Vinpocetine- a cerebral metabolic
Vincamine is an alkaloid extracted from the
Periwinkle plant, Vinca minor. Vinpocetine is produced slightly altering the Vincamine
Vincamine and Vinpocetine have been widely
researched and used clinically for over 25 years, in disorders ranging from cerebral
arteriosclerosis and senile dementia, to Menieres disease, tinnitus, and diabetic
Research has gradually shown Vinpocetine to be the
superior Vinca alkaloid, usually having a few (and minor) if any side effects and a
greater range of clinical and metabolic benefits than Vincamine.
Vinpocetines actions www.vinpocetine.info
Vinpocetine has been shown to be a cerebral
metabolic enhancer and a selective cerebral vasodilator (1,2).
Vinpocetine has been
shown to enhance oxygen and glucose uptake from blood by brain neurons, and to increase
neuronal ATP bio-energy production, even under hypoxic (low oxygen) conditions (3,4).
Vinpocetine has been shown to reduce the cell death
that normally occurs when a brain region is temporarily but severely deprived of blood
The human brain and its energy
To fully appreciate the medical and life enhancement
importance of these key aspects of Vinpocetine pharmacology, it is first necessary to
review some basics of brain physiology and biochemistry.
The human brain typically weighs about 3 pounds
(1-3% of total bodyweight). The brain is generally estimated to contain 10-100 billion
neurons (electrically active nerve cells), and approximately 10 times as many glial cells,
which are structural and nutritional support cells surrounding neurons. The brain normally
receives 15-20% of the bodys total blood supply, and uses 15-20% of the bodys
total inhaled oxygen.
The brain must use this oxygen, along with its chief
fuel- glucose- to produce and use 15-20% of the bodys total ATP energy.
Unlike most other cells, which can burn either fat
or sugar (glucose) for their energy production needs, neurons can only burn glucose under
normal, non-starvation conditions, and they typically consume 50% of the total blood
sugar. Unlike liver and muscle cells, which can store large amounts of sugar as glycogen,
neurons can only store at most a minute or twos worth of glucose, and so they are
dependant upon a continuous and uninterrupted blood supply to maintain normal energy
metabolism and avoid injury or death.
Most other cells (except heart and skeletal muscle
cells) reproduce continually throughout a lifetime yet after the brain reaches a full
complement of neurons (birth to 2 years of age), neurons never reproduce, they are an
irreplaceable essential of life.
Under normal conditions of adequate oxygen supply,
neurons convert glucose into energy (ATP) through a 3-phase process.
The first phase occurs in the cytoplasm of the cell
(the gel-like stuff between the nucleus and outer cell membrane), and is called
"aerobic [oxygen using] glycolysis." As each molecule of glucose is metabolized
through aerobic glycolysis, two molecules of ATP are produced.
In addition, two other by-products result which are
used to make further ATP in the next two phases of energy production.
The "ash" from aerobically burning glucose
is pyruvic acid, which is then converted to acetyl-coenzyme A (ACoA).
ACoA is then metabolized through the Krebs or
citric acid cycle to generate more ATP. The Krebs cycle occurs inside the
mitochondria, the "power plants" of the cell.
The other energy-rich substance produced through
aerobic glycolysis is NADH- the active coenzyme of vitamin B3.
Aerobic glycolysis produces two molecules of NADH
for each molecule of glucose burned. The NADH is then transported to the mitochondria,
where it serves as a fuel in the third phase of energy metabolism- the electron transport
side chain. Each NADH run through the electron transport
side chain, with adequate oxygen, produces 3
molecules of ATP. Eventually, through the successful interaction of aerobic
the Krebs/ citric acid cycle, and the electron transport
side chain, a single molecule of glucose can yield a
maximum of 38 molecules of ATP bio-energy, assuming adequate oxygen for both glycolysis
and mitochondrial "respiratory" metabolism.
When neurons are under-supplied with oxygen,
however, different forms of sugar burning occurs- anaerobic (without oxygen)
For each molecule of glucose burned, anaerobic
glycolysis yields two molecules of ATP. However, instead of producing the valuable
Krebs cycle fuel, pyruvic acid, anaerobic glycolysis produces the somewhat toxic
waste product, lactic acid. And anaerobic glycolysis yields no bonus of NADH to be
converted to ATP through the electron transport
side chain. And with inadequate oxygen, mitochondrial metabolism
proceeds poorly, if at all.
brain formula Raise your IQ
Thus anaerobic glycolysis produces a total of only
two ATP's for each glucose burned.
In other words, when glucose brain fuel is burned
without adequate oxygen, it produces only 5% as much ATP energy as when glucose is burned
with adequate oxygen!
There are 3 main uses for ATP inside neurons- the
"housekeeping-maintenance," electrical and neurotransmitter functions.
neurons dont reproduce and must last a lifetime, they are continually expending
energy to repair or replace various cell components- cell membrane segments, microtubules,
Neurons also use ATP to produce, transport, package,
secrete and reuptake neurotransmitters, which provide cell to cell communication.
massive amounts of ATP are necessary to facilitate the frequent discharges of electrical
energy from the receiving end of the neuron- the dendrites- through the cell body, where
signal processing occurs, and down the transmitting end- the axon. For this electrical
process to occur there must be a rapid and continuous exchange of sodium and potassium
ions back and forth across the neuronal membranes.
This exchange process depends on sodium-potassium
pumps, powered by sodium-potassium ATPase enzyme systems.
Some physiologists estimate as much as 45% of a
neurons ATP may be used to power the sodium-potassium pumps.
It should now be evident why unconsciousness rapidly
occurs if breathing stops, or brain blood flow is interrupted even briefly.
As the delivery of oxygen to the brain halts,
neurons rapidly shift from aerobic to anaerobic energy metabolism, with a consequent drop
in energy production, up to 95%!
There will simply not be enough ATP energy to
facilitate neuronal electrical activity and neurotransmitter discharge- the
electrochemical basis for consciousness. And if aerobic metabolism ceases for too long,
eventually either irreparable damage or even cell death may occur, as even the
"housekeeping-maintenance" neuronal activities fall behind or fail due to energy
For most of us, falling unconscious or suffering
brain death due to cessation of breathing or brain blood flow is not a regular problem to
contend with! However, a more subtle, insidious, slow-developing form of brain energy
crisis can and does occur in most people to some degree over a lifetime, in the form of
cerebral arteriosclerosis, ministrokes, or transient ischaemic attacks (brief
interruptions of brain blood supply, often due to blood vessel spasm).
In its early stages, this brain energy crisis may
lead to only the slightest of symptoms- subtle memory impairment, occasional confusion or
lapses in concentration, slightly more difficulty in learning etc.
At a more advanced stage the brain energy crisis may
show itself as senility or senile dementia, and eventually may terminate in coma or death.
Thus as Branconnier notes "...the severity of
the dementia is directly correlated to the loss of functional brain tissue, independent of
the primary neuropathology. This view is consistent with evidence from studies of cerebral
blood flow, oxygen uptake, and glucose utilization that have shown that brain carbohydrate
metabolism is impaired in a variety of dementias and that the degree of reduction in brain carbohydrate
metabolism is correlated with the severity of the dementia..." (6)
Orthomolecular psychiatry pioneer Abram Hoffer has
suggested that when the brain oxygenation becomes chronically deficient enough, neurons
switch to anaerobic glycolysis as their main energy source. This may provide (barely)
enough energy for the neurons to survive, but it will not provide enough energy to power
their functional roles as electrochemical signal processors/ transmitters.
affected neurons will be "off-line," in an electrically quiescent
However, if normal aerobic metabolism is restored
before irreparable cell damage or death occurs, then the neurons and their functions can
be restored (7).
Vinpocetines clinical studies
Both animal experimental and human clinical research
have shown Vinpocetine to restore impaired brain carbohydrate/ energy metabolism.
In 1976 Vamosi and colleagues reported their
favorable results comparing Vinpocetine with Xanthinol Nicotinate in treating 143 patients
with various cerebrovascular diseases.
They measured a large number of blood and
cerebrospinal fluid variables before and after treatment, such as glucose, lactate,
pyruvate, oxygen, pH, electrolyte levels, etc. They concluded from their study
"Though not all the changes are significant statistically, yet connected with each
other they prove that Cavinton [Vinpocetine] enhances both glycolytic and oxidative
reactions of glucose breakdown in CNS [brain]. The changes in the concentration of K
[potassium] and Mg [magnesium]... may be considered a sign of recovery of the energy
metabolism of the nerve cells." (1)
Vamosis study also demonstrated a superior
clinical efficacy of Vinpocetine over Xanthinol Nicotinate.
In his review on the use of Vinca alkaloids in
dementia, Nicholson observed that "...vincamine increases mitochondrial respiratory
rate in mitochondrial suspensions..., indicating that vinca alkaloids can increase the
rate of ATP synthesis... In addition, elevation of cortical cyclic AMP levels may increase
ATP availability... and this may contribute to the metabolic activity of
Karpati and Szporny resulted favorable results of
Vinpocetine used to treat anaesthetized dogs. Anesthetics reduce brain aerobic metabolism
and ATP production- this is a key aspect of their ability to produce unconsciousness.
Based on their experiments they note that "Increase of cerebral arterial-venous
oxygen difference, cerebral metabolic rate for oxygen and cerebral oxygen utilization
indicate that vinpocetine affects cerebral metabolism, with a dose-dependant
rise in endogenous respiration of cerebral tissue... Our results indicate that rate of
cerebral [energy production] metabolism is increased by [vinpocetine]."
Karpati and Szporny conducted a study with cats that
were subjected to repeated episodes of brain hypoxia. They reported that "...
transitory and partial interference even with normal cerebral circulation caused an
increase of Neurochemical disturbances due to hypoxia... deficient formation of
intermediaries in the Krebs cycle was observed, mainly due to shortage of oxygen. These
and cytological studies refer to a selective failure of mitochondrial metabolism...
Vinpocetine had favorable effects on these parameters... It seems probable that
the effect of Vinpocetine is even more pronounced in vascular
These are just a few of the many reports indicating
the ability of Vinpocetine to safely and effectively restore failing neuronal energy
metabolism, even under hypoxic or ischaemic (poor blood flow) conditions.
Vinpocetines unique and selective
Vinpocetine has also been shown to be a unique,
selective cerebral vasodilator. Solti and co-workers reported their results using
Vinpocetine with 10 men suffering from cerebrovascular disorders (average age: 49). They
conclude; "Cavinton [Vinpocetine] belongs to the rather few drugs which exert a
potent, favorable effect on the cerebral circulation. The effect of Cavinton [Vinpocetine]
on the cerebral circulation has two main features;
1. It strongly reduces cerebral vascular
resistance, which is typically high in cerebral vascular disease;
2. Cerebral fraction of cardiac output is
increased. No marked effect on systemic circulation, blood pressure and total vascular
resistance decreased very slightly on acute vinpocetine effect. Since the drug, far from
increasing RATHER reduces effort of the heart, its effects may be assumed to be favorable
in cerebral alterations associated with heart disease and hypertension." (2)
Hadjiev and Yancheva also reported favorable
clinical results with 50 patients suffering cerebral circulation impairment.
that Vinpocetine does not elicit the "steal effect" that occurs with
non-selective vasodilators. (The "steal effect" occurs when a vasodilator opens
up blood vessels in brain regions that do not suffer from reduced circulation even more
than it opens up blood vessels in regions suffering damaged circulation. This causes a net
shift of cerebral blood flow away from the injured area, causing even further damage to
the already blood starved part). (10)
Vinpocetine and the eyes
In another study with 100 patients suffering from
poor blood circulation to the eye, Kahan and Olah note Vinpocetines inhibition of
platelet aggregation. The microvessels that feed neurons in the brain and retina are
smaller in diameter than a single red blood cell- they are easily "clogged up"
by clumps of platelets, impairing local microcirculation. This provides another mechanism
of action for Vinpocetines ability to enhance cerebral blood flow- inhibition of
unnecessary platelet aggregation, which may be triggered by a high fat diet, magnesium
deficiency, and stress hormones, among other factors
Vinpocetine and brain aging
Another key benefit from Vinpocetine derives from
its activating effect on the noradrenaline nerve cluster in the reticular activating
system called the "locus coeruleus." Olpe and co-workers have shown that
Vincamine and some of its derivatives (Vinpocetine) to be some of the most effective
activators of locus coeruleus neurons. This small group of neurons extends its
noradrenaline-secreting nerve fibers diffusely throughout the cerebral cortex (the
thinking, planning, integrative brain).
Olpe notes that locus coeruleus neurons decline in number with
increasing age, with degeneration advancing slightly faster in men than women.
lessening number and activity of locus coeruleus neurons that occurs with aging is known to play a
significant role in the reduction of concentration, alertness, and information processing
speed and ability that occurs with aging.
Thus Vinpocetines ability to improve the
cerebral cortical activating power of remaining locus coeruleus neurons makes it a true "cognition
enhancing" agent (12).
Vinpocetine, EEG and aging
Saletu and Grunberger have published considerable
pioneering research on EEG correlates of vigilance, and the effects of various drugs on
EEG recordings. They report that "Human brain function as measured by...
electroencephalogram (EEG) shows significant alterations in normal and pathological aging
characterized by an increase of [slow wave] delta and theta activity and a decrease of
alpha and ... beta activity [fast wave] as well as by slowing of the dominant [EEG]
These changes are indicative of deficits in the
vigilance regulatory systems, [which includes the locus coeruleus neurons]. By the term vigilance we
[mean] the... dynamic state of total neural activity... Elderly subjects with bad memory
exhibit slower [EEG] activity and less alpha and alpha-adjacent beta activity than those
with good memory... Antihypoxidotic/ nootropic drugs such as... vincamine-alkaloids
[Vincamine and Vinpocetine] induce interestingly just oppositional changes [to the age
related slowing of EEG waves] in human brain function, thereby improving vigilance."
Vinpocetines side effects
Vinpocetine thus possesses a unique profile; Potent
metabolic enhancer; selective (non "steal effect") cerebral blood flow enhancer;
neural oxygenator; anti-platelet aggregation blood thinner; locus coeruleus activator; EEG
normalizing vigilance enhancer. And yet human and animal studies consistently show a
remarkable safety profile and freedom from side effects.
Thus, in a study on Vinpocetines ability to
improve sensorineural hearing disorders, Ribari and colleagues note that "The drug
[Vinpocetine] has no side effects." (14)
In their extremely detailed examination of
Vinpocetine use in 100 patients with neuro-vascular diseases Szobor and Klein report that
"Laboratory tests, urinalysis, blood picture, blood sugar, liver function, SGOT,
SGPT, CN, electrolytes, cholesterol and total [lipids] did not change... The glucose
tolerance did not deteriorate in the diabetic patients." (4)
In a highly successful double-blind placebo study of
Vinpocetine with 84 elderly patients suffering from chronic vascular senile brain
dysfunction, Balestreri et al, found only 12 adverse effect reports in the Vinpocetine
group (mostly digestive complaints) versus 17 in the placebo group!
No significant adverse laboratory findings were
found in either group (15).
A major Japanese study by Otomo and colleagues with 207
patients suffering various cerebral disorders found only a 2% incidence of mild adverse
side effects- anorexia in 2 patients, hives and stomach pain in 1 and hot flashes in 1. No
significant adverse laboratory findings occurred in the 207 Vinpocetine patients (16).
In their summary of various animal safety tests,
Cholnoky and Domok found the oral LD50 for Vinpocetine (the dose lethal for 50% of the
test animals) to be 534mg/ Kg of bodyweight for mice, 503 mg/Kg of bodyweight for rats.
This would equate to approximately 35,000mg for a
150 pound human. The usual therapeutic dose for Vinpocetine for humans is 15-30mg per day!
Because of side effects at high doses when used with
pregnant rats (uterine bleeding in some), Cholnoky and Domok caution against using
Vinpocetine in pregnant women, or those trying or expecting to get pregnant (17).
Overall, Vinpocetine side effects reported in the
literature are rare, usually minor, frequently disappear with prolonged use, and rarely
require discontinuance of the drug.
Stomach/ GI upset; dry mouth, rapid heart beat, low
blood pressure, and rash/ hives are the main (rarely occurring) reported side effects.
Who might benefit from Vinpocetine?
1. Anyone over 40, cerebral arteriosclerosis is
less well known to the public than heart disease, but it is just as common, and develops
gradually over a lifetime. By the time serious symptoms develop, as with heart disease,
the blood vessel occlusion is usually well advanced. Vinpocetine can minimize the
structural/ functional damage to brain neurons that may accompany gradually developing
2. Anyone who has noticed a decrease in memory,
alertness, concentration, learning speed/ ability, neuro-muscular co-ordination and
reaction time, vision, hearing, or who suffers from tinnitus.
3. Anyone who suffers from, or is known to be at
risk for, various cerebral disorders- cerebral hemorrhage, stroke, senile dementia,
transient ischaemic attacks, chronic cerebral circulatory insufficiency, etc.
4. Anyone wishing to use a generally very safe,
low side effect, brain metabolism enhancing, vigilance enhancing, cognition activating
While Vinpocetine may need to be used for weeks or
months before seeing major improvement in medical situations, the cognitive enhancement
benefits may be noticeable from even a single dose, or within the first several days
use. Improvements in cerebral disorders and in hearing and vision problems may last only
as long as the drug continues to be taken.
Because Vinpocetine enhances cerebral blood flow, it
may potentate other nootropic/ cerebro-active drugs taken simultaneously, thus allowing/
requiring then to be taken in lower doses.