Ginkgo Biloba: Research, Benefits and Side Effects

Ginkgo is derived from the leaves of the ginkgo tree, one of the oldest species of trees, and has been used for thousands of years by the Chinese as an herbal remedy for a variety of ailments. The typical daily dose of ginkgo biloba is 120 milligrams of dried extract in two or three oral doses. The extract contains several flavonoids, a large group of natural plant products that are characterized by a specific chemical structure containing a series of carbon rings. Ginkgo extract also contains some biflavonoids, a related group of compounds, and two different types of terpenes, a class of naturally occurring chemicals that includes the active ingredients in catnip and marijuana.

Today ginkgo biloba is perhaps the most widely used herbal treatment aimed at augmenting cognitive functions — that is, improving memory, learning, alertness, mood and so on. In Europe, ginkgo is an important part of mainstream medicine, with sales accounting for more than 1 percent of all pharmaceutical purchases. In the U.S. alone, $310 million dollars worth was sold in 1998. But is its popularity based on folklore or on experimental findings?

While dozens of investigations have examined the cognitive effects of ginkgo in humans, many of the research reports are in non-English publications or in journals with very restricted distribution, making assessment of the findings difficult. The great majority of studies have involved subjects with mild to moderate mental impairment, usually a diagnosis of early Alzheimer's. Most of the experiments that show evidence of cognitive enhancement in Alzheimer's patients have used a standardized ginkgo extract known as EGb 761.

Ginkgo Biloba and Alzheimer’s

In 1998 Barry S. Oken of Oregon Health Sciences University and his colleagues considered more than 50 studies involving subjects with mental impairment and selected four that met a conservative set of criteria, including sufficient characterization of the Alzheimer's diagnosis, use of a standardized ginkgo extract, and a placebo-controlled, double-blind design (in which neither the subjects nor the investigators know until the end whether a given patient is receiving the extract or the placebo). Each of these studies showed that the Alzheimer's patients who received ginkgo performed better on various cognitive tests than did patients who received a placebo. Improvements were evident in standardized tests measuring attention, short-term memory and reaction time; the average extent of improvement resulting from ginkgo treatment was 10 to 20 percent.

Oken and his colleagues reported that ginkgo's effect was comparable to that of the drug donepezil, which is currently the treatment of choice for Alzheimer's.

Despite these apparently encouraging findings, though, another recent, large and well-controlled trial of EGb 761 (sponsored by its manufacturer, Dr. Willmar Schwabe Pharmaceuticals in Karlsruhe, Germany) involving patients with a mild or moderate stage of dementia reported no "systematic and clinically meaningful effect of ginkgo" on any of the cognitive tests employed.

Ginkgo Biloba for Age-Related Memory Loss

Researchers at the UCLA Neuropsychiatric Institute examined the impact of ginkgo biloba, compared to a placebo, in 10 patients, aged 45 to 75, who did not have dementia but complained of mild age-related memory loss. Over a period of six months four subjects received 120 mg of ginkgo biloba twice daily, and six received a placebo or inactive substance such as a sugar pill.

Researchers used cognitive tests to measure verbal recall and PET to measure brain metabolism before and after the treatment regimen. When compared with the group that received a placebo, they found significant improvement in verbal recall among the group of people who received ginkgo biloba. However, actual changes in brain metabolism, measured by PET for the first time, did not differ significantly between the study's two volunteer groups.

It should be noted that ginkgo has also been shown to impair performance. For example, in a small study of elderly people with mild to moderate memory impairment, Gurcharan S. Rai of Whittington Hospital in London and his team found that after 24 weeks of treatment, patients who took ginkgo could not recall digits as well as patients who received a placebo.

Ginkgo Biloba and Multiple Sclerosis

Another study, presented at the American Academy of Neurology's 57th Annual Meeting in Miami Beach, Fla., suggests that ginkgo may be effective in improving the attention of multiple sclerosis patients with cognitive impairment.

The study's lead author, Jesus Lovera, M.D., a research fellow and instructor in neurology, OHSU School of Medicine, said those receiving ginkgo "performed better on a test that measures a person's ability to pay attention and to sort conflicting information."

Of 39 patients completing the study, 20 received ginkgo biloba and 19 received a placebo. Researchers found there were no differences in results between the two groups in the areas of gender, education, type of MS, years since onset, or baseline performance on a battery of neuropsychological tests.

But the ginkgo group was four seconds — about 13 percent — faster than the placebo group on a timed color and word test that measures attention and such "executive functions" as planning, decision making, and controlling goal-directed behavior and execution of deliberate actions.

Ginkgo Biloba and Healthy Older Adults

However, researchers at Williams College in Williamstown, Mass. and The Memory Clinic in Bennington, Vt. found no beneficial effect on memory and related mental functions of healthy older adults. This study was reported in the Aug. 21st issue of the Journal of the American Medical Association.

The researchers identified 230 volunteers over the age of 60 who were physically and mentally healthy. They gave them 14 tests of learning, memory, and attention and concentration, and had them and their companions (e.g. spouses, partners, close friends) rate the participants' mental functions on subjective scales. Participants were then randomly divided into two groups: one to take ginkgo and one placebo. The study was double blind; neither the participants nor the researchers knew who was taking ginkgo and who was taking placebo.

After six weeks, participants in the study retook the 14 standardized tests and they and their companions re-rated participants' mental functions. There were no significant differences between those taking ginkgo and those taking placebo on any of the objective or subjective measures.

Ginkgo Biloba for Brain and Breast Tumors

Animal experiments, conducted at the Georgetown University Medical Center, found that ginkgo biloba may have preventive effects for cancerous human brain and breast tumors.

In the January-February 2006 issue of the journal Anticancer Research, the investigators reported that treating mice with an extract of leaves of ginkgo biloba both before and after implanting human breast or brain (glioma) tumors decreased expression of a cell receptor associated with invasive cancer. This decreased expression slowed the growth of the breast tumors by 80 percent as long as the extract was used, compared to untreated mice, and also reduced the size of the brain tumors, but temporarily, and to a lesser extent.

"It is very encouraging that ginkgo biloba appeared to reduce the aggressiveness of these cancers, because it suggests that the leaves could be useful in some early stage diseases to prevent them from becoming invasive, or spreading," said the study's senior author, Vassilios Papadopoulos, DPharm, PhD, Director, Biomedical Graduate Research Organization and Associate Vice President of Georgetown University Medical Center.

"But I must stress that this is a study in mice, and so we cannot say what anticancer effects, if any, ginkgo biloba might offer humans," he said.

Safety and Precautions

In general ginkgo is quite safe, though some people will experience upset stomach or nausea, says Dr. Ben Kligler in an article entitled, "Herbal medicines for older adults". "The one concern has to do with ginkgo’s blood-thinning properties," he says. "Ginkgo can interfere with the action of platelets, a type of blood element which is crucial to blood clotting. There are a few (and only a few) case reports of patients on ginkgo having unusual or excessive bleeding. Given the huge numbers of people who have been taking ginkgo over the past few years, the number of cases of bleeding reported is actually very small. To be on the safe side, however, patients on strong blood-thinning medications like Coumadin should probably not take ginkgo. If you take aspirin or other blood thinners, you should discuss this issue with your doctor. And if you are preparing for a surgical procedure and you take ginkgo, you should probably stop a week or so before the surgery to reduce the chance of any bleeding complications."

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