Metabolic Disturbance—One patient taking ginkgo who died after a seizure was found to have subtherapeutic levels of valproate and phenytoin,25 which could be due to ginkgo’s effect on cytochrome p450 enzyme CYP2C19.26 Ginkgo interactions with many cytochrome enzymes have been studied for potential drug interactions. Any other direct effects remain variable and controversial.27,28
Hemorrhage—Another serious effect associated with taking ginkgo supplements is hemorrhage, often in conjunction with warfarin14; however, a meta-analysis indicated that ginkgo generally does not increase the risk of bleeding.29 Other studies have shown that taking ginkgo with warfarin showed no difference in clotting status, and ginkgo with aspirin resulted in no clinically significant difference in bruising, bleeding, or platelet function in an analysis over a period of 1 month.30,31 These findings notwithstanding, pregnant women, surgical patients, and those taking a blood thinner are advised as a general precaution not to take ginkgo extract.
Carcinogenesis—Ginkgo extract has antioxidant properties, but there is evidence that it might act as a carcinogen. An animal study reported by the US National Toxicology Program found that ginkgo induced mutagenic activity in the liver, thyroid, and nose of mice and rats. Over time, rodent liver underwent changes consistent with hepatic enzyme induction.32 More research is needed to clarify the role of ginkgo in this process.
Toxicity by Ingestion—Ginkgo seeds can cause food poisoning due to the compound 4’-O-methylpyridoxine (also known as ginkgotoxin).33 Because methylpyridoxine can cause depletion of pyridoxal phosphate (a form of vitamin B6 necessary for the synthesis of γ-aminobutyric acid), overconsumption of ginkgo seeds, even when fully cooked, might result in convulsions and even death.33
Nomenclature and Distribution of Plants
Gingko biloba belongs to the Ginkgoaceae family (class Ginkgophytes). The tree originated in China but might no longer exist in a truly wild form. It is grown worldwide for its beauty and longevity. The female ginkgo tree is a gymnosperm, producing fruit with seeds that are not coated by an ovary wall15; male (nonfruiting) trees are preferentially planted because the fruit is surrounded by a pulp that, when dropped, emits a sour smell described variously as rancid butter, vomit, or excrement.5
Identifying Features and Plant Facts
The deciduous ginkgo tree has unique fan-shaped leaves and is cultivated for its beauty and resistance to disease (Figure 2).4,34 It is nicknamed the maidenhair tree because the leaves are similar to the pinnae of the maidenhair fern.34 Because G biloba is resistant to pollution, it often is planted along city streets.17 The leaf—5- to 8-cm wide and a symbol of the city of Tokyo, Japan34—grows in clusters (Figure 3)5 and is green but turns yellow before it falls in autumn.34 Leaf veins branch out into the blade without anastomosing.34
FIGURE 2. Fan-shaped leaves of the ginkgo tree.
Male flowers grow in a catkinlike pattern; female flowers grow on long stems.5 The fruit is small, dark, and shriveled, with a hint of silver4; it typically is 2 to 2.5 cm in diameter and contains the ginkgo nut or seed. The kernel of the ginkgo nut is edible when roasted and is used in traditional Chinese and Japanese cuisine as a dish served on special occasions in autumn.33
FIGURE 3. Ginkgo leaves in clusters of 3 to 5.
Final Thoughts
Given that G biloba is a beautiful, commonly planted ornamental tree, gardeners and landscapers should be aware of the risk for allergic contact dermatitis and use proper protection. Dermatologists should be aware of its cross-reactivity with other common plants such as poison ivy and poison oak to help patients identify the cause of their reactions and avoid the inciting agent. Because ginkgo extract also can cause a cutaneous reaction or interact with other medications, providers should remember to take a thorough medication history that includes herbal medicines and supplements.