Ginkgo Biloba
Ginkgo biloba, commonly known as ginkgo, is a species of tree (also known as duck foot, maidenhair, and silver apricot) native to China. Extracts of the leaves and seeds have long been used in alternative medicine for their antioxidant properties and to address mental conditions such as poor concentration, impaired blood flow to the brain, and dementia1,2. Active chemicals include the diterpenes ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J; the sesquiterpene bilobalide; flavonols, including kaempferol, quercetin, and isorhamnetin; flavones, including luteolin and tricetin; biflavones, mainly bilobetin, ginkgetin, isoginkgetin, and sciadopitysin; catechins; proanthocyanidins; sterols; and 6-hydroxykynurenic acid (6-HKA)3.
In a randomized placebo-controlled clinical study in MS patients, Ginkgo biloba extract at a dose of 240 mg/day was associated with improvement in fatigue, symptom severity, and functionality (physical, social, and emotional)4.
Interestingly, while Ginkgo biloba has been linked to improved cognition (a type of mental functioning) in individuals with neurodegenerative conditions like Alzheimer’s5,6, clinical studies focusing on MS specifically have not yet found an advantage7,8.
When selecting a Ginkgo biloba supplement, it is generally recommended to seek a standardized extract yielding 24% ginkgolides1,3,9.
In the fetus, the possible impact of Ginkgo biloba extract has been well-documented in animal models, but with conflicting results. In one study, doses of 7 mg/kg/day and 14 mg/kg/day were associated with impaired fetal growth10, where in another, no toxic effect on mothers and no fetal malformations were observed after using up to 14 mg/kg/day11. At a dose of 100 mg/kg/day, malformations were observed12, whereas in another doses of 100 mg/kg/day and 300 mg/kg/day administered to pregnant animals were associated with neurotrophic benefits in their fetuses. Of note, the latter study also demonstrated activation of the genes associated with the benefits at a much lower dose of 25 mg/kg/day13. When high doses of the Ginkgo compounds ginkgolide A (98-1571 mcg) and ginkgolide B (147-836 mcg) were analyzed in embryonic chick heart and mouse stem cells, it was also concluded that these compounds used in the first trimester of pregnancy might not be safe for fetal development14. No less important, some scientific evidence from non-clinical studies suggests that Ginkgo leaf may prolong bleeding time, which could be of concern during labor15.
Data on the safety of Ginkgo biloba in nursing mothers is currently limited16,17. An experiment in nursing rats found no toxic effects on mothers or to the physical, motor and sensory development of their offspring17.
References
1.Liu XG, Lu X, Gao W, Li P, Yang H. Structure, synthesis, biosynthesis, and activity of the characteristic compounds from Ginkgo biloba L. Nat Prod Rep. Sep 28 2021;doi:10.1039/d1np00026h
2.Murray MT, Nowicki, J. Ginkgo biloba (Ginkgo Tree). In: Pizzorno JE, Murray, M.T., ed. Textbook of Natural Medicine (Fifth Edition). Churchill Livingstone; 2020:620-628.e2:chap 82.
3.Council. AB. Ginkgo biloba leaf extract. Herbal Medicine: Expanded Commission E Monographs Accessed 21 Jan 2022. https://www.herbalgram.org/resources/expanded-commission-e/ginkgo-biloba-leaf-extract/
4.Johnson SK, Diamond BJ, Rausch S, Kaufman M, Shiflett SC, Graves L. The effect of Ginkgo biloba on functional measures in multiple sclerosis: a pilot randomized controlled trial. Explore (NY). Jan 2006;2(1):19-24. doi:10.1016/j.explore.2005.10.007
5.Kandiah N, Chan YF, Chen C, et al. Strategies for the use of Ginkgo biloba extract, EGb 761((R)) , in the treatment and management of mild cognitive impairment in Asia: Expert consensus. CNS Neurosci Ther. Feb 2021;27(2):149-162. doi:10.1111/cns.13536
6.Nowak A, Kojder K, Zielonka-Brzezicka J, et al. The Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer’s Disease. Front Pharmacol. 2021;12:775034. doi:10.3389/fphar.2021.775034
7.Lovera J, Bagert B, Smoot K, et al. Ginkgo biloba for the improvement of cognitive performance in multiple sclerosis: a randomized, placebo-controlled trial. Mult Scler. Apr 2007;13(3):376-85. doi:10.1177/1352458506071213
8.Lovera JF, Kim E, Heriza E, et al. Ginkgo biloba does not improve cognitive function in MS: a randomized placebo-controlled trial. Neurology. Sep 18 2012;79(12):1278-84. doi:10.1212/WNL.0b013e31826aac60
9.van Beek TA, Montoro P. Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals. J Chromatogr A. Mar 13 2009;1216(11):2002-32. doi:10.1016/j.chroma.2009.01.013
10.Pinto RM, Fernandes ES, Reis JE, Peters VM, Guerra Mde O. Intra-uterine growth retardation after prenatal administration of Ginkgo biloba to rats. Reprod Toxicol. Jun 2007;23(4):480-5. doi:10.1016/j.reprotox.2006.12.008
11.Fernandes ES, Pinto RM, de Paula Reis JE, de Oliveira Guerra M, Peters VM. Effects of Ginkgo biloba extract on the embryo-fetal development in Wistar rats. Birth Defects Res B Dev Reprod Toxicol. Apr 2010;89(2):133-8. doi:10.1002/bdrb.20235
12.Zehra U, Tahir M, Lone KP. Ginkgo biloba induced malformations in mice. J Coll Physicians Surg Pak. Feb 2010;20(2):117-21.
13.Li W, Trovero F, Cordier J, Wang Y, Drieu K, Papadopoulos V. Prenatal exposure of rats to Ginkgo biloba extract (EGb 761) increases neuronal survival/growth and alters gene expression in the developing fetal hippocampus. Brain Res Dev Brain Res. Sep 10 2003;144(2):169-80. doi:10.1016/s0165-3806(03)00168-8
14.Mohammed OJ, Latif ML, Pratten MK. Evaluation of embryotoxicity for major components of herbal extracts using the chick embryonic heart micromass and mouse D3 embryonic stem cell systems. Reprod Toxicol. Jan 2016;59:117-27. doi:10.1016/j.reprotox.2015.12.003
15.Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of ginkgo (Ginkgo biloba) during pregnancy and lactation. Can J Clin Pharmacol. Fall 2006;13(3):e277-84.
16.Ginkgo. Drugs and Lactation Database (LactMed(R)). 2006.
17.de Faria DE, Borges LV, Peters VM, et al. Postnatal development of pups from nursing rats treated with Gingko biloba. Phytother Res. Feb 2008;22(2):185-9. doi:10.1002/ptr.2282