- Your Brain's Master Antioxidant Defense
© 2004 Priya Shah
radicals and oxyradicals play an important role in the development
and progression of many brain disorders such as brain injury,
neurodegenerative disease, schizophrenia and Down syndrome.
Glutathione is the brain's master antioxidant
and plays an important protective role in the brain.
According to Dr. Jimmy Gutman, "The brain
is particularly susceptible to free radical attack because it
generates more oxidative by-products per gram of tissue than any
Many neurological and psychiatric disease processes
are characterized by... abnormalities in glutathione metabolism
and antioxidant defenses."
Generation of reactive oxygen species (free radicals)
and oxidative damage are an important cause of neuron (brain cell)
death from brain injury.
Chemicals that cause toxicity to certain brain
cells are known to decrease cerebral glutathione (GSH), making
the cells more vulnerable to reactive oxygen species (ROS). (1)
On the other hand, over-expression of the glutathione
peroxidase (GPX) enzyme potently decreases cell death from brain
Brain Injury and Glutathione - The Gender Difference
Researchers at Children's Hospital of Pittsburgh
have found that males and females respond differently to brain
In animal models, levels of glutathione remain
constant in females who have suffered a brain injury, but drop
by as much as 80 percent in males with the same injury.
When glutathione levels drop, brain cells die
much more quickly. This suggests that boys with brain injuries
may require different life-saving treatments than girls.
N-acetyl-cysteine (NAC), a precursor of glutathione,
already approved for use by the U.S. Food and Drug Administration
to treat people who have overdosed on acetaminophen, may be an
effective treatment for brain injury in boys whose brains are
deprived of oxygen.
Brain Disorders and Glutathione - A Genetic Cause?
Genetics researchers have found that the glutathione
S-transferase gene controls the onset of Alzheimer's, Parkinson's
disease and determines, not if we get these diseases, but when.
The glutathione S-transferase gene has previously
been linked to the risk for Parkinson's disease among people who
A previous article covered the importance of glutathione
in Parkinson's Disease.
Alzheimer's Disease and Glutathione
Free radicals and oxidative damage in neurons
is known to be a primary cause of degenerative diseases like Alzheimer's
Amyloid-ß peptide (Aß) accumulation
in senile plaques, a pathological hallmark of Alzheimer's disease
(AD), has been implicated in neuronal degeneration.
Amyloid plaques encroaching on the brain increase
the production of free radicals, or oxidative stress. Antioxidants,
such as vitamin C and E "mop up" the damaging free radicals.
Glutathione (GSH) precursors can prevent death
of brain cells induced by amyloid plaques in Alzhiemer's disease,
while substances that deplete GSH increase cell death. (5)
Evidence has been piling up over the link between
the amount of an amino acid called homocysteine in the blood and
the chance of developing Alzheimer's.
For people not genetically predisposed to developing
Alzheimer's, cholesterol and homocysteine, largely caused by an
unhealthy lifestyle, are the core causal factors.
Welsh GP, Andrew McCaddon, showed that the more
homocysteine that patients with Alzheimer's had, the worse their
mental performance, and the worse their "cognitive impairment,"
the less they had of the antioxidant glutathione. (6)
Glutathione and Mood Disorders
Studies have found that the mood stabilizing drug,
valproate, used to treat epilepsy and bi-polar disorder, regulates
expression of the genes that make glutathione-S-transferase (GST).
In addition, chronic treatment with lithium, another
commonly prescribed mood stabilizer used in treating manic-depression,
also increased levels of GST.
These findings led researchers to conclude that
glutathione S-transferase may be a novel target for mood stabilizing
Alcohol Consumption and Glutathione
Alcohol abuse is known to impair memory and other
brain functions and increase brain cell death. A new study in
rats has shown that alchol consumption causes fewer new brain
cells to form and results in greater cell death. (8)
But rats that were fed alcohol along with Ebselen
- a glutathione peroxidase mimic that acts as a free radical scavenger
- showed no similar reduction in brain-cell formation and no increase
in cell death.
Substances that Boost Glutathione Levels and Protect Brain
Taking glutathione itself as a supplement does
not boost cellular glutathione levels, since it breaks down in
the digestive tract before it reaches the cells.
However, intravenous glutathione therapy and glutathione
precursors or dietary supplements are effective in boosting intracellular
levels of glutathione.
Intravenous Glutathione Injections:
Intravenous glutathione injections have been shown
to produce amazing and rapid results, in patients with Parkinson's
disease. Following even a single dosage of intravenous glutathione,
many of the symptoms of Parkinson's disease rapidly improve, often
in as little as 15 minutes.
In the Alzheimer's study conducted by Welsh GP, Andrew McCaddon,
adding the glutathione precursor, N-acetyl-cysteine (NAC) to a
protocol that lowered homocysteine levels by simple supplementation
with B12 and folate, resulted in prompt, striking, and sustained
clinical improvement in nearly all the patients. (9)
Studies have shown that the Indian curry spice, cucurmin, has
neuroprotective effects because of its ability to induce the enzyme,
hemeoxygenase-1 (HO-1), which protects neurons exposed to oxidant
stress. Treatment of brain cells called astrocytes, with curcumin,
increases expression of HO-1 protein as well as glutathione S-transferase.
Ebselen: Ebselen is
a glutathione peroxidase mimic and potent synthetic antioxidant
that acts as a neuroprotective agent and an inhibitor of free-radical
induced apoptosis (cell death). It can protect brain cells from
the neuro-toxic effects of alcohol consumption. (8)
Whey Protein: Undenatured whey protein provides
glutathione precursors, has been shown to raise intracellular
glutathione levels in clinical trials, and has anecdotally been
reported to improve the symptoms of Parkinson's disease.
of Neurochemistry, Vol. 88, No. 3, 2004 513-531
of Neurochemistry, Vol. 87, No. 6, 2003 1527-1534
Find Brain Cells Die Differently in Males and Females; Pediatric
Academic Societies Press release; 21-Apr-2004
S-transferase omega-1 modifiesage-at-onset of Alzheimer disease
and Parkinson disease; Human Molecular Genetics, 2003, Vol.
12, No. 24 3259-3267
peptide induces oligodendrocyte death by activating the neutral
sphingomyelinase–ceramide pathway The Journal of Cell
Biology, Volume 164, Number 1, 123-131; 5 January 2004
disease and total plasma aminothiols. Biol Psychiatry. 2003
of Neurochemistry, Vol. 88, No. 6, 2004 1477-1484
impairment of hippocampal neurogenesis by chronic alcoholism:
protective effects of an antioxidant. Proc Natl Acad Sci
U S A. 2003 Jun 24;100(13):7919-24. Epub 2003 Jun 05.
pilot study of vitamins to lower plasma homocysteine levels
in Alzheimer disease. Am J Geriatr Psychiatry. 2003 Mar-Apr;11(2):246-9
Curry Protect Against Alzheimer's?; American Physiological
Society (APS) Press Release; 16-Apr-2004
was first published in the May 2004 issue of The
Glutathione Report, a newsletter featuring regular updates
on the health benefits of glutathione. Get a Free
report on Glutathione in Health and Disease