NutriGenomics of Ginkgo Biloba
Written By: Morgan Abramson
Edited By: Valerie Duodes,
Fredric Abramson, Ph.D., S.M.
The science of
NutriGenomics focuses on how gene expression is influenced and shaped by the
chemistry of a person’s dietary environment. By understanding how the diet-gene
relationships translate into wellness or disease, the prospect is opened to
actually manage how genes function by appropriately matching key dietary inputs.
This active management process is Directive Genomics.
Ginkgo Biloba is one
of the oldest herbal remedies. Its use for a variety of health situations is
well documented. This brief paper assembles NutriGenomics relationships for
Ginkgo, based upon published scientific literature. These relationships may help
explain some of the historical observations. They also may help explain why
Ginkgo works in one person and not another, for we are not genetically alike.
The ginkgo tree
is the last living descendant of the many species in the Ginkgoaceae family,
200 million years ago. Ginkgo Biloba was recorded as a medicinal plant to
prevent memory loss due to aging more than 5,000 years ago, in one of the oldest
Chinese classical writings by Sheng Nung Ben Cao (The Herbal Classic of the
Devine Plowman); Sheng Nung (the Devine Plowman). Today, Ginkgo plays a role in
many traditional medical approaches for a variety of purposes.
The Ginkgo Biloba tree
itself is very hearty. The best example of just how much so is the fact that
Several Ginkgo Biloba trees were the only surviving large life forms within 1km
of the epicenter of the Hiroshima atomic blast. The trees suffered no apparent
genetic damage and are still alive today.
Ginkgo Biloba is
considered a "living fossil” as it is the oldest surviving plant species on
earth. It covered the entire world during the Jurassic Period, but was almost
wiped out in the last ice age. The characteristic shape of Ginkgo Biloba leaves
(fan-shaped with an indentation in the middle) gave birth to the species name
Biloba, a Latin word meaning bi-lobed. Ginkgo Biloba, unlike all other trees,
has separate male and female trees. Mature male and female trees commonly stand
facing each other at some distance. Pollen from male flowers is carried by the
wind to the female tree, which produces ovules that fertilize and develop into
yellowish seeds about a half an inch to one inch in length. The Ginkgo fruits
have rancid, unpleasant odor, often described as being comparable to vomit. This
can be a potential issue when planting young Ginkgo trees for it takes about 50
years before one can with certainty identify whether it is a male or female
Ginkgo survived in
Asia as a sacred herb used to treat many ailments. Chinese monks are credited
with keeping the tree in existence over the centuries.
Ginkgo is also an ingredient
of the traditional Hindu medicine called "Soma". Ginkgo was imported from Japan
to the Botanical Garden in Utrecht, Holland in 1727, and then to the United
States 57 years later.
Ginkgo Biloba is
arguably the most interesting medicinal tree in the world. It is considered safe
to use and has wide range of benefits that no other tree on earth has. It is
also one of the best researched in the world with more than 400 scientific
studies conducted on standardized Ginkgo Biloba extracts in the past three
decades. Clinical studies demonstrate that daily doses of 120-240 mg of
standardized Ginkgo Biloba extract can lead to an improvement many medical
conditions mentioned below.
have established rules governing the sale or use of the herb. In German, for
example, Commission E approves Ginkgo Biloba for effective therapy in cases of:
- memory deficits
- tinnitus (ringing
in the ears)
- improvement of
pain-free walking in patients diagnosed with intermittent claudication
(temporary pain while walking)
arterial occlusive disease (clogging of diseased arteries)
Improvement in the
memory loss, depression, and tinnitus could be achieved within 8-12 weeks. In
both intermittent claudication and peripheral arterial occlusive disease,
symptomatic relief can be achieved by increased circulation.
Small studies have
shown that Ginkgo Biloba can also treat infertility in men, impotence, and
inability to achieve orgasm stemming from anti-depressant drugs, but should NOT
be used to treat this without strict doctor supervision.
While Ginkgo is
believed to be one of the safest herbs in the world, side effects have been
-Increase risk of
These effects are rare
and mild and have been known to be caused by people simply taking too much of
the herb (the recommended dosage being 40 mg to 240 mg a day). The main groups
at risk are infants, pregnant or breast feeding women, people who experience
epileptic seizures, and people taking anti-depressants.
allegedly causes seizures in infant’s that ingest the herb directly or through
mother’s milk. One study found that Ginkgo Biloba caused seizures in a 78 year
old man and an 84 year old woman, both with a history of epileptic seizures and
both taking sodium valproate as an anti-epileptic drug. It is not recommend for
patients taking anti-depressants to take Ginkgo to treat sexual dysfunction
without strict doctor supervision as there may be complications.
Ginkgo Biloba owes its
remarkable abilities to two groups of phytochemicals, the ginkgo flavone
glycosides and terpene lactones. They are considered to be the
primary active constituents. The ginkgo flavone glycosides include the
chemicals quercetin, kaempherol and isorhamnetin. These are believed to be
responsible for the antioxidant properties of ginkgo biloba. The terpene
lactones include the chemicals ginkgolides A, B and C, as well as bilobalide,
and have shown several activities. These activities include neuroprotection from
free radicals, improvement of choline (a neurotransmitter) uptake in brain
synapses, and a reduction in the tendency of the blood to clot. Ginkgo Biloba
extract has been standardized to contain 24% flavonoids and 6% terpenoids.
Ginkgo, phytochemicals, genes, and
Bilobalide-A, found only in Ginkgo Biloba, is known to up-regulate the
expression of the gene VEGF, encoding the mitogen (mitosis-inducing protein)
vascular endothelial growth factor. Other rare chemicals, Ginkgolide-A, -B, and
-C, found in Ginkgo Biloba are all known to down-regulate the expression of VEGF
in cardiovascular tissue.
VEGF is known to
stimulate the proliferation of endothelial cells and controls blood vessel
formation and permeability. Research conducted by Dantz and associates in 2002
showed that VEGF can enable the brain to adapt to neuroglycopenia quickly, and
that it maintains neurocognitive function.
In another study, it was discovered that VEGF has neurotrophic and
neuroprotective effects, promoting cell proliferation which can enhance neural
functioning such as memory.
It was also found that it inhibits Caspase-3 which induces apoptosis. Further
research conducted at the Weill Medical College of Cornell University further
revealed that VEGF does in fact induce neurogenesis and improve cognition,
learning and memory when it is present and expressed.
While VEGF expression is beneficial in the brain, it can be a problem when it is
expressed, in some cases at levels that are too high, for other areas of the
body like the heart. VEGF is known to make the vascular and endothelial cells
more permeable to molecules like LDL, causing problems for coronary tissue and
This also leads to loss of plasma proteins due to the leakage and permeability
problem. In addition to neurocognitive functioning and cardiovascular disease,
the expression of VEGF is also associated with oxygen-induced retinopathy and
neovascularization. Research has been conducted to determine the effects of
Ginkgo Biloba on VEGF and the occurrence of retinopathy in mice. Although no
specific chemical from Ginkgo Biloba is credited as down-regulating VEGF, when
the mice were treated with Gingko Biloba they did not develop retinopathy while
those who received no Ginkgo Biloba did in fact develop the condition.
With the up-regulation
of VEGF in the brain by the Bilobalide-A chemical found in Ginkgo biloba,
an increase in neurogenesis and neural functioning would result. As a result a
person would experience enhanced neurocognitive functioning and memory
capabilities. While Bilobalide-A induces higher expression of VEGF in the brain
astrocytes, the chemicals Ginkgolide-A, -B, and -C, found in Ginkgo Biloba, all
suppress VEGF expression in coronary tissue4. Thus, the condition and
function of the coronary tissue would be improved, reducing heart disease.
There are several rare
chemicals found in Ginkgo Biloba whose effects on the expression of various
genes have been studied and identified. One such chemical called Bilobalide-A,
found exclusively in Ginkgo Biloba, has been identified as a negative (down)
regulator of the human gene BAX (BCL-2 Associated Protein).
In other words, in the presence of Bilobalide-A, the BAX gene will lower its
activity or be turned off completely (no gene expression).
The BAX protein,
encoded for by the BAX gene, is a death affecter required for large proportion
of Atm-dependent apoptosis of neurons with genomic damage.
It is a cell death-signaling molecule. It seems possible that if BAX is causing
more than necessary amounts of apoptosis in an individual, they are more
susceptible to diseases like Bipolar disorder. It is also possible that a
patient suffering from Bipolar Disorder has a higher level of genomically
incorrect neurons than an individual without the disorder. In either case, with
the BAX gene activity elevated, cell death would be occurring at a rate that is
faster than that of neurogenesis, leaving the patients with a smaller prefrontal
cortex of the brain which could lead to Bipolar disorder or make the symptoms
It was found that
patients with Bipolar disorder had a prefrontal cortex 38% smaller than that of
an individual without the disorder.
In another study conducted by Stanford’s Robert Sapolsky, PhD, it was found that
when animals are stressed, like that experienced with mood disorders, the
hippocampal neurons undergo cell death or become severely atrophied.
This loss of neurons can contribute to the onset of mood disorders. This is
resulting from stress-induced release of proteins and neurotransmitters which
trigger death effectors (BAX being one such effecter) which kill the cells,
leading to problems like Bipolar disorder.
Since Bilobalide-A is
known to lower BAX gene expression, it is conceivable that neuronal cell death
can be reduced, leaving a patient with more neurons, and reduced symptoms of
There is another
chemical in Ginkgo Biloba that is shown to negatively regulate BAX gene
activity. Via a signaling cascade, the chemical 6-Heptadecenylsalicylic-Acid has
been found to lead to BAX inhibition, yielding the same effects as Bilobalide-A.
Another chemical in
Ginkgo Biloba, Apigenin, has been found to positively regulate the function of
the human gene JUN (“AP1”).
When Apigenin is present, JUN will be higher regulated or turned on in the cell.
has been found to directly activate the gene transcription within a cell in
response to cell stimulation.
As reported on the OMIM database, JUN, when accompanied with the N-terminal
kinase JNK, is essential for neuronal microtubule assembly and apoptosis. These
two processes are known to play a role in mood disorders such as depression and
Bipolar Disorder. An in depth explanation of this relationship is explained
below with information concerning the gene BAX.
As reported in an
article in Molecular Psychiatry, August 2004, factors believed to lead to
the development of Bipolar Disorder include improper or incomplete signaling
cascades within the cell, and loss of cellular plasticity and cellular hardiness
Based on the information reported in OMIM, it seems logical that JUN would be a
genetic factor for Bipolar Disorder when also considering the information from
Molecular Psychiatry. In another study, conducted by Synyal and
colleagues, a drosophila model synapse was used to demonstrate that AP1
functions to positively regulate (increase) synaptic strength and synapse number.
Greater synaptic strength should mean stronger signaling between cells. Greater
cellular signaling, when considering the information above, would seemingly
benefit those suffering from brain disorders such as Bipolar disorder.
Since Apigenin is
known to positively regulate expression of JUN, it would induce strengthening of
the synapse as described above, to alleviate the symptoms experienced by those
with Bipolar Disorder.
In addition to
Apigenin, the chemical 6-Pentadecenylsalicylic-Acid, found in Ginkgo Biloba,
also enhances the expression of JUN.
The research done at
AlphaGenics Inc. examined the health benefits of Gingko Biloba in the context of
how specific Ginkgo phytochemicals influence the activity of different genes. By
identifying the phytochemical-gene connection documented in the scientific
literature, AlphaGenics was able to link what a gene does to claimed benefits of
Ginkgo. The findings provide preliminary genetic validation for Ginkgo Biloba
benefits that are historically described. Using computer data search methods,
AlphaGenics has come to reasonable explanations about how the remarkable effects
of Ginkgo Biloba work at the level of the human genome. All areas of thought and
theory were included; folklore, centuries old medical documents, home remedies,
medical research and reports from the last 100 years, and genetic information
discovered only recently. All of this was combined and analyzed to provide new
insights into how Ginkgo Biloba works.