N-acetylcysteine
(NAC) boosts production of glutathione, an important antioxidant that
helps reduce free radical damage and plays a role in the detoxification
of heavy metals and other harmful substances
In
emergency medicine, NAC is used as an antidote for acetaminophen
toxicity resulting from an overdose. Mortality due to acetaminophen
toxicity is largely eliminated when NAC is promptly administered
The
most common use of NAC is for liver support, but it’s also showing
tremendous promise in the treatment of neurodegenerative disorders such
as Parkinson’s disease
NAC
also shows particular promise in the treatment of mental health
disorders, including PTSD, depression and drug abuse, and appears to
improve fertility in both men and women
NAC
is safe and inexpensive, and has been commercially available for a long
time. It’s also generally well-tolerated and has no known serious side
effects
By Dr. Mercola
N-acetylcysteine (NAC) — a precursor which is needed for glutathione
biosynthesis — is an incredibly useful supplement that few people have
even heard of. Many of its benefits relate back to the fact that it
helps boost production of glutathione, an important antioxidant your body produces naturally that helps reduce free radical damage and plays a role in the detoxification of heavy metals and other harmful substances.
NAC is both safe and inexpensive, and has been commercially available
for a long time. It's also generally well-tolerated and has no known
serious side effects. Considering its wide array of health benefits,
it's a supplement worthy of consideration for many. As noted in a recent
medical review of NAC's many clinical uses, it is a:1
"… potential treatment option for diseases characterized by the
generation of free oxygen radicals. Studies have shown no maternal or
fetal harmful effects of NAC treatment … NAC prevents apoptosis
[editor's note: programmed cell death] and oxygen related genotoxicity
in endothelial cells by increasing intracellular levels of glutathione
and decreasing mitochondrial membrane depolarization."
NAC Helps Counter Toxic Effects of Alcohol
NAC supplementation can also help "pre-tox" your body when taken
before alcohol, thereby minimizing the damage associated with alcohol
consumption — a tidbit that may be useful to know in light of the
approaching holidays. NAC is a form of the amino acid cysteine, which in
addition to increasing glutathione also reduces acetaldehyde toxicity
that causes many hangover symptoms.2
Taking NAC (at least 200 milligrams) 30 minutes before you drink can
help lessen the alcohol's toxic effects. NAC is thought to work even
better when combined with vitamin B1 (thiamine).3 Vitamin B6 may also help to lessen hangover symptoms.
Since alcohol depletes B vitamins, and B vitamins are required to help
eliminate alcohol from your body, a B vitamin supplement taken
beforehand, as well as the next day, can be helpful. All of that said,
it's important to realize that this protocol will not reduce your
susceptibility to alcohol poisoning or other acute adverse events associated with binge drinking, so please use common sense and drink responsibly.
NAC Is a Potent Antidote to Acetaminophen Toxicity
NAC is also used in medicine as an antidote for acetaminophen
toxicity. Like alcohol, one way that acetaminophen causes liver damage
is by depleting glutathione. If you keep your glutathione levels up, the
damage from the acetaminophen may be largely preventable. This is why
anyone who overdoses on Tylenol receives large doses of NAC in the
emergency room — to increase glutathione.
Mortality due to acetaminophen toxicity has actually been shown to be
virtually eliminated when NAC is promptly administered in cases of
acetaminophen overdose. While I generally do not recommend using
acetaminophen-containing drugs for minor aches and pains, they are
sometimes necessary to temporarily suppress severe pain, such as
post-surgical pain. So, if you ever use acetaminophen I strongly
recommend taking it along with NAC.
And, if you have children and keep acetaminophen in your home, I
strongly recommend keeping a bottle of NAC as well in case of accidental
overdose. NAC therapy should be initiated within eight hours of an
acute overdose for best results. If you suspect an overdose has
occurred, seek medical help right away. If this isn't an option, the
World Health Organization (WHO) recommends the following protocol:4
"Oral administration is the preferred route for NAC therapy unless
contraindications exist (e.g aspiration, persistent vomiting). The usual
recommended loading dose is 140 mg/kg followed in 4 hours by a
maintenance dose of 70 mg/kg orally given every 4 hours. This dosing is
commonly recommended to be continued for 72 hours; however more recent
clinical experience supports tailoring the duration of therapy to the
patient's clinical condition."
NAC Offers Important Liver Support
The most common use of NAC is for liver support in general. A 2010 study5
— in which it was noted that the antioxidant resveratrol has been found
to enhance replication of the hepatitis C virus and hence is not a
suitable supplement for those with hepatitis C — suggests NAC may be a
better alternative for this and other chronic liver diseases.
"Consistently, we found that [NAC] modulates the expression of iNOS
[editor's note: iNOS is an inducible and calcium-dependent isoform of
the enzyme nitric oxide synthase or NOS, which helps synthesize nitric
oxide] in human hepatocytes stimulated by proinflammatory cytokines," the authors write.
"The effect occurs by blocking the activation of the iNOS
promoter, and is associated with modulation of NF-κB activity, a central
transcription factor for induction of iNOS expression. The biological
phenomenon might well be the basis of the therapeutic effects of NAC on
chronic liver diseases different from those caused by acetaminophen
intoxication."
Other Health Benefits of NAC
Aside from its hepatoprotective effects, research suggests NAC may also help:6,7,8
Prevent contrast-induced kidney damage during imaging procedures
Protect against Alzheimer's disease when taken in combination with lipoic acid
Attenuate influenza when started before infection
Reduce symptoms associated with ulcerative colitis
Treat pulmonary fibrosis
Prevent asthma
Improve male fertility by improving sperm quality,
and treat infertility in female patients with clomiphene-resistant
polycystic ovary syndrome. It's also been shown to reduce risk of
premature birth and miscarriage
Treat
certain forms of cancer and protect against toxicity of radiotherapy;
DNA damage has been shown to be "completely blocked" by NAC.
Beware that some of the evidence suggests NAC may not work well with
some forms of chemotherapy, so do not use as a cancer treatment adjunct
without consulting your doctor
Prevent addictive behaviors such as binge eating,
drug addiction (especially cocaine addiction) and other compulsive
behaviors such as nail biting by normalizing the neurotransmitter
glutamate
Prevent depression, bipolar disorder and obsessive compulsive disorder, and improve daily function in those with these disorders
Improve intestinal barrier function, reducing your risk of leaky gut
Enhancing the regeneration of bone; speeding up bone mineralization
Improve sleep and reduce snoring in those with obstructive sleep apnea
Treatment of polycystic ovary syndrome
Increase survival rate in patients with chronic heart failure
Increase survival rate in patients who have had a heart attack
Reduce your risk of heart disease
Aid in recovery from brain injury
Treat Helicobacter pylori infection when used as an adjunct to other therapy
Protect against gentamicin-induced hearing loss in patients on renal dialysis
NAC Offers Hope for Patients With Parkinson's and Other Neurodegenerative Conditions
As you can see, the list of NAC's potential uses is quite long;
there's even evidence it may be an effective remedy against acne,
decreasing acne outbreaks by about half.9
Some of its most promising uses is as a neuroprotectant. Scientists are
currently investigating it as a treatment for Parkinson's disease — a
disorder that has been linked to glutathione deficiency in the
substantia nigra, a region that houses dopamine neurons.10
Research looking at autopsied brains suggests Parkinson's patients
have barely detectable levels of glutathione in this brain region. This
deficiency is not restricted to Parkinson's, however. Subsequent studies
have found glutathione deficiency in the substantia nigra is common in a
number of other neurodegenerative conditions as well, including
progressive supranuclear palsy, multiple system atrophy and Alzheimer's
disease.11 As noted in a recent article by Science of Parkinson's:12
"Researchers have subsequently found that decreased levels of
glutathione does not directly result in dopamine cell loss … but it does
make the cells more vulnerable to damaging agents (such as neurotoxins …
) This has [led] investigators to ask whether administering glutathione
to people with Parkinson's disease would slow [down] the condition."
In one small-scale clinical trial,13
600 milligrams (mg) of intravenous glutathione was administered twice a
day for 30 days, after which the patients were monitored for up to four
months. All experienced significant improvement, with an average
decline in disability of 42 percent. The effects lasted for two to four
months after the treatment ended. The remarkable effects of the
treatment are demonstrated in the following video.
Other studies have confirmed the usefulness of NAC in the treatment of
Parkinson's. Several are discussed on Science of Parkinson's, so for
more information, please see that original article.14
As just one example, a randomized study15,16
on 23 patients found a combination of 600 mg of oral NAC twice a day
plus a weekly IV infusion of NAC at 50 mg per kilogram of body weight,
had a very consistent, neuroprotective effect, improving patients'
mental and physical abilities. Brain imaging also confirmed beneficial
changes were in fact occurring in the brain.
PTSD, Depression and Treatment of Addiction
Another area where NAC shows particular promise is in the treatment of mental health disorders, including post-traumatic stress disorder (PTSD), depression and substance use disorders. In one recent study,17
PTSD symptoms in war veterans decreased by 46 percent, substance use
cravings by 81 percent, and depression by 48 percent after NAC
treatment. Here, patients took 2,400 mg of NAC a day for eight weeks.
As a group, the veterans no longer met diagnostic criteria for PTSD at
the end of their treatment. This, lead author Sudie Back, Ph.D., said,
"are some of the best outcomes we have seen in the literature for a
medication." As reported by Medical University of South Carolina (MUSC):18
"Currently, there are no well-explored pharmacological treatments
for patients with co-occurring PTSD and substance use disorder. Although
selective serotonin reuptake inhibitors, a class of drugs used as
antidepressants, have been approved by the FDA for treatment of PTSD,
pharmacological treatments for co-occurring conditions haven't been as
effective as some hoped for.
Groundbreaking basic science research by [Back and Peter Kalivas,
Ph.D., chairman of the department of neuroscience at MUSC] has shown
that levels of glutamate transporters in the brain are decreased in
substance use disorders, and NAC can help restore those levels and guard
against relapse in animal models of substance use disorder.
Because evidence suggests that substance use disorder and PTSD
share overlapping neurobiological pathways, Sudie Back … hypothesized
that NAC treatment with therapy would be a novel approach to treating
the co-occurring conditions. Back is a professor in the Department of
Psychiatry and Behavioral Sciences at MUSC and a staff psychologist at
the Ralph H. Johnson VA Medical Center."
In studies19 looking at NAC for bipolar depression,
individuals taking 1 gram of NAC twice a day for two months reduced
their depression score by eight points and reported improvement in
functioning and quality of life. It's also been shown to help those with
treatment resistant depression and, to a lesser degree, major
depressive disorder.
Do beware, however, that NAC may interact with certain
antidepressants if you take them together, making the antidepressant
more potent. As a result, you need to work with your doctor as you may
need to reduce the dose of your antidepressant medication if you take it
concomitant with NAC.
NAC May Improve Fertility in Both Men and Women
The last area I will home in on here is fertility, as both male and female infertility are on the rise. A number of studies20
have demonstrated the benefits of NAC for fertility in both men and
women. As noted above, NAC has been shown to improve sperm quality in
men. It's also been shown to improve the ovulation rate in women by 52
percent.21
In this study, women took 1,200 mg per day of oral NAC for five days,
starting on the third day of their menstrual cycle. Endometrial
thickness also significantly improved.
Other research shows NAC helps improve the quality of a woman's eggs22
— a factor that can improve your chances of not only getting pregnant
naturally, but also improve your odds of successful IVF treatment. It
also lowers your risk of miscarriage, and increases the pregnancy rate
in women who have had recurrent miscarriages.23 Endometriosis, which is a common cause for female infertility, is also improved by NAC supplementation.24 In one Italian study,25
women who took 600 mg of NAC three times a day for three consecutive
days per week, for three months, saw such significant improvement that
half of the treatment group — 24 out of 47 — were able to cancel their
surgeries. Eight of the 47 women receiving NAC had complete remission of
cysts. In comparison, only one of the 45 women in the control group
(which received a placebo) was able to cancel her surgery and only four
had remission of cysts.
General Dosing and Safety Guidelines
NAC is widely available as an oral dietary supplement and is
relatively inexpensive. Unfortunately, it's rather poorly absorbed when
taken orally. According to some studies,26,27
oral bioavailability may range between 4 and 10 percent. Its half-life
is also in the neighborhood of two hours, which is why most study
subjects take it two or three times a day.
Due to its poor bioavailability, the recommended dosage can go as high
as 1,800 mg per day. No maximum safe dose has yet been determined, but
as a general rule, it's well-tolerated, although some do experience
gastrointestinal side effects such as nausea, diarrhea
or constipation. Should this occur, reduce your dosage. It's also best
taken in combination with food, to reduce the likelihood of
gastrointestinal effects.
Also keep in mind that since NAC boosts glutathione, which is a powerful
detox agent, you may experience debilitating detox symptoms if you
start with too high a dose. To avoid this, start low, with say 400 to
600 mg once a day, and work your way up. Also, if you are currently
taking an antidepressant or undergoing cancer treatment, be sure to
discuss the use of NAC with your physician, as it may interact with some
antidepressants and chemotherapy.
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