N Acetyl l cysteine is made from the amino acid cysteine joined to an acetyl group. Acetylcysteine (sometimes abbreviated as N-A-C or NAC) is a strong antioxidant. It donates the amino acid cysteine to help form the antioxidant glutathione. Glutathione is a powerful antioxidant normally found in the body.
Health benefit
N-acetylcysteine is an
excellent source of sulfhydryl groups and is converted in the body into
metabolites capable of stimulating glutathione synthesis, promoting
detoxification, and acting directly as a free radical scavenger.
Administration of this nutrient has historically been as a mucolytic
[mucus dissolving] agent in a variety of respiratory illnesses; however,
it appears to also have beneficial effects in conditions characterized by
decreased glutathione or oxidative stress, such as HIV infection, cancer,
heart disease, and cigarette smoking. NAC has liver
protecting benefits and could protect from the toxic effects of acetaminophen
use. In hospitals, acetylcysteine is often used intravenously for liver
protection in cases of acetaminophen toxicity.
This nutrient may also be of benefit in men who infertility, those
with cystic fibrosis, and for cocaine craving.
N
Acetyl Cysteine
Supplement to purchase, 500 mg capsule for oral use
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Benefits
Benefit
for cocaine
craving
Dr. Peter W. Kalivas from the Medical University of South Carolina,
Charleston evaluated the effects of N-Acetylcysteine on cue-induced cocaine
craving of 15 people with cocaine dependence. Those who were taking the N-Acetylcysteine
supplements had less cocaine craving and interest evoked by depictions of
cocaine use on photographic slides. The neurotransmitter system involved
may be glutamate transmission. Dr. Peter W. Kalivas is now starting a
double-blind study is being conducted to evaluate the effect of N-Acetylcysteine
on relapse rates and also evaluating the effects of N-Acetylcysteine on
nicotine and marijuana craving.
Is cocaine desire reduced by N-acetylcysteine?
Am J Psychiatry. 2007 Jul;164(7):1115-7. LaRowe SD, Myrick H, Hedden
S, Mardikian P, Saladin M, McRae A, Brady K, Kalivas PW, Malcolm R.
Department of Psychiatry and Behavioral Sciences, Medical University of
South Carolina, Charleston, SC 29425,
In this double-blind, placebo-controlled trial, 15 volunteers received
acetylcysteine or placebo during a 3-day hospitalization. Participants
were crossed over to receive the opposite condition on a second, identical
3-day stay occurring 4 days later. During each hospital stay, participants
completed a cue-reactivity procedure that involved collecting
psychophysical and subjective data in response to slides depicting cocaine
and cocaine use. While taking N-acetylcysteine, participants reported less
desire to use and less interest in response to cocaine slides and watched
cocaine slides for less time.
An open-label trial of N-acetylcysteine for the
treatment of cocaine dependence: a pilot study.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):389-94.
Mardikian PN, LaRowe SD, Hedden S, Kalivas PW, Malcolm RJ. Center for Drug
and Alcohol Programs, Department of Psychiatry and Behavioral Sciences,
Medical University of South Carolina, 67 President Street, Charleston, SC
29425, USA.
Twenty three treatment-seeking cocaine-dependent patients participated in
a 4-week medication trial and received N-acetylcysteine
at doses of 1200 mg/day, 2400 mg/day or 3600 mg/day. Results suggested
that the three doses were well tolerated. Overall, the retention rates
appeared to favor higher doses of NAC (2400 mg/day and 3600 mg/day). The
majority of subjects who completed the study either terminated use of
cocaine completely or significantly reduced their use of cocaine during
treatment.
A study funded by the National Institutes of Health (NIH) suggests
that acetylcysteine can reduce the cravings associated with chronic
cocaine use. This research, released at the American College of
Neuropsychopharmacology's (ACNP) annual conference is among the first to
identify N-acetylcysteine (NAC) as a potential agent to modulate the
effects of cocaine addiction. There is also early evidence in animal
models of addiction to suggest that this chemical works similarly in the
treatment of heroin addiction, and possibly alcoholism. NAC is available
over the counter as an herbal supplement known for its antioxidant
effects. In the first phase of the study, the research team conditioned
rats on a regimen of cocaine to establish their addiction. The rats in the
treatment group were then treated with N acetylcysteine. After treatment,
the cocaine-addicted rats exposed to N-acetylcysteine were significantly
less likely to seek out cocaine than those without N acetylcysteine. Those
treated with NAC ceased to actively seek cocaine, but showed normal
food-seeking behaviors.
In the second phase of the study, acetylcysteine treatment was
investigated in a small inpatient study (n=15) involving non-treatment
seeking cocaine-dependent subjects. In this phase of research, subjects
were asked to look at pictures that were either neutral (e.g., trees,
boats) or cocaine-related (e.g., drug paraphernalia). Those individuals
treated with N-acetylcysteine reported less craving for cocaine and spent
less time looking at the cocaine-related pictures. In addition, when using
a functional magnetic resonance imaging test, subjects treated with
acetylcysteine had reduced brain activity in the prefrontal cortex, the
area of the brain activated during cocaine craving and used to modulate
the addictive behavior of chronic cocaine use. An open label trial, which
was recently completed, indicated that cocaine-dependent patients could
take N-acetyl cysteine on an extended outpatient basis, with minimal side
effects. More importantly, patients taking higher doses of NAC were more
likely to complete the trial, providing further indication of the
potential benefits of N-acetylcysteine.
Cystic fibrosis
Oral N-acetylcysteine, through its actions on glutathione, may
reduce inflammation in cystic fibrosis.
Homocysteine level
Oral N acetylcysteine may lower homocysteine levels.
Infertility
Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in
infertile men: a double-blind, placebo controlled, randomized study.
J Urol. 2009 Feb; Safarinejad MR, Safarinejad S. Urology and Nephrology
Research Center, Shahid Beheshti University, MC, Tehran, Islamic Republic of
Iran.
We explored the efficacy of selenium and/or or N-acetyl-cysteine for
improving semen parameters in infertile men, and the associations among semen
quality and the concentrations of selenium and N-acetyl-cysteine in seminal
plasma. The study included 468 infertile men with idiopathic
oligo-asthenoteratospermia who were randomized to receive 200 microg selenium
orally daily, 600 mg NAC orally daily, 200 microg selenium plus
600 mg N-acetyl-cysteine orally daily or similar regimen of placebo for 26
weeks, followed by a 30-week treatment-free period. These patients provided
blood samples for the measurement of serum testosterone, estradiol,
follicle-stimulating hormone, luteinizing hormone, prolactin, inhibin B,
selenium and N-acetyl-cysteine. Semen samples were also obtained for routine
semen analysis, and the measurement of seminal plasma selenium and NAC.
In response to selenium and N-acetyl-cysteine treatment serum
follicle-stimulating hormone decreased but serum testosterone and inhibin B
increased. All semen parameters significantly improved with selenium and
N-acetyl-cysteine treatment. Administering selenium plus N-acetyl-cysteine
resulted in additive beneficial effects. Our results indicate that supplemental
selenium and N-acetyl-cysteine improve semen quality. We advocate their use for
male infertility treatment.
Kidney protection - Acetylcyteine prevents toxicity to the kidneys
during x-ray testing after injection with a contrast material in the
bloodstream.
Patients with a heart attack undergoing primary angioplasty are at high risk for
contrast-medium–induced kidney damage because of hemodynamic instability,
the need for a high volume of contrast medium, and the lack of effective
prophylaxis. We investigated the antioxidant N-acetylcysteine for the
prevention of contrast-medium–induced kidney damage in patients undergoing
primary angioplasty. We randomly assigned 354 consecutive patients undergoing primary
angioplasty to one of three groups: 116 patients were assigned to a
standard dose of N-acetylcysteine (a 600-mg intravenous bolus before
primary angioplasty and 600 mg orally twice daily for the 48 hours after
angioplasty), 119 patients to a double dose of N-acetylcysteine (a 1200-mg
intravenous bolus and 1200 mg orally twice daily for the 48 hours after
intervention), and 119 patients to placebo.
The serum creatinine concentration increased 25 percent or more
from baseline after primary angioplasty in 33 percent of the control patients, 15
percent of the patients receiving standard-dose N-acetylcysteine, and 10 patients receiving high-dose N-acetylcysteine. Overall in-hospital mortality was higher in patients with
contrast-medium–induced nephropathy than in those without such nephropathy
(26 percent vs. 1 percent). Thirteen patients (11 percent) in the
control group died, as did five (4 percent) in the standard-dose N-acetylcysteine
group and three (3 percent) in the high-dose N-acetylcysteine group. Intravenous and oral N-acetylcysteine may prevent
contrast-medium–induced nephropathy with a dose-dependent effect in
patients treated with primary angioplasty and may improve hospital
outcome.
Liver damage due to Tylenol toxicity
This nutrient is often used by intravenous administration to those who come to
the ER with Tylenol poisoning, accidental or intentioned.
Which is more potent for liver detoxification,
silymarin or NAC?
It's difficult to say, We think NAC is more potent but they
work in different ways.
Ulcerative colitis
N-acetyl-L-cysteine combined with mesalamine in the treatment of
ulcerative colitis: randomized, placebo-controlled pilot study.
World J Gastroenterol. 2008 May. Unidad de Toxicologia Molecular
Hepatica, Department de Bioquimica & Biologia Molecular, Universidad de
Alcala, E-28871, Alcala de Henares, Spain.
To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC)
co-administration with mesalamine in ulcerative colitis (UC) patients.
Thirty seven patients with mild to moderate ulcerative colitis were
randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus
N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo
(group B). Clinical remission rates were 63% and 50% after 4 wk
treatment with mesalamine plus N-acetyl-L-cysteine (group A) and
mesalamine plus placebo (group B) respectively. In group A (oral NAC
combined with mesalamine) contrarily to group B (mesalamine alone), the
clinical improvement correlates with a decrease of chemokines such as
MCP-1 and IL-8. NAC addition not produced any side effects.
N Acetylcysteine side effects
Other than large doses causing nausea, acetylcysteine does not have
any significant side effects and appears to be a safe nutrient as long
as the dosage is kept to less than 500 mg. Nausea can occur for a few
minutes within an hour of taking two or three 600 mg pills on an empty stomach.
One possible acetylcysteine side effect that should be kept in mind
(it could also be a benefit) is that this supplement has
anticoagulant and platelet-inhibiting properties.
Oral overdosage of acetylcysteine could result in side effects such as
nausea, vomiting and other gastrointestinal symptoms. Rare
side effects could include bronchospasm, which is much more likely when
used by the
intravenous route.
Acetylcysteine supplement use
In addition to its antioxidant properties,
acetylcysteine is currently used in a variety of other ways: to counteract
the effects of an overdose of acetaminophen (i.e., Tylenol), to break up
mucus in respiratory ailments, to lessen the symptoms of colds or the flu,
and even to reduce the effects of hangovers.
Acetyl cysteine is sold in dosages ranging from 250 to 600 mg.
Acetylcysteine can help form the powerful antioxidant glutathione but the
formation of glutathione synthesis is under feedback control.
Administration of acetylcysteine with the resulting increase in
glutathione levels may cause a feedback inhibition in glutathione
synthesis. Thus, it may be best to take acetylcysteine every other day.
This supplement certainly
should be considered in protecting various
cells from damage in the elderly and those with Parkinson’s disease. If
you are planning to use acetylcysteine along with other antioxidants,
limit your daily dosage to 100 to 500 mg and don’t take it all the time. Acetylcysteine could protect the liver
in those who take acetaminophen on
a regular basis.
Supplement
dosage availability
You can find oral acetylcysteine in varying dosages
N acetylcysteine 200 mg oral tablets or capsules, 250 mg, 500 mg, and 600
mg oral pills - unless you are being treated for a medical condition,
there is no reason to take 600 mg
tablets or capsules on a daily basis.
What is the ideal daily dose?
There are no strict guidelines on the best dose to
take daily. It may be a good idea to limit the use of acetylcysteine
supplements to two or three times a week rather than daily unless your
doctor has prescribed this supplement as a treatment for a medical
condition.
Counteracting Tylenol toxicity
Regular use of the painkiller acetaminophen is associated with
higher rates of liver and kidney toxicity, asthma, and chronic obstructive
pulmonary disease and reduced lung function. Animal experiments have suggested that
acetaminophen might lower antioxidant activity in the lungs, and causes
harm to the liver and kidneys.
With hundreds of people each year dying
from acetaminophen overdose, thousands more with liver damage or other
health problems, why is acetaminophen still available for sale without a
prescription whereas regulators have tried to pull away certain
nutritional supplements that are far less toxic?
Those who need to take acetaminophen for a health
condition should consider Acetylcysteine, a nutrient that protects the
liver from this drug's toxicity. The antidote for acetaminophen poisoning
is N acetyl cysteine. Acetylcysteine is thought to work through a number
of protective mechanisms. Acetylcysteine is a precursor of glutathione
and increases glutathione availability. Acetylcysteine also functions as
an anti-inflammatory and antioxidant and has positive inotropic effects.
Acetylcysteine increases local nitric oxide concentrations, and this vasodilatory effect on microcirculatory blood flow enhances local oxygen
delivery to peripheral tissues. These vasodilating effects decrease
morbidity and mortality even in the setting of established liver damage.
Doctors prescribe intravenous or IV acetylcysteine to patients with liver damage due to acetaminophen
(Tylenol) overdose. Acetylcysteine IV protects the liver quite well.
Comments: With hundreds of people each year dying
from acetaminophen overdose, thousands more with liver damage or other
health problems, why is
acetaminophen still available for sale without a prescription whereas
regulators have tried to pull away certain nutritional supplements that
are far less toxic?
Those who need to take acetaminophen for a health
condition should consider acetylcysteine, a nutrient that protects the
liver from this drug's toxicity.
A patient-tailored N-acetylcysteine protocol for acute acetaminophen
intoxication.
Clin Ther. 2005 Mar;27(3):336-41.
Liver damage as a result of acetaminophen (APAP) intoxication has
become an important problem, but early intervention with N-acetylcysteine is effective in preventing hepatic injury. Two Acetylcysteine regimens are currently approved for acute APAP
intoxication: Acetylcysteine administered orally every 4 hours for 72
hours, and Acetyl cysteine administered intravenously for 20 hours within
8 to 10 hours after ingestion of a potentially hepatotoxic amount of APAP.
However, clinical observations suggest that a variable treatment duration
may be more appropriate than use of these predetermined, fixed-duration
protocols. This study investigated the tolerability and
efficacy of a patient-tailored N Acetylcysteine protocol for acute
acetaminophen
intoxication by comparing the incidence of hepatotoxicity in patients
receiving this protocol and in historical controls receiving 1 of 2
fixed-duration protocols: oral Acetylcysteine for 72 hours and intravenous
Acetylcysteine for 20 hours within 8 to 10 hours after ingestion of a
potentially hepatotoxic amount of acetaminophen. This was a retrospective
case series study that included all patients admitted through the
emergency department (ED) of the National Taiwan University Hospital with
a diagnosis of APAP intoxication between October 1997 and October 2002.
According to the patient-tailored protocol, which had been used in the ED
since 1997, patients with a serum APAP concentration above the limit for
possible risk based on a modified Rumack-Matthew nomogram received oral
treatment with Acetylcysteine 140 mg/kg, followed by maintenance doses of
70 mg/kg every 4 hours. For the purposes of assessing clinical outcomes, patients
were divided into 3 groups based on duration of treatment: the
short-course group (</=36 hours), the intermediate-course group (37-72
hours), and the long-course group (>/=73 hours). The primary outcome
measure was development of hepatotoxicity, defined as a serum AST or
alanine aminotransferase concentration >1000 IU/L. Twenty-seven
patients were included in the study, 17 in the short-course group, 4 in
the intermediate-course group, and 6 in the long-course group. The mean
(SD) durations of Acetyl l cysteine treatment in the respective groups
were 22.1 (5.5) hours, 45.0 (8.2) hours, and 97 (33) hours. All 6
patients (22%) in the long-course group had hepatotoxicity (peak AST
range, 1083-9770 IU/L); their treatment duration ranged from 80 to 164
hours. No patients in the short- or intermediate-course group had evidence
of hepatotoxicity. One woman in the long-course group in whom initiation
of Acetylcysteine treatment was delayed by 28 hours died of fulminant
hepatic failure. The overall incidence of hepatotoxicity was similar to
that in the historical controls. In this retrospective case
series inpatients who received patient-tailored Acetylcysteine therapy for
acute APAP intoxication, the incidence of hepatotoxicity was low and
comparable to that in historical controls who received treatment with 1 of
2 fixed-duration regimens. Use of this protocol may have the potential to
shorten hospital stays without increasing the risk to patients. However,
the sample size was small, and the findings require confirmation in
prospective clinical trials.
Research and
studies
Effect of dietary restriction and n acetyl cysteine supplementation on
intestinal mucosa and liver mitochondrial redox status and function in
aged rats.
Exp Gerontol. 2004 Sep;39(9):1323-32.
The age-related changes of glutathione (GSH) levels and the effect of
hypocaloric regimen and acetylcysteine supplementation were investigated
in intestinal mucosa and liver mitochondria of 28 months rats. Old rats
exhibited lower proteins, GSH and protein sulphydrils
concentrations, higher GSH-peroxidase (GSH-Px) activity and protein
carbonyl deposit, partial inhibition of succinate stimulated mitochondrial
state III respiration and decreased mitochondrial nitrosothiols
concentration. In conclusion, ageing
is characterized by a decrease of GSH concentrations, increased
protein oxidation and decreased mitochondrial NO content. Hypocaloric diet
ameliorated intestinal transport and, as well as acetylcysteine, was
effective in enhancing GSH levels but at different extent according to the
investigated districts. Both interventions reduced the age-associated
increase of GSH-Px and protein carbonyls and improved mitochondrial
respiration.
Treatment by acetylcysteine and melatonin
increases cardiac baroreflex and improves antioxidant reserve.
Am J Hypertens. 2004 Oct;17(10):947-54.
The aims of this study were to investigate the effects of
melatonin and acetylcysteine on the baroreflex sensitivity and to verify
whether those effects were correlated with their antioxidant capacity in
Wistar-Kyoto and spontaneously hypertensive rats (SHR). Rats were treated
with 30 mg/kg/day of melatonin or 4 g/kg/day of acetylcysteine
for 4 weeks. Changes in mean arterial pressure, heart rate, plasma
norepinephrine, and epinephrine were measured in conscious rats after an
intravenous injection of phenylephrine or sodium nitroprusside.
Melatonin and acetylcysteine produced a significant reduction in mean
arterial pressure and heart rate in SHR. Melatonin and acetylcysteine
improved bradycardic and tachycardic baroreflex responses in SHR without
modifying catecholamine responses. The antioxidant reserve, which was
reduced in SHR as reflected by the lower glutathione peroxidase activity
in plasma, was normalized by acetylcysteine and melatonin. Acetylcysteine
and melatonin increased glutathione peroxidase activity in erythrocytes
from SHR. The results of the present study suggest that
melatonin and acetylcysteine improve the baroreflex response in SHR in
correlation with the antioxidant effects of these substances.
N Acetyl cysteine in nephrology; contrast nephropathy
and beyond.
Curr Opin Nephrol Hypertens. 2004 Nov;13(6):649-54.
Since the first publication appeared in 2000 showing
that prophylactic oral administration of the antioxidant acetylcysteine,
along with adequate hydration, can prevent the reduction in renal function
induced by non-ionic, low-osmolality contrast agents, acetylcysteine has
rapidly become widely used in clinical practice. Meanwhile, other
applications of acetylcysteine in nephrology have been reported. This
review analyses recent literature on the effects of acetylcysteine on
radiocontrast-induced nephropathy, on plasma homocysteine concentrations,
and on cardiovascular events in patients with end-stage renal failure.
At least 19 randomized trials evaluating acetylcysteine
for the prevention of radiocontrast-induced nephropathy, at least five
meta-analyses, and several reviews on that topic have been published
within the past 4 years. One study recently indicated that the administration of acetylcysteine during a haemodialysis session significantly lowered plasma
homocysteine concentrations. Another study indicated that long-term
antioxidative treatment with acetylcysteine significantly reduced
cardiovascular events in patients with end-stage renal failure.
Although there are controversies on dosing and timing, the use of acetylcysteine together with hydration should be considered to protect
patients from radiographic contrast media-induced nephropathy. Long-term
antioxidative treatment with acetylcysteine in patients with end-stage
renal failure may also be useful to prevent adverse cardiovascular events.
N Acetyl Cysteine
dietary pill questions
Q. I was wondering if I could overdose on NAC. What is the safest
maximum per-day dosage?
A. Each person has a different threshold for N acetyl cysteine, but as with most supplements, more is not better, there could be
a feedback loop, or tolerance, or displacement of other crucial nutrients,
etc. I personally prefer not to exceed 250 mg of acetylcysteine a few
times a week, but a different doctor may have a different opinion.
Q. Hi, what exactly is the difference between
Cysteine and N Acetyl cysteine ? Which one is better to take?
A. Most often, aceytylcysteine is the one taken since
it has stronger antioxidant potential, however it depends on the condition
being treated. Acetylcysteine has an additional acetyl group which makes
it more potent as an antioxidant.
Q. What is the right n acetylcysteine dosage as a
daily supplement?
A. There are no accepted guidelines on the appropriate
n acetylcysteine daily dosage. Some people may need none, others may
benefit from taking 500 mg of n acetylcysteine a few days a week. If you
are taking other antioxidants, we suggest you reduce your dosage of n
acetylcysteine. Some people think that the more antioxidants they take the
healthier they will be, but there is no proof of this.
Q. Should one take n acetyl l cysteine if they are taking Tylenol
(acetaminophen) ? I understand that acetaminophen can damage the liver and
n acetylcysteine can protect the liver from Tylenol harm.
A. This is a good question. If your doctor approves, it
may be a good idea to take a small daily amount or a few times a week of a
n acetylcysteine supplement, although there is little research to guide us
on how much is needed and how often one should take the acetylcysteine.
Q. I would like to use acetylcysteine to protect my
liver from the amount of acetaminophin I am required to take on a daily
basis due to my injuries. How much would I need to take
if I use 1,000 mg of acetaminophen?
A. We have not seen any studies regarding the long term
use of acetaminophen and acetylcysteine, however a dose of 100 mg a day
would seem reasonable.
Q. I bought n acetylcysteine tablets at 600mg, is it
okay to break these tablets in two pieces and take half a tablet two or
three times a week?
A. Yes, it is okay to take half a tablet of acetylcysteine 600 mg.