Ginkgo biloba

Ancient Remedy Mitigates the Harmful Effects of Stress and Aging.

What is Ginkgo biloba?

The ginkgo (biloba) is a member of an ancient family of trees, very possibly the oldest living tree species on earth. The first fossil records of ginkgos date back to over 270 million years ago. In evolutionary terms, the ginkgo is more closely related to pine trees (gymnosperms), than to flowering trees (angiosperms), a fact that makes evolutionary sense, given that gymnosperms are phylogenetically much older than angiosperms. The reason that the ginkgo has thus far escaped extinction up to now is its high resistant to disease, pest and environmental insult, a genetic resilience that is also reflected in its potential to live to over 4,000 years.

Also known as the Maidenhair tree, ginkgos were once indigenous to many parts of the world. Today, however, the ginkgo only grows naturally in China. Nevertheless, due to its ability to survive harsh environments, man has once again transplanted the ginkgo to cover many parts of the globe. In fact, the ginkgo is one of the few trees that can survive 'big city' environments and hence, is often found lining the streets in some of the world's busiest metropolitan areas. However, despite the fact that the fruit and the leaves of the Ginkgo have been used in traditional Chinese medicine for over six centuries, its re-appearance in the North American continent only took place a little over two centuries ago. The ginkgo's species name, biloba, is derived from the fact that its leaves possess two lobes (see image). Scientific nomenclature is generally straightforward.

Uses of Ginkgo biloba

Extracts of dried ginkgo leaves are among the best selling herbal medications in Europe, especially in France and Germany where it ranks among the top five of all prescriptions written. Achieving nearly a 300 million dollar a year industry at the commencement of the 21st century, ginkgo sales will continue to increase in the upcoming years as research reveals more about its healthful properties. Let there be no doubt, the increasing use of ginkgo for medical purposes stems from its success in the clinical arena.

Ginkgo biloba derivatives are currently being used to remedy asthma, coughs, age-related macular degeneration (reduced vision in the elderly) and bladder inflammation. Ginkgo also improves peripheral and cerebral circulation and, in this capacity, has been shown to be effective in mitigating cases of erectile dysfunction, intermittent claudication (pain caused by inadequate blood flow to the legs) and cerebral insufficiency (reduced blood flow to the brain in the elderly causing symptoms of cognitive decline). In fact, one of the more promising uses of ginkgo is as a neuroprotectant and cognitive enhancer; ginkgo is proving to be an effective anti-Alzheimer's treatment (see below). Finally, ginkgo also reduces signs of stress, both mentally and physically (see Stress Inhibition).

Components of a standardized extract of Ginkgo biloba: EGb 761

Unwanted contaminants: Ginkgolic acid should constitute less than 10 ppm (parts per million) to a final extraction, since it might cause skin irritation.

Biological activities of the components of Ginkgo biloba

Extracts of Ginkgo biloba have been found to increase circulation, enhance mood, accentuate cognitive capacity and improve memory. These effects are more often, than not, the result of the combined actions of the individual components of Ginkgo biloba working in concert, the so-called polyvalent effects (see below). Next is a description of the biological activities that each separate fraction of Ginkgo biloba (EGb 761) has at the cellular level.

Ginkgo-flavonol glycosides: Flavonoids (such as quercetin, kaempferol and isorhamnetin) are potent antioxidants. Acting as such, ginkgo's falvonoids scavenger and neutralize free radicals that might cause the breakdown of integral cell membranes via a deleterious process of lipid peroxidation as well as damage DNA, leading to mutations of the cell's genetic information. The ginkgo flavonoids thus extend cell survival under conditions (oxidative and free radical stress) that might otherwise lead to cell death or the development of cancer.

In particular, a specific flavonoid fraction of EGb 761 (CP 205) has been recently shown to prevent the death of neurons in an area of the brain known as the hippocampus in response to NO (nitrix oxide) over production (see reference below). As the hippocampus is the part of the brain that consolidates and stores memories, any damage to this part of the brain will severly interfere with normal cognitive capacity.

By acting as free radical scavengers the flavonoids also relax blood vessels by preventing a rise in intracellular calcium concentration that would otherwise cause vascular smooth muscle contraction (vasoconstirction).

Ginkgo terpenoids: Ginkgolides improve blood flow by reducing the stickiness of platelets, supporting cellular energy metabolism and by acting as antioxidants.

• Ginkgolides: These agents are highly selective antagonists of platelet aggregation mediated by platelet-activating factor (PAF) receptor. PAF, synthesized locally, mediate pain perception, blood coagulation, and smooth muscle contraction. When overexpressed, PAF contributes to various inflammatory, cardiovascular, and respiratory disorders.

  Ginkgolide B is most active of the ginkgolides in this capacity, followed by ginkgolides A, C, M in order of reducing potency.

   

• Bilobalide: Bilobalide is a sesquiterpene. Recent evidence indicates that bilobalide improves cellular energy metabolism, especially in response to cerebral ischemia, or greatly reduced blood flow. Specifically, bilobalide allows mitochondria to maintain respiratory activity when oxygen levels drop precipitously and by doing so maintains cellular energy (ATP) content from dropping dangerously.

  Bilobalide derivatives are currently used for treating neuropathy, edema, encephalopathy, spinal cord disease and senile dementia. There is also convincing evidence supporting an antioxidant role for bilobalide.

Bilobalide might also prove useful as an anticonvulsant. Over excitation by neurotransmitters, namely glutamate, can give rise to seizures.

Polyvalent effects: Ginkgo's broad systemic effects are the consequence of interactions between the individual biological activities (increased circulation, antioxidant effects and metabolic effects) of its separate components (flavonoids, ginkgolides and bilobalide). Such multifaceted actions of ginkgo are most evident in the area of dementia and the decline in mental capacity observed with aging. This needs to be contrasted with synthetic medications that instead target a single cellular pathyway and are more limited in scope. For instance, ginkgo biloba is demonstrating to be effective in retarding the development of Alzheimer's disease.

Interestingly, a significant proportion of patients suffering from dementia and depression exhibit elevated cortisol levels (see Stress Inhibition). Stress kills brain cells...

Precautions and counterindications of mixing Ginkgo biloba with certain prescribed medications

Ginkgo is widely considered safe and side effects are rare. In a few cases, gastrointestinal upset, headaches, skin reactions, sleeeplessness and dizziness have been reported.

• Because Ginkgo biloba decreases clot formation (platelet aggregation) there is some concern that it may increase the risk of intracranial (brain) hemorrhage. Therefore, until more is known, one should not mix ginkgo with other blood-thinning medications, including aspirin.

   

• Ginkgo biloba should not be taken within 36 hours of surgery to the possibility of bleeding complications.

   

• Ginkgo biloba should not be taken in combination with anticonvulsant medication.

This website provides other possible counterindications of Ginkgo biloba use.

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Stress Inhibition

Scientific studies examining the effects of Ginkgo biloba (EGb 761) on indicators of systemic stress

Two recent studies examined the ability of Ginkgo biloba (EGb761) to attenuate indicators of stress, namely elevated blood pressure and serum cortisol levels.

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Scientific study #1: EGb 761 suppresses cortisol release in response to stressors

Diurnal Cortisol Rhythm

Serum cortisol levels obey a circadian rhythm; they are highest in the morning and recede throughout the remainder of the day until almost totally disappearing around midnight.

In males, the stress-evoked release of cortisol was abolished with the administration of a single dose of EGb 761, but only in the afternoon when the ability of stress to increase serum cortisol levels over baseline is most apparent. Due to the large drop in serum cortisol levels in the early morning hours, however, the ability of exercise to increase serum cortisol levels was largely hidden by the declining wave and hence, precluded any apparent effect of EGb 761. That is, baseline and stress measurements were made one hour apart, which was much too slow to discern a change in serum cortisol in response to exercise, or ginkgo, treatment.

Interestingly, women did not exhibit a stress-provoked rise in serum cortisol at any point in the day and accordingly, ginkgo biloba had no effect over serum cortisol levels in women.

Heart rate and blood pressure consistently increased in response to the combined stressors. EGb 761 reduced blood pressure during the handgrip trial in all cases, males and females, at all times of the day, but without altering heart rate.

Therefore, at least in males, Ginkgo biloba appears to reduce the release of cortisol and rise in blood pressure following a combination of physical and mental stresses. These results therefore suggest that ginkgo supplementation might represent a possible way to circumvent the release of cortisol following prolonged exercise and possibly help circumvent the development of Overtraining Syndrome.

Scientific study #2: EGb 761 does not decrease resting cortisol levels

Earlier animal studies have suggested that Ginkgo biloba, or more specifically, one of ginkgo's components may inhibit the synthesis of the glucocorticoid hormones. This would be good news with reference to cortisol, but may have negative repercusions as far as the steroid sex hormones are concerned, especially testosterone and progesterone.

To paraphrase, the second study (Ref. 2) found that Ginkgo biloba produced a small, yet statistically insignificant, drop in serum cortisol levels after administration of EGb 716 for fourteen days. Other products of steroid hormone synthesis (17a-hydroxyprogesterone, bound testosterone, free testosterone, free androgen index, androstenedione, dihydrotestosterone, sex hormone–binding globulins, etc) were similarly unchanged by ginko administration. With respect to the little change in resting steroid hormone production following ginkgo administration, this study agreed well with the findings of the first study. It thus appears that ginkgo biloba does not alter the resting production of the steroid hormones humans.

Comparison of the two studies

Here is a list of the principal differences between the two studies examining the effects of EGb 761 over serum cortisol levels.

• Dose: 120 milligrams (Ref.1) versus 240 milligrams (Ref. 2) per day; 120 milligrams is the typical dose recommended in the medical literature.

   

• Duration: Single dose (Ref.1) versus 14 day trial (Ref 2.).

   

• Sample Size: Seventy subjects (Ref.1; 33 males and 37 females) versus eleven subjects (Ref.2; 6 males and 5 females) participated in the study. The larger sample size was a major advantage of the first study (Ref.1). Too many studies are restricted to small sample sizes, making it more difficult to interpret the statistical significance of the generated data.

   

• Assay: Salivary sample (Ref.1) versus blood test (Ref.2).

   

• Product: European manufacturered extract EGb 761 elixir (Ref.1) versus American produced tablets of EGb 761 (Ref.2).

   

• Study Design: Stress-induced (Ref.1) versus resting cortisol levels (Ref.2).

Both studies utilized relatively young subjects of between 20 and 40 years of age. I would like to see similar studies conducted on older group subjects given that this demographic is where Ginkgo biloba is currently showing the most promise.

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