Effect of ginkgo biloba on blood pressure and incidence of ...

NIH Public Access Author Manuscript Am J Hypertens. Author manuscript; available in PMC 2010 November 21.

NIH-PA Author Manuscript

Published in final edited form as: Am J Hypertens. 2010 May ; 23(5): 528–533. doi:10.1038/ajh.2010.14.

Effect of ginkgo biloba on blood pressure and incidence of hypertension in elderly men and women Tina E. Brinkley, PhD1, James F. Lovato, MS1, Alice M. Arnold, PhD2, Curt D. Furberg, MD, PhD1, Lewis H. Kuller, MD, DrPH3, Gregory L. Burke, MD, MS1, Richard L. Nahin, PhD, MPH4, Oscar L. Lopez, MD3, Sevil Yasar, MD, PhD5, and Jeff D. Williamson, MD, MHS1 for the Ginkgo Evaluation of Memory (GEM) Study Investigators 1 Wake Forest University School of Medicine, Winston-Salem, NC 2

University of Washington, Seattle, WA

3

University of Pittsburgh, Pittsburgh, PA

4


National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 5

Johns Hopkins University, Baltimore, MD

Abstract Background—Accumulating evidence suggests that ginkgo biloba is cardioprotective, in part, through its vasodilatory and antihypertensive properties. However, definitive data on its blood pressure-lowering effects in humans is lacking. Methods—We determined the effects of ginkgo biloba extract (240 mg/day) on blood pressure and incident hypertension in 3,069 participants (mean age, 79 yrs; 46% female; 96% White) from the Ginkgo Evaluation of Memory study. We also examined whether the treatment effects are modified by baseline hypertension status.


Results—At baseline 54% of the study participants were hypertensive, 28% were prehypertensive, and 17% were normotensive. Over a median follow-up of 6.1 years, there were similar changes in blood pressure and pulse pressure in the ginkgo biloba and placebo groups. Although baseline hypertension status did not modify the antihypertensive effects of ginkgo biloba, it did influence the changes in blood pressure variables observed during follow-up, with decreases in hypertensives, increases in normotensives, and no changes in pre-hypertensives. Among participants who were not on antihypertensive medications at baseline, there was no difference between treatment groups in medication use over time, as the OR (95% CI) for being a never-user in the ginkgo biloba group was 0.75 (0.48–1.16). The rate of incident hypertension also did not differ between participants assigned to ginkgo biloba vs. placebo (HR, 0.99, 95% CI, 0.84– 1.15). Conclusions—Our data indicate that ginkgo biloba does not reduce blood pressure or the incidence of hypertension in elderly men and women.

Corresponding Author: Tina E. Brinkley, Sticht Center on Aging, Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157. Phone: 336-713-8534; Fax: 336-713-8588; [email protected]. Disclosures The authors have no conflicts of interest to report.

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Keywords


gingko biloba; blood pressure; hypertension; elderly

Introduction Ginkgo biloba extract is an herbal dietary supplement commonly used for the treatment and prevention of aging-related cognitive decline and dementia.1 Several studies also suggest a cardioprotective effect of ginkgo biloba through its antioxidant, antiplatelet, antithrombotic, and vasodilatory properties.2 Furthermore, ginkgo biloba may have significant antihypertensive properties as well, providing a possible alternative mechanism for cardiovascular disease prevention. In hypertensive rats treatment with ginkgo biloba attenuated the rise in blood pressure (BP), such that systolic BP was 11–21% lower, diastolic BP was 7–10% lower, and mean BP was 28% lower in treated vs. untreated rats.3– 7 Interestingly, these BP-lowering effects appeared to occur early in the development of hypertension and were not observed in normotensive rats.


Few studies have investigated the effects of ginkgo biloba on BP in humans. Two small studies in young, normotensive subjects showed no change in BP after 1 to 6 weeks of gingko biloba.8, 9 In contrast, 3 months of ginkgo biloba led to a 6% reduction in systolic BP and a 21% reduction in diastolic BP in a slightly older, pre-hypertensive population.10 The reasons for these contrasting results are likely due, in part, to differences in the treatment duration and study population. Taken together, these findings emphasize the need for a large, randomized controlled trial that can address the effects of ginkgo biloba on BP in humans. The Ginkgo Evaluation of Memory (GEM) study provides a unique opportunity to examine this relationship in elderly community-dwelling adults. In the present analysis we hypothesized that participants randomized to the treatment arm would have greater reductions in BP and pulse pressure (PP) than participants randomized to placebo. Based on previous studies in rats and humans, we also hypothesized that these BP-lowering effects would be influenced by the baseline hypertension status.

Methods Study Population


The GEM study is a double-blind, placebo-controlled, randomized clinical trial evaluating the effectiveness of ginkgo biloba (240 mg/day) in the prevention of dementia in older adults over a median follow-up of 6.1 years.11 A total of 3,069 participants were recruited between September 2000 and June 2002 from four clinical centers: Johns Hopkins University, University of California at Davis, University of Pittsburgh, and Wake Forest University. Eligibility requirements included being free of dementia,≥75 yrs of age, a primary English speaker, and able to enroll a proxy. Individuals were excluded if they were demented or taking warfarin, antipsychotic medications, or cholinesterase inhibitors. Individuals who were unwilling to reduce their vitamin E intake to 400 IU/day or stop taking ginkgo biloba were also excluded from the trial. Additional exclusions included a history of bleeding disorders, cancer within the past 5 years, congestive heart failure with disability, untreated depression, hospitalization for depression in the past year, and Parkinson's disease. All sites obtained approval from their institutional review boards. Signed informed consent was obtained from GEM study participants and their respective proxies.

Am J Hypertens. Author manuscript; available in PMC 2010 November 21.

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Study Intervention


Participants were randomized to either 120-mg of ginkgo biloba extract (EGb 761; Schwabe Pharmaceuticals, Karsruhe, Germany) or an identically appearing placebo twice a day. The composition of the active and placebo tablets was confirmed by independent laboratory testing.11 Group assignment was determined by permuted block design by clinical site, and each site used a computer-generated, randomly permuted list to randomize participants. All participants and clinical personnel were blinded to the treatment assignment. Only the study pharmacist who allocated the treatments into batches and the coordinating center personnel who reported to the study Data and Safety Monitoring Board knew which pills were active; however, they were unaware of participant information. Study Outcomes


The primary outcomes were systolic and diastolic BP, PP, and incident hypertension. BP was measured in the right arm using a standard mercury sphygmomanometer (W.A. Baum Company, Inc., Copiague, NY) with the subject seated and resting quietly for at least 5 minutes. An appropriately-sized cuff was inflated rapidly to 20 mmHg above the palpated systolic pressure and deflated at 2 mmHg/s. The 1st-phase and 5th-phase Korotkoff sounds were used to identify systolic and diastolic BP, respectively. The average of 2 measurements was used in the analysis. PP was calculated as the difference between systolic and diastolic BP. At baseline, individuals were categorized into 3 groups according to guidelines from The Seventh Report of the Joint NationalCommittee on Prevention, Detection, Evaluation, and Treatmentof High Blood Pressure (JNC-7).12 Individuals were classified as hypertensive if any of the following criteria were met: 1) self-reported hypertension and concomitant use of antihypertensive medications; 2) systolic BP≥140 mmHg; or 3) diastolic BP ≥90 mmHg. Individuals were classified as normotensive if they had a systolic BP