Researchers found the popular plant supplement ginkgo biloba may help preserve memory in older octogenarians, but it may increase the risk of stroke.

by Judith Groch, Senior Writer, MedPage Today 

Corvallis, Ore., Feb. 27 —
The popular plant supplement ginkgo biloba may help preserve memory in older octogenarians, but it may increase the risk of stroke, researchers found.

Among 118 people 85 or older, those who took the supplement reliably had a 70% lower risk of developing mild memory problems than those who took a placebo, Hiroko Dodge, Ph.D., of Oregon State University here, and colleagues reported online in Neurology.

However there were six strokes and one TIA among those taking ginko and none in the placebo group.

The findings came from a randomized, placebo-controlled, double-blind, 42-month pilot study with cognitively intact individuals (about 60% women) randomized to standardized ginkgo extract or placebo. Sixty individuals took a ginkgo extract three times a day and 58 took placebo.

Gingko biloba was chosen as a possible preventive agent because it is already widely used even among the oldest old, is readily available, relatively inexpensive, and it has been shown in preclinical studies to have a plausible biologic efficacy as an antioxidant and on other brain aging mechanisms, the researchers wrote.

Participants were recruited by mass mailings from August 2000 through September 2001 to age-eligible individuals in the greater Portland area.

All participants had annual in-person interviews with six-month follow-up to assess changes in health status, including Mini-Mental State Examination (MMSE) scores. These individuals had common stable medical conditions such as heart disease and hypertension.

Kaplan-Meier estimation, Cox proportional hazard, and random-effects models were used to compare the risk of progression from Clinical Dementia Rating (CDR)=0 to CDR=0.5 and also the decline in episodic memory function between the two groups.

Overall, 21 people developed mild memory problems or questionable dementia, including 14 in the placebo group and seven who took the gingko extract, the researchers found.

In the unadjusted intention-to-treat analysis, ginkgo showed no protective effect on memory. The investigators found no reduced risk of progression to a clinical dementia rating of 0.5 (log-rank test, P=0.06) in the ginkgo group. There was also no decrease in the decline in memory function (P=0.05).

However, the researchers recognized that not all the people took the medications reliably, so they did a secondary analysis accounting for compliance.

Controlling for medication adherence, the ginkgo group had a lower risk of progression in the CDR=0 to CDR=0.5 (HR 0.33, 95% CI 0.12 to 0.89, P=0.02), and a smaller decline in memory scores (P=0.04).

The almost 70% protective effect did not change after controlling for other covariates at baseline, the researchers said. Only depressive symptoms predicted progression.

There was no overall difference in adverse events in the two groups during the study period (P=0.44 for difference in proportions).

However there were six ischemic strokes and one TIA (11.7%) in the ginkgo group compared with none in the placebo group (P=0.01).

Gingko has been reported to cause bleeding-related complications, the researchers said, but the strokes in this case were caused by blood clots, not excessive bleeding. More studies are needed to confirm this finding, they said.

There were no deaths from stroke, and there was no difference in rates of other events such as gastrointestinal ulcer, epitasis, or ecchymoses. Five individuals in each group died.

Dr. Dodge noted that this is the first randomized, controlled trial of dementia prevention in people 85 or older.

These data, he said, suggest that other larger studies should be able to establish a brain protective effect for ginkgo, assuming that such variables as dosing and the nature of the population samples enrolled (not a younger elderly group) are not major determinants.

To control medication management, the researchers suggested that once-a-day dosing might be preferable, although the optimum dosing regimen for ginkgo is not known.

The suggestion of a protective effect in this study needs to be confirmed in larger prevention trials taking into account medication compliance as well as the stroke findings, the researchers said.

These results suggest that this oldest population should not be excluded because of notions of frailty, poor adherence, or confounding medical problems. In fact, the investigators said, the participants were pleased to contribute to science and to “feel useful” at their advanced age.

The study was supported by grants from the National Institute on Aging and the National Center for Complementary and Alternative Medicine.

The ginkgo biloba extract was provided by Thorne Research, Inc.

The authors reported no conflicts of interest.

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Reviewed by Zalman S. Agus, MD; Emeritus Professor, University of Pennsylvania School of Medicine. 

Published: February 27, 2008

Primary source:


Source reference:

Dodge HH, et al “A randomized placebo-controlled trial of ginkgo biloba for the prevention of cognitive decline” Neurology 2008; 70: doi:10.1212/01.wwnl.0000303814.13509.db.