Information On N-Acetyl Cysteine (NAC)
N-Acetyl Cysteine (NAC) is the pre-acetylized form of the simple amino acid Cysteine. A
powerful antioxidant, a premier antitoxin and immune support substance, and is found
naturally in foods. It is a precursor for glutathione, an important antioxidant that
protects cells against oxidative stress. In addition to maintaining intracellular
glutathione levels, NAC supplementation has been shown to suppresses Human
Immunodeficiency virus (HIV) replication, to be protective against cell damage caused by
chemotherapy and radiation therapy, to be immune enhancing, to protect against toxins as
acetametaphen and other drugs, mercury, lead, and others, and is mucolytic, that is, it
breaks up mucus seen in bronchoulmonary disease as cystic fibrosis, chronic bronchitis,
asthma, and pneumonia.
Antioxidants neutralize free radicals, which are produced by normal metabolic activity.
When free radicals are left unchecked they cause damage to cells and DNA and are
considered by scientists to be a major factor in the aging process. NAC is a more stable
form of L-Cysteine because it has an acetyl group (CH3CO) attached. NAC has all the
properties of L-Cysteine but is more water soluble and said to be more bioavailable than
L-Cysteine.
It is known & marketed as an "anti-amalgam" medicine, because it helps remove
(chelate) mercury from the body. It also generally improves the bodys immune system,
making it better able to fight off disease. It is freely available from health-food shops
in many countries. NAC has neither a sedative or stimulant effect, and is a safe substance
showing excellent tolerance in patients.
Oxidative stress has emerged in recent years as a suspected component in the
pathogenesis of HIV disease. Increasing numbers of researchers agree that even in the
earliest stages of infection, a deleterious reductive-oxidative (redox) imbalance may
occur, This means that increased damage causing reactive oxygen intermediates (also called
"free radicals") are generated at the same time that stores of naturally occurring
antioxidant reducing agents are depleted. The possible result is the uncontrolled presence
of oxygen-containing molecules which may cause damage to cell membranes, proteins and
nucleic acids, and alterations in the intra- and inter-cellular environments. The net
effect of this damage has been termed oxidative stress.
NAC is essential for the synthesis of glutathione (GSH) in the body. It has been used
as a possible treatment for HIV infection for over three years. In the U.S. it is
available as the prescription aerosolized drug Mucomyst by Bristol Laboratories, a
division of Bristol-Myers and is used to treat acetaminophen (Tylenol) overdose and
chronic bronchitis. In Europe where it has been used orally for decades it is marketed
under the trade name of Fluimucil by Italy's Zambon group. The oral European version of
NAC is available at buyers' clubs in the United States.
The rationale for the use of NAC in HIV treatment is based on
evidence from in vitro studies that cells deficient in GSH are
particularly sensitive to inflammatory cytokines (tumor necrosis factor
alpha). Elevated levels of TNF are known to activate and increase
replication. That is when TNF stimulates the nuclear transcription
factor kB (NF-kB) in HIV-infected cells, virus transcription and
replication is greatly increased. By increasing the levels of
intracellular GSH, proponents of NAC therapy hope to offset
TNF-mediated HIV replication. GSH is present in almost all human
tissues. It is critical for a number of important cellular functions.
Of primary importance, however, is its vital role as the principal
intracellular defense against oxidation by free radicals and their
compounds. In their 1992 review article Staal et al reported that
"adequate levels of GSH are required for mixed lymphocyte reactions,
T-cell proliferation, T and B cell differentiation, cytotoxic T-cell
activity, and natural killer cell activity. Decreasing GSH by 10 to 40
percent can inhibit completely T-cell activation in vitro. Thus, an
intracellular GSH deficiency in lymphocytes has profound effects on
immune functions."
Staal et al, among others, advocate for the use of NAC as a therapeutic agent in AIDS.
The reasons they state: "NAC has antiretroviral effects in vitro, low toxicity in vivo, a
long history of use in patients, can be given orally in a palatable form and is
inexpensive."
Free radical mediated mechanisms have been suggested as contributing to the development
of several neurodegenerative diseases. Our initial emphasis was the treatment of
hereditary movement disorders, particularly the hereditary ataxias. More recently,
patients with other neurodegenerative conditions including amyotrophic lateral sclerosis
(ALS), multiple sclerosis (MS), diabetic neuropathy and Alzheimer's disease have been
treated with NAC. We report here results of studies with NAC
Treatment with high dose NAC has produced modest improvement in several patients with
neurodegenerative disorders. Where improvement has been noted, it has usually been early
in treatment and then tends to plateau. Some patients have not seen an initial improvement
but remain on NAC as a possible means to prevent further progression of their disorder. In
some 40 patients tested (including patients with HSCA, AT, FA, ALS, MS, DN and HC)
pretreatment FRESA analysis indicated an imbalance in antioxidant enzyme activity.
Although a few patients claimed some benefit from more traditional antioxidant
therapies (e.g vitamins A,C,E,B2, and selenium), most patients said these were without
noticeable benefit. As suggested, improvement in physical condition may correlate with
improved free radical status. This suggests that these enzyme abnormalities are not
primary in these disorders but occur secondary to whatever gene defects trigger excess
free radical activity (e.g., GSHpx and SOD are readily destroyed by excess superoxide).
This study indicates the possibility that if improvement in the antioxidant status occurs,
the potential exists for arresting progression of the disease and in some cases an
improvement in patient condition.
The high level of safety and variety of antioxidant actions of NAC suggest it as a very
promising new tool for treatment of neurodegenerative disorders. In recent months,
scientific reports of animal and in-vitro studies indicate that NAC inhibits neuronal
apoptosis and toxicity in models of multiple sclerosis, amyotrophic lateral sclerosis and
diabetic necrosis.
The most commonly used chemopreventive agents in the prevention of
oral leukoplakia, head and neck cancer, and lung cancer are
beta-carotene, vitamin A, and other retinoids. One of the few
chemopreventive agents not in this group and presently being used in a
clinical trial is N-acetyl-l-cysteine (NAC). NAC, an antioxidant, is
used in EUROSCAN, a European Organization of Research and Treatment of
Cancer (EORTC) chemoprevention study in curatively treated patients
with oral, laryngeal, or lung cancer. The rationale for choosing NAC is
based on a variety of experimental data showing its ability to exert
protective effects, including extracellular inhibition of mutagenic
agents from exogenous and endogenous sources, inhibition of
genotoxicity of reactive oxygen species, modulation of metabolism
coordinated with blocking of reactive metabolites, protection of DNA
and nuclear enzymes, and prevention of the formation of carcinogen-DNA
adducts. NAC has also demonstrated an effect on mutagen-induced
chromosomal sensitivity assays, and on anticarcinogenicity in
experimental animal models. In addition, preliminary data from EUROSCAN
show good compliance in treated patients and a low frequency of side
effects.
The thiol N-acetylcysteine (NAC) is a promising cancer
chemopreventive agent which acts through a variety of mechanisms,
including its nucleophilic and antioxidant properties. We have recently
shown that NAC inhibits type-IV collagenase activity as well as
invasion, tumor take and metastasis of malignant cells in mice. NAC is
also known to attenuate the cardiotoxicity of the cytostatic drug
doxorubicin (DOX, Adriamycin). The present study was designed to
evaluate whether the combination of NAC and DOX treatments in mice
injected with cancer cells could affect their tumorigenic and
metastatic properties. Six separate experiments were carried out, using
a total of 291 adult female mice. In experimental metastasis assays, in
which B16-F10 melanoma cells were injected i.v. into (CD-1)BR nude
mice, DOX significantly reduced the number of lung metastases when
administered i.v. at a dose of 10 mg/kg body weight, 3 days after the
i.v. injection of cancer cells. NAC inhibited lung metastases when
added to the medium of cancer cells before their i.v. injection. The
combined treatment with DOX and NAC, under various experimental
conditions, was highly effective, showing a synergistic reduction in
the number of mestastases. In tumorigenicity and spontaneous metastasis
assays, in which B16-BL6 melanoma cells were injected s.c. into the
footpad of C57BL/6 mice, DOX decreased the number of lung metastases
when given i.p. at 2 mg/kg body weight. Oral NAC exerted significant
protective effects, and considerably prolonged survival of mice. The
combined treatment with DOX and NAC again showed synergistic effects on
the frequency and weight of primary tumors and local recurrences, and
completely prevented the formation of lung metastases in the experiment
in which these end-points were evaluated at fixed times. While
injection of DOX 7 days after implantation of cancer cells failed to
improve the cancer-protective effects of NAC, its injection after I day
resulted in a striynergism between DOX (given parenterally) and NAC
(given with drinking water) in preventing tumorigenicity and
metastases. The indications of these animal studies warrant further
evaluation in clinical trials.
N-Acetyl Cysteine (NAC) is the pre-acetylized form of the simple amino acid Cysteine. A
powerful antioxidant, a premier antitoxin and immune support substance, and is found
naturally in foods. It is a precursor for glutathione, an important antioxidant that
protects cells against oxidative stress. In addition to maintaining intracellular
glutathione levels, NAC supplementation has been shown to suppresses Human
Immunodeficiency virus (HIV) replication, to be protective against cell damage caused by
chemotherapy and radiation therapy, to be immune enhancing, to protect against toxins as
acetametaphen and other drugs, mercury, lead, and others, and is mucolytic, that is, it
breaks up mucus seen in bronchoulmonary disease as cystic fibrosis, chronic bronchitis,
asthma, and pneumonia.
Antioxidants neutralize free radicals, which are produced by normal metabolic activity.
When free radicals are left unchecked they cause damage to cells and DNA and are
considered by scientists to be a major factor in the aging process. NAC is a more stable
form of L-Cysteine because it has an acetyl group (CH3CO) attached. NAC has all the
properties of L-Cysteine but is more water soluble and said to be more bioavailable than
L-Cysteine.
It is known & marketed as an "anti-amalgam" medicine, because it helps remove
(chelate) mercury from the body. It also generally improves the bodys immune system,
making it better able to fight off disease. It is freely available from health-food shops
in many countries. NAC has neither a sedative or stimulant effect, and is a safe substance
showing excellent tolerance in patients.
Oxidative stress has emerged in recent years as a suspected component in the
pathogenesis of HIV disease. Increasing numbers of researchers agree that even in the
earliest stages of infection, a deleterious reductive-oxidative (redox) imbalance may
occur, This means that increased damage causing reactive oxygen intermediates (also called
"free radicals") are generated at the same time that stores of naturally occurring
antioxidant reducing agents are depleted. The possible result is the uncontrolled presence
of oxygen-containing molecules which may cause damage to cell membranes, proteins and
nucleic acids, and alterations in the intra- and inter-cellular environments. The net
effect of this damage has been termed oxidative stress.
NAC is essential for the synthesis of glutathione (GSH) in the body. It has been used
as a possible treatment for HIV infection for over three years. In the U.S. it is
available as the prescription aerosolized drug Mucomyst by Bristol Laboratories, a
division of Bristol-Myers and is used to treat acetaminophen (Tylenol) overdose and
chronic bronchitis. In Europe where it has been used orally for decades it is marketed
under the trade name of Fluimucil by Italy's Zambon group. The oral European version of
NAC is available at buyers' clubs in the United States.
The rationale for the use of NAC in HIV treatment is based on
evidence from in vitro studies that cells deficient in GSH are
particularly sensitive to inflammatory cytokines (tumor necrosis factor
alpha). Elevated levels of TNF are known to activate and increase
replication. That is when TNF stimulates the nuclear transcription
factor kB (NF-kB) in HIV-infected cells, virus transcription and
replication is greatly increased. By increasing the levels of
intracellular GSH, proponents of NAC therapy hope to offset
TNF-mediated HIV replication. GSH is present in almost all human
tissues. It is critical for a number of important cellular functions.
Of primary importance, however, is its vital role as the principal
intracellular defense against oxidation by free radicals and their
compounds. In their 1992 review article Staal et al reported that
"adequate levels of GSH are required for mixed lymphocyte reactions,
T-cell proliferation, T and B cell differentiation, cytotoxic T-cell
activity, and natural killer cell activity. Decreasing GSH by 10 to 40
percent can inhibit completely T-cell activation in vitro. Thus, an
intracellular GSH deficiency in lymphocytes has profound effects on
immune functions."
Staal et al, among others, advocate for the use of NAC as a therapeutic agent in AIDS.
The reasons they state: "NAC has antiretroviral effects in vitro, low toxicity in vivo, a
long history of use in patients, can be given orally in a palatable form and is
inexpensive."
Free radical mediated mechanisms have been suggested as contributing to the development
of several neurodegenerative diseases. Our initial emphasis was the treatment of
hereditary movement disorders, particularly the hereditary ataxias. More recently,
patients with other neurodegenerative conditions including amyotrophic lateral sclerosis
(ALS), multiple sclerosis (MS), diabetic neuropathy and Alzheimer's disease have been
treated with NAC. We report here results of studies with NAC
Treatment with high dose NAC has produced modest improvement in several patients with
neurodegenerative disorders. Where improvement has been noted, it has usually been early
in treatment and then tends to plateau. Some patients have not seen an initial improvement
but remain on NAC as a possible means to prevent further progression of their disorder. In
some 40 patients tested (including patients with HSCA, AT, FA, ALS, MS, DN and HC)
pretreatment FRESA analysis indicated an imbalance in antioxidant enzyme activity.
Although a few patients claimed some benefit from more traditional antioxidant
therapies (e.g vitamins A,C,E,B2, and selenium), most patients said these were without
noticeable benefit. As suggested, improvement in physical condition may correlate with
improved free radical status. This suggests that these enzyme abnormalities are not
primary in these disorders but occur secondary to whatever gene defects trigger excess
free radical activity (e.g., GSHpx and SOD are readily destroyed by excess superoxide).
This study indicates the possibility that if improvement in the antioxidant status occurs,
the potential exists for arresting progression of the disease and in some cases an
improvement in patient condition.
The high level of safety and variety of antioxidant actions of NAC suggest it as a very
promising new tool for treatment of neurodegenerative disorders. In recent months,
scientific reports of animal and in-vitro studies indicate that NAC inhibits neuronal
apoptosis and toxicity in models of multiple sclerosis, amyotrophic lateral sclerosis and
diabetic necrosis.
The most commonly used chemopreventive agents in the prevention of
oral leukoplakia, head and neck cancer, and lung cancer are
beta-carotene, vitamin A, and other retinoids. One of the few
chemopreventive agents not in this group and presently being used in a
clinical trial is N-acetyl-l-cysteine (NAC). NAC, an antioxidant, is
used in EUROSCAN, a European Organization of Research and Treatment of
Cancer (EORTC) chemoprevention study in curatively treated patients
with oral, laryngeal, or lung cancer. The rationale for choosing NAC is
based on a variety of experimental data showing its ability to exert
protective effects, including extracellular inhibition of mutagenic
agents from exogenous and endogenous sources, inhibition of
genotoxicity of reactive oxygen species, modulation of metabolism
coordinated with blocking of reactive metabolites, protection of DNA
and nuclear enzymes, and prevention of the formation of carcinogen-DNA
adducts. NAC has also demonstrated an effect on mutagen-induced
chromosomal sensitivity assays, and on anticarcinogenicity in
experimental animal models. In addition, preliminary data from EUROSCAN
show good compliance in treated patients and a low frequency of side
effects.
The thiol N-acetylcysteine (NAC) is a promising cancer
chemopreventive agent which acts through a variety of mechanisms,
including its nucleophilic and antioxidant properties. We have recently
shown that NAC inhibits type-IV collagenase activity as well as
invasion, tumor take and metastasis of malignant cells in mice. NAC is
also known to attenuate the cardiotoxicity of the cytostatic drug
doxorubicin (DOX, Adriamycin). The present study was designed to
evaluate whether the combination of NAC and DOX treatments in mice
injected with cancer cells could affect their tumorigenic and
metastatic properties. Six separate experiments were carried out, using
a total of 291 adult female mice. In experimental metastasis assays, in
which B16-F10 melanoma cells were injected i.v. into (CD-1)BR nude
mice, DOX significantly reduced the number of lung metastases when
administered i.v. at a dose of 10 mg/kg body weight, 3 days after the
i.v. injection of cancer cells. NAC inhibited lung metastases when
added to the medium of cancer cells before their i.v. injection. The
combined treatment with DOX and NAC, under various experimental
conditions, was highly effective, showing a synergistic reduction in
the number of mestastases. In tumorigenicity and spontaneous metastasis
assays, in which B16-BL6 melanoma cells were injected s.c. into the
footpad of C57BL/6 mice, DOX decreased the number of lung metastases
when given i.p. at 2 mg/kg body weight. Oral NAC exerted significant
protective effects, and considerably prolonged survival of mice. The
combined treatment with DOX and NAC again showed synergistic effects on
the frequency and weight of primary tumors and local recurrences, and
completely prevented the formation of lung metastases in the experiment
in which these end-points were evaluated at fixed times. While
injection of DOX 7 days after implantation of cancer cells failed to
improve the cancer-protective effects of NAC, its injection after I day
resulted in a striynergism between DOX (given parenterally) and NAC
(given with drinking water) in preventing tumorigenicity and
metastases. The indications of these animal studies warrant further
evaluation in clinical trials.
- Carole Lemens, Craig Sterrit. Antioxidants, Oxidative
Stress, and NAC. From Project Inform. For more information, contact the
National HIV/AIDS Treatment Hotline, 800-822-7422, or visit our
website, www.projectinform.org - Staal
FJ, Ela SW, Roederer M, Anderson MT, Herzenberg LA, Herzenberg LA.
Glutathione deficiency and human immunodeficiency virus infection.
Lancet,1992;339(8798):909-912. - B.J.Wilder, M.D., Russell W.
Hurd, M.S., Et al. Treatment of neurodegenerative disease with
N-Acetylcysteine. Department of Neurology and Brain Institute,
University of Florida, Gainesville, FL 32610 - De Vries N, De Flora S. N-acetyl-l-cysteine. J Cell Biochem Suppl 17F:270-277; 1993.
- De
Flora S. D'Agostini F. Et al. Institute of Hygiene and Preventive
Medicine, University of Genoa, Italy. Int J Cancer (UNITED STATES) Sep
17 1996, 67 (6) p842-8
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