Introduction
The Chinese have revered Ginkgo biloba as a sacred tree for thousands of years and extracts from its leaves, seeds, and roots are an essential part of classical Chinese medical practice (1). The Chinese name for Ginkgo biloba is “Silver Almond tree” (Yin-xing) and the Japanese call it the “White Nut tree.” The Japanese word for “silver nut” is “yinguo,” which is pronounced roughly as “ginkgo.” “Biloba” refers to the fact that its leaves form two lobes, i.e. they are bi-lobed.
Dutch traders brought ginkgo trees to Europe in the early 1700s, where it acquired the name “Maidenhair Tree” because of its leaves’ resemblance to a local species of fern. In Germany, the trees are called “Ginkobaum.” Ginkgo trees were introduced to America in 1784 and today are widely used as ornamental trees in cities where they tolerate pollution and poor soil well.
In the 14th to 16th centuries, the predominant medical uses of ginkgo extracts were for treating lung diseases (asthma and tuberculosis) and to treat skin diseases by topical application. In the 21st century, the medical uses of ginkgo extracts as herbal supplements are described in detail below.
Drugs containing a standardized ginkgo extract (see below) are prescription medicines in Germany and France, where they are known by the trade names Tebonin® and Tanakan®.
What Is Ginkgo Biloba?
Modern research on ginkgo began in the 1920s, with chemical analyses of its active components. Ginkgo nut extract is a complex mixture of organic compounds. The two main groups of active ingredients are terpene lactones (ginkgolide A, B, C), Bilobalide, and flavone glycosides (flavonoids) (2).
The names of the individual chemicals are not as important as knowing that Ginkgo biloba extract is a mixture of compounds and not a single molecular entity as are most FDA-approved drugs. This fact often complicates research on specific medical conditions.
In 1965, a German physician and pharmacist named Willmar Schwabe III developed “Extract of Ginkgo biloba 761” or EGb 761®. Since that time, this is the form of Ginkgo biloba that has been used in most medical research studies.
The two main pharmacologic properties of EGb 761 (3) that may explain why people think it might be useful in addressing a number of health problems include:
- It can regulate the behavior of blood vessels (vasoregulation), increase oxygen and nutrient supply to tissues, and prevent ischemia (inadequate blood supply).
- It is an antioxidant that can scavenge free radicals and other reactive oxygen species (ROS), thus reducing oxidative damage to cells.
Note: Oxidative stress is an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by antioxidants.
One of the reasons that use of EGb 761 as a drug remains controversial is that its physiological effects or mechanism of action cannot be attributed to a single constituent of the extract. Instead, the components of EGb 761 (and their metabolites) appear to act in a complementary or synergistic manner to produce health-related benefits (3).
Is There Any Research?
As of January 10, 2018, the biomedical literature (PubMed.gov) contained 3,888 articles about Ginkgo biloba dating back to 1934. Most of these research studies involve experiments with laboratory animals (mostly rats) or “test tubes” (in vitro studies). Of all the articles mentioning Ginkgo biloba, only 16% (617 studies) appear to involve human subjects.
When I repeated these searches with the name of the controlled formulation EGb 761, I found 1,587 articles in total, with about 20% (317 studies) appearing to involve human subjects.
Turning to the U.S. government’s database of clinical research trials (ClinicalTrials.gov), “Ginkgo biloba” yields 69 studies. Searching with EGb 761 yields only 19 studies. These studies involve the following medical conditions: Alzheimer’s disease, Friedreich ataxia, Raynaud’s phenomenon, multiple sclerosis, glaucoma, cognitive function disorders, memory impairment, ischemic stroke, asthma, and sexual dysfunction.
To put these findings in perspective, I searched for a type of drug (cholinesterase inhibitor) that has been FDA-approved to treat Alzheimer’s disease, dementia, and cognitive impairment and got the following results:
- In PubMed.gov there were 52,237 studies with 3,232 involving human subjects: 13 times and 5 times as many studies compared with Ginkgo biloba, respectively.
- In ClinicalTrials.gov there were 643 studies, 9 times more than for Ginkgo biloba.
Bottom Line
More research is needed to understand exactly how the combination of chemicals in extracts of Ginkgo biloba work together to produce beneficial medical effects.
Does Ginkgo Biloba Increase Concentration?
Laws and colleagues (4) published a meta-analysis (basically a comprehensive review of the literature) that aggregated data from 10 well-designed (randomized, controlled) studies relevant to mental concentration. There were three groups of studies:
- Memory studies used data from 1,132 human subjects.
- Studies of executive function used data from 534 human subjects.
- Attention studies used data from 910 human subjects.
These studies employed several different Ginkgo biloba extracts (Blackmore’s Ginkgoforte, EGb 761, and Lichtwer’s Li1370). For most studies, the dosages varied from 120 mg to 240 mg, and the durations were over periods 6 to 12 weeks.
Statistical analysis of the data showed that Ginkgo biloba had no significant impact on memory, executive function, or attention regardless of participant age, extract dosage, which extract was used, or the duration of treatment.
Bottom Line
Ginkgo biloba has no discernable positive effects on memory, executive brain function, and attention in healthy individuals. However, poor concentration can be a feature of many other conditions, such as ADHD, depression, and dementia, which are discussed separately below.
Does It Decrease the Risk of Alzheimer’s Disease or Dementia?
There are a fairly large number of in vitro and animal studies which show that ginkgo has the potential to be protective of neurons in the brain. A review by Ahlemeyer and Drieglstein (5) lists a number of these studies where EGb 176 decreases the response to agents used to cause oxidative stress in nerve cells or animals.
Regarding human subjects, there are many studies (6, 7) of variable design and size that show mixed results for whether ginkgo can prevent or treat dementia. However, the most comprehensive is the Ginkgo Evaluation of Memory (GEM) Study (8) co-funded by the National Center for Complementary and Alternative Medicine (NCCAM), National Institute on Aging (NIA), National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements.
The University of Washington oversaw the study. Four GEM institutions participated: University of Pittsburgh, Wake Forest University, Winston-Salem N.C., Johns Hopkins University, Baltimore, and University of California, Davis.
GEM enrolled 3,069 participants aged 75 or older with normal cognition or mild cognitive impairment. Those with dementia were excluded from participation. After extensive medical and neuropsychological screening, participants were randomly assigned to receive twice daily doses of either 120 milligrams of ginkgo extract or an identical-appearing placebo.
“Study participants were followed for an average of approximately 6 years (maximum of just over 7 years). During the study, 523 participants were diagnosed with dementia, 246 in the placebo group and 277 in the ginkgo group. Thus, ginkgo showed no overall effect for reducing all types of dementia or Alzheimer’s disease.” (8)
Bottom Line
Ginkgo biloba extract at a dose of 120 mg twice a day does not help in reducing either the overall incidence rate of dementia or Alzheimer’s disease incidence in elderly individuals with normal cognition or those with mild cognitive impairment.
Does It Help With Anxiety or Depression?
In a 2015 review by Montes and colleagues (9), the authors review nine animal studies where mice or rats are subjected to stressful situations with or without treatment with EGb 761. Nearly all the studies showed that “anxiety-like or depressive-like behavior” was reduced, although only a few used quantifiable chemical levels to assess the results.
In patients, there are very few studies in which the effect of EGb 761 on anxiety or depression are specifically addressed. In a study by Woelk et al. (10), 107 patients with generalized anxiety disorder were treated with either a high dose (480 mg), a low dose (240 mg), or a placebo for four weeks.
The participants were evaluated pre- and post-treatment with the Hamilton rating scale for Anxiety (HAM-A). The HAM-A total scores decreased by -14.3 (+/-8.1), -12.1 (+/-9.0), and -7.8 (+/-9.2) in the high-dose EGb 761, the low-dose EGb 761, and the placebo group, respectively. Changes were significantly different from placebo for both treatment groups with p=0.0003 (high-dose group) and p=0.01 (low-dose).
In a double-blind, placebo-controlled study, 70 young volunteers (pharmacology students) were subjected to a stress model which consisted of a mental load (a short memory test) and static exercise (two 3-minute bouts with handgrips). Blood pressure and salivary cortisol levels were measured before and after a single dose of EGb 761 was given. EGb 761 reduced a stress-induced rise in blood pressure without affecting the heart rate.
Only in the male volunteers was there a statistically significant decrease in salivary cortisol after EGb 761 treatment compared to those given the placebo.
Bottom Line
High doses of Ginkgo biloba extract may help in relieving depression and anxiety, and lowering blood pressure and stress hormones in men.
Does It Help With Premenstrual Syndrome (PMS)?
I could find only two studies which use EGb 761 to ameliorate symptoms of PMS. Ozgoli et al. (11) was a single-blind study on 85 women. The women received 40 mg of leaf extract or placebo three times a day from the 16th day of the menstrual cycle to the 5th day of the next cycle.
There was a significant decrease in physical and psychological symptoms in both the ginkgo (23.68%) and the placebo groups (8.74%), but the improvement was greater in the ginkgo group.
Tarborini and Taurelle (12) studied 165 women, aged 18-45, who suffer from PMS at least 7 days each cycle. Like with Ozgoli, they received Egb 761 or a placebo from the 16th day of the first cycle to the 5th day of the cycle. This was repeated for a second cycle. A double evaluation system of self-reporting, as well as an assessment by a practitioner, was used.
According to the authors, EGb 761 was effective against the congestive symptoms of PMS, particularly breast symptoms with a statistical significance between EGb 761 and placebo. Neuropsychological symptoms were also improved.
Bottom Line
Yes, Ginkgo biloba extract may help reduce the symptoms of PMS.
Does It Help With Vision or Eye Health?
Ginkgo may have some beneficial effects when it comes to eye health, although the number of studies is very limited.
In 2013, a systematic review of the use of Ginkgo biloba for treating AMD by Jennifer Evans (13) identified two published trials with 119 participants. A study of 20 patients in France with AMD randomly assigned them to treatment with EGb 761 80 mg twice a day or a placebo.
In Germany, 99 AMD patients were randomly assigned to two different doses of EGb761- 240 mg/day or 60 mg/day. Both trials lasted 6 months. Both trials reported positive effects on vision, but specific details were not reported.
A study by Shim et al. (14) looked at 332 patients with normal tension glaucoma. Of these, 132 received anthocyanins, 103 received ginkgo extract, and 99 no medical treatment.
The average follow-up of these patients was about 2 years. After ginkgo treatment, a visual field measurement called the Humphrey Visual Field test (HVF) improved from 5.25 (±6.13) to -4.41 (±5.60) (P=.002), suggesting that ginkgo may be “helpful in improving visual function in some individuals with NTG.”
A paper by Cybulska-Heinrich, Mozaffarieh, and Flammer (15) discusses the pharmacologic properties of ginkgo that target the factors involved in causing glaucoma:
- Disturbed ocular microcirculation
- Oxidative stress
- Impairment of mitochondrial function in the retinal ganglion (nerve) cells
Based primarily on the general pharmacological properties of ginkgo, in vitro and in animal and human studies of ginkgo in other conditions, the authors speculate that:
“Ginkgo would probably be beneficial for all glaucoma patients. However, the use of ginkgo can be recommended as an adjuvant therapy only for normal tension glaucoma patients and for high tension glaucoma patients progressing despite a normalized IOP.
Such a limitation is economically meaningful and medically possible, as for these two conditions, there are no other therapeutic alternative so far (beside the IOP [intraocular pressure]-lowering treatment).”
Bottom Line
Ginkgo biloba may be beneficial to patients with age-related macular degeneration and in certain glaucoma patients.
Does It Prevent or Treat Attention Deficit/Hyperactivity Disorder (ADHD)?
I found three studies related to the use of ginkgo for the treatment of ADHD. The first study (16) looked at six subjects (age 17-19) diagnosed with ADHD. They were evaluated using a scale of ADD-spectrum behaviors developed by Ward et al. (17) before and one month after a 4-week trial of EGb 761 (200 mg/day).
The mean score decreased after ginkgo, indicating that the patients have fewer ADD symptoms during treatment. When evaluating individual behavioral items, ginkgo reduced hyperactivity, enhanced frustration tolerance, decreased restlessness, and increased attention.
In an open clinical pilot study, Uebel-von Sandersleben et al. (16) treated 20 children with ADHD with EGb 761 over 3 to 5 weeks. They were assessed with clinical scores, as well as by brain wave activity recorded during a Continuous Performance Test (CPT). Their results detected “possible improvements in quality of life, ADHD core symptoms, as well as CPT performance.
Salehi et al. (18) did a randomized, double-blind, controlled trial involving 50 children, aged 6-14, with ADHD. Half were given 80-120 mg/day ginkgo, while the other half received 20-30 mg/day of methylphenidate. The trial lasted 6 weeks. Although both groups showed improvement in ADHD symptoms, ginkgo was less effective than Ritalin®.
Bottom Line
A qualified “yes,” but first ask your child’s doctor if she thinks Ginkgo biloba might be tried prior to giving a prescription medicine or if ginkgo could be used as a supplement for children already on an FDA-approved medication.
Does It Improve Libido?
As ginkgo can improve blood flow, influence nitric oxide (NO) levels in the body, and have a relaxant effect on smooth muscle, it has been postulated that it can be useful in the treatment of sexual dysfunction in both men and women.
A study by Cohen and Bartlik (19) originated from the observation that a geriatric patient on Ginkgo biloba for memory enhancement noted improved erections. This led to an open trial of ginkgo extract for the treatment of antidepressant-induced sexual dysfunction caused by selective serotonin reuptake inhibitors.
Ginkgo extract was found to be 84% effective in treating drug-induced sexual dysfunction. Women (n = 33) were more responsive to the sexually enhancing effects of Ginkgo biloba than men (N = 30), with relative success rates of 91% versus 76%. Ginkgo biloba generally had a positive effect on all 4 phases of the sexual response cycle: desire, excitement (erection and lubrication), orgasm, and resolution (afterglow).
Subsequently, however, two randomized, placebo-controlled trials (20, 21) have found no significant benefit on sexual function with ginkgo extracts.
Finally, in 2010, Meston et al. (22) published a study of the effects of both short- and long-term treatment with Ginkgo biloba extract (GBE) on women with Sexual Arousal Disorder. There were 99 study female participants aged 18 to 65, 36 of whom were taking antidepressants and 63 who were not.
The women’s responses to GBE were assessed both subjectively and by using vaginal photoplethysmography to measure blood flow into vaginal tissues. The women were treated with one of the following treatments:
- 300 mg of GBE daily for 8 weeks
- A placebo
- Sex therapy focused on training women to better focus on genital sensations
- Sex therapy plus 300 mg of GBE
The investigators concluded from the data that GBE alone does not substantially impact sexual function in women. The participants did as well with sex therapy by itself.
Bottom Line
Preponderance of the evidence provides little proof that ginkgo is useful in the treatment of sexual dysfunction, in either healthy patients or those taking antidepressants.
Does It Help Headaches or Migraine?
I found a few articles in PubMed about the use of ginkgo in the treatment of migraines.
Researchers have discovered that platelet-activation factor (PAF) is a strong proinflammatory factor increased in patients with migraines. One component of ginkgo, “Ginkgolide B,” is an antagonist of PAF and has therefore been proposed for migraine prevention.
A small study by Usai et al. (23) showed a decrease in the frequency of migraine headaches in a group of 30 young patients suffering from migraines. The study lasted one year.
My main problem with this study (apart from there being an open-label study without controls) is that all the patients were treated with a combination of Ginkgolide B, coenzyme Q10, vitamin B2, and magnesium. How do we know which component(s) were at work?
D’Andrea et al. (24) studied 50 women with migraines in a six-month trial of Migrasoll (a combination of 60 mg Ginkgo biloba terpenes phytosome, 11 mg coenzyme Q10, and 8.7 mg vitamin B2).
They found a statistically significant decrease in the number and duration of migraine episodes. Eleven percent of patients had no episodes in the first 2 months of treatment, and 42% had none by in the second two-month period.
Bottom Line
It’s unclear from the research whether ginkgo alone does reduce migraines. Small studies where it was combined with CoQ10 and B12 show an effect, but more research is needed.
Does It Help Asthmatics?
Despite the use of Ginkgo biloba to treat asthma in ancient and traditional Chinese medicine, there is remarkably little in the contemporary scientific literature to support this use.
Bottom Line
No.
Does It Help With Hemorrhoids?
According to Czech gastroenterologist A. Hep (25), ginkgo has the following effects which would be helpful in the treatment of acute hemorrhoids:
- influence on the tone of blood vessel walls
- decrease of the capillary permeability
- improved circulation
- decrease of edema
- blockage of the inflammatory mediators
He found benefits in the use of a preparation called Ginkor Fort in 45 patients with acute hemorrhoids. Ginkor Fort contains Ginkgo biloba extract with 24% Ginkgo glycosides and 6% bilobalide ginkgolides: 14 mg, Troxerutin 300 mg, and Heptaminol hydrochloride 300 mg per capsule.
I also found an article from Thailand about the use of a ginkgo preparation similar, if not identical, to Ginkor Fort in the treatment of hemorrhoids (26). Twenty-two patients found significant improvement in the symptoms of bleeding, pain, tenesmus (the feeling that you “have to go”), and discharge.
Bottom Line
There are no studies that support the sole use of ginkgo for the treatment of hemorrhoids. The combination of ginkgo, Troxerutin, and Heptaminol (such as in Ginkor Fort) may have some benefits.
Does It Help With Fibromyalgia?
A search in PubMed found only a single entry by RE Lister (27). It is an open pilot study to evaluate the potential benefits of coenzyme Q10 combined with ginkgo in the treatment of fibromyalgia.
Twenty-three volunteers with fibromyalgia (from a British Fibromyalgia Association patient support group) were given 200 mg coenzyme Q10 and 200 mg of Ginkgo biloba each day.
They filled out quality-of-life self-assessment questionnaires before the study and again on days 28, 56, and 84. Sixty-four percent of patients subjectively felt they were better after 4 months; 9% felt worse, and 27% felt the same. The data from the questionnaires showed a statistically significant (P< 0.02) improvement in quality of life.
The authors suggest that the study results justify a larger-scale clinical trial; however, I couldn’t find that this was ever conducted.
Bottom Line
Conclusions are hard to draw because ginkgo was used in combination with other substances. More research is needed.
Is Ginkgo Biloba Safe?
According to the U.S. National Center for Complementary and Integrative Health (NCCIH):
- For many healthy adults, Ginkgo biloba extracts appear to be safe when taken by mouth in moderate amounts.
- Side effects of ginkgo may include headache, stomach upset, and allergic skin reactions. If you’re older, have a known bleeding risk, or are pregnant, you should be cautious about ginkgo possibly increasing your risk of bleeding.
- In a 2013 research study, rodents given ginkgo had an increased risk of developing liver and thyroid cancer at the end of the 2-year tests.
- Ginkgo may interact with some conventional medications, including anticoagulants (blood thinners).
- WARNING: Eating fresh (raw) or roasted ginkgo nuts (seeds) can be poisonous and have serious side effects.
The statement above regarding the 2013 study of cancer in rats and mice refers to work done by the National Toxicology Program (NTP) (28), which I reviewed. Regarding this study, the U.S. Food and Drug Administration reportedly stated that “… it is not scientifically valid to conclude with certainty that dietary supplement products containing Ginkgo biloba are unsafe based solely on data from the new NTP study.”(29)
Conclusions
Ginkgo biloba is a complex mixture of at least 37 phytochemicals (plant-derived) that has been used in traditional Chinese Medicine for thousands of years. Modern scientific evaluations of a standardized extract (EGb 761) from ginkgo that primarily involve in vitro and animal experiments over the last 50 years suggest that EGb 761 has pharmacologic properties that could be useful in the treatment of neurologic and cardiovascular diseases (3).
However, many published clinical studies are plagued by small numbers of human subjects, flaws in their designs, and inconsistent results. Large, double -lind, placebo-compared studies are needed to provide a higher standard of scientific evidence that would be required for FDA approval for specific disease indications in the U.S.
That said, ginkgo has a reasonably good safety profile, and healthy individuals wishing to try Ginkgo biloba as dietary supplement need not be unduly concerned about toxic side effects identified in animals given high doses.
Be aware, however, that ginkgo can and does interact with some prescription medicines you may be taking, and it’s best to check with your doctor or pharmacist about potential ginkgo-drug interactions. These medicines include aspirin, warfarin, trazodone, omeprazole, and some drugs for high blood pressure and diabetes (30).
For people who might want to try ginkgo to alleviate a major health condition, absolutely check with your doctor before taking any non-FDA-regulated dietary supplements.
Lastly, Ginkgo biloba extract (EGb 761) is approved and available as a prescription drug in Europe and Asia. U.S. healthcare professionals might want to familiarize themselves with information about the indications, usage, and side effects reported by non-U.S. drug regulatory agencies.
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