Gingko biloba for Prevention of Dementia

Some posts back, I wrote about the use of Gingko biloba for the prevention of acute mountain sickness (AMS). Now there appears an article in the Journal of the American Medical Association (JAMA) [2008;30(19):2253-2262] entitled, "Gingko biloba for prevention of dementia: a randomized controlled trial," authored by Steven T. DeKosky et al.

The authors note that G. biloba is widely used for its potential effects on memory and cognition. They further note that prior to their clinical trial, there was no adequate investigation from which G. biloba's effects could be determined. So, their objective was to determine the effectiveness of G. biloba versus a placebo in reducing the incidence of all-cause dementia and Alzheimer disease in elderly persons with normal cognition and in those with mild cognitive impairment. In a statistically valid number of individuals, using twice-daily doses of 120 mg extract of G. biloba versus placebo, they concluded that this treatment regimen was not effective in reducing either dementia or Alzheimer disease.

There are many reasons offered for why G. biloba might be effective as a drug, including possible reduction of oxidative stress that perhaps leads to dementia or cerebrovascular disease, reduction of amyloid aggregation, or other effect(s). However, based upon this study, it does not appear that there is a benefit to taking G. biloba.

What is the implication of this for the outdoor medicine community? I think it highlights how little we know about drugs, supplements, and natural products that are often recommended as remedies, cures, and preventive agents for a wide variety of environmental medical problems, such as high-altitude illness, allergic reactions, snakebite, insect bite, marine envenomations, and others. We are still relatively early in our understanding of the pathophysiology of issue such as acute mountain sickness. We are becoming confident that it reflects a degree of brain swelling, but how much and why? Is there a logical reason why ingesting G. biloba would be expected to hasten acclimatization, or prevent or reverse a fundamental or subtle pathophysiological process related to hypoxia and brain dysfunction? The strength of our empirical observations will in large part be determined by designing and implementing large, statistically valid investigations, such as these authors did for looking at G. biloba and its (failed) effect on the prevention of dementia. Granted, in extrapolating from dementia to AMS, we may be comparing apples and oranges, but I am still cautioned about placing too much reliance on G. biloba for the prevention of AMS until someone can show me why it makes sense that it should be effective.

Tags: Gingko biloba, dementia, AMS, wilderness medicine, outdoor medicine, healthline

Labels: acute mountain sickness, AMS, dementia, Ginkgo, Ginkgo biloba

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Update on AMS and HACE

This is the seventh post based upon educational sessions and syllabus material presented at the Wilderness Medical Society Annual Meeting & 25th Anniversary held in Snowmass, Colorado from July 25-30. This post relates expert advice about acute mountain sickness (AMS) and high altitude cerebral edema (HACE) from Dr. Peter H. Hackett, MD, FACEP, who is Director of Emergency Services at Telluride Medical Center and Director of The Institute for Altitude Medicine in Telluride, Colorado.

The incidence of acute mountain sickness (AMS) varies with location, depending on both absolute altitude reached and rate of ascent to altitude. It has been estimated that 15 to 40% of Colorado resort skiers (depending on the altitude of the resort) develop AMS, and studies have shown an incidence of 40% in Mt. McKinley climbers and 70% in Mt. Rainier climbers. Given the huge numbers of Colorado tourists (10 million a year), this is not a trivial problem. High altitude cerebral edema (HACE), or brain swelling, is defined as the progression of cerebral symptoms and findings of ataxia (difficulty with balance, walking, and muscular coordination) and change in consciousness.

The sleeping altitude is the critical factor, with 9,000 feet being a significant threshold for illness (>20% incidence), and 8,000 to 9,000 feet less of a problem (perhaps 10 to 15% incidence), while below 8,000 feet, AMS is uncommon (but still possible). Susceptibility to AMS is not related to physical fitness or gender, although women less frequently suffer from pulmonary edema (fluid in the lungs). Older adults may be less susceptible, while limited data suggest that children probably have the same incidence as does the general adult population.

Individual susceptibility and reproducibility are well documented. Contributing factors include low lung capacity, a less vigorous breathing response to conditions of low oxygen content in the blood, and exaggerated pulmonary hypertension (high pressures in the circulation of the lungs) in response to hypoxia (for high altitude pulmonary edema, or HAPE). Brain circulatory responses and dynamics play an important role, but are difficult to test at sea-level.

Currently, past history of AMS is the most significant risk factor and best predictor. Early diagnosis is the key to successful management and a high index of suspicion is critical. The setting is rapid ascent to a higher altitude in unacclimatized persons. The symptoms include headache, poor or no appetite, dizziness, nausea, insomnia, feeling tired, fatigue, and shortness of breath. Difficulty with (erratic) breathing is common during sleep, but not a sign of AMS. Early AMS feels exactly like a hangover. In the early stages, physical findings may be lacking. When advanced, the findings are those of fluid in the lungs and brain swelling. Ataxia, change in mental status and bluish skin discoloration (particularly noted in the fingers and toes and around the lips, also known as cyanosis) are the most useful indicators of serious illness.

The differential diagnosis of AMS includes dehydration, exhaustion, carbon monoxide poisoning (this is very important indoors, or in a tent or igloo), infections of lung or brain, viral syndromes, migraine events, transient ischemic attack (TIA, of the brain), hypothermia, drugs, and psychiatric problems.

The pathophysiology of moderate to severe AMS and HACE is clearly related to brain swelling. Whether early AMS, especially the headache, is due to brain swelling is not yet established. Factors contributing to brain swelling include, but are not limited to, the degree and rate of onset of hypoxemia (low oxygen content in the blood), inadequate breathing (known as hypoventilation, which can be due to low innate breathing response to hypoxemia, respiratory depressant drugs, or ascent too rapid for adequate acclimatization), poor gas exchange (oxygen for carbon dioxide) in the lungs, fluid retention, individual anatomy (such as ability to accommodate increased brain volume).

As brain volume increases, the pressure within the brain (intracranial pressure, or ICP) rises, although very little (perhaps only 20 to 30 milliliters) until a critical threshold is reached. A dehydrated brain is much more compliant than a “wet” brain. Dilation of cerebral blood vessels causes increased cerebral blood flow and increased cerebral blood volume, engorging the brain and making it stiffer and less compliant. As brain swelling continues, ICP rises beyond the ability of blood to flow into brain tissue. Eventually (and sometimes quite rapidly), cerebral blood flow stops, causing death.

Treatment is directed toward reducing brain volume and stopping any leak of fluid from the blood vessels into brain tissue:

1. Increase oxygenation and thereby reduce low oxygen concentration in the blood and tissues:

a. Descent - 1,000 feet may be adequate to effect improvement, but one should descend as far as is necessary until there is visible clinical improvement.
b. Administer supplemental oxygen if it is available. This is especially good for headaches and altered mental status.
c. Initiate hyperbaric oxygen therapy (e.g., within a portable pressure bag) if such is available

2. Speed the process of acclimatization:

a. Administer acetazolamide (Diamox) 125 to 250 mg by mouth every 12 hours. For children, the dose is 5 mg/kg of body weight/day. This drug promotes increased urination, stimulates ventilation, and decreases cerebrospinal fluid formation. Because acetazolamide carries some cross-reactivity with “sulfa” drugs, it should be used with extreme caution in persons suspected or known to be allergic to sulfa drugs.
b. Acclimatization at the same altitude is okay for mild AMS, but a sick person should never be left alone.

3. Treat symptoms:

a. For the headache, use analgesics.
b. For nausea and vomiting, use antiemetics, such as ondansetron (Zofran) dissolving wafer tablets 4 mg by mouth every 4 hours as needed

4. Reduce the fluid leak from the brain capillaries:

a. Administer dexamethasone 4 mg by mouth (or if a health care professional, by injection) every 6 hours. This may need to be continued until the victim is evacuated to a lower altitude, since rebound brain swelling may occur with cessation of this medication, and because the drug per se does not improve or hasten acclimatization.

Prevention of altitude illness:

1. As best possible, ascend slowly. “Climb high and sleep low.” The ideal rate of ascent is difficult to establish because of marked individual variation in the ability to acclimatize. A reasonable recommendation is to not sleep at an altitude 2,000 feet higher than the previous night’s sleeping altitude once above 8,000 feet. Take an extra day for acclimatization with every 3,000 to 4,000 feet of elevation gain.
2. A high (>70%) carbohydrate diet reduced AMS by 30% in some studies, but had little effect in other reports. It is not likely to be harmful and might help.
3. Avoid respiratory depressants (especially sleeping pills), and only ingest alcohol in small amounts.
4. Chemoprophylaxis:

a. Indications are forced rapid ascent or history of recurrent illness.
b. Take acetazolamide by mouth up to 5 mg/kg body weight/day divided into 2 or 3 doses, beginning one day prior and until one day after ascent. 125 mg twice a day may be sufficient for most persons. Recall that there may be a cross-reactivity (allergic reaction) in persons allergic or sensitive to “sulfa drugs.”
c. Take dexamethasone 4 mg by mouth every 6 to 12 hours, or 2 mg every 6 hrs. This is useful for persons intolerant of acetazolamide, or if the travel will be to extreme altitude. The drug may need to be continued for three or four days, since it does not speed acclimatization. It is commonly used by climbers on “summit day.”
d. Use of acetazolamide and dexamethasone simultaneously is promoted by some - acetazolamide to speed acclimatization and dexamethasone to prevent brain swelling, but only in first few days of ascent.
e. Ginkgo biloba was used in three studies, and shown to reduce AMS from 35 to 100%. It may be more effective during a moderate rate of ascent. The dose is 100 mg by mouth twice a day starting 2 to 3 days before and while at altitude. It is safe and inexpensive, but it has not been proven effective in all studies. Furthermore, preparations of the compound vary.

Tags: acute mountain sickness, AMS, HACE, wilderness medicine, outdoor medicine, healthline

Labels: acute mountain sickness, AMS, HACE, high altitude cerebral edema, high altitude medicine

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Acetylsalicylic Acid (Aspirin) Analog versus Acetazolamide for Acute Mountain Sickness

In Volume 9, Number 1 (2008) of the journal High Altitude Medicine & Biology, published by the International Society for Mountain Medicine, Bengt Kayser, Ronald Hulsebosch, and Frank Bosch report a randomized controlled study of the acetylsalicylic acid (aspirin) analog, calcium carbasalate, compared with a placebo and acetazolamide (Diamox) during a rapid ascent of Mount Kilimanjaro (5896 meters or 19,344 feet). The dose of calcium carbasalate used was 380 mg per day; the dose of acetazolamide was 500 mg per day. Ascent of Mt. Kilimanjaro is typical of a rapid ascent that does not require technical mountaineering skills, and is undertaken by numerous persons who are neither experienced in high altitude travel nor particularly knowledgeable about high altitude illness.

The results showed that calcium carbasalate did not prevent acute mountain sickness (AMS) or headache. A very interesting finding was that more than half the individuals taking acetazolamide developed AMS. This may indicate that the dose taken is not sufficient in general, or perhaps only that the ascent rate was too fast for this (or any) dose of acetazolamide to be effective in prevention of AMS. This is even more intriguing, and deserves further investigation, because the trend in recent clinical recommendations has been to use lower doses (e.g., 250 mg per day) of acetazolamide for the purpose of high altitude acclimatization, in order to achieve a beneficial effect while minimizing the side effects. So, it is very important to understand which circumstances of ascent call for a higher dosing regimen.

AMS is a very debilitating disorder, and is likely the harbinger of high altitude cerebral edema (brain swelling). At the very least, it causes headache, poor appetite, fatigue, nausea, and soft tissue swelling, and is markedly disruptive for adventures and recreation at high altitude. This particular study supports our current understanding that non-steroidal antiinflammatory drugs and common analgesics, such as aspirin, ibuprofen, and acetaminophen, are not useful to prevent AMS, and may only serve to mask an important symptom (headache) that indicates when a person is entering a dangerous physiological situation. Of course, if the patient and observers are confident that the headache is mild and that AMS is not progressing, it is reasonable to treat the headache with an analgesic.

photo courtesy of www.7summits.com

Tags: acetazolamide, acute mountain sickness, AMS, wilderness medicine, outdoor medicine, healthline

Labels: acetazolamide, acute mountain sickness, AMS, calcium carbasalate, high altitude, high altitude medicine

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Ginkgo biloba for Prevention of Acute Mountain Sickness

The fourth issue of Volume 18 of the journal Wilderness & Environmental Medicine has recently been published. The lead article is entitled "Ginkgo biloba Decreases Acute Mountain Sickness in People Ascending to High Altitude at Ollague (3696 m) in Northern Chile," authored by Fernando A. Moraga and his associates.

The article describes a study, the objective of which was to determine the effect of Ginkgo biloba in preventing acute mountain sickness (AMS) at an altitude of 3696 meters (12,126 feet) in participants without high-altitude experience. Thirty-six persons who reside at sea level were transported by ground transportation over 8.5 hours to an altitude of 3696 meters. The study participants were divided into three equal groups of 12 persons each. One group received Ginkgo biloba in a dose of 80 milligrams every 12 hours by mouth, one group received acetazolamide (Diamox, a drug commonly used to hasten acclimatization to altitude or to treat AMS) in a dose of 250 milligrams every 12 hours by mouth, and the final group received a placebo (e.g., no active drug). Each group began its treatment 24 hours before ascending and continued treatment during the 3-day stay at altitude. A standard Lake Louise Questionnaire was administered to determine the Self-Report Score, which is an accepted method for determining the presence and degree of AMS. In addition, selected physiological measurements were taken.

The results are the most compelling data to date supporting the efficacy of Ginkgo biloba in prevention of AMS. The group taking the Ginkgo biloba had no increase in their AMS score (which is remarkable), while the acetazolamide and placebo groups showed increases of 36% and 54%, respectively. The authors concluded that their study provides evidence supporting the use of Gingko biloba in the prevention of AMS, demonstrating that 24 hours of pretreatment with Gingko biloba and subsequent maintenance during exposure to high altitude are sufficient to reduce the incidence of AMS in participants with no previous high-altitude experience.

No doubt, others will attempt to replicate this investigation. If the results are corroborated, then Ginkgo biloba may prove to be a very useful adjunct in the prevention and treament of AMS.

Ginkgo biloba plant image courtesy of www.artofbonsai.org

Tags: Ginkgo biloba ,AMS, altitude, acetazolamide, high altitude, wilderness medicine, outdoor medicine, healthline

Labels: acetazolamide, acute mountain sickness, AMS, Ginkgo, Ginkgo biloba, high altitude, high altitude medicine

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