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Can Ginkgo Prevent Alzheimer’s Disease?

Greg Prince

10/9/2008

 

Purpose and History of Ginkgo  

With origins dating back almost 200 million years ago, Ginkgo Biloba is one of the world’s oldest trees. Ginkgo also has long-standing roots in herbal remedy, as the first medical uses of ginkgo were traced back to 2800 BC through traditional Chinese medicine. A native to Southeast Asia, the ginkgo tree is now grown all over the world so that the leaves and fruits may be harvested over the summer. Ginkgo trees are widely recognized for their green to yellow fan-shaped leaves and round fruits that are approximately 1 cm in diameter (http://altmed.creighton.edu/ginkgo/History.htm). The tree is also known for its extreme resistance to pollution, insects, and disease (http://archneur.ama-assn.org/cgi/content/full/55/11/1409). Today, ginkgo is one of the best selling herbal supplements in the world and is among the leading prescription drugs in both Germany and France (http://altmed.creighton.edu/ginkgo/History.htm). The ginkgo extract is made by soaking the ginkgo leafs in alcohol, drying the leafs, and then grinding the leafs into a powder. The extract commonly is used in a variety of forms, such as tablets, capsules, teas, and skin products, in an attempt to heal existing conditions like asthma or bronchitis. Recently, ginkgo extract is used to treat memory issues ranging from a general memory boost to preventing/treating dementia, a deterioration of the brain (http://nccam.nih.gov/health/ginkgo/). Although there have not been sufficient scientific studies done on the effects of ginkgo with Alzheimer’s patients, there are a number of studies that suggest that the use of ginkgo can reduce the effect of dementia, such as that caused by Alzheimer’s Disease.

 

Picture Source: (http://z.about.com/d/forestry/1/0/o/i/ginkgo_leaf.JPG)

 

What is Alzheimer’s Disease?     

Alzheimer’s Disease is a progressive, genetically heterogeneous disease of the brain that affects 15 million people worldwide (http://www.molecularneurodegeneration.com/content/3/1/1). Common symptoms of patients with Alzheimer’s includes confusion, agitation, metabolic disturbances, as well as a loss in cognitive, intellectual, functional, and social abilities (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1697743). Early signs of Alzheimer’s are characterized by memory impairment and subtle behavioral changes, although this takes place before any extreme structural damage to the brain (http://www.molecularneurodegeneration.com/content/3/1/1). The symptoms of the disease were first described by Alois Alzheimer in 1906 during an autopsy of a 56-year-old woman that showed signs of mental deterioration. Alzheimer noticed that the nerve cells in the woman’s brain were disorganized and clustered. This led Alzheimer to develop the early theory, which is still somewhat prevalent today, that the nerve “plaque” at these areas was a probable cause for the memory loss (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1697743). According to the Creighton University School of Medicine, dementia of the brain due to Alzheimer’s is associated with “the loss of cholinergic neurons that innervate the cerebral cortex.” In other words, the pathways that send signals through the brain are lost along with the means to recall memories or perform certain functions. Alzheimer’s is now widely believed to have a genetic link on either chromosome 1 or 14 (http://altmed.creighton.edu/ginkgo/Alzheimers.htm).

 

Picture Source: (http://www.about-dementia.com/articles/images/Neurons.jpg)

 

How Does Ginkgo Help Those with Alzheimer’s Disease?

            Even though various studies have proven that the use of ginkgo has benefited patients with Alzheimer’s, the exact mechanisms as to how it works are still unknown; however, there are two commonly accepted theories. The first theory comes from ginkgo’s antioxidant qualities. When cells in the body use oxygen, they naturally produce free radicals, which are highly unstable, as a product. The free radicals will try and stabilize by reacting with other cells, which causes a damaging chain reaction. Antioxidants, such as those in ginkgo, act as “free radical scavengers” that prevent damage caused by the free radicals (http://www.healthcastle.com/antioxidant.shtml). This relates to the effects of Alzheimer’s disease, as ginkgo’s antioxidant qualities prevent, or at least slow down, a membrane breakdown in the brain that is common among the elderly and Alzheimer’s patients (http://altmed.creighton.edu/ginkgo/Ginkgo for memory disorders.htm). The exact physiological features of Alzheimer’s are unknown, but the primary hypothesis is based on age-related oxidative injury, similar to the kind ginkgo helps prevent (http://archneur.ama-assn.org/cgi/content/full/55/11/1409). The other theory on ginkgo’s effects on Alzheimer’s patients is centered on ginkgo’s anti-inflammatory properties. Inflammation in the body is the localized reaction of tissue to irritation, injury, or infection, which can result in the loss of function for that tissue (http://nutrition.about.com/od/dietsformedicaldisorders/a/antiinflamfood.htm). The anti-inflammatory products in ginkgo helps reduce the “plaque” buildup of dysfunctional neurons as well as regulating neurotransmitter function. This is important for Alzheimer’s patients because the neuron buildup, or “plaque,” that is commonly found in Alzheimer’s patients is believed to be a primary cause for the loss in brain function (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1697743).

Picture Source: (http://www.alzheimersmemoryloss.info/alzheimers-disease.jpg)

 

Scientific Results

            Even though ginkgo is one of the most popular herbal supplements worldwide, there are few conclusive experiments done testing its effectiveness, specifically with degenerative disorders like Alzheimer’s disease. What’s more, I found a variety of results that both support and disprove the notion that the use of ginkgo has a beneficial effect on Alzheimer’s patients. However, most of the experiments disproving the beneficial effects of ginkgo were generally reported before the results of the experiments supporting the beneficial effects of ginkgo on Alzheimer’s patients. This is likely due to a better modern-day understanding of the properties of ginkgo as well as the effects of Alzheimer’s disease on the brain. Therefore, I have chosen to focus on the more recent reports on the effect of ginkgo and Alzheimer’s, in which all three chosen studies support the notion that there is a positive correlation between the two.

            The first experiment, conducted by the New York University Medical Center and Memory Centers of America, tested the effect of a ginkgo extract, EGb 761, on patients with Alzheimer’s. The experiment was a 52-week, randomized, double blind, placebo-controlled, parallel-group, multicenter study that treated the variable test subjects with 120mg/day of EGb 761. In order to qualify for the experiment, patients had to score between 23 and 14 on the Mini-Mental State Examination, a test of a person’s mental aptitude; scores between 23 and 14 were common for Alzheimer’s patients. These precautions were taken to insure that participants in this study were efficiently randomized and that one potential result was not influenced over the other. To test the effectiveness of ginkgo, the participants underwent two different tests, the Alzheimer’s Disease Assessment Scale and the Geriatric Evaluation by Relative’s Rating Instrument, that measured that participant’s cognitive functions. The results showed that the ginkgo extract EGb 761 improved the cognitive state of those with mild or moderately severe dementia, while it noticeably slowed down the effects of dementia among those with severe dementia (http://www.ncbi.nlm.nih.gov/pubmed/11803237). This model was effective in that it eliminated outside influencing factors, while providing a quantitative means of comparing results between the ginkgo group and the placebo group.

            The second study, conducted by the Institute for Pharmacology and Toxicology at Philipps University of Marburg, focused on what qualities of the ginkgo extract EGb 761 produces the neuroprotective effects that have aided Alzheimer’s patients. To do this, EGb 761 was split into its main constituents, ginkgolides A, B, C, J and bilobalide. Each of these was added independently to various animal brains (mice, rats, chick embryos). Once added, the extraction-aided brain was tested with the addition of neuronal-damaging compounds such as glutamate and cyanide. The results of this experiment suggested that each of the EGb 761 constituents have some protective properties against neuronal damage (http://www.ncbi.nlm.nih.gov/pubmed/13130383). While well presented, this study serves more of a theoretical purpose than a practical one. First, the design of the experiment assumes a few things: that the use of animal brains is an acceptable substitute for the use of human brain, that the benefits of ginkgo must come from any of the four ginkgolides or bilobalide, that the effects of neuronal damagers such as glutamate or cyanide are an acceptable substitute for the effects of Alzheimer’s. While these changes were made to accommodate for ethical restrictions and based on a generally accepted train of thought, the foundation for the experiment is not entirely well grounded, therefore, neither are the results.

            The third study, published by the Department of Pathology and Infectious Disease of Royal Veterinary College, follows a similar in vitro, or outside of the living organism, structure to that of the second experiment. However, the second experiment focuses more on the response of the ginkgo extract EGb 761 on synapse damage due to the production of Aβ1–42, a peptide closely connected to the early stages of Alzheimer’s. As Aβ1–42 is produced in the early stages of Alzheimer’s, synapse damage occurs, lowering the amount of neurotransmissions that take place. By pre-treating neurons with ginkgolides A or B, components of the ginkgo extract EGb 761, neurons were protected from the damage possible due to the presence of Aβ1–42 (http://www.molecularneurodegeneration.com/content/3/1/1). As mentioned, this experiment is similar to the second experiment discussed in that both test the effects of ginkgo extracts on neurons subjected to harmful products in an in vitro model; whereas the first experiment mentioned studied the effects of ginkgo extracts in an in vivo, or inside the living organism, model. Likewise, the shortcomings of the third experiment are similar to that of the second in that this study provides theoretical knowledge, but does little as to providing evidence that ginkgo will have the same effect in a living human with Alzheimer’s. The third experiment’s credibility is aided by the fact that it was published in 2008, about six years after the first two, so it has more outside research to support its findings than the two previously mentioned.

Picture Source: (http://rauljurado.com/images/Alzheimers.gif)

Conclusion

            The studies provided uphold the general belief that ginkgo has positive results for those suffering from Alzheimer’s disease. Nonetheless, the “myth” is often discredited based on other research experiments that prove otherwise and because there are not a sufficient number of directly relevant or long-term studies done that can prove ginkgo’s remedial properties once and for all. However, there are studies currently underway to satisfy these demands. The GuidAge Study Group is in the midst of a five-year double-blind randomized trial to evaluate the efficacy of 240mg/day of EGb 761, the ginkgo extract, in the prevention of Alzheimer’s disease; the results should be available in 2010 (http://www.neurology.org/cgi/content/abstract/67/9_suppl_3/S6). As health care is becoming more and more expensive, herbal remedies, such as the use of ginkgo, are becoming accepted, cheap alternatives or complimentary supplements. Unfortunately, not all of these herbal alternatives are proven to work, so it is important that more clinical trials are done to debunk common myths. If ginkgo is an accepted substitute for Alzheimer’s treatment as current studies suggest, then it could be an important discovery for the medical community. However, more long-term, clinical in vivo trials, like the one by The GuidAge Study Group, are necessary to prove the relevance and effectiveness of ginkgo in Alzheimer’s patients.

 

Picture Source: (http://wb3.indo-work.com/pdimage/73/177773_gingko.jpg)

 

References

 

Ahlemeyer, B., Krieglstein, J. (2003). Pharmacological studies supporting the terapeutic use of Ginkgo biloba extract for Alzheimer’s disease. PubMed, 36(1), S8-14. Retrieved October 7, 2008 from PubMed database.

 

Bate, Clive, Tayebi, Mourad, & Williams, Alun (2008). Ginkgolides protect against amyloid-β1–42-mediated synapse damage in vitro. Molecular Neurodegeneration, 3(1). Retrieved October 9, 2008 from Molecular Neurodegeneration database.

 

Chiappelli, Francesco, Navarro, Audrey M., Moradi, David R., Manfrini, Ercolano, & Prolo, Paulo (2006). Evidence-Based Resarch in Complementary and Alternative Medicine III: Treatment of Patients with Alzheimer’s Disease. PubMed Central, 3(4), 411-424. Retrieved October 7, 2008 from PubMed database.

 

Creighton University School of Medicine. Ginkgo Biloba: Alzheimer’s Disease. Retrieved October 9, 2008 from http://altmed.creighton.edu/ginkgo/Alzheimers.htm

 

Creighton University School of Medicine. Ginkgo Biloba: Ginkgo for Memory Disorders. Retrieved October 9, 2008 from http://altmed.creighton.edu/ginkgo/Ginkgo for memory disorders.htm

 

Creighton University School of Medicine. Ginkgo Biloba: History. Retrieved October 9, 2008 from http://altmed.creighton.edu/ginkgo/History.htm

 

Jegtvig, Shereen (2008). Anti-Inflammatory Foods: Can the Foods You Eat Make a Difference in Chronic Pain? Retrieved October 9, 2008 from http://nutrition.about.com/od/dietsformedicaldisorders/a/antiinflamfood.htm

 

Le Bars, P.L., Velasco, F.M., Ferguson, J.M., Dessain, E.C., Kieser, M., Hoerr, R. (2002). Influence of the severity of congnitive impairment on the effect of the Ginkgo biloba extract EGb 761 in Alzheimer’s disease. PubMed, 45(1), 19-26. Retrieved October 7, 2008 from PubMed database.

 

National Center for Complimentary and Alternative Medicine. Herbs at a Glance: Ginkgo. Retrieved October 9, 2008 from http://nccam.nih.gov/health/ginkgo/

 

Oken, Barry S., Storzbach, Daniel M., & Kaye, Jeffrey A. (1998). The Efficacy of Ginkgo biloba on Cognitive Function in Alzheimer Disease. Archives of Neurology, 55(11), 1409-1415. Retrieved October 7, 2008 from PubMed database.

 

Tsang, Gloria (2007).  Antioxidants 101. Retrieved October 9, 2008 from http://www.healthcastle.com/antioxidant.shtml

 

Vellas, B., Andrieu, S., Ousset, P.J., Ouzid, M., Mathiex-Fortunet, H. (2006). The GuidAge study: Methodological issues. A 5-year double-blind randomized trial of the efficacy of EGb 761 for prevention of Alzheimer’s disease in patients over 70 with a memory complaint. Neurology, 67, S6-S11. Retrieved October 9, 2008.

 

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