What are ginkgo's therapeutic uses?
Traceable to three hundred million years ago, the ginkgo is the oldest surviving species of tree. Although it died out in Europe during the Ice Age, ginkgo survived in China, Japan, and other parts of East Asia. It has been cultivated extensively for both ceremonial and medical purposes, and some particularly revered trees have been tended for more than one thousand years.
In traditional Chinese herbology, tea made from ginkgo seeds has been used for numerous problems, most particularly asthma and other respiratory illnesses. The leaf was not used. In the 1950s, however, German researchers started to investigate the medical possibilities of ginkgo leaf extracts rather than remedies using the seeds. Thus, modern ginkgo preparations are not the same as the traditional Chinese herb, and the comparisons often drawn are incorrect.
The standard dosage of ginkgo is 40 milligrams (mg) to 80 mg three times daily of a 50:1 extract standardized to contain 24 percent ginkgo-flavone glycosides. Levels of toxic ginkgolic acid and related alkylphenol constituents should be kept under five parts per million. In an analysis performed in 2006 by a respected testing organization, some tested ginkgo products were found to be contaminated with lead.
Fairly good evidence indicates that ginkgo is effective for Alzheimer’s disease and other severe forms of memory and mental function decline. When used for this purpose, ginkgo appears to be as effective as standard drugs.
Inconsistent evidence hints that ginkgo might also be helpful for enhancing memory and mental function in seniors without severe memory loss. Weak evidence hints that ginkgo, alone or in combination with ginseng or vinpocetine, may be helpful for enhancing memory or alertness in younger people. Combining phosphatidylserine, another substance used to enhance mental function, with ginkgo might increase its efficacy.
In addition, ginkgo may be effective for the treatment of restricted circulation in the legs due to hardening of the arteries, known as intermittent claudication. One substantial, well-designed double-blind, placebo-controlled study found evidence that ginkgo extract taken at a dose of 240 mg or 480 mg daily may be helpful for anxiety. Weak, and in some cases inconsistent, evidence from preliminary double-blind trials hints that ginkgo might be helpful for glaucoma, macular degeneration, conjunctivitis, premenstrual syndrome (PMS), Raynaud’s disease, sudden hearing loss, vertigo, and vitiligo. Although study results conflict, on balance the evidence suggests that ginkgo is not helpful for tinnitus (ringing in the ear).
Three small, double-blind trials enrolling a total of about one hundred people found preliminary evidence that use of the herb Ginkgo biloba can help prevent altitude sickness. However, a large-scale, double-blind study enrolling 614 people failed to find benefit. (The drug acetazolamide, however, did provide significant benefits compared to placebo.) A similarly designed smaller study enrolling fifty-seven people also failed to find ginkgo effective. Overall, the balance of evidence suggests that ginkgo is not effective for this purpose.
Numerous case reports and uncontrolled studies raised hope that ginkgo might be an effective treatment for sexual dysfunction in men or women, particularly in those cases related to certain antidepressant medications. However, the results of a number of double-blind studies indicate that ginkgo is no more effective than placebo, whether or not subjects are taking antidepressants.
One small study failed to find ginkgo helpful for the treatment of cocaine dependence. Two studies failed to find ginkgo helpful in multiple sclerosis.
Chinese research suggests that ginkgo might enhance the effects of drugs used for schizophrenia, both phenothiazines as well as atypical antipsychotic drugs. Antipsychotic drugs can cause a neurological condition called tardive dyskinesia, which involves troubling, uncontrollable body movements. One randomized study found that ginkgo (240 mg/day for twelve weeks) was more helpful than placebo in reducing tardive dyskinesia symptoms in people with schizophrenia.
An open study evaluated combination therapy with ginkgo extract and the chemotherapy drug 5FU for the treatment of pancreatic cancer, on the theory that ginkgo might enhance blood flow to the tumor and thereby help 5FU penetrate better. The results were promising, but much better research must be performed before ginkgo can be recommended for this use. Similarly inadequate evidence hints at benefits in dyslexia. Ginkgo has also been proposed as a treatment for depression and diabetic retinopathy, but there is little evidence that it is effective for these conditions.
Alzheimer’s disease and non-Alzheimer’s dementia. In the past, European physicians believed that the cause of mental deterioration with age (senile dementia) was reduced circulation in the brain due to atherosclerosis. Since ginkgo is thought to improve circulation, they assumed that ginkgo was simply getting more blood to brain cells and thereby making them work better.
However, the contemporary understanding of age-related memory loss and mental impairment no longer considers chronically restricted circulation the primary issue. Ginkgo (and other drugs used for dementia) may instead function by directly stimulating nerve cell activity and protecting nerve cells from further injury, although improvement in circulatory capacity may also play a role.
Numerous double-blind, placebo-controlled studies have found ginkgo extract effective for dementia; among these, studies rated as “high-quality” by accepted scientific norms enrolled a total of more than two thousand people. For example, one major trial in the United States published in 1997 enrolled more than three hundred people with Alzheimer’s disease or non-Alzheimer’s dementia. Participants were given either 40 mg of Ginkgo biloba extract or placebo three times daily for a period of fifty-two weeks. The results showed significant but not entirely consistent improvements in the treated group.
Another study, published in 2007, followed four hundred people for twenty-two weeks and used twice the dose of ginkgo. The results of this trial indicated that ginkgo was significantly superior to placebo. (Technically, it was superior in the primary outcome measure, the SKT cognitive test battery, as well as on all secondary outcome measures.) The areas in which ginkgo showed the most marked superiority, compared with placebo, included “apathy/indifference, anxiety, irritability/lability, depression/dysphoria and sleep/nighttime behaviour.” In addition, a six-month study found ginkgo just as effective as the drug donepezil (taken at a dose of 5 mg daily).
On the other hand, one fairly large study drew headlines for finding ginkgo extract ineffective. This twenty-four-week, double-blind, placebo-controlled study of 214 people with either mild to moderate dementia or ordinary age-associated memory loss found no effect with ginkgo extract at a dose of 160 mg or 240 mg daily. This study has been sharply criticized for a number of serious flaws in its design. However, in another community-based study among 176 elderly subjects with early-stage dementia, researchers found no beneficial effect for 120 mg of ginkgo extract given daily for six months.
A 2011 systematic review of nine placebo-controlled, randomized trials found more promising evidence for ginkgo. The trials, which involved 2,372 people with Alzheimer’s disease or another form of dementia, ranged from twelve to fifty-two weeks. Those in the ginkgo group did have improvements in their cognition scores. A subgroup of people with Alzheimer’s disease also showed improvements in their activities of daily living.
The ability of ginkgo to prevent or delay a decline in cognitive function is less clear. In a placebo-controlled trial of 118 cognitively intact adults eighty-five years or older, ginkgo extract seemed to effectively slow the decline in memory function in a forty-two-month period. The researchers also reported a higher incidence of stroke in the group that took ginkgo, a finding that requires more investigation.
In a 2009 review of thirty-six randomized trials involving 4,423 persons with declining mental function, including dementia, researchers concluded that ginkgo appears to be safe. However, there is inconsistent evidence regarding whether it works.
Enhancing mental function in healthy people. Ginkgo has shown less consistent promise for enhancing mental function in people who experience the relatively slight decline in cognitive function that typically accompanies increased age. For example, in a double-blind, placebo-controlled trial, 241 elderly persons with mildly impaired memory were given either placebo or ginkgo for twenty-four weeks. The results showed that ginkgo produced modest improvements in certain types of memory.
Another double-blind, placebo-controlled trial examined the effects of ginkgo extract in forty men and women, aged fifty-five to eighty-six, who did not have any mental impairment. In a six-week period, the results showed improvements in measurements of mental function. Possible benefits were also seen in six other trials involving a total of about 250 people.
Set against these positive findings is the twenty-four-week study mentioned above, which found no benefit in ordinary age-related memory loss. The reason for this negative outcome may be flaws in this trial’s design. However, three other studies enrolling a total of about four hundred elderly persons also failed to find significant benefit with daily use of ginkgo. Another double-blind, placebo-controlled study used a one-time dose of ginkgo and again found no benefits.
Besides these negative trials, there is another weakness in the evidence: inconsistency even among positive trials. There are numerous measurable aspects of memory and mental function, and studies of ginkgo have examined a great many of these, but the exact areas of benefits seen vary widely.
For example, in one positive study, ginkgo may speed the ability to memorize letters but not expand the number of letters that can be retained while in another positive study, the reverse may be true. This type of inconsistency tends to decrease the confidence one can place in these apparently positive studies, because if ginkgo were really working, one would expect its effects to be more reproducible.
A total of about fifteen controlled trials have examined the effects of ginkgo on memory and mental function in younger people. However, results are again inconsistent, with many negative results and the positive ones failing to indicate a consistent pattern of benefit.
Several small double-blind, placebo-controlled studies have evaluated combined treatment with ginseng or vinpocetine for enhancing mental function in young people. The results, overall, are unconvincing. Weak evidence suggests that combining phosphatidylserine with ginkgo might increase its efficacy. In two studies, ginkgo combined with the Ayurvedic herb brahmi failed to improve mental function.
It remains unclear whether ginkgo actually enhances memory and mental function in healthy seniors or healthy younger people. Benefits, if they do exist, are probably slight.
Intermittent claudication. In intermittent claudication, impaired circulation can cause a severe, cramplike pain in one’s legs after walking only a short distance. According to nine double-blind, placebo-controlled trials, ginkgo can significantly increase pain-free walking distance.
One double-blind study enrolled 111 people for twenty-four weeks. Subjects were measured for pain-free walking distance by walking up a 12 percent slope on a treadmill at 3 kilometers per hour (about 2 miles per hour). At the beginning of treatment, both the placebo and ginkgo (120 mg daily) groups were able to walk about 350 feet without pain. By the end of the trial, both groups had improved, although the ginkgo group had improved significantly more. Participants taking ginkgo showed about a 40 percent increase in pain-free walking distance, compared with only a 20 percent improvement in the placebo group. Similar improvements were also seen in a double-blind, placebo-controlled trial of sixty people who had achieved maximum benefit from physical therapy.
A twenty-four-week, double-blind, placebo-controlled study of seventy-four people with intermittent claudication found that ginkgo was more effective at a dose of 240 mg per day than at 120 mg per day. A 2009 review of eleven trials with 477 participants suggested that those who took Ginkgo biloba were able to walk farther than control patients, although the results were limited by differences among the trials. However, not all studies have been positive. In a randomized trail involving sixty-two persons averaging seventy years of age, 300 mg of ginkgo per day was no better than placebo at improving pain-free walking distance over four months of treatment.
PMS symptoms. One double-blind, placebo-controlled study evaluated the benefits of ginkgo extract for women with PMS symptoms. This trial enrolled 143 women, eighteen to forty-five years of age, and followed them for two menstrual cycles. Each woman received either the ginkgo extract (80 mg twice daily) or placebo beginning on day sixteen of the first cycle. Treatment was continued until day five of the next cycle and resumed on day sixteen of that cycle. Compared with placebo, ginkgo significantly relieved major symptoms of PMS, especially breast pain and emotional disturbance. In another, similarly designed trial involving eighty-five university students, Ginkgo biloba L. significantly reduced PMS symptom severity compared to placebo.
Anxiety. In a double-blind, placebo-controlled study of 107 people with various forms of anxiety (specifically, generalized anxiety disorder or adjustment disorder with anxious mood), ginkgo extract taken at a dose of 240 mg or 480 mg daily proved significantly more effective than placebo.
Macular degeneration. Macular degeneration, one of the most common causes of vision loss in seniors, may respond to ginkgo. In a six-month, double-blind, placebo-controlled study of twenty people with macular degeneration, use of ginkgo at a dose of 160 mg daily resulted in improved visual acuity.
A twenty-four-week, double-blind study of ninety-nine people with macular degeneration compared ginkgo extract at a dose of 240 mg per day with ginkgo at a dose of 60 mg daily. The results showed that vision improved in both groups, but to a greater extent with the higher dose.
Vertigo. A three-month, double-blind trial of seventy people with a variety of vertigo conditions found that ginkgo extract given at a dose of 160 mg twice daily produced results superior to placebo. By the end of the trial, 47 percent of the people given ginkgo had significantly recovered, versus only 18 percent in the placebo group.
Glaucoma. A small double-blind, placebo-controlled trial found that use of ginkgo extract at a dose of 120 mg daily for eight weeks significantly improved the visual field in people with glaucoma.
Tinnitus. Studies of Ginkgo biloba extract for treating tinnitus have yielded conflicting results. While some small studies found benefit, the largest and best-designed of these trials failed to find ginkgo effective. In a twelve-week, double-blind trial, 1,121 people with tinnitus were given either placebo or standardized ginkgo at a dose of 50 mg three times daily. The results showed no difference between the treated and the placebo groups.
Ginkgo appears to be relatively safe. Extremely high doses have been given to animals for long periods of time without serious consequences, and results from human trials are also generally reassuring. Safety in young children, pregnant or nursing women, or those with severe liver or kidney disease, however, has not been established.
In all the clinical trials of ginkgo up through 1991 combined, involving a total of almost ten thousand participants, the incidence of side effects produced by ginkgo extract was extremely small. There were twenty-one cases of gastrointestinal discomfort and even fewer cases of headaches, dizziness, and allergic skin reactions.
However, there are some potential problems. Perhaps the most serious have been the numerous case reports of internal bleeding associated with use of ginkgo (spontaneous as well as following surgery). Based on these reports, as well as previous evidence that ginkgo inhibits platelet function, studies have been performed to determine whether ginkgo significantly affects bleeding time or other measures of blood coagulation, with somewhat inconsistent results. Prudence suggests that ginkgo should not be used by anyone during the periods before or after surgery or labor and delivery, or by those with bleeding problems such as hemophilia. It also seems reasonable to hypothesize that ginkgo might interact with blood-thinning drugs, amplifying their effects on coagulation. However, two studies found no interaction between ginkgo and warfarin (Coumadin), and another found no interaction with clopidogrel. (Although, it did find a slight interaction with the related drug cilostazol.) While these findings are reassuring, prudence indicates physician supervision before combining ginkgo with blood-thinning drugs.
One study found that when high concentrations of ginkgo were placed in a test tube with hamster sperm and ova, the sperm were less able to penetrate the ova. However, since researchers have no idea whether this much ginkgo can actually come into contact with sperm and ova when they are in the body rather than a test tube, these results may not be meaningful in real life.
The ginkgo extracts approved for use in Germany are processed to remove alkylphenols, including ginkgolic acids, which have been found to be toxic. The same ginkgo extracts are available in the United States. However, other ginkgo extracts and whole ginkgo leaf might contain appreciable levels of these dangerous constituents.
Seizures have also been reported with the use of ginkgo leaf extract in people with previously well-controlled epilepsy; in one case, the seizures were fatal. It has been suggested that ginkgo might interfere with the effectiveness of some antiseizure medications, specifically phenytoin and valproic acid. Another possible explanation is contamination of ginkgo-leaf products with ginkgo seeds; the seeds of the ginkgo plant contain a neurotoxic substance called 4-methoxypyridoxine (MPN). Finally, the drug tacrine (also used to improve memory) has been associated with seizures, and ginkgo may affect the brain in ways similar to tacrine. Regardless of the explanation, prudence suggests that people with epilepsy should avoid ginkgo.
According to a study in rats, ginkgo extract may cause the body to metabolize the drug nicardipine (a calcium channel blocker) more rapidly, thereby decreasing its effects. In addition, this finding also suggests potential interactions with numerous other drugs, although more research is needed to determine which ones might be affected.
Antibiotics in the aminoglycoside family can cause hearing loss by damaging the nerve carrying hearing sensation from the ear. One animal study evaluated the potential benefits of ginkgo for preventing hearing loss but found instead that the herb increased damage to the nerve. Based on this finding, individuals using aminoglycosides should avoid ginkgo.
It has been suggested that ginkgo might cause problems for people with type 2 diabetes by altering blood levels of medications, as well as by directly affecting the blood-sugar-regulating system of the body. However, the most recent and best-designed studies have failed to find any such actions. Nonetheless, until this situation is clarified, people with diabetes should use ginkgo only under physician supervision.
Taking blood-thinning drugs–such as aspirin and other nonsteroidal anti-inflammatory drugs (ibuprofen), cilostazol, clopidogrel (Plavix), heparin, pentoxifylline (Trental), ticlopidine (Ticlid), and warfarin (Coumadin)–while simultaneously using ginkgo could theoretically cause bleeding problems and should not be undertaken without physician supervision. Ginkgo might also reduce the effectiveness of channel blockers.
Using ginkgo while also taking antipsychotic medications in the phenothiazine family, as well as atypical antipsychotic drugs, such as clozapine and olanzapene, might help these drugs work better with fewer side effects. Use of ginkgo simultaneously with aminoglycoside antibiotics might increase risk of hearing loss. Finally, ginkgo might interfere with the effectiveness of medications to prevent seizures.
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