Ginkgo biloba for Dementia Prevention

Abstract & Commentary

By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.

Synopsis: A randomized, double-blind trial found no difference comparing Ginkgo biloba with placebo in the incidence of dementia or Alzheimer's disease.

Source: DeKosky ST, et al. Ginkgo biloba for prevention of dementia: A randomized controlled trial. JAMA 2008;300:2253-2262.

A randomized, double-blind, placebo-controlled trial comparing Ginkgo biloba with placebo for the prevention of dementia enrolled 3069 elderly individuals (older than age 75) in 5 academic centers in the United States. The participants were randomized to bid doses of 120 mg ginkgo or placebo (45% female in the ginkgo group and 47% female in the placebo group). The ginkgo formulation and dosage were that used in many of the brands sold in the United States. The dementia rate steadily increased in both groups over a 7-year period of follow-up, accumulating 277 cases (17.9%) in the treatment group and 246 cases (16.1%) in the placebo group. The rate of dementia did not differ between the two groups, nor did the rate of Alzheimer's disease. There were no differences in adverse events or mortality rates. The authors concluded that ginkgo at a dose of 120 mg bid was ineffective for the prevention of dementia.


Ginkgo biloba is an extract prepared from the leaves of the G. biloba tree. It contains flavonoids and unique terpene lactones. Ginkgo biloba is a multi-million dollar herb sold in the United States for the preservation of memory. In vitro studies suggested that ginkgo had antioxidant (from the flavonoids) and anti-amyloid (from the lactones) effects. Indeed, the biologic studies provided a strong rationale for the use of ginkgo, but early clinical trials had mixed results. This American trial and one ongoing trial in Europe are the first to be adequately powered to evaluate the efficacy and safety of ginkgo.

The American trial robustly demonstrated that Ginkgo biloba in the tested and commonly used dose did not delay the onset of dementia. The concept of "delay" is important. A treatment that could delay the onset of dementia by 5 years would reduce the number of dementia cases by 50%. In fact, this clinical trial found a statistically significant increase in the risk for developing dementia with ginkgo treatment in the 25% of participants who had cardiovascular disease prior to enrollment (hazard ratio = 1.56; confidence interval, 1.14-2.15). However, the authors appropriately urge caution in interpreting this subgroup analysis. A Cochrane review in 2007 of 35 clinical trials with 4247 participants concluded that there was no convincing evidence that ginkgo treatment benefited individuals who already had dementia or cognitive impairment.1

This was a well-designed, strong study, with a high rate of follow-up and adherence to treatment (a real tribute to the motivation of this elderly population). This is mainly a true primary prevention trial in that the participants had normal cognition at baseline. Nevertheless, some of the participants must have had the early pathology of Alzheimer's, even though they were free of symptoms. But it should be noted, that there was no difference between the groups when participants with mild cognitive impairment before treatment were compared. The outcomes were adjudicated by a blinded expert committee. It is possible that some benefit might have emerged with longer treatment, but this is unlikely. Most importantly, the formulation and dose of the herb were standardized and comparable to what is being sold and used in the United States. Besides the lack of effect on dementia, the study detected no favorable effects on cardiovascular events. A warning was raised because of more hemorrhagic strokes in the treated group, but the numbers were very small (16 in the treated group and 8 in the placebo group).

Besides the negative results of this clinical trial, there are other lessons to be emphasized. First, "alternative" treatments that are not regulated must be subjected to the same rigorous studies as branded drugs. Second, it is striking that studies that are independently funded usually have negative results in contrast to alternative industry-funded studies. Third, preclinical studies that are encouraging do not always translate into true clinical efficacy.

I have often stated that "there is only one medicine." When alternative treatments yield beneficial results in well-designed clinical trials, then these treatments will be incorporated into our practices. When they fail to demonstrate efficacy and safety, as is often the case, it is appropriate to discourage their use, and ultimately, this will be the future of alternative medicine.


  1. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2007;(2):CD003120; doi:10.1002/14651858.