Ginkgo Benefits Brain Function

Ginkgo biloba Has Multiple Effects on Alzheimer's Disease
An ancient tree gives new hope to those suffering from this terrible affliction
By Dr. Edward R. Rosick

n today's world, events occur at such a fast pace that even the most avid of TV viewers or Internet surfers can be hard-pressed to keep up on all the latest developments. The realms of medicine and health care are certainly not immune to this ever-increasing overload of information, and doctors and patients alike are often left feeling as if they need 25 hours a day just to keep up. Nonetheless, the old axiom "The more things change, the more they stay the same" still holds true for many things in life.

 
The leaves of the
Ginkgo biloba tree

For instance, one thing that hasn't changed appreciably for the past 200 million years is the Ginkgo biloba tree. Ancient Chinese medical manuscripts indicate that at least 5000 years ago, extracts of the leaves of the ginkgo tree were being used to treat a variety of medical conditions, including asthma, Raynaud's syndrome (a circulatory disorder affecting the hands and feet), and age-related memory loss.1

Unfortunately, like so many other herbs used by practitioners of alternative therapies, ginkgo has generally been shunned by mainstream medicine. A number of recent studies, however, have forced traditional medical practitioners to give a second look at ginkgo, especially since it could turn out to be a valuable remedy against one of the emerging epidemics of the twenty-first century: Alzheimer's disease.

Alzheimer's Disease Afflicts Millions

In 1906, a distinguished German neuropathologist, Dr. Alois Alzheimer, gave the first clinical description of the disease that eventually bore his name (his work attracted little attention at the time, however). The most common cause of dementia in those aged 65 or older, Alzheimer's disease is characterized by a progressive decline in cognition and memory. Current statistics indicate that this debilitating condition affects over 15 million people worldwide. With the rapidly aging population in the United States (demographers estimate that 30% of the population will be 65 or older by the year 2050), it is projected that 14 million people in the U.S. alone will be affected during the next few decades.2,3

Even before Dr. Alzheimer's time, ginkgo extracts were being used to treat cognitive decline in the elderly - and they still are. Not until the 1990s, in fact, was there any effective prescription medication to even begin to deal with the tragic symptoms so vividly associated with Alzheimer's disease.

What Occurs in a Brain with Alzheimer's?

There are at least five major pathological changes that occur in the brains of patients with Alzheimer's disease, all of which act to bring about the progressive cognitive impairment and memory loss:4

  • A decrease in levels of the neurotransmitter acetylcholine in certain regions of the brain, resulting in a decline in cholinergic function (brain activity that depends on acetylcholine)
  • An accumulation of destructive deposits known as plaques and tangles in and around the neurons (brain cells)
  • Oxidative damage to neurons brought about by highly reactive molecular species called free radicals (no, they're not the latest heavy metal band or leftover hippies from the 1960s)
  • Inflammatory processes that may lead to the death of neurons
  • A progressive loss of neuronal mass (brain tissue)

Since healthy acetylcholine levels are vitally important for memory formation and retention, the first class of prescription medications for Alzheimer's disease has been targeted to increase the amount of this important neurotransmitter. These drugs inhibit the action of an enzyme called acetylcholinesterase, which breaks down acetylcholine; they are thus called acetylcholinesterase inhibitors. Although they lead to a modest decrease in the rate of progression of Alzheimer's, they do not stop the disease, nor do they affect any of the other pathological changes that make it so devastating.

Fortunately, however, recent studies have shown that a standardized extract of Ginkgo biloba has favorable activity against the first four of the five major pathological changes listed above.

Ginkgo Improves Cholinergic Function

The German Commission E Monographs are the most comprehensive reports in the world on the uses and efficacy of most major herbal medications. The monograph on Ginkgo biloba, published in 1994, outlined its known pharmacological effects.5 Two of the most important of these in terms of treating Alzheimer's disease are inhibition of the age-related decline in acetylcholine receptors on the neurons, and stimulation of acetylcholine uptake in the hippocampus, a brain structure vitally important to memory.


Recent studies have shown that
ginkgo can actually protect
sensitive neurons from the
destructive effects of beta-amyloid.

A more thorough study done in 2000 gave a detailed analysis of ginkgo's effects on brain acetylcholine levels.6 This study reported that ginkgo protects the brain against age-related losses of cholinergic neurons and increases the uptake of acetylcholine in the hippocampus. Another recent study, in the journal Phytomedicine, compared the efficacy of ginkgo to that of the four major anti-Alzheimer's drugs, all of which are acetylcholinesterase inhibitors.7 The report concluded that there were no major differences among the four drugs and ginkgo in terms of the slowing of symptom progression.

Ginkgo Protects Brain Neurons

The accumulation of plaques called beta-amyloid in the brains of Alzheimer's patients is another pathological change that contributes to the disease progression and can lead to the death of neurons in the brain. While current prescription medications for Alzheimer's disease do nothing to prevent or treat these effects, recent studies have shown that ginkgo can actually protect sensitive neurons from the destructive effects of beta-amyloid.

Two recent studies have demonstrated a protective effect of a standardized ginkgo extract against the death of neurons in the brain - specifically, in the hippocampus - induced by beta-amyloid.8,9 The authors of the second study hypothesized that the ginkgo extract worked by inhibiting the formation of neurotoxic molecules that are thought to be involved in the development of Alzheimer's disease.

Ginkgo Improves Antioxidant Activity

Oxidative damage to the brain caused by the production of free radicals is thought to play an important role in the progressive cognitive impairments characteristic of Alzheimer's and other age-related dementias. Free radicals are produced abundantly inside brain neurons and every other cell in the body when energy is generated by glucose metabolism, but natural antioxidant mechanisms for keeping them in check are always at work. In certain diseases, such as Alzheimer's, however, free radicals are produced in even greater amounts then normal and can cause significant damage to the brain and body, including neuronal death.


The study showed that patients
given 120 mg/day of the ginkgo
extract improved on cognitive
assessments, regardless of the
severity of their condition.

A large study in 1997 that examined 442 elderly patients in Basel, Switzerland, found a direct correlation between the blood levels of two common antioxidants (beta-carotene and alpha-tocopherol) and memory retention.10 A review article in 2000 reported that in the autopsied brains of patients with Alzheimer's, there were many hallmark pathological changes caused by free radical activity, including DNA damage, protein oxidation, and lipid peroxidation.11 An even more recent study examined the antioxidant activity of a ginkgo extract on brain cells.12 The authors found that a standardized ginkgo extract effectively increased the levels of antioxidant enzymes and decreased the levels of lipid peroxidation.

Ginkgo Cools the Inflammation of Alzheimer's

Post-mortem examinations of the brains of Alzheimer's victims have revealed signs of inflammation, much like that which one often sees after suffering trauma to some part of the body. Many scientists and physicians who are studying the disease believe that this inflammatory process is quite active in the brains of Alzheimer's patients and in fact leads to much of the neuronal death that is also seen at autopsy.

A great deal of research is therefore underway on the use of anti-inflammatory agents to treat and perhaps even prevent Alzheimer's. In 2000, the National Institute of Aging began a large, multicenter study examining the effects of certain nonsteroidal anti-inflammatory drugs (NSAIDs) on the progression of Alzheimer's. Ginkgo biloba extract is also an effective anti-inflammatory agent. The authors of a recent study state that ginkgo's effect on Alzheimer's is most probably multifaceted and includes its anti-inflammatory action.13

Evidence for Ginkgo's Efficacy Continues to Mount

Long before all these scientific studies validating the use of ginkgo in patients with age-related cognitive loss were done, practitioners of alternative medicine were giving their patients this amazing herb, based on its 5000-year history of use. It is gratifying to see that the kind of rigorous proof of alternative therapies that mainstream medicine demands is finally forthcoming.

The first report of a large-scale, randomized, controlled trial of a standardized ginkgo extract was published in 1996.14 Conducted in Berlin, the study examined the effects of ginkgo vs. placebo in 216 elderly patients with diagnosed Alzheimer's dementia. For 24 weeks, the patients received 240 mg per day of ginkgo or placebo. At the end of this period, the patients who had received ginkgo scored significantly higher than the controls on tests measuring attention, memory, and activities of daily life.

American Physicians Are Being Won Over

Even though the well-designed German study showed that ginkgo had significant positive effects on the mental functioning of Alzheimer's patients, many physicians in the United States were still skeptical of ginkgo's usefulness, perhaps because of the long tradition in Europe of being more open to alternative therapies.

Their doubts were allayed in 1997, however, when an American study on ginkgo was published in The Journal of the American Medical Association.15 This was a randomized, placebo-controlled, double-blind trial of a standardized ginkgo extract on patients with Alzheimer's disease and multi-infarct dementia (a type of vascular dementia caused by a series of ministrokes). For 52 weeks, 309 patients received 120 mg/day (half the dose of the German trial) of either a standardized ginkgo extract or placebo. The results of this study led the researchers to conclude that the ginkgo extract was safe and that it was capable of stabilizing and even improving the cognitive performance and social functions of demented patients for six months to a year.

More recent studies have confirmed the beneficial effects of ginkgo on Alzheimer's disease. For example, a large, placebo-controlled, double-blind study of a standardized ginkgo extract was conducted on 244 Alzheimer's patients whose condition ranged from mild to severe.16 Like the study published in JAMA, this one showed that patients given 120 mg/day of the ginkgo extract improved on cognitive assessments, regardless of the severity of their condition. There was also no difference in the safety profiles of the patients taking ginkgo or placebo.

Yet another study has reinforced the acceptance of ginkgo.17 This randomized, placebo-controlled study showed that 120 mg/day of standardized ginkgo extract produced some improvement in cognitive performance and social functioning of Alzheimer's patients with mild cognitive impairment. In those with more severe impairment, the patients' rate of decline was significantly slowed compared with that of the control group.

Ginkgo Helps Even the Young and Healthy

Alzheimer's is a tragic and devastating disease, both for the people who develop it and for their families and friends. Fortunately, with help from Ginkgo biloba, a tree that was flourishing long before humans walked upon the earth, there is real hope to be seen amid the darkness of this disease. With the abundance of information on ginkgo now available, it should be clear to the most skeptical of mainstream doctors that the use of Ginkgo biloba should be part of the treatment regimen for every Alzheimer's patient.

Remarkably, ginkgo also appears to have beneficial effects on memory even in young and healthy individuals who show no signs of cognitive decline. (For more on this aspect of the use of ginkgo, see "Expanding Attention and Memory in the Young and Healthy" in Life Enhancement, December 2001.)

References

  1. Jonas W, Levin J. Essentials of Complementary and Alternative Medicine. Lippincott Williams and Wilkins, Philadelphia, 1999.
  2. Grundman M, Thal L. Treatment of Alzheimer's disease. Neurol Clinics 2000;18(4):807-28.
  3. Mayeux R, Sang M. Treatment of Alzheimer's disease. New Engl J Med 1999;341:1670-9.
  4. Raskind M, Peskin E. Advances in the pathophysiology and treatment of psychiatric disorders: implications for internal medicine. Med Clin N Am 2001;85(3):803-17.
  5. Blumenthal, Busse, Goldberg, et al. The Complete German Commission E Monographs. The American Botanical Council, Austin, Texas, 1998.
  6. DeFeudis FV, Drieu K. Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. Curr Drug Targets 2001;1(1):25-58.
  7. Wettstein, A. Cholinesterase inhibitors and Ginkgo extracts - are they comparable in the treatment of dementia? Comparison of published placebo-controlled efficacy studies of at least six months duration. Phytomed 2000;6(6):393-401.
  8. Bastianetto S. The Ginkgo biloba extract (EGb761) protects hippocampal neurons against cell death induced by beta-amyloid. Eur J Neurosci 2000;12(6):1882-90.
  9. Yao Z. The Ginkgo biloba extract EGb761 rescues the PC12 neuronal cells from beta-amyloid-induced cell death by inhibiting the formation of beta-amyloid-derived diffusible neurotoxic ligands. Brain Res 2001;889(1-2):181-90.
  10. Perrig WJ, Perrig P, Stahelin HB. The relationship between antioxidants and memory performance in the old and very old. J Am Geriatr Soc 1997;45(6): 718-25.
  11. Christen Y. Oxidative stress and Alzheimer's disease. Am J Clin Nutr 2000;71(2):621-9.
  12. Bridi R, Crossetti FP, Steffen VM, et al. The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats. Phytother Res 2001;15(5):449-51.
  13. Youdim KA, Joseph JA. A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Rad Biol Med 2001;30(6):583-94.
  14. Kanowski S, Herrmann WM, Stephan K, et al. Proof of efficacy of the Ginkgo biloba extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer's type or multi-infarct dementia. Pharmacopsychiatry 1996;29(2):47-56.
  15.  Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind randomized trial of an extract of Ginkgo biloba for dementia. J Am Med Assoc 1997;278(16):1327-32.
  16. Le Bars PL, Kieser M, Itil KZ. A 26 week analysis of a double-blind, placebo-controlled trial of the Ginkgo biloba extract EGb761 in dementia. Dement Geriatr Cogn Disord 2000;11(4):230-7.
  17. Le Bars PL, Velasco FM, Ferguson JM, et al. Influence of the severity of cognitive impairment on the effect of the Ginkgo biloba extract EGb761 in Alzheimer's disease. Neuropsychobiology 2002;45(1):19-26.


Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master's degree in healthcare administration.


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