KUDOLO GINKGO BILOBA EXTRACT AND INSULIN PRODUCTION HERBAL MEDICINE HERBAL MEDICINE The Effect of 3-Month Ingestion of Ginkgo biloba Extract on Pancreatic β-Cell Function in Response to Glucose Loading in Normal Glucose Tolerant Individuals George B. Kudolo, PhD I t is currently estimated that alternative or comple- mentary medicine is used by more than 30% of the general North American population. In the United States alone, people have spent an estimated $21.2 bil- lion on alternative medicine; about $1.5 billion per year is spent on herbal medicines, with a projected an- nual growth of 15%. The use is said to be most common in individuals with chronic conditions, such as back problems, depression, and headaches. 1,2 Ginkgo biloba extract is an over-the-counter herbal dietary supple- ment that is taken to improve mental alertness and has been used clinically in Europe for the treatment of pe- ripheral and cerebral insufficiency and age-associated loss of cognitive function as seen in Alzheimer’s dis- ease. 3-5 A recent request for application (RFA) from the National Institute of Health (March 1999) for Ginkgo biloba clinical trials for treating loss of cognitive func- tion in the elderly confirms the growing importance of this herbal extract. Single-herb preparations of the Ginkgo biloba ex- tract are usually standardized to contain 24% flavone glycosides and 6% terpenoids. The flavonoid fraction, of which kaempferol and quercetin are recognized representatives, contributes to the antioxidant and free-radical scavenger properties of the Ginkgo biloba extract. They are believed to be responsible for protect- ing the brain from oxidative damage. 6-10 The terpenoid fraction, on the other hand, contains predominantly the ginkgolides that are antagonists of platelet- activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3- phosphocholine), a potent glycerophospholipid pro- duced by a variety of mammalian cells, including blood platelets and the brain. 11,12 I have recently hy- pothesized that control of the events surrounding the metabolism of PAF may play a significant role in ex- plaining the association of a cluster of metabolic de- fects with insulin resistance—termed the insulin resis- tance syndrome or syndrome X. 13-15 The metabolic defects constantly associated with diabetes include J Clin Pharmacol 2000;40:647-654 647 From the Department of Clinical Laboratory Sciences, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Submitted for publication December 2, 1999; revised version accepted February 22, 2000. Address for reprints: George B. Kudolo, PhD, FAIC, CPC, Depart- ment of Clinical Laboratory Sciences, School of Allied Health Sciences— 6246, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. Ginkgo biloba extract is ingested on a chronic basis for en- hancing mental focus and improving cognitive function in the elderly. This study was undertaken to determine the effect of Ginkgo biloba extract on glucose-stimulated pancreatic -cell function in normal glucose-tolerant individuals. Twenty individuals (14 females and 6 males, ages 21-57 years) underwent a 2-hour 75 g oral glucose tolerance test (OGTT) before and after ingestion of Ginkgo biloba extract (120 mg/day at bedtime) for 3 months. Ginkgo biloba extract ingestion caused a decrease in systolic blood pressure from 125 15 to 118 12 mmHg (p < 0.05) and in diastolic blood pressure from 86 10 to 68 10 (p < 0.01). Fasting plasma insulin and C-peptide were increased, and the insulin and C-peptide areas under the curve during the OGTT changed from 136 55 to 162 94 U/ml/h (p = 0.1232) and 9.67 5.34 to 16.88 5.20 ng/ml/h (p < 0.001), respectively. The observed dissimilar insulin/C-peptide response curves may be due to Ginkgo biloba–induced increase of the rate of insu- lin metabolic clearance. Journal of Clinical Pharmacology, 2000;40:647-654 ©2000 the American College of Clinical Pharmacology