| ||Interviews with Nutritional Experts: N-Acetylcysteine (NAC): An Old Nutrient Attracts New Research||
In a previous articel, I discussed why AIDS researchers were excited
about two nutrients, Vitamin C and N-acetylcysteine (NAC). While most Whole
Foods readers know a great deal about the roles of vitamin C in nourishing
the body, some readers may not be all that familiar with the roles of the
sulfur-containing nutrients, such as NAC, in nourishing the body. Therefore,
I promised to provide more background on NAC in this article. 
Our understanding of the many nutritional and biochemical roles of sulfur-containing
nutrients is expanding rapidly at this time. We are learning more about
how glutathione and its sulfur-containing precursors are important in keeping
our bodies nourished, our immune systems healthy, and in protecting us against
cancer and heart disease.
Glutathione, cysteine, methionine, selenocysteine and selenomethionine have
been important in my research for over thirty years. Even before that, I
believe that some of the health pioneers indirectly realized the importance
of these compounds as a group, even though they didn't understand much about
the roles of the individual 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
nutrients. Not much has been said about them in "mainstream" nutrition,
but today, interest in learning how sulfur-containing nutrients nourish
the body is increasing.
Researchers are rushing to study the roles of these nutrients 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. Since these nutrients are normally
produced in plants, man and other animals, they have always been a part
of the human diet.
Sulfur-containing nutrients play several critical roles in the body including
detoxification and protecting cells and cellular components against oxidative
stress. 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. They did, and twenty-one years ago I reported that, "sulfhydryl
compounds that are excellent radiation protectors are also free-radical
scavengers, peroxide decomposers, catalysts of sulfhydryl-disulfide exchange,
and possibly can implement repair of damaged sites. Sulfhydryl compounds
and vitamin E also increase the body's tolerance to selenium." 
Today, NAC is of greater interest than glutathione itself. 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. [3,4] These dual properties help repair oxidative
damage in the body.
Both NAC and glutathione are well absorbed. [5-8] NAC is rapidly metabolized,
and only about ten percent of the amount consumed stays in the blood for
an appreciable time.  Much of the NAC is very rapidly consumed in producing
intracellular glutathione. However, even the thiol metabolites of NAC are
NAC readily crosses cell membranes, even in HIV-infected cells, whereas
glutathione does not enter into HIV-infected cells in adequate amounts.
[10-12] Even so, NAC does not seem to raise tissue or blood levels of glutathione
above the desired ranges.  Thus, the nutrient role of NAC is to help
maintain healthy levels of intracellular glutathione , especially
whenever a condition has limited glutathione production. This nutrient role
of maintaining optimal levels of essential body compounds is different from
"drug roles" in which body compounds are just elevated without
homeostasis or normal body regulation.
Since NAC is a powerful antioxidant nutrient, it has been of special interest
to athletes for some time as heavy exercise increases oxidative damage in
the body. [13-15] But the latest research interests are in AIDS and heart
A growing 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. [16-20] 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.
Diets and drugs designed to lower blood cholesterol levels do not lower
Lp(a) levels. 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%. [22-25]
Lp(a) consists of a LDL particle attached to the large glycoprotein apo(a)
by one or more disulfide bonds. NAC breaks up the disulfide bonds by converting
each disulfide group into two sulfhydryl groups now in two separate compounds.
NAC also inhibits heart damage by preventing LDL from being oxidized and
by destroying free radicals produced after an infarction. [26-29]
Immunity and AIDS
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 . [12,30] In addition, intracellular glutathione
availability affects the production of phagocytes (macrophages,
monocytes and neutrophils). T-cells and B-cells are lymphocytes (white cells
that are the principal cells of lymph). B-cells produce antibodies and are
responsible for humoral response, while T-cells help produce antibodies,
secrete interferon and other lymphokines, and are responsible for cell-mediated
response. The phagocytes have the function of killing viruses, bacteria
Free radicals can impair the immune system and NAC can protect against free
radicals and enhance the immune system. [31-33]
As discussed in detail in the previous issue, NAC has been shown to block
the AIDS virus (HIV) production in vitro, apparently by increasing glutathione
levels in HIV-infected cells. [34-46] In the previous article, I also discussed
the synergism of NAC and vitamin C. Beside vitamin C reducing oxidized glutathione
back to free reduced (active) glutathione, vitamin C and NAC had complementary
actions to slow the replication of the AIDS virus.
I reported last month that in addition to NAC and vitamin C (especially
Ester-C (tm)), AIDS Related Complex (ARC) and AIDS patients should be sure
that they are well-nourished with cysteine, selenium, garlic, vitamin B-12,
folic acid, zinc and Dimethylglycine (DMG). Add Coenzyme Q-10 to this list.
Dr. Karl Folkers and colleagues at the Institute for Biomedical Research
at the University of Texas have expanded on their recent study of ARC patients
who have now lived for over four years with ARC without developing "full-blown"
AIDS by taking 200 milligrams of Coenzyme Q-10 daily. Their first small-scale
study was published in Biochemical and Biophysical Research, and their expanded
study will be published in the Journal of Applied Nutrition. Detoxification
These sulfur-containing nutrients are also gaining new interest because
they protect against toxins. NAC is particularly effective and NAC detoxifies
several toxic agents including the heavy metals such as mercury, lead and
cadmium [48-54], drugs including acetaminophen (e. g. Tylenol (tm)) [9,55-61],
herbicides such as paraquat , environmental pollutants such as carbon
tetrachloride and urethane [63-67], and microorganism including aflatoxin
and Escherichia coli [68-70].
NAC, cysteine and glutathione contain sulfur in the form of sulfhydryl groups.
Sulfhydryl groups directly react with many poisons, especially heavy metals
such as lead, mercury and cadmium. These sulfur-containing nutrients are
the bodies first line of defense against many poisons as they tie-up the
poisons right in the gut. They also offer second-line and third-line defenses
in the liver and various individual cells. Sulfhydryl groups also help remove
toxins indirectly via an enzyme system called the P-450 System.
NAC also has a secondary role in detoxification since it helps produce optimal
amounts of glutathione which also conjugates with most "foreign"
compounds and excess oxidizers that enter cells. The harmful compounds that
have been conjugated with glutathione then pass harmlessly out of the body
through the biliary system. 
Although NAC is a food component and a nutrient accessory factor, it is
also marketed as a drug with approved medical claims. Other nutrients also
have dual classifications, but just because a nutrient is also approved
for "drug" usage, its role as a nutrient is not affected unless
drug claims are made. If the nutrient is used to nourish the body, it remains
a nutrient. If the nutrient is used to treat a non-deficiency disease, then
this use changes its legal classification to a drug.
NAC is approved as a drug for use to prevent liver damage from acetaminophen
overdose. Either NAC tablets or solutions may be used to protect against
acetaminophen overdose. Normally, the 20 percent solution is mixed 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, ifosphamide,
valproic acid and alcohol. [9,60,61]
NAC protects against cancer by both of its roles as antioxidant and detoxifier.
NAC also reduces the toxic effects of some chemotherapy agents such as cisplatin
and oxazophosporine-based agents. [77,78]
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. When a nutrient is topically
applied or sprayed into the lungs, it can then be classified also as a drug
because it does not then enter into metabolism to nourish the body when
it is administered in this way. (However, this is different from having
a nutrient absorbed into the body by sublingual or nasal membrane
application which allows the nutrient to nourish the body.)
Optimal Intake Ranges
There are a few toxicological studies of NAC available and the following
observations can be made. NAC in normal food supplementation ranges is without
known toxicity and has been administered by physicians under supervision
in doses of 500 milligrams to four grams daily. Daily levels of 1,000 milligrams
of NAC per kilogram in rats for several months did not produce adverse effects
in behavior, weight gain, hematology, liver function and kidney function.
 (That's the equivalent of 60 grams of NAC per day for a 132 pound person,
80 grams per day for a 176 pound person, or 100 grams per day for a 220
When administered via nebulizer, adverse effects can include stomatitis,
nausea and nasal irritation.  Intravenous administration could also
produce edema and a rapid heart beat. 
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. intravenous administration of
more than 150 milligrams of NAC per kilogram of body weight within a fifteen
minute period may produce toxic or other undesirable effects. 
The mouse LD50 of oral NAC is reported to be about 8,000 milligrams of NAC
per kilogram in the mouse, and 5050 milligrams per kilogram in the rat.
[81,82] For more details on NAC safety, please refer to references 83 through
|Richard A. Passwater, Ph.D. has been a research biochemist since 1959. His first areas of research was in the development of pharmaceuticals and analytical chemistry. His laboratory research led to his discovery of......more