Free 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 other organ.”
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 injury. (2)
Brain Injury and Glutathione – The Gender Difference
Researchers at Children’s Hospital of Pittsburgh have found that males and females respond differently to brain injury. (3)
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. (4)
The glutathione S-transferase gene has previously been linked to the risk for Parkinson’s disease among people who used pesticides.
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 disease.
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 Alzheimer’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 drugs. (7)
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 alcohol 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 Cells
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.
Glutathione Precursors: 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)
Curcumin (turmeric): Studies have shown that the Indian curry spice, curcumin, 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. (10)
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)
Undenatured 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.
1. Journal of Neurochemistry, Vol. 88, No. 3, 2004 513-531
2. Journal of Neurochemistry, Vol. 87, No. 6, 2003 1527-1534
3. Researchers Find Brain Cells Die Differently in Males and Females; Pediatric Academic Societies Press release; 21-Apr-2004
4. Human Molecular Genetics, 2003, Vol. 12, No. 24 3259-3267
5. The Journal of Cell Biology, Volume 164, Number 1, 123-131; 5 January 2004
6. Biol Psychiatry. 2003 Feb;53(3):254-60
7. Journal of Neurochemistry, Vol. 88, No. 6, 2004 1477-1484
8. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7919-24. Epub 2003 Jun 05.
9. Am J Geriatr Psychiatry. 2003 Mar-Apr;11(2):246-9
10. Can Curry Protect Against Alzheimer’s?; American Physiological Society (APS) Press Release; 16-Apr-2004