Once again another clinical trial demonstrates that the supplement ginkgo biloba is ineffective in preventing Alzheimer's Disease.

Forget About Ginkgo to Ward Off Alzheimer's

By Kristina Fiore, Staff Writer, MedPage Today

Published: September 05, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

 

 

Yet another large trial has failed to find long-term ginkgo biloba supplements effective at preventing Alzheimer's disease.

 

In a randomized, controlled trial of elderly patients who had complaints about their memory -- but no overt dementia -- there were no significant differences in the number of patients who progressed to dementia over 5 years whether they were taking ginkgo or placebo, Bruno Vellas, MD, of Hopital Casselardit in Toulouse, France, and colleagues reported in The Lancet Neurology.

Ginkgo has been used in some countries by patients with cognitive disorders, and its plausible mechanisms of action for brain benefits include antioxidant effects and potential inhibition of caspase-3 activation and amyloid-beta aggregation, the researchers wrote.

Yet several studies -- including the Ginkgo Evaluation of Memory trial reported in 2008 -- haven't been able to demonstrate that the plant extract can prevent dementia. Indeed, the entire field of prevention of Alzheimer's disease is lacking, with little effects seen for various therapies including hormone replacement therapy, NSAIDs, vitamins, and cholinesterase inhibitors, the researchers noted.

To further assess ginkgo's effects, Vellas and colleagues conducted the GuidAge trial of adults, ages 70 and up, who were free of dementia but reported memory complaints to their primary care doctors in France.

A total of 2,854 patients were enrolled between March 2002 and November 2004 and randomized to placebo or to 120 mg of ginkgo biloba extract twice a day.

Patients were followed for a median of 5 years, with 2,487 completing the trial.

Overall, the researchers found no significant difference in the proportion of patients who developed dementia over those 5 years: 61 in the ginkgo arm and 73 in the placebo group (HR 0.84, 95% CI 0.60 to 1.18, P=0.306).

That translated to a similar incidence of probable Alzheimer's disease: 1.2 per 100 person-years in the ginkgo group compared with 1.4 per 100 person-years in the placebo group.

Nor were there significant differences in diagnoses of pure Alzheimer's or mixed dementia: 70 among those on ginkgo and 84 among those on placebo, for a rate of 1.4 per 100 person-years and 1.6 per 100, respectively (P=0.267).

Also, the incidence of adverse events was similar between groups:

• Death: 76 for ginkgo, 82 in placebo (HR 0.94, 95% CI 0.69 to 1.28, P=0.68)
• Stroke: 65 for ginkgo, 60 in placebo (RR 1.12, 95% CI 0.77 to 1.63, P=0.57)

There were no differences in the incidence of other hemorrhagic or cardiovascular events, either, they added.

The study was limited because the number of dementia events was much lower than expected, leading to a lack of statistical power to detect effects, the researchers noted. There was also some evidence of selection bias, as those who chose to participate had a higher level of education than the general elderly population.

In an accompanying editorial, Lon Schneider, MD, of the University of Southern California in Los Angeles, wrote that more than 10,000 patients have now been involved in clinical trials of ginkgo biloba with no reported benefits.

"The GuidAge trial adds to the substantial evidence from the Ginkgo Evaluation of Memory trial ... that ginkgo biloba does not prevent dementia in elderly individuals with or without memory complaints or cognitive impairment and is not effective for prevention of Alzheimer's disease," Schneider wrote.

"It would be unfortunate if users of ginkgo biloba, nevertheless, are led to believe that the extract prevents the dementia. Some users will rationalize that, in the absence of effective treatments, ginkgo biloba could still possibly help, and appearing safe, will not harm them," he added.

But other users, he wrote, "might now consider letting it go."

Nikos Scarmeas, MD, from Columbia University Medical Center in New York City, said in an email to MedPage Today that the trial was "very well designed and executed" with a "long enough follow-up to see conversion."

When asked about the dearth of preventive strategies for Alzheimer's, Scarmeas acknowledged that there's little advice for Alzheimer's prevention. But "with an increasing number of scientists and researchers in the field and commitment and investment from society, we can be hopeful it will change in the future," he said.

The study was supported by Ipsen, producer of ginkgo biloba extract.
Two researchers are employees of Ipsen.
Scheider reported relationships with Ipsen and Schwabe, both makers of ginkgo extract. He also reported relationships with Baxter, Genentech, Johnson & Johnson, Eli Lilly, Novartis, Pfizer, Abbott Laboratories, AC Immune, Allon, AstraZeneca, Bristol-Myers Squibb, Elan, Exonhit, GlaxoSmithKline, Lundbeck, MedAvante, Merck, Roche, Sanofi, Servier, Takeda, Toyama, and Zinfandel.

Primary source: The Lancet Neurology
Source reference:
Vellas B, et al "Long-term use of standardized ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): A randomized placebo-controlled trial" Lancet Neurol 2012; DOI: 10.1016/S1474-4422(12)70206-5.

Additional source: The Lancet Neurology
Source reference:
Schneider LS "Ginkgo and AD: Key negatives and lessons from GuidAge" Lancet Neurol 2012; DOI: 10.1016/S1474-4422(12)70212-0.