666 REVIEW ARTICLE Ginkgo biloba Extract: Mechanisms and Clinical Indications Bruce J. Diamond, PhD, Samuel C. Shiflett, PhD, Nancy Feiwel, MD, Robert J. Matheis, MA, Olga Noskin, BA, Jennifer A. Richards, BA, Nancy E. Schoenberger, PhD- ABSTRACT. Diamond BJ, Shiflett SC, Feiwel N, Matheis RJ, Noskin 0, Richards JA, Schoenberger NE. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil 2000;81:668-78. Objective: Ginkgo biloba may have a role in treating impairments in memory, cognitive speed, activities of daily living (ADL), edema, inflammation, and free-radical toxicity associated with traumatic brain injury (TBI), Alzheimer’s dementia, stroke, vasoocclusive disorders, and aging. The purpose of this review is to provide a synthesis of the mechanisms of action, clinical indications, and safety of Ginkgo biloba extract. Data Sources: Empirical studies, reviews, chapters, and conference proceedings were identified in the following data- bases: Medline, the Research Council for Complementary Medicine based on the British Library database, and PsychInfo. Ginkgo bifoba, EGb 761, Tanakan, Tebonin, Rokan, and LI 1370 were the principal index terms. Study Selection and Data Extraction: Controlled clinical studies with both positive and negative findings are included, in addition to animals studies illustrating mechanisms of activity. Data Synthesis: Ginkgo has shown activity centrally and peripherally, affecting electrochemical, physiologic, neuro- logic, and vascular systems in animals and humans with few adverse side effects or drug interactions. Ginkgo shows promise in patients with dementia, normal aging, and cerebrovascular- related disorders. Clinical indications include memory, informa- tion processing, and ADL. Conclusions: Ginkgo shows promise in treating some of the neurologic sequelae associated with Alzheimer’s disease, TBI, stroke, normal aging, edema, tinnitus, and macular degenera- tion. Mechanisms of action may include antioxidant, neurotrans- mitter/receptormodulatory, and antiplateletactivatingfactor proper- ties. While safe,caution is advisedwhen recommending ginkgo to patients taking anticoagulants. Future studiesshould examine dose effects,component activity, mechanisms, and clinical applications. Key Words: Ginkgo biloba; EGb 761; Traumatic brain injury; Stroke; Aging; Dementia; Rehabilitation. 0 2000 by the American Congress of Rehabilitation Medi- cine and the American Academy of Physical Medicine and Rehabilitation Fmm the Center for Research in Complementary and Alternative Medicine. Kessler Medical Rehabilitation Research and Education Corporation, West Orange. NJ: the Deoartment of Phvsical Medicine and Rehabilitation and Deoartment of Psvchiatrv. University of Me&zinc and Dentistry, Newark, NJ (Drs. Diakond, ShiRett,‘&hocn- bcrger); and Department of Psychology, William Paterson University, Wayne. NJ (Dr. Diamond). Submitted March 22. 1999. Accepted in revised form July 27, 1999. Supported by grant U24HD32994 from the National Institutes of Health. No commercial party having a direct financial interest in the results of the research supporting this article ha.. or will confer a bcnefir upon the authors or upon any organization with which the authors arc associated. Reprint requests to Dr. Bruce J. Diamond, Kessler Medical Rehabilitation Research and Education Corporation, Department of Research, II99 Pleasant Valley Way. West Orange. NJ 07052. 0 2ooO by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation 0003~9993/00/8105-5527$3.00/O doi: IO. 1053/mr.2000.3840 H ERBAL PRODUCTS account for a substantial portion of the current interest in alternative treatments and Ginkgo biloba (GB) figures prominently in this interest. Interest in GB. however, has a long history. Fossil records place its origins 150 to 250 million years ago.’ Ginkgo (derived from the Chinese Yin-Kuo, meaning “silver apricot”) biloba (refering to its two-lobed, fan-shaped leaves) is derived from the leaf of the Maidenhair tree, which is believed to live 2,000 to 4,000 years.? Interest in the medicinal properties of GB can be traced back some 5,000 years to ancient China, where the healer Chen Noung (2767 to 2687 BC) described the medicinal properties of the plant in the first known pharmacopoeia. called the Chen Noung Pen T’sao.’ Indications included ailments of the heart and lungs with the notation that inhaling its steam and imbibing its tea were palliative for both asthma and bronchitis.? While firmly rooted in antiquity, GB is today the most frequently prescribed herbal preparation in Germany3 and one of the most commonly used over-the-counter (OTC) herbal preparations in the United States.4 In 1964, a GB extract called EGb 761 was developed by a German pharmaceutical company, and since that time hundreds of studies have examined ginkgo’s effects in human and animal models. The German Commission Es (equivalent to the US Food and Drug Administration for botanicals) has approved GB for symptomatic treatment of deficits in memory, concentration, and depression from organic brain disease. GB extract or one of its components has been extensively studied in terms of its effects on the cognitive, physiologic, and psychiatric sequelae associated with neurologic and vascular conditions. Specific functions and conditions include recall/ recognition memory, reaction time, attention, concentration, psychomotor function, fatigue, mood, outcomes, and informa- tion processing speed. GB has also been used experimentally in treating impairments and symptoms in Alzheimer’s and age- associateddementia, traumatic brain injury, stroke, multi-infarct dementia, cerebral atherosclerosis, cerebral insufficiency, cerebral edema, inflammation, glutamate toxicity, necrosis, apoptosis,tinni- tus, sexual dysfunction, and macular degeneration. This review will provide a synthesis of the mechanisms of action, clinical indications, and safety of GB extract. DATA SOURCES AND DEFINITIONS This review consists of peer-reviewed articles, conference proceedings, and relevant book chapters including a number of articles translated from German. Sources were identified using various strategies: (1) computer searches of the National Library of Medicine’s Medline database (1966 to 1998), PsychInfo, and the British Library’s Research Council for Complementary Medicine’s database; and (2) citation tracking of references in articles and textbooks. The search words and acronyms were Ginkgo biloba, EGb 761, Tanakan, Tebonin, Rokan, and LI 1370 (Kaveri), the latter being brand names of GB extract. Dozens of GB extract products are currently available to consumers. Most of these products use a 5O:l ratio by weight (50 pounds of leaf for each pound of extract) and are standard- ized to include 24% to 26% ginkgo flavonol glycosides. Many of the OTC ginkgo products may not be standard- Amh Phys Mad Rehabil Vol81, May 2000