Cynthia R. Biron, RDH
Of the many herbs on the market today, ginkgo biloba is one that truly has promise. The research shows consistent, although not astounding, effects in the treatment of mild to moderate dementia (Alzheimer`s disease or multi-infarct dementia) and claudication. Of interest to most middle-aged people is the improvement of memory and concentration that can be a result of taking ginkgo biloba.
Finding valid research that is not biased by those selling ginkgo is a time-consuming undertaking. In 1997, sales of ginkgo biloba reached an all-time high of $240 million. The first U.S.-based trial evaluated ginkgo`s effectiveness for the treatment of dementia, and found the studies to be valid, accurate, and consistent. Somehow, Americans want own country`s approval of a medicine or herb before we will believe in its effectiveness, even if there have been myriad studies conducted worldwide that speak to a product`s effectiveness.
Where does ginkgo come from?
The most ancient tree of the botanical division, ginkgophyte, the ginkgo biloba tree has leaves with extracts that contain flavanoid substances, specific terpens called bilobalides, and ginkgolides. The trees grow in plantations in South Korea, Japan, and France. The leaves are harvested and processed to produce the extracts used in the products, which usually are in the form of capsules or tablets.
Ginkgo has been widely used in Chinese medicine for thousands of years to treat brain disorders. The standardized extract of ginkgo is labeled EGb 761. It has been the most widely prescribed medication by physicians in Germany since 1988.
Ginkgo is most well known for the treatment of dementia. A study conducted in North America assessed the efficacy and safety of EGb 761 in Alzheimer`s disease and dementia. It consisted of a placebo-controlled, double-blind, randomized trial involving 309 patients in an "intent-to-treat analysis." Patients were prescribed 120mg. of EGb 761 or a placebo. At the end of 52 weeks, a compliant 202 patients were assessed with the use of Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation-Relative`s Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC).
The EGb 761 group scored 1.4 points higher than the placebo group in the ADAS (P=.04) and 0.14 points higher than the placebo on the GERRI score (P=.004). No difference was noted on the CGIC and no significant differences in adverse effects were noted in the placebo or EGb 761-treated patients. Similar results were shown with the evaluable data set for 27 percent of patients taking EGb 761. These patients scored a 4-point improvement on the ADAS-Cog, compared with 14 percent of patients who took the placebo (P=.005).
On the GERRI test, 37 percent taking EGb 761 were improved, while only 23 percent taking the placebo improved (P=.003). This valid study has shown that the ginkgo EGb 761 made noticeable improvements in the cognitive performance and social functioning of patients with Alzheimer`s disease and multi-infarct dementia. Numerous clinical trials have been conducted to evaluate ginkgo`s effectiveness in improving dementia and Alzheimer`s disease, and several have met inclusion criteria for meta-analysis.
The effects may not be overwhelming, but they are consistent and promising. Because of the safeness of EGb 761 noted in this study, physicians may choose to prescribe ginkgo to treat these conditions, unless adverse effects are presented in patients during the treatment. Contraindications to the use of ginkgo include anticoagulants (e.g. warfarin), and antiplatelet agents, including aspirin.
Another common use for ginkgo is treatment of claudication (lameness and difficulty walking due to arteriopathy of the lower extremities). A 65-week study involving 36 patients with intermittent claudication revealed that the ginkgo biloba extract gave greater pain relief and walking tolerance than the placebo after 6 months of treatment. There were adverse effects from the medication for the remainder of the study.
One study showed that the mean difference in walking distance of ginkgo-treated patients was 0.75 times that of the standard deviation than those patients taking the placebo. An isolated study revealed a highly significant therapeutic effect of ginkgo in the treatment of peripheral arterial disease. In contrast, one study showed no changes with ginkgo treatment in patients with symptoms due to claudication.
Overall, more than 15 European studies have shown that ginkgo provides some relief of claudication symptoms. Furthermore, EGb 761 consistently has demonstrated modest improvements in central and peripheral perfusion. The benefits of such perfusion were demonstrated in a randomized, placebo-controlled study involving 44 Himalayan mountain climbers (n=22). Those taking 160mg/day of EGb 761 had no cerebral symptoms at all, while 41 percent of climbers taking the placebo did have cerebral symptoms (P<.002). Respiratory symptoms occurred in only 13.6 percent of climbers taking EGb 761, while 81.8 percent of climbers taking the placebo experienced respiratory symptoms (P<.001).
Numerous studies have suggested that ginkgo is effective in improving the effects of cerebral insufficiency, not only in improving memory and cognitive function, but possibly acute cerebral ischemia (stroke). In India, a double-blind placebo trial involved patients who were given large doses of ginkgo biloba extract, or placebo, within six hours after an acute cerebral ischemic infarct. Modest improvement differences occurred in the group taking ginkgo biloba extract. More research needs to be conducted in this area to determine the true effectiveness of the extract.
Mechanism action of ginkgo
Our understanding of the mechanism of action of ginkgo biloba extract is incomplete. It is believed that the antioxidant properties of the extract are responsible for most of the therapeutic effects. The ginkgolide B portion of the extract appears to have platelet-activating factor (PAF) antagonist. The flavonoids fraction is thought to contain free-radical scavengers. This is a possible reason for the neuroprotective effects believed to be provided by ginkgo biloba. The anti-inflammatory effects of ginkgo make it similar to other anti-inflammatory agents, in that it reduces thrombosis and interferes with mediators from phagocytes. The vasodilating effects create an improvement in perfusion of all bodily tissues, not just those of the brain.
One of the changes noticed in patients taking ginkgo for dementia was improvement in attitude and mood. This prompted researchers to look at the chemical effects the ginkgo extracts had on neurotransmitters. A study conducted on rats suggested that extract of ginkgo biloba caused reversible inhibition of monamine oxidase inhibitors (MAO). MAO inhibitors block the reuptake of norepinephrine, the mood elevator commonly increased by many antidepressants. This may be why those taking ginkgo describe it as an anti-stress and antianxiety product.
Studies also have suggested that ginkgo biloba prevents mitochondrial aging by protecting against oxidative stress, providing proliferation of human skin fibroblast, and increasing production of collagen and extracellular fibronectin. Much more research needs to be conducted to support these beliefs, but there are studies that can be reviewed which indicate such anti-aging properties from ginkgo biloba are possible.
Other areas that have been researched include hormonal effects of ginkgo extract, pertaining to increased libido, premenstrual syndrome, and vasospasms (hot flashes) due to menopause. A double-blind study vs. placebo was conducted with 165 women, ages 18-45, who suffered from congestive symptoms of premenstrual syndrome. The EGb 761 extract was very effective in preventing breast tenderness and neuropsychological symptoms characteristic of premenstrual syndrome.
Adverse effects of ginkgo biloba
The adverse effects of ginkgo include gastrointestinal-tract disturbance, headache, contact dermatitis, bleeding disorders even in healthy patients who are not taking aspirin or anticoagulants (rare). The New England Journal of Medicine described a case report involving spontaneous bleeding from the iris in a male patient who had been taking ginkgo for one week. The 70-year-old patient had been on a one-aspirin-per-day regimen to prevent stroke or heart attack for three years after he had coronary artery by-pass graft surgery. One week after taking 80mg (50:1 extract) of ginkgo biloba per day he presented with blurred vision and a red streak in his eye. There was no history of eye disorders or traumas. The patient was told to stop taking ginkgo, but to continue taking aspirin. There was no recurrent bleeding throughout the next three months of treatment with aspirin alone.
There were two cases of retinal hemorrhage reported from different physicians whose patients were not taking any other drugs, just ginkgo biloba. A kidney-dialysis patient presented with clotting problems that only occurred when he was taking ginkgo biloba. Therefore, ginkgo biloba should not be taken with coumarin, warfarin, heparin, aspirin, or any other blood-thinning herbs.
How much should be taken?
Research shows that the therapeutic dose of standardized EGb 761 extract is 120mg. per day. There are 40mg.-tablets available to be taken morning, noon, and night or at 4-hour intervals. Higher doses of the extract have not been proven to provide increased benefits for improvement in memory and cognitive function. More studies with higher doses of the extract need to be evaluated to determine if it would be advantageous for specific problems.
The safety of the extract has been evaluated mostly in dose ranges of 120mg. to 160mg. per day. Food does not interfere with the absorption of the extract, although the extract is absorbed in the upper gastrointestinal tract. The same studies showed that glandular and neuronal tissues, as well as eyes, seemed to have a high affinity for the extract. Studies in rats have shown that blood levels of the extract peak at one to two hours, and that a biological half-life occurs at four to five hours. It usually takes two to four weeks before the effects of ginkgo are noticeable.
The research on ginkgo biloba is very exciting. Understandably, we all want to try the herb to reap the modest benefits of memory improvement, antiaging effects, and all the other suggested effects. Before diving in and consuming the extract, remember that no herb, natural or not, is a panacea and without adverse effects. Alert patients who are taking aspirin, anticoagulants, or any blood-thinning agents of the synergistic effects of ginkgo biloba with such agents. Remember that patients are under the misconception that herbs are natural and harmless, so they fail to mention to you that they are taking them when answering the medical history questionnaire.
Y Ernst E. Ginkgo biloba extract in peripheral arterial diseases: a systematic research based on controlled studies in the literature. Fortsch Med. 1996;114:85-87.
Y Hopfenmuller W, Evidence for a therapeutic effect of Ginkgo biloba special extract: meta-analysis of 11 clinical trials in patients with cerebrovascular insufficiency in old age. Arzneim Forsch. 1994;44:1005-1013.
Y Janssens D, et.al, Increase in circulating endothelial cells in patients with primary chronic venous insufficiency: protective effect of Ginkor Fort in a randomized double-blind, placebo-controlled clinical trial. J Cardiovasc Pharmacol 1999 Jan;33(1):7-11.
Y Kleijnen J, Knipschild P. Ginkgo biloba. Lancet. 1992;340:1136-1139.
Y Kleijnen J, Knipschild P. Ginkgo biloba for cerebral insufficiency. Br J Clin Pharmacol. 1992;34:352-358.
Y Knapp M, Knopman D, Solomon P. A 30-week randomized controlled trial of high dose tacrine in patients with Alzheimer?s disease. JAMA. 1994;271:985-991.
Y Le Bars P, Katz M, Berman N, Turan M, Freedman A, Schatzberg A. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. JAMA. 1997;278:1327-1332.
Y Maitra I, Marcocci L, Droy-Lefais M, Packer L. Peroxyil radical scavenging activity of Ginkgo extract EGb 761. Biochem Pharmacol. 1995;49:1649-1655.
Y Oken BS, Storzbach DM, Kaye JA. The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Arch Neurol 1998 Nov; 55(11):1409-
Y Pitchumoni SS, Doraiswamy PM. Current status of antioxidant therapy for Alzheimer?s Disease. J Am Geriatr Soc 1998 Dec;46(12): 1566-72.
Y Roncin J, Schwartz F, D?Arbigny P. EGb 761 in control of acute mountain sickness and vascular reactivity to cold exposure. Aviat Space Environ Med. 1996;67:445-452.
Y Rosenblatt M., Mindel J. Spontaneous hyphema associated with ingestion of ginkgo biloba extract. NEJM (1997) 336; 15:1108
Y Sastre J, et. al. A ginkgo biloba extract (Egb 761) prevents mitochondrial aging by protecting against oxidative stress. Free Radid Biol Med. 1998 Jan, 24:2, 298-304.
Y Tamborini A, Taurelle R. Value of standardized Ginkgo biloba extract (Egb 761) in the management of congestive symptoms of premenstrual syndrome. Rev Fr Gynecol Obstet. 1993 Jul-Sep;88(7-9):447-57.
Y White HL, Scates PW, Cooper BR. Extracts of Ginkgo biloba leaves inhibit monamine oxidase. Life Sci. 1996;58(16): 1315-21.
Y Woerdenbag HJ, Van Beck TA. Ginkgo Biloba. Adverse Effects of Herbal Drugs. Vol 3. Berlin, Germany: Springer-Verlag; 1997.
Y Wong AH, Smith M, Boon HS. Herbal remedies in psychiatric practice. Arch Gen Psychiatry. 1998 Nov;55(11):1033-44.
Cynthia R. Biron, RDH, is chair of the dental hygiene program at the Tallahassee Community College. She is also a certified emergency medical technician.