N-Acetyl-L-cysteine ​​(NAC)-SOHF (2023)

• N-acetylcysteine ​​(NAC) is a sulfur-containing derivative of the amino acid L-cysteine
• NAC can be used for protein synthesis after conversion to L-cysteine
• NAC is a precursorGlutathione, a powerful intracellular antioxidant
• NAC can be used to treat a variety of diseases in which oxidative stress and/or inflammation play a role
• NAC can be used, for examplechronic obstructive pulmonary disease,Asma,autism,tiredCdetoxification

briefly

What is N-Acetyl-L-Cysteine ​​(NAC)?

N-acetylcysteine, abbreviated as NAC, is a derivative of the amino acid L-cysteine. This semi-essential amino acid is a sulfur-containing substance that the body produces from another amino acid called L-methionine.

This synthesis is not sufficient in some cases. NAC can be used for protein synthesis after conversion to L-cysteine. In the body, it is a source of sulfhydryl groups (-SH), so it acts as a strong antioxidant. NAC is also the predecessorGlutathione, an important intracellular antioxidant. N-acetylcysteine ​​increases glutathione levels in the body; glutathione deficiency is associated with several pathological conditions^1,2,3,4,5,6NAC can be used to treat a variety of diseases in which oxidative stress and/or inflammation play a role.

What is N-Acetyl-L-Cysteine ​​(NAC)?

Oral N-acetylcysteine ​​may improve stimulus processing but not other symptoms associated with autism spectrum disorder^37,38

acetaminophen poisoning

Oral and intravenous N-acetylcysteine ​​as a prescription drug is effective in treating acetaminophen poisoning. Reduce mortality and prevent permanent effects of acetaminophen poisoning^33,34,35,36。

despise

Inhaled N-acetylcysteine ​​is effective in treating atelectasis. It is effective against atelectasis caused by mucus obstruction and is FDA-approved for this use. Inhalation also helps people prepare for a bronchial diagnosis. When inhaled and used as an adjunct therapy, N-acetylcysteine ​​is effective in preventing tracheal scaling in patients with tracheostomy.

Bronchial Diagnostic Tests
N-acetylcysteine ​​inhalation solution may be used to prepare an individual for bronchial diagnostic testing. It is FDA-approved for this use. Taking 1200-1500 mg of N-acetylcysteine ​​by mouth daily for 4 months seems to reduce shortness of breath and cough and improve lung capacity in people with sulfur mustard bronchitis^39,40. In addition, taking N-acetylcysteine ​​by mouth (usually 400-600 mg per day) in moderation appears to reduce the risk of chronic bronchitis exacerbations when taken for 3-36 months.^21,41,30。

Tracheostomy care (trachea/neck stoma)
N-acetylcysteine ​​inhalation solution is effective when used as an anti-intubation agent during tracheotomy. It is FDA-approved for this use.

use

Indications

Generally speaking

N-acetylcysteine ​​is the N-acetyl derivative of the amino acid L-cysteine¹⁰¹N-acetylcysteine ​​is a precursor to glutathione, a powerful antioxidant. Glutathione cannot penetrate cell membranes. N-acetylcysteine ​​readily crosses cell membranes, is converted to cysteine, and then to glutathione. Reactive oxygen species (ROS), such as hydrogen peroxide and hydroxyl radicals, reduce intracellular and extracellular glutathione concentrations. N-acetylcysteine ​​is a very efficient way to convert glutathione and reduce the damage caused by ROS^102.103。

antibacterial effect

N-acetylcysteine ​​disrupts disulfide bonds in mucus glycoproteins, destabilizing biofilms and theoretically facilitating access of antibiotics to biofilm-producing bacteria¹⁰⁴。

Anticancer effect

Some in vitro and animal studies suggest that N-acetylcysteine ​​has anticancer effects.^{105.106.107.108.109.110.111}. Although the anticancer mechanism has not been identified, several in vitro and animal studies have shown that N-acetylcysteine ​​can inhibit the invasive activity and angiogenesis of cancer cells.¹¹². Other animal models suggest that N-acetylcysteine ​​may promote anti-angiogenic effects through the production of angiostatin, thereby promoting tumor vessel collapse¹¹³。

Anticoagulation

Preliminary Evidence Suggests N-Acetylcysteine ​​May Reduce Platelet Aggregation¹¹⁴¹¹⁵.N-acetyl cysteine ​​appears to increase the synthesis of nitric oxide, a potent inhibitor of platelet function¹¹⁶。

Detoxification (paracetamol toxicity)

N-acetylcysteine ​​is effective against acetaminophen hepatotoxicity as it restores hepatic glutathione levels and acts as an alternative substrate for the conjugation of toxic acetaminophen metabolites. The mechanism of protective action of N-acetylcysteine ​​against paracetamol toxicity is speculated to be the inhibition of O-distillation of ethoxylated resorufin (cytochrome P-448), including¹¹⁷。

anti-inflammatory effect

N-acetylcysteine ​​appears to reduce cellular production of pro-inflammatory mediators such as tumor necrosis factor alpha (TNF-α) and interleukin 1 (IL-1)¹¹⁸Several in vitro studies have shown that N-acetylcysteine ​​inhibits markers of inflammation such as phospholipid metabolism, pro-inflammatory cytokine release, and protease activity¹¹⁹Although the mechanism has not been elucidated, some in vitro studies suggest that nitric oxide synthesis may explain some of the anti-inflammatory effects of N-acetylcysteine.¹²⁰。

Anti-oxidize effect

Its antioxidant and free radical scavenging properties may make N-acetylcysteine ​​useful in the treatment of lung and heart disease.¹⁰¹¹²¹Administration of N-acetylcysteine ​​counteracts oxidative stress associated with oxygen uptake and prevents oxidation of GSH and erythrocyte proteins in patients with chronic obstructive pulmonary disease (COPD)¹²². N-acetylcysteine ​​has no effect on MDA levels in COPD patients treated for 15 days¹²³。

antiviral effect

N-acetylcysteine ​​might increase glutathione levels in patients with human immunodeficiency virus (HIV) disease. Increasing glutathione appears to reduce oxidative stress associated with HIV disease and improve CD4 T cell count and activity¹²⁴. Despite this, most clinical studies show that N-acetylcysteine ​​does not provide any additional benefit to people living with HIV.^{125 126 127}. Additionally, some in vitro studies have shown that N-acetylcysteine ​​can actually increase the growth of HIV in certain cell types. The mechanism of this effect is unclear.¹²⁸。

NAC has the potential to improve treatment strategies for COVID-19. It can be administered intravenously, orally or by inhalation. Early application can inhibit SARS-CoV-2 replication and improve outcomes. Potential therapeutic benefits of NAC include extracellular scavenging of ROS free radicals, intracellular GSH replacement, suppression of cytokine storm and protection of T cells, reduction of inflammation and tissue damage. NAC in combination with other antivirals significantly reduces hospitalization, mechanical ventilation, and mortality¹⁶⁶。

Based on multiple antioxidant and anti-inflammatory mechanisms, oral NAC may reduce the risk of COVID-19, as previously demonstrated for influenza and influenza-like illness.¹⁶⁷. Additionally, high-dose intravenous NAC is expected to play an adjunctive role in the management of severe cases of COVID-19 and its fatal complications, including pulmonary and cardiovascular side effects.^{168 169, 170 171}。

cardiovascular effects

Some in vitro and animal studies have shown that the antioxidant effect of N-acetylcysteine ​​can inhibit LDL oxidation, delay the progression of atherosclerotic lesions, and increase the expression of nitric oxide synthase in vascular smooth muscle cells.^{129 130 131}. However, preliminary clinical evidence suggests that 1200-2400 mg of N-acetylcysteine ​​per day does not improve oxidized LDL or blood lipids in healthy adults.¹³². There is some interest in using N-acetylcysteine ​​to protect the heart after myocardial infarction, and continuous infusion of N-acetylcysteine ​​in combination with nitroglycerin has been shown to reduce the extent of myocardial infarction in clinical trials. Administration of N-acetylcysteine ​​was also associated with a 42% reduction in mean creatine kinase levels¹³³。

Effects of Cystic Fibrosis

Some evidence suggests that N-acetylcysteine ​​may play a role in cystic fibrosis. In vitro studies suggest that N-acetylcysteine ​​may induce electrolyte secretion from airway epithelial cells¹³⁴In addition, some evidence from children suggests that N-acetylcysteine ​​improves electrolyte transport in the epithelium either through osmotic effects or by altering some factors affecting electrolyte transport.¹³⁵。

detoxification

Studies have shown that glutathione, the precursor of NAC, binds fat-soluble toxins such as heavy metals, solvents, and pesticides, making them water-soluble so they can be excreted in urine.¹⁶⁴¹⁶⁵. The liver is the largest storehouse of glutathione, which in turn protects liver function itself.

tooth effect

Some early clinical studies show that using a mouthwash containing N-acetylcysteine ​​can reduce plaque and gingivitis¹³⁶¹³⁷N-acetyl cysteine ​​can limit the growth of bacteria, including pathogenic bacteria in the oral cavity, by breaking the disulfide bonds of bacterial proteins. N-acetylcysteine ​​may also inhibit bacterial adhesion¹³⁷。

better sports performance

In human studies, N-acetylcysteine ​​appears to improve athletic performance by reducing respiratory muscle fatigue.¹³⁸. The reported training benefits of N-acetylcysteine ​​also lie in its antioxidant effects.^{139 140 141}. N-acetylcysteine ​​also appears to improve potassium regulation, which may play a role in reducing fatigue.¹⁴²。

Immunomodulatory effect

N-acetylcysteine ​​appears to improve disease activity by blocking mTOR on T cells in patients with systemic lupus erythematosus¹⁴³N-acetylcysteine ​​increases CD4+ cell numbers in patients with suboptimal glutathione levels¹⁴⁴. Phagocytosis of neutrophils is improved after treatment with N-acetylcysteine¹⁴⁵。

nervous system effects

The glutamate and antioxidant properties of N-acetylcysteine ​​are thought to help treat neuropsychiatric disorders such as autism¹⁴⁶¹⁴⁷, bipolar disorder^{148 149 150}Hair puller^26,42There is also interest in using N-acetylcysteine ​​to improve compulsive behaviors associated with hyperactivity of corticostriatal-thalamocortical circuits, possibly due to abnormal glutamate levels.¹⁵¹. N-acetyl cysteine ​​appears to increase cysteine ​​uptake. Intake of cysteine ​​activates reverse transport of glutamate into the extracellular space. Reintroduction of glutamate into the extracellular space inhibits further release of glutamate and improves compulsive behavior⁴²。

Neuroprotection

N-acetylcysteine ​​may provide neuronal protection by preserving mitochondria and protecting motor neurons¹⁵²It has been hypothesized that scavenging free radicals and reducing oxidative stress beyond the blood-brain barrier may also contribute to neuroprotection.

lung effects

Several clinical, animal, and in vitro studies suggest that N-acetylcysteine, due to its antioxidant and anti-inflammatory effects, may help break down mucus and protect against smoking or ischemia-induced lung damage.^{153 154 155 156 157 158 159 160 161 162 163}。

Indications

The most common dose of N-acetylcysteine ​​is 600-1200 mg per day. Daily doses of 1200 mg or higher are usually given in divided doses. Higher doses up to 1000 mg twice daily have been used for up to 6 months. N-acetylcysteine ​​is available orally, intravenously, intratracheally, or inhaled and is an FDA-approved prescription drug.^{7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31, 32}。

N-acetylcysteine ​​inhalation solutions are available in 10% and 20% strengths. Typically, use 2-4 ml of 10% solution or 1-2 ml of 20% solution. Frequency of use depends on the condition being treated. treat.

children

N-acetylcysteine ​​inhalation solutions are available in 10% and 20% strengths. Typically, use 2-4 ml of 10% solution or 1-2 ml of 20% solution. Frequency of use depends on the condition being treated. treat.

When taken orally and used correctly, N-acetylcysteine ​​can be safely used in children at doses of 900-2700 mg per day for 8-12 weeks^42,38,37,43。

pregnancy and lactation

Intravenous N-acetylcysteine ​​140 mg/kg/day plus oral N-acetylcysteine ​​70 mg/kg four times daily for 10 months is safe.

After oral, intratracheal, intravenous or inhalation administration, N-acetylcysteine ​​​​can cross the placenta, but no adverse effects on the fetus have been found.^44,45,46,47. However, N-acetylcysteine ​​should only be used during pregnancy when clearly indicated, such as in the case of paracetamol poisoning.

There is not enough reliable information about lactation; avoid use.

side effect

In general:Oral, intravenous, and inhaled N-acetylcysteine ​​is generally well tolerated when used in typical doses. Most N-acetylcysteine ​​side effects occur with single doses greater than 9 grams or with doses greater than 30 grams per day. This day is tracked.

most common side effects:

oral: Diarrhea, dry mouth, indigestion, heartburn, loss of appetite, nausea and vomiting.
vein: Rash and allergic reaction.
inhale: Bronchospasm, cough, epigastric pain, throat irritation and wheezing.

serious side effects (rare):

oral: There were reports of chest tightness, hemoptysis, and palpitations.
vein: Anaphylaxis, angina pectoris, dystonic reactions, tachycardia and transient sinus bradycardia have been reported.

Safety

interactive

drug

N-acetylcysteine ​​can reduce the effects of activated charcoal, which can reduce the absorption of N-acetylcysteine. N-acetylcysteine ​​appears to reduce the ability of activated charcoal to adsorb paracetamol and salicylic acid⁴⁹Although activated charcoal can reduce the absorption of N-acetylcysteine ​​by up to 40%, its clinical effect does not appear to be reduced.^{50,51,52,53,54}. Other clinical evidence suggests that activated charcoal does not affect N-acetylcysteine ​​absorption^55,56。

In theory, taking N-acetylcysteine ​​with blood thinners or antiplatelet drugs may increase the risk of bleeding. Clinical trials have shown that intravenous injection of N-acetylcysteine ​​can reduce prothrombin time in surgical patients, prolong clotting time, reduce platelet aggregation, and increase blood loss^57,58。

Taking NAC may interfere with the antimalarial effects of chloroquine. N-acetylcysteine ​​may also increase the risk of hypotension when taken with antihypertensive medications. Clinical studies have shown that co-administration of N-acetylcysteine ​​with intravenous or transdermal nitroglycerin causes severe hypotension¹²and can cause severe headaches^59,60。

supplements

Taking N-acetylcysteine ​​with other products that increase the risk of bleeding may have additional effects. Clinical Studies Show N-Acetyl Cysteine ​​Can Reduce Platelet Aggregation⁵⁷。

Combining N-acetylcysteine ​​with other antihypertensive herbs or supplements may increase the risk of hypotension. Animal studies show that N-acetylcysteine ​​enhances the blood pressure-lowering effects of the angiotensin-converting enzyme (ACE) inhibitors captopril and enalaprilat⁶¹。

interactive

adult - by mouth

acetaminophen poisoning
The oral loading dose of the 5% solution is 140 mg/kg. In addition, commercially available 10% and 20% nebulizable solutions can be diluted with water, carbonated or non-carbonated beverages, and administered through a straw to reduce the unpleasant odor of N-acetylcysteine. An additional 17 doses of 70 mg/kg 5% solution can be given every 4 hours for a total of 1330 mg/kg over 72 hours.^34,35,36。

Ototoxicity due to aminoglycosides
Adults with end-stage renal disease (ESRD) were treated with N-acetylcysteine ​​600 mg twice daily for a total of 14 days, or up to 7 days after discontinuation of aminoglycoside therapy.⁶²。

Asma
Preliminary clinical trial shows that daily aerosolized N-acetylcysteine ​​10% for one week improves lung capacity and reduces sputum viscosity in asthmatic patients compared with placebo⁶³。

sports achievement
N-acetylcysteine ​​1200 mg per day for 9 days⁶⁴。

bipolar disorder
N-acetylcysteine ​​1000 mg twice daily for 24-36 weeks^65,66,67。

bronchiectasis
N-Acetylcysteine ​​600 mg twice a day has been used for 12 months⁶⁸。

Chemotherapy-induced peripheral neuropathy
N-acetylcysteine ​​1200 mg 1.5 hours before treatment with oxaliplatin⁶⁹。

Chronic Obstructive Pulmonary Disease (COPD)
N-acetylcysteine ​​400-1200 mg per day in divided doses for 4-6 months^70,71。

cocaine addiction
N-acetylcysteine ​​600 mg every 12 hours for four doses⁷²。

contrast nephropathy
N-acetylcysteine ​​400-600 mg twice daily before and after contrast administration⁷⁴. The contrast agent was administered with a bolus dose of 1200 mg N-acetylcysteine, followed by oral administration of 1200 mg N-acetylcysteine ​​twice daily for 48 hours.

Endometriosis
In the case of a combined preparation containing 600 mg N-acetylcysteine, 200 mg alpha lipoic acid, 25 mg bromelain and 10 mg zinc, two tablets were used daily for 6 months.⁷³。

epilepsy
4 to 6 grams of N-acetylcysteine ​​per day for up to 30 months⁷⁵。

hearing loss
N-acetylcysteine ​​1200 mg per day for 14 days⁷⁶。

Helicobacter pylori
N-acetyl cysteine ​​400 mg 3 times daily for 10 days with clarithromycin and lansoprazole⁷⁷。

Hereditary Hemorrhagic Telangiectasia (HHT)
N-acetylcysteine ​​600 mg 3 times a day for 12 weeks⁷⁸。

homocysteine
N-acetylcysteine ​​600 mg daily for 8 weeks⁷⁹. Also for patients with end-stage renal disease requiring dialysis, 1200 mg of N-acetylcysteine ​​has been used 1.5-3 hours before dialysis⁸⁰。

Hyperlipidemia
N-acetylcysteine ​​1.2 grams per day for 6 weeks or 2 grams per day for 4 weeks, then 4 grams per day for 4 weeks^81,82。

idiopathic interstitial pneumonia
N-acetylcysteine ​​600 mg 3 times a day for 12 weeks⁸³。

complain
Use N-acetylcysteine ​​effervescent tablet 600 mg twice a day for 6 months⁸⁴。

male infertility
N-acetylcysteine ​​600 mg/day orally for 26 weeks in men^85,86。

abortion
N-acetylcysteine ​​600 mg per day plus folic acid 500 mcg per day (duration unknown)⁸⁷。

Nitrate tolerance
N-acetyl cysteine ​​1800 mg per day for 4 months⁸⁸。

Nonalcoholic steatohepatitis (NASH)
N-acetylcysteine ​​1.2 g plus metformin 850-1500 mg per day for 48 weeks⁸⁹。

Obsessive Compulsive Disorder (OCD)
N-acetylcysteine ​​1000 mg twice daily in combination with fluvoxamine 200 mg daily for 10 weeks⁹⁰。

Polycystic ovary syndrome (PCOS)
Severely obese PCOS patients have used higher doses, up to 3 grams per day⁹¹. A specific combination product (Ovaric HP; Just Pharma, Rome, Italy) containing 600 mg of N-acetylcysteine, 2 g of inositol, and 200 µg of folic acid twice daily for 12 months was also used.⁹²。

Post Traumatic Stress Disorder (PTSD)
N-acetylcysteine ​​1200 mg twice daily for 8 weeks in combination with cognitive behavioral therapy⁹³。

premature birth
N-acetylcysteine ​​0.6 g/day orally in combination with 17-hydroxyprogesterone caproate (17-OHPC) for 16 to 18 weeks of gestation and ongoing active labor⁴⁵。

schizophrenia
N-acetylcysteine ​​1 g, twice a day, for 6 months⁹⁴. N-acetylcysteine ​​started at 600 mg/day for 4 weeks and then increased to 3600 mg/day for a total of 52 weeks⁹⁵。

Sjogren's syndrome
N-acetylcysteine ​​200 mg 3 times a day for 4 weeks⁹⁶。

Systemic Lupus Erythematosus (SLE)
N-acetylcysteine ​​2.4-4.8 grams orally daily for 3 months⁹⁷。

Trichotillomania (hair pulling)
N-acetylcysteine ​​at doses up to 2400 mg per day for 12 weeks⁹⁸。

inhale/breathe

Asma
Once daily inhalation of 10% N-acetylcysteine ​​aerosol in combination with isoproterenol for one week⁹⁹。

despise
N-acetylcysteine ​​is FDA-approved to treat breathing problems, including atelectasis. The recommended dose is 3-5ml of 20% solution or 6-10ml of 10% solution using the nebulizer 3-4 times a day. In addition, the solution can also be dripped directly into the tracheotomy, once every 1-4 hours, the dose is 1-2ml 10% or 20% solution. It can be administered directly through a percutaneous endotracheal tube, adding 1-2ml of 20% solution or 2-4ml of 10% solution every 1-4 hours.

Bronchial Diagnostic Tests
N-acetylcysteine ​​is approved by the FDA through nebulization or intratracheal instillation, the dose is 1-2ml of 20% solution or 2-4ml of 10% solution, 2-3 times before surgery.

Chronic Obstructive Pulmonary Disease (COPD)
Nebulized N-acetylcysteine ​​20% every other day for at least four days¹⁰⁰。

Traquiotomizog
The FDA has approved the insertion of 1-2 mL of a solution containing 10% to 20% N-acetylcysteine ​​directly into the tracheostomy as a method of preventing scabbing of the trachea during tracheostomy.

dose