety issues with herbal medicine. Pharmacotherapy 2000;20:25769.
- 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 1999;71:51722.
- Wong AHC, Smith M, Boon HS. Herbal remedies in psychiatric practice. Arch Gen Psychiatry 1998;55:103344.