- Why is N -acetylcysteine (NAC) beneficial in late presentations of acetaminophen toxicity/poisoning?
- Can N-Acetylcysteine Treat COPD, Diabetes, and Infertility?
- N-Acetyl Cysteine (NAC): Lower Inflammation and Stop Cravings
- 1. NAC stops cravings and addiction
- 2. NAC for inflammation and aging
- 4. NAC boosts fertility in men and women
- NAC dosage and sourcing
- NAC (N-acetyl-cysteine)
- What is NAC?
- How does NAC work?
- 1. As an antioxidant and to help reduce inflammation
- 2. To maintain GSH and muscle mass
- 3. To protect the liver and kidneys from the toxicity of drugs
- 4. Other potential uses
- Side effects
- Drug interactions
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N-acetylcysteine is an effective drug for acetaminophen overdose and to break up mucus. It has not been proven to be an effective treatment for cancer.
N-acetylcysteine (NAC) is a compound that is found naturally in the body. It is converted to a chemical called glutathione, which plays a role in the detoxification of foreign substances in the body. It is used as an antidote for acetaminophen overdose. NAC itself is an antioxidant that is thought to neutralize free radicals that cause damage to DNA.
Animals fed with NAC have less cellular damage and fewer lung, colon, and bladder tumors, compared with those fed a normal diet. In addition, NAC interferes with tumor invasion, metastasis, and blood vessel growth in lab experiments. However, few of these effects have been shown to occur in humans.
An animal study shows NAC can speed up the growth of lung cancer cells due to its antioxidant activity.
NAC can dissolve and loosen mucus in patients with respiratory disorders such as chronic bronchitis and chronic obstructive pulmonary disease (COPD), but study results are mixed. Animal studies also show that it might protect against tissue damage from drugs such as doxorubicin, ifosfamide, and cyclophosphamide. These effects are currently being studied in humans.
NAC regulates glutamate levels in the brain. It has been studied for several psychiatric disorders in humans with limited success.
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Food is not a significant source of N-acetylcysteine.
NAC is a precursor to glutathione (GSH). It is used as both an antidote for acetaminophen-induced hepatotoxicity and as a mucolytic agent for respiratory diseases. NAC reduces disulphide bonds to sulfhydryl bonds to reduce mucus formation (20).
Its hepatoprotective action may occur by cytokine-mediated mechanisms as well as GSH replenishment (21). In animal studies, NAC exhibits chemopreventive effects against lung (22), hepatocellular (23), esophageal (24), and immune system (25) cancers.
An in vitro study shows NAC may improve the benefit of ifosfamide by decreasing the risk of nephrotoxicity without interfering with the agent’s antitumor effect (26).
Another study finds that NAC alters doxorubicin-induced NF-κB activity via concentration-dependent anti- and pro-oxidant mechanisms (27). This biphasic effect is also time-dependent (28).
In androgen-independent human prostate cancer PC-3 cells, NAC has an antiproliferative effect by upregulating Cyr61 protein expression (28).
NAC amide can increase bioavailability and reduce oxidative stress, but it does not decrease doxorubicin-induced cell death in H9c2 cardiomyocytes (29). In an animal study, NAC increased lung cancer cell proliferation due to its antioxidant activity by reducing reactive oxygen species (ROS), DNA damage and p53 expression (36).
NAC crosses the blood-brain barrier and increases the brain GSH levels. NAC acts as a glutamine modulator (11) and plays a role in treating psychiatry disorders (12).
Common (Oral): Gastrointestinal disturbance, diarrhea, nausea, vomiting, fatigue, conjunctival irritation, skin rash (26) (28)
Other: Hypotension, anaphylaxis, asthma attacks, headache (29)
Photosensitivity not attributable to location, season, or concomitant medication: Occurred among pulmonary fibrosis patients more frequently with acetylcysteine than placebo in combination with pirfenidone (39).
Nitroglycerin: Severe headache due to added vasodilation effect (34).
Antidepressants: May increase the effects of imipramine and escitalopram (35).
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Why is N -acetylcysteine (NAC) beneficial in late presentations of acetaminophen toxicity/poisoning?
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Can N-Acetylcysteine Treat COPD, Diabetes, and Infertility?
N-acetylcysteine (NAC) is the supplement form of the amino acid cysteine. The supplement helps facilitate essential biological functions by bonding with two other amino acids—glutamine and glycine—to create a powerful antioxidant known as glutathione.
Glutathione plays a key role in regulating numerous cellular activities and helps keep the immune system in check. As an antioxidant, glutathione helps neutralize free radicals that damage cells and tissues at the molecular level.
Proponents claim that taking N-acetylcysteine supplements can protect against a plethora of health concerns, including respiratory diseases, liver disease, psychiatric disorders, diabetes, certain cancers, and chemical dependency.
In complementary and alternative medicine, N-acetylcysteine is believed to help a wide range of medical conditions. Because N-acetylcysteine can increase the production of glutathione, some practitioners have posited that it not only prevents conditions cancer and heart disease by maintaining the integrity of cells but also support the treatment of certain diseases.
Proponents contend that N-acetylcysteine has the potential to prevent or treat an almost encyclopedic range of health problems, including:
- Allergic rhinitis (hay fever)
- Alzheimer's disease
- Bipolar disorder
- Carbon dioxide poisoning
- Chronic kidney disease
- Chronic obstructive pulmonary disorder (COPD)
- Cocaine dependence
- Colorectal cancer
- Cystic fibrosis
- Heart disease
- Hypercholesterolemia (high cholesterol)
- Lou Gehrig's disease
- Lung cancer
- Polycystic ovary syndrome (PCOS)
- Post-traumatic distress syndrome (PTSD)
- Preterm labor or miscarriage
- Unstable angina
- Upper respiratory infections
The expansive nature of these claims occasionally borders on the far-fetched. Even those claims that have benefited from clinical research typically fall short, either because the studies are small or the evidence doesn't support the often far-reaching conclusions.
With that being said, there have been some positive findings that warrant serious scientific consideration. Here is a look at some of the research investigating the benefits of N-acetylcysteine supplements:
A 2015 analysis published in European Respiratory Review, evaluating 13 studies and a total of 4,155 people with COPD, concluded that 1,200 milligrams of N-acetylcysteine per day reduced the incidence and severity of flares (known as exacerbations) compared to a placebo.
N-acetylcysteine may aid in the prevention management of diabetes, suggests a 2016 study in the American Journal of Translational Research.
The research involved mice that were either fed a high-fat diet (replicating the effects of type 2 diabetes) or had medical-induced diabetes (closely mirroring type 1 diabetes).
Each group was further divided into smaller groups N-acetylcysteine dose. Among the findings:
- Doses of 600 to 1,800 milligrams per kilogram per day (mg/kg/day) improved glucose tolerance in mice with medically-induced diabetes.
- Mice fed high-fat diets had improved glucose at doses of 400 mg/kg/day and also achieved weight loss compared to mice not given N-acetylcysteine.
- Doses of 1,200 mg/kg/day increased insulin sensitivity.
While the results are preliminary, they do show promise both in the prevention and management of diabetes.
N-acetylcysteine may provide better control of diabetes by increasing a person's sensitivity to insulin. On the flip side, by increasing glucose tolerance, N-acetylcysteine may prevent people with prediabetes from progressing to diabetes.
N-acetylcysteine is often said to reduce the risk of heart disease by reducing the oxidative stress on the heart and cardiovascular system. This is evidenced in part by research in which the daily use of N-acetylcysteine can reduce hypertension (high blood pressure), a major factor for atherosclerosis.
According to a 2015 study in the American Journal of Clinical Nutrition, N-acetylcysteine reduces levels of homocysteine in the blood. Homocysteine an amino acid you commonly get from eating red meat. High levels are an independent risk factor for heart disease, kidney disease, and even recurrent miscarriage.
The researchers reported that a four-week course of N-acetylcysteine was associated with a significant drop in systolic and diastolic blood pressure irrespective of smoking, weight, or blood lipid values.
N-acetylcysteine may help treat polycystic ovary syndrome (PCOS), according to a 2015 systematic review in Obstetrics and Gynecology International. in evaluating eight studies with a total of 910 women with PCOs, the investigators showed that N-acetylcysteine improved ovulation and pregnancy rates compared to a placebo.
The cause for this is not entirely clear. Despite the following findings, the researcher reported that N-acetylcysteine did not improve other characteristic symptoms of PCOS, including menstrual irregularities, weight gain, and the development of secondary male traits.
While N-acetylcysteine may improve fertility in with PCOS, there is evidence that it can do the same with men with infertility.
According to a 2016 study in the International Journal of Fertility and Sterility, 35 men who underwent surgery to treat varicoceles had higher rates of conception if given N-acetylcysteine prior to and after surgery. Varicoceles is one of the leading causes of male infertility, resulting from the formation of varicose veins in the scrotum.
Moreover, the quality of sperm was also seen to improve, both on the physical and genetic level. The researchers believe that the alleviation of oxidative stress resulted in “healthier” sperm and improved fertility following varicoceles surgery.
There is some evidence that N-acetylcysteine can enhance the effects of psychotropic drugs used to treat bipolar disorder. A 24-week study published in the International Journal of Bipolar Disorder reported that 3,000 grams of N-acetylcysteine significantly improved depression scores in people on bipolar medications.
It is believed the antioxidant effects triggered by N-acetylcysteine may be responsible for the response. Most experts agree that an imbalance of oxidants and antioxidants is a central feature of clinical depression.
Some scientists believe that the same benefits may extend to other psychiatric disorders, including substance abuse disorders and early schizophrenia.
One of the medical indications of N-acetylcysteine is Tylenol (acetaminophen) poisoning. The procedure involves three consecutive intravenous (IV) infusions given over 24 hours to prevent liver damage and other symptoms of acetaminophen toxicity.
Tylenol poisoning is considered a medical emergency. Taking oral N-acetylcysteine in no way prevents or treats symptoms of a Tylenol overdose.
Call Poison Control at (800) 222-1222 if you or someone you know has taken excessive amounts of Tylenol or experiences poisoning symptoms if taking Tylenol with alcohol.
N-acetylcysteine is considered safe and well-tolerated if used appropriately. With that said, it may cause side effects in some.
Common side effects are generally mild and typically resolve on their own once treatment is stopped. These may include nausea, stomach ache, and diarrhea. Less commonly, people may experience a runny nose, drowsiness, and fever.
Allergies to N-acetylcysteine are uncommon but can occur. The risk is highest during N-acetylcysteine infusions. In rare cases, an infusion may cause anaphylaxis, a potentially life-threatening allergy characterized by severe rash, hives, clamminess, shortness of breath, rapid heart rate, and the swelling of the face, throat, and tongue.
Allergies to oral N-acetylcysteine tend to be mild and may cause a runny nose, sneezing, and nasal congestion. Call your doctor if the symptoms persist or worsen, or if you develop a rash or dizziness.
N-acetylcysteine is generally considered safe to use during pregnancy and breastfeeding. Even so, speak with your doctor or OB/GYN to fully understand the risks and benefits of N-acetylcysteine and whether you actually need the supplement or not.
N-acetylcysteine has few known drug interactions. It may intensify the effects of nitroglycerin and isosorbide dinitrate used to treat angina, causing headaches, dizziness, lightheadedness, and fainting.
There is also a theoretical risk of hypoglycemia (low blood sugar) if N-acetylcysteine is taken with diabetes medications. The routine monitoring of blood glucose can help identify any abnormal drops in blood sugar.
Caution should also be exercised in people with kidney disease. The metabolized drug is excreted via the kidneys and has been known in rare cases to cause kidney stones even in people without kidney disease.
Oral N-acetylcysteine supplements are available over the counter in tablet, capsule, soft gel, effervescent, and powdered form. Most are sold in 600-milligram (mg) formulations, although some are as high as 1,000 mg.
There are no universal guidelines on the appropriate use of N-acetylcysteine. Doses of up to 1,200 mg per day (generally taken in divided doses) have been used safely in adults. As a rule of thumb, never take more than the recommended dosage listed on the product label.
The safe and effective oral dose of N-acetylcysteine in children has not been established. Unless directed by a physician, N-acetylcysteine supplements should not be in children.
Single amino acid supplements, N-acetylcysteine, are best taken on an empty stomach. The absorption of amino acids can be affected by the foods you take them with and by other amino acids.
N-acetylcysteine supplements can be stored at room temperature in a cool, dry room. Discard of any supplements that have expired, are discolored or show signs of deterioration.
Dietary supplements are not strictly regulated in the United States and can vary significantly from one brand to the next. To ensure the utmost safety and quality, only buy supplements that have been tested by an independent certifying body the U.S. Pharmacopeia (USP), ConsumerLab, or NSF International.
Certification does not mean that the supplement is effective in treating any medical condition; it simply confirms that it contains the ingredients listed on the product label and is a good indication that the ingredients are safe.
You should avoid any supplement that makes claims about cures. Under the law, dietary supplement manufacturers are barred from doing so as they lack the large-scale clinical research to support such claims.
N-acetylcysteine supplements are manufactured in the lab with synthetic compounds and are vegan- and vegetarian-friendly. If you are strictly vegetarian and prefer soft gel caps, only opt for products with “vegan” on the label to avoid animal-based gelatins.
Only minute amounts of N-acetylcysteine are found in food. By contrast, cysteine is both naturally produced in the body and obtained from animal- and plant-based foods. Because of this, cysteine is considered a semi-essential amino acid (un essential amino acids that must be obtained externally).
Excellent food sources of cysteine include:
- Red meat (especially pork)
- Red peppers
- Brussels sprouts
- Wheat germ
Cysteine deficiency is not very common, although vegetarians and vegans with a low intake of cysteine-rich plant foods may be at risk.
N-Acetyl Cysteine (NAC): Lower Inflammation and Stop Cravings
- N-acetyl cysteine (NAC) is a powerful supplement for brain function, addiction, depression, and more.
- NAC increases glutathione, your body’s master antioxidant, by about 30 percent. It helps you fight off oxidative stress and free radical damage, which blocks inflammation and slows down aging.
- It can also help with addiction, depression, and obsessive compulsive disorder (OCD). In some cases NAC is as effective as prescription drugs, without any of the side effects.
- Read below for the best NAC supplements and the right NAC dosage.
N-acetyl cysteine (NAC) is an amino acid (a building block of protein) that can supercharge your performance and slow down aging.
NAC is on the World Health Organization’s list of essential medicines because it can treat a variety of issues, from liver damage to asthma.
Now, new research shows that NAC carries a host of other benefits, too.
“N-acetyl cysteine is a precursor to glutathione, and it’s a great antioxidant itself,” says neuroscientist Bill Walsh in a recent Bulletproof Radio podcast episode [iTunes]. “It’s also good for shopping disorders, gambling disorders, [other] addictions, and severe OCD.”
Here are the four top reasons to add NAC to your daily supplement stack.
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1. NAC stops cravings and addiction
NAC is a powerful way to get rid of cravings, and could potentially treat addiction.
Every addictive substance or behavior affects dopamine, one of your brain’s main feel-good chemicals and a driver of motivation. Specifically, addictive substances or behaviors light up dopamine reward pathways in your nucleus accumbens, a small part of your brain just below your temple.
When you’re addicted to something, it causes a dopamine imbalance and changes gene expression in your nucleus accumbens, which contributes to cravings.
NAC balances reward pathways, which reduces or eliminates cravings, and also decreases glutamate, a brain chemical that triggers reward-seeking behavior. Research shows that taking NAC can help decrease cravings and prevent relapse in people addicted to:
- Cocaine. Addicts had decreased cravings after just three days of taking NAC.
- Nicotine (cigarettes). Smokers showed decreased cravings after four days on NAC, and nearly 50 percent of people who took NAC successfully quit smoking, versus 20 percent in the placebo group.
- Binge eating, although this research was in rats and hasn’t yet been tried on people
If you struggle with cravings or are trying to beat an addiction, taking NAC could help.
2. NAC for inflammation and aging
NAC is also a favorite supplement in the anti-aging community. It’s a precursor to glutathione, the most powerful antioxidant in the human body.
Taking NAC increases your glutathione levels by nearly 30 percent, which makes you much more resistant to inflammation and oxidative stress and slows down aging at a cellular level. NAC works quickly, too: it measurably increases your antioxidant status in about a week, and your ability to fight off oxidative stress lasts long-term if you keep taking NAC.
It also protects your cells from environmental pollutants and toxins, including pesticides, heavy metals lead, and gasoline and diesel fumes.
NAC even restored lung function in soldiers exposed to mustard gas, and is a standard at hospitals for treating poisons that cause damage through extreme oxidative stress.
If you struggle with depression or obsessive-compulsive (OCD) behavior, NAC may help.
Several large studies have found that NAC relieves symptoms of depression and anxiety, with none of the side effects you get from antidepressants. NAC also improved mood in depressed people who took it on top of their normal medication — again, with no side effects or drug interactions.
Related: Mood-Boosting Supplements for Depression, Anxiety & Stress
NAC also decreases OCD behavior, possibly through the same mechanism by which it relieves addiction. It improved symptoms in people with severe OCD, and also decreased OCD in people who didn’t respond to drug treatment.
There’s no reason not to take NAC if you’re depressed or have OCD. It doesn’t interact with other medication and seems to help in many cases, even when drugs don’t.
4. NAC boosts fertility in men and women
NAC improves egg quality and increases pregnancy rates in women with polycystic ovary syndrome (PCOS), and also balances testosterone, one of the main drivers of infertility in women with PCOS. NAC even reverses weight gain and prediabetes, two common symptoms of PCOS.
In men, NAC improves sperm quality and, in some cases, even reverses infertility. Researchers think this happens because NAC is so good at protecting you from oxidative damage. Increasing antioxidant status keeps sperm healthier.
If you and your partner are trying to conceive, try adding NAC to your routine.
Related: Follistatin: Grow Muscle, Fight Fat, and Boost Fertility
NAC dosage and sourcing
With so many different benefits, NAC has something for everyone. It’s a great general supplement to protect your cells from stress and slow down aging, and is well worth adding to your morning supplement stack.
Most studies use a dose of between 1200-2400 mg NAC, taken in 600 mg doses throughout the day. You’ll absorb NAC best if you take it on an empty stomach, at least an hour away from eating.
Look for a supplement that’s either pure NAC or NAC with vitamin C (the two pair well together). You can expect to spend about $15 for a 30-day supply.
Read next: From Staying Young to Hacking Hangovers: A Guide to Glutathione
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NAC (N-acetyl-cysteine) is a supplement used by people with HIV, usually as part of an antioxidant regimen. NAC is usually taken two or three times daily and is available in capsule and tablet forms in some health food stores. NAC is also available by prescription in liquid form from pharmacies.
What is NAC?
NAC is a supplement used by some people living with HIV. NAC stands for N-acetyl-cysteine and is similar to the amino acid cysteine. Taking NAC helps to increase levels of the protective compound glutathione (GSH) in the body.
How does NAC work?
Before explaining how NAC works, we first need to give you some background information about GSH.
GSH is a compound that the body makes using various nutrients including the amino acid cysteine. GSH is the body's chief protector from the injury caused by harmful substances. Results from a number of studies suggest that in people with HIV the demand by the body for GSH exceeds the supply.
Less-than-normal levels of GSH may result in impaired performance by cells of the immune system and perhaps increased sensitivity to the toxic effects of some drugs. When there is not enough cysteine available to make GSH, the body tears down muscles, which are rich in protein, to find the nutrients needed to make GSH.
NAC works by acting as a source of cysteine and stimulating the production of GSH.
1. As an antioxidant and to help reduce inflammation
In the late 1980s, researchers found that people with HIV were ly to have higher-than-normal levels of highly active compounds called “free radicals.” These compounds damage cells in much the same way that rust damages a car.
Some people with HIV take NAC as part of an antioxidant regimen to help counter the damaging effects of high levels of free radicals. NAC continues to be studied in clinical trials with HIV-positive participants such as the Maintain study in Canada.
Excessive levels of free radicals can also lead to higher-than-normal levels of inflammation. Persistent and elevated levels of inflammation may degrade major organ-systems.
A pilot study has found that a supplement of NAC and the amino acid glycine can significantly and quickly reduce excess inflammation in a small group of HIV-positive men. The study had only 10 participants, used very high doses of NAC and lasted for two weeks. Longer and larger studies are required to confirm these results.
2. To maintain GSH and muscle mass
HIV-positive people—whether or not they are taking potent combination anti-HIV therapy (commonly called ART)—can experience a loss of critical sulfur-containing amino acids, such as cysteine and methionine. Supplements of NAC may be able to replace lost cysteine, help maintain protein levels and possibly reduce muscle wasting.
Together, all of these potential benefits may explain why one American study found that supplements of NAC—an average of 4 grams daily—prolonged survival for up to three years in the time before ART was widely available.
That study was the impetus for the widespread use of NAC by HIV-positive people and so it may be useful to briefly review findings from that study.
In the early 1990s, researchers at Stanford University in California conducted an eight-week randomized, placebo-controlled study of NAC in HIV-positive people. The dose of NAC used was about 4,400 mg daily. After the initial eight weeks, all participants were offered NAC for six months.
Researchers collected data on the survival of participants for several years after they stopped using NAC. They found that this supplement significantly increased GSH levels within CD4+ cells. However, NAC did not significantly raise CD4+ cell counts.
The data also suggested that people who used NAC were twice as ly to survive over the next two years compared to people who did not ever use NAC. At the time of the study, ART was not available and most participants used AZT (zidovudine, Retrovir) with or without another nuke (nucleoside analogue).
Due to the study design, firm conclusions about the effect of NAC on survival in HIV infection cannot be drawn and it is important to note that a large proportion of NAC users did eventually die. However, the trial did heighten interest in the use of antioxidants.
In the time before ART was available, researchers in Montreal also tested whey protein concentrates, which are rich in cysteine, in HIV-positive volunteers and found that they improved weight. In that era a sustained increase in weight was unusual in HIV-positive people.
A small study in the current era has found that NAC taken orally does replenish GSH levels inside cells and also reduces inflammation.
3. To protect the liver and kidneys from the toxicity of drugs
In some people, the pain reliever acetaminophen (Tylenol) can cause injury to the liver and kidneys even when used within normal doses.
In hospitals in North America, in cases of overdose with paracetamol or acetaminophen, doctors can sometimes prevent the onset of severe liver injury (and death) by giving NAC intravenously.
In theory, since the body uses GSH to protect cells from injury, it is possible that NAC may be protective in cases of poisoning from other drugs. However, NAC has not been tested for this purpose in well-designed clinical trials, so there is no firm data to support such a use in people.
4. Other potential uses
NAC is being studied for the treatment of addiction disorders.
At high doses, NAC may cause the following symptoms in some people:
- abdominal discomfort
In lab experiments with cells, high concentrations of NAC can weaken some activities of the immune system. There have been no studies of this in people.
If you are taking antibiotics, NAC should not be taken, as it may weaken their beneficial effects.
The best dose of NAC for people with HIV is not clear, but reviewing the data from clinical trials in people with HIV may be useful.
In the previously mentioned American study, use of about 4 grams per day of NAC was associated with improved survival.
However, anecdotal reports suggest that taking such large doses of NAC for prolonged periods can cause abdominal discomfort, nausea, vomiting and diarrhea.
According to results from two German studies, a dose of 3 grams every other day is effective at increasing GSH levels and does not appear to cause toxicity. Alternatively, some people with HIV take smaller doses of NAC, between 500 to 1,000 mg, once or twice daily.
Taking NAC with meals or acidic drinks (orange juice, cola beverages) may reduce nausea.
In drug stores, NAC is available in liquid form with a prescription. Some health food stores sell NAC in capsule form.
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