Extracts from the leaves of the ginkgo biloba tree have been used therapeutically in China for millennia. According to fossil records, the ginkgo tree has been around for over 200 million years and is one of the oldest still-existing tree species on earth. Individual trees live up to one thousand years. Ginkgo, like ginseng, is mentioned in the traditional Chinese pharmacopoeia. Ginkgo extracts are among the most widely studied and prescribed drugs in Europe to alleviate symptoms associated with a wide range of conditions. The main indications for these extracts are peripheral vascular disease and the therapy of age-related cognitive decline. Ginkgo contains many different substances, but most of them fall into two main categories: flavonoids and terpene lactones.
Flavonoids are natural substances that are also found 1n fruits and vegetables. Flavonoids act as antioxidants, have an influence on the immune system, and interfere with tumor formation. Ginkgo contains many flavonoids, but the most concentrated are kaempferol, quercetin, and isorhamnetin. Most ginkgo products on the market list a flavonoid concentration of 24 percent - you will often see "24%" printed on packages or bottles of ginkgo. Terpene lactones are what give ginkgo a bitter and strong flavor. The most important terpenes are the ginkgolides and bilobides. Ginkgolides have not yet been found in any other living plant species.
At least two-thirds of individuals I have treated or interviewed have noticed positive benefits from ginkgo. Gerry, a seventy-seven-year-old retired postal worker, says. "Ginkgo has helped my tinnitus [ringing in the ears]. It also works very well in keeping me alert and focused. I take 60 mg for breakfast and lunch." Mandy, a sixty-six-year-old actress, likes the effect of this herb. She reports, "I've been taking ginkgo for about four months now, and the improvement in my memory function is so much better I wouldn't even consider not taking it now."
However, not everyone notices benefits. Sandra, a thirty-seven-year-old, is disappointed. She says, "I took ginkgo for a period of six months after I heard all the positive benefits that other people were experiencing. Frankly, I haven't noticed any major difference."
The active ingredients in ginkgo are believed to produce their beneficial effects by acting as antioxidants, preventing red blood cells and from aggregating to form clots, allowing more oxygen to each neurons, and improving circulation in tiny blood vessels by inducing relaxation of the muscles surrounding blood vessels. Even circulation to the eyes improves when subjects are given ginkgo (Chung 1999).
The primary indications for ginkgo use are age-related cognitive decline (ARCD) and Alzheimer's dlsease.
Age-related cognitive decline is a term that describes a collection of symptoms; these include difficulty in concentration and memory, absentmindedness, confusion, lack of mental energy, and, sometimes depressive mood. Some of these symptoms may be associated with not enough blood reaching the braln, hence a potential justification for the use of gingko in lessening these symptoms. Ginkgo improves communication between nerve cells and enhances blood flow to the brain. It is licensed in Germany for the treatment of ARCD. Ginkgo may have promise in the treatment of Parkinson's disease and Alzheimer's when used together with other conventional medicines. A well-publicized study in the Journal of the American Medical Association indicated that 120 mg of ginkgo extract per day for one year was able to slightly improve cognitive performance in patients with Alzheimer's disease (Le Bars 1997).
The majority of the studies done thus far with ginkgo have used daily dosages of 120 to 160 mg (50:1 concentration, 24% flavonoids). Patients generally took 40 mg three to four times a day. Treatment may be needed for a few weeks before positive results can be fully appreciated. Most manufacturers sell pills that contain 40 or 60 mg of ginkgo.
You may wish to start with one or two pills a day to see if there is any improvement in memory or thinking. Ginkgo is best taken early in the day, and no later than afternoon.
I have found that I think more clearly and faster, and am slightly more alert and talkative when I use gingko. The effects, though, are subtle.
No serious side effects have been noted in formal studies with ginkgo. In rare cases, mild stomach or intestinal complaints, headache, and allergic skin reactions have been reported. There have been rare mentions of internal bleeding when ginkgo was combined with other blood thinners such as aspirin or coumadin. Ginkgo has antiplatelet activity and hence can prolong the time it takes to form a blood clot.
Ginkgo appears to be useful in memory loss due to aging or Alzheimer's disease. Because of its antioxidant properties, it may be useful in individuals with cerebrovascular disease. Due to its blood-thinning properties, a dose of 60 mg a day should not be exceeded on a long-term daily basis unless a health-care provider monitors you. Keep in mind that other nutrients and drugs have blood-thinning properties, including coumadin, aspirin, fish oils, and vinpocetine.
Ginkgo biloba, an herbal medicine extracted from the leaves of the ornamental ginkgo tree, appears to slow mental decline in some people with Alzheimer's disease (AD), suggests a study in the October 22/29, 1997 Journal of the American Medical Association.
Used for centuries in China, ginkgo is one of the most popular plant medicines in Europe, used mainly to improve circulation and treat symptoms linked to memory and thinking disorders. Just how it may work isn't clear, though scientists believe chemicals in ginkgo work as antioxidants, mopping up harmful substances that may contribute to the brain cell damage seen in AD.
The results were gleaned from 202 people with dementia, most of whom had mild or moderate AD. About half took a pill form of the extract (40 mg, three times daily), while the others took dummy pills. After six months, 27 percent of the patients who took ginkgo showed modest improvements on a standard test designed to assess AD, compared to 14 percent in the placebo group. In another test based on evaluations by caregivers, 37 percent of the ginkgo-takers were deemed better, versus 23 percent of the other patients. A third test showed no difference.
Ginkgo is the latest in a long list of substances--ibuprofen, vitamin E, estrogen, tacrine (Cognex) and donepezil (Aricept)--that may help people with AD. But none can claim more than a minimal improvement in this devastating illness, says HealthNews associate editor Arthur Feinberg, MD. "Gingko appears to be relatively safe, causing only mild--mainly gastrointestinal--side effects in some people. But talk to your doctor before starting, especially if you're taking blood-thinning drugs such as aspirin or warfarin (Coumadin), because ginkgo can inhibit blood clotting. And don't expect a dramatic improvement. We are still far from a treatment that significantly changes the course of this disease."
It has been blended into Chinese tea, prescribed by German doctors and sprinkled on a wedding cake in Michigan. Believers claim it cures memory loss, impotence and ringing in the ears. But after centuries of legend, the world’s leading health institution has commissioned a test of real science: Is there magic in the fan-shaped leaves of the Ginkgo biloba tree?
If the test shows that Ginkgo helps prevent Alzheimer’s, the news will be significant, particularly as the huge baby boomer generation drifts toward old age.
"Finally, scientists are taking botanicals seriously," Joseph Betz, a vice president of the American Herbal Products Association, said of the coming study by the National Institutes of Health.
A few years ago, spending $15 million to investigate an herbal supplement would have been labeled by many a waste of taxpayer money, a foolish exploration into the realm of hocus-pocus.
But the herbal industry continues its boom. With rising frustration toward traditional medicine, U.S. consumers now spend about $15 billion a year on dietary supplements.
And a large, albeit uneven body of research suggests that extract from the Ginkgo biloba may have a significant effect on the memory functions of the human brain.
The evidence is compelling enough for the NIH. Its fledgling National Center for Complementary & Alternative Medicine has launched a five-year test of whether Ginkgo prevents Alzheimer’s disease. It represents the largest study ever of intellectual decline of older Americans.
"It’s a fascinating event for any number of reasons," said Bill Thies, vice president for medical and scientific affairs at the Chicago-based Alzheimer’s Association. "It’s certainly going to generate some worthwhile information about Alzheimer’s disease. It’s also an attempt to take a complementary therapy and put it in the environment of a rigorous clinical trial."
The test is a milestone for the fledgling NCCAM. The center is small compared to NIH institutes that tackle cancer and other major health problems. But its budget, just $2 million in 1993, has grown to about $69 million.
Among the center’s best-known projects is a study of St. John’s Wort, the herb used widely to treat depression. Other inquiries are measuring acupuncture as a pain reliever, shark cartilage as a cancer treatment and meditation to calm heart disease patients.
But the Ginkgo biloba study is the largest. When enrollment is complete, about 3,000 men and women in four states, all ages 75 and older, will start taking two pills a day.
Some will take Ginkgo. Others, for the sake of comparison, will unknowingly swallow do-nothing placebos. By the time the study ends, researchers estimate, about 200 will have left the study each year, because they either die or become too sick.
"The importance goes beyond Ginkgo itself," said Dr. Richard L. Nahin, director of extramural research, training and review at NCCAM. "We’ll be collecting very valuable data on a group of 3,000 people who don’t have Alzheimer’s disease, and we’ll be following them over a five-year period. It will give us a true rate at which the disease occurs and answer questions about its natural progression."
Ginkgo biloba trees are known for their long life spans, some surviving 1,000 years. They grow in the southern and eastern United States and China. The Chinese began relying on the Ginkgo about 5,000 years ago, using its nuts to treat respiratory ailments and its leaves for tea to boost memory.
The idea to test Ginkgo as a preventive for Alzheimer’s began circulating at NIH in late 1998, Nahin said. To decide whether the research would be worthwhile, NCCAM asked basic questions:
Is the disease serious? Are participants available for the test? Does preliminary research show that the substance has promise? And would the substance, if proved helpful, have widespread use?
The proposal met every standard. About 4 million Americans suffer from Alzheimer’s. Plenty of test subjects were available. Preliminary research showed Ginkgo had intriguing potential. And Ginkgo use is already common.
Today, mail-order companies use the Internet to pitch Ginkgo in various forms: Cardio Ginkgo-Power, Ginkgo Biloba Forte, Ginkgo Leaf Alcohol Free, Ginkgocure, Ginkgomax, Ginkgo Smart and Ginkgo-24 NutraSpray.
Shayne B. Foley, national herbal educator for Gaia Herbs, said his company has spent $4 million on a "natural products lab" to refine manufacturing techniques in Brevard, N.C.
To make products like their Extra Strength Ginkgo Leaf, which sells for about $16 an ounce over the Internet, Gaia puts the Ginkgo leaves through a multi-step process. Harvested leaves are dried, ground and mixed with solvents to get their extract.
The company has planted about 200 trees on "certified organic land."
"We realized that if you keep the trees trimmed, you get stalkier leaves," Foley said. "Instead of growing tall, the trees grow out. You get leaves that are two to three times the thickness of regular trees'."
Americans spent about $310 million on Ginkgo in 1998, making it a larger seller than St. John’s Wort, ginseng, echinacea and garlic, according to the Nutrition Business Journal.
One mail order company asserts that Ginkgo increases blood flow to the brain "and thus improves memory and cognitive functions," as well as relieves depression, chronic hepatitis and asthma.
Another maintains that the herb may ease leg pain from hardening arteries, reduce ringing in the ears and help men plagued by impotence.
Many of the claims are misleading, said Larry Sasich, a pharmacist for the Washington-based Public Citizen Health Research Group. He blamed the 1994 Dietary Supplement Health and Education Act, which deregulated the herbal products industry.
Unlike pharmaceutical manufacturers, dietary supplement producers are not required to prove a product’s effectiveness before putting it on the market. They are only forbidden from exaggerating benefits, a requirement that often results in a game of semantics, Sasich said.
In promotion of extract from the saw palmetto palm, for example, "you can’t say it’s used to treat enlarged prostate," Sasich said. "You can say using it promotes good prostate health, whatever that means. But it sells. Most people don’t differentiate."
The result, Sasich said, is that retailers often "market and promote these products for unsubstantiated uses. There’s a whole class of products that are untested and can be promoted for just about anything."
Most research on Ginkgo has occurred in Europe, where use is prevalent. In Germany, for example, the herb is prescribed as a drug. But many U.S. doctors regard most of the research as substandard, and tests showing the quality of products available to U.S. consumers varies enormously.
"You stuff some weeds in a bottle, you call it whatever you want, and then you sell it," said Dr. Marcia Angell, editor of the New England Journal of Medicine. "It doesn’t even have to have Ginkgo in it."
After dozens of studies, the consensus is that Ginkgo may prevent or delay dementia. Dr. Steven DeKosky, the University of Pittsburgh neurologist who is leading the NCCAM study, characterizes Ginkgo is as a mild blood thinner and an antioxidant.
"Oxidation is rust," he said. "And you want to stop the rust."
DeKosky’s brigade of researchers will test subjects in four locations: Pittsburgh, Winston-Salem, N.C., Hagerstown, Md., and Sacramento, Calif. Recruitment is under way, and testing will begin in July.
Because Ginkgo is being explored as a preventive, participants must not have dementia. Also screened out will be people with Parkinson’s disease or other disorders that lead to dementia, as well as people on medications that would interfere with performance on memory tests.
A computer will divide the 3,000 subjects into two groups: those who receive Ginkgo and those who receive a placebo. No one - not the doctors, nurses, patients or their families - will know who’s getting which.
The capsules for all participants will be identical. They’ll come in so-called "blister packs," labeled by date, 240 milligrams to be taken once in the morning, once at night.
Each subject must have a "proxy," a family member or friend to watch for behavior changes. Researchers will periodically check for "cognitive changes" through phone calls and neurological exams.
Over time, participants will take simple tests, such as reciting the date or their home address or recalling something that happened just a few minutes earlier. They might also be asked to discuss their moods or undergo tests, such an electrocardiogram to measure heart function.
The idea is to measure who gets Alzheimer’s more, the people in the Ginkgo group or people in the placebo group. About 400 to 500 altogether are expected to contract the disease over five years.
"We know there’s a mild cognitive state where people begin to get the disease," DeKosky said. "They don’t actually have the disease, but they’re at greater risk. We’ll see if more people hold at that point. We will find out something about progression."
If the test shows that Ginkgo helps prevent Alzheimer’s, the news will be significant, particularly as the huge baby boomer generation drifts toward old age. Currently, the only Alzheimer’s drugs available slow progression of the disease.
"It’s a great step forward, to have a chance to test these products," said a research team member, Dr. Linda P. Fried, a professor of medicine and epidemiology at the Johns Hopkins School of Public Health.
"If it turns out that Ginkgo is useful in preventing dementia and memory loss, that’s important to know. If it turns out it doesn’t do anything, that’s important to know because people won’t waste their money."
Thies, the Alzheimer’s Association vice president, said the most credible data suggest Ginkgo may have a mild effect.
"I suppose that means Ginkgo will not be revolutionary," Thies said. "But that would be an advance. ... There’s often a rancorous debate between supporters and detractors of these complementary techniques, usually because there’s a lack of data.
"There’s the cat’s claw herbal remedy, green tea, acupuncture, things like that. It doesn’t mean every one justifies a clinical trial, but for some, I think we should go to the trouble and have the argument."
