and Glutathione: New Understandings About "old" Nutrients.
by Richard A. Passwater, Ph. D.
Our understanding of the many nutritional and biochemical roles of glutathione and its precursors is expanding rapidly at this time. We are learning how the precursors to sulfur-containing peptides and amino acids are important in keeping our bodies nourished, our immune systems healthy, and in protecting us against cancer and heart disease.
Glutathione and cysteine have been important in my research for over thirty years. Even before that, I believe that some pioneers in the health food profession indirectly realized the importance of these compounds even though they didn't know about the specific compounds. When the "pioneers" spoke so favorably of getting adequate "sulfur" in the diet, I believe that they were really testifying to the importance of these sulfur-containing compounds. Now, the interest in learning how sulfur-containing amino acids and their precursors nourish the body is increasing.
Researchers are rushing to study the roles these nutrients to also discover their role in halting the dreaded Human Immunodeficiency Virus (HIV), breaking up lipoprotein(a) [Lp(a)], detoxifying harmful chemicals, scavaging free radicals and possibly protecting against some cancer processes.
I have discussed cysteine and glutathione several times before. , Later in this article, I will discuss the role of glutathione precursors and why they are more effective than glutathione itself in AIDS patients. These non-fuel nutrients are nutritional accessory factors that are normally produced in plants, man and other animals. Thus, they have always been a part of the human diet.
Glutathione plays several critical roles in the body. Its more important roles are protecting cells and cellular components against oxidative stress and in detoxification. My interest in glutathione and cysteine began in the 1960's when they were found to be protective against nuclear radiation. I reasoned that the same mechanism of action would make them excellent free-radical scavengers as well. 
NAC is produced in living organisms from the amino acid cysteine. Thus, NAC is a natural sulfur-containing amino acid derivative found naturally in foods and is a powerful antioxidant. These dual properties help repair oxidative damage in the body. This has made this nutrient of special interest to athletes for some time as heavy exercise increases oxidative damage in the body. But the latest research interests are in AIDS and heart disease.
AIDS and Immunity
Now the biochemical and medical research communities have taken special interest in this nutrient because of its importance in increasing intracellular glutathione levels and other biochemical properties. Oral glutathione is largely broken down in the digestive system into dipeptides and free amino acids. Although some glutathione is absorbed intact, it still must cross the cell walls to serve many body needs. As will be seen later, HIV infection decreases the transport of glutathione into cells, and as a result, the immune system fails. Thus, even injections of glutathione fail to restore intracellular glutathione levels in AIDS patients. (Later we will discuss the evidence that shows that glutathione is well absorbed and transported across cellular membranes of healthy persons.) NAC, on the other hand, is well absorbed, readily passes through cellular membranes in AIDS patients, and stimulates glutathione production within the cells. [2-7] Approximately ten percent of orally ingested NAC shows up in the blood.
Earlier research has suggested that NAC suppresses Human Immunodeficiency virus (HIV) in infected cell cultures. [8-14] NAC is also of interest to AIDS patients as it protects against some of the damage produced by radiation.  AIDS patients undergoing radiotherapy for Kaposi's syndrome may have a double benefit from this nutrient.
Another area of interest is that research has pinpointed a specific lipoprotein called Lp(a) as one of the two most reliable indicators of heart disease risk. The other reliable indicator is the level of vitamin E in the blood. Lp(a) is a much more reliable indicator than blood cholesterol level, low density lipoprotein, high-density lipoprotein or their ratios to each other.
Now recent research has found that NAC is the most effective nutrient known to lower Lp(a) levels. NAC reduces Lp(a) by almost 70%. [16-19]
NAC affects immunity via its role in intracellular glutathione production. This role becomes critical when normal glutathione production pathways are impaired, as for example, by the Human Immunodeficiency Virus (HIV). Eck has shown that reduced intracellular glutathione is the "direct and early consequence of retroviral infection." 
Intracellular glutathione has a powerful influence on how well T- and B-lymphocyte cells function. [20,21] In addition, intracellular glutathione availability affects the production of phagocytes (macrophages, monocytes and neutrophils). The T-cells *** The phagocytes have the function of killing viruses, bacteria and fungi.
NAC has been shown to block the AIDS virus (HIV) production in vitro, apparently by increasing glutathione levels in HIV-infected cells.  In 1989, Dr. Leonore Herzenberg told Associated Press writer Steve Wilson, "I am really excited about this. Looking at the scientific evidence for what (NAC) does, and the scientific evidence for how AIDS works, our guess is that treatment with (NAC) may be quite good. But, until we get it tested in patients, we won't know if it will work."
This food-factor is also gaining new interest because it protects against toxins and has been widely used to treat bronchopulmonary diseases.
NAC detoxifies several poisons including acetaminophen and other drugs, mercury, lead, cadmium, paraquat, urethane, aflatoxin and Escherichia coli. NAC, cysteine and glutathione contain sulfur in the form of sulfhydryl groups. Sulfhydryl groups directly react readily with many toxins, especially heavy metals such as lead, mercury and cadmium. [22-25] Sulfhydryl groups also help remove toxins indirectly via an enzyme system called the P-450 System.
Although NAC is a food component and a nutrient accessory factor, it is also marketed as a drug with approved medical claims. NAC is approved for use in bronchopulmonary diseases and to prevent liver damage from acetaminophen overdose.  Either NAC tablets or solutions may be used to protect against acetaminophen overdose. [26-29] Normally, the 20 percent solution is drank after dilution with a cola drink.
The Lancet reports that NAC is also effective in reducing the toxic effects of carbon tetrachloride, chloroform and carbon monoxide.  NAC can also reduce the side effects of drugs such as doxorubicin and ifosphamide. 
NAC has been used for about thirty years to break up mucus in persons having bronchopulmonary diseases including chronic bronchitis, cystic fibrosis, asthma, sinusitis and pneumonia.  NAC helps reduce the viscosity of mucus so that it may be more easily coughed up.  NAC accomplishes this by converting the disulfide bonds of the mucoproteins into sulfhydryl bonds and cleaving the mucoproteins into smaller molecules.
Several companies provide a 10 or 20 percent NAC solution as a nebulizer spray (such as Bristol Laboratories' Mucomyst TM), while others such as Italy's Zambon group provides NAC in tablet form.
Optimal Intake Ranges
NAC in normal food supplementation ranges is without known toxicity and has been administered by physicians under supervision in doses of two to four grams daily. Larger quantities used for treating acetaminophen overdoses have produced adverse reactions such as nausea, vomiting, and other gastrointestinal symptoms. Rash, with or without mild fever, has been reported on rare occasions with very large quantities. When administered via nebulizer, adverse effects can include stomatitis, nausea and nasal irritation. Intravenous administration could also produce edema and a rapid heart beat.
Ingestion of more than 150 milligrams per kilogram of body weight (that is nine grams per day for a 132 pound person, twelve grams per day for a 176 pound person, or fifteen grams per day for a 220 pound person) may produce toxic or other undesirable effects.
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