Acetylcysteine (NAC) has been used as a drug (for more than 1960 years) since the 50s and is included in the World Health Organization’s Standard List of Essential Medicines.
In addition to its use as a phlegm-reducing agent and clinical treatment of acetaminophen poisoning, it has also been used in several other diseases such as chronic bronchitis, influenza, heart disease, chronic obstructive pulmonary disease, cystic fibrosis and contrast. nephropathy.
What are the benefits of acetylcysteine in empirical medicine? Are there any side effects of acetylcysteine? See text analysis for details
What is acetylcysteine (NAC)?
Acetylcysteine, also known as N-acetylcysteine (NAC), is an acetylated derivative of cysteine (a sulfur-containing amino acid), a plant antioxidant naturally found in onions, and a precursor to the body’s main endogenous antioxidant glutathione
Unlike glutathione itself, NAC has better oral and topical bioavailability.
What are the proven benefits of acetylcysteine?
1. Treatment of rodenticide poisoning
Rodenticides, often referred to as “rat poison,” are chemical agents designed to eliminate small rodents because they are vectors of disease transmission, destroy crops/grains, and multiply rapidly.
The composition of different rodenticides differs (the most common drug is 4-hydroxycoumarin, followed by bromomethylnaphthalene, warfarin and metal phosphide) and the toxicity varies.
However, many of them are hepatotoxic and can lead to acute liver failure, with high mortality in patients admitted to hospital for rodenticide consumption in the absence of a clear antidote.
A systematic literature review and meta-analysis (including two controlled trials, one prospective study, and three retrospective studies) noted that acetylcysteine (NAC) treatment had better survival and lower mortality compared with non-NAC treatment groups. Note 1
*Conclusion: Acetylcysteine (NAC) may be a positive help for rodenticide poisoning, but it is limited by the small sample size and needs further verification
2. Beneficial for chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease in the world and is associated with an abnormal inflammatory response to toxic particles or gases such as cigarette smoke. Characterised by inflammation of the small airways, fibrosis, and destruction of the lung parenchyma (emphysema), eventually leading to irreversible airflow obstruction.
Standard treatment for stable COPD includes bronchodilators (e.g., beta-2 agonists, anticholinergics, and theophylline), glucocorticoids, expectorants, and long-term oxygen therapy.
A systematic literature review and meta-analysis (including 15 controlled trials, a total of 905 patients with COPD) pointed out that acetylcysteine (NAC) can improve the rate of symptom improvement (such as cough, sputum production, dyspnea), improve lung function indicators (FEV1 and FEV1/FVC), and enhance the body’s antioxidant capacity in patients with acute exacerbation of COPD. Note 1
*Conclusion: For acute exacerbation of chronic obstructive pulmonary disease, acetylcysteine intervention may bring positive help, but limited by the small sample size, more studies are needed for further verification
3. Adjunct COVID-19 treatment
The coronavirus disease 2 (COVID-2019) pandemic, caused by the novel coronavirus SARS-CoV-19, has had devastating medical, social and economic impacts across the globe.
Atypical symptoms such as rash, thrombosis, and loss of smell, as well as multisystem failure due to acute respiratory distress syndrome and cytokine release syndrome.
A bicenter retrospective cohort study (82 patients with moderate to severe COVID-19 pneumonia receiving standard care) significantly reduced progression of severe respiratory failure, 14- and 28-day mortality, improved oxygenation index (PaO2/FiO2) ratios, and reduced leukocyte, CRP, D-Dimer, and LDH levels compared with controls. Note 1
*Conclusion: For patients with moderate and severe COVID-19 pneumonia, acetylcysteine adjuvant therapy may bring positive help, but limited by the small sample size, more precisely designed interventional studies are still needed for further verification
4. Beneficial for male idiopathic infertility
Infertility is a disease with psychological, economic, and medical implications that can cause trauma, stress, especially in a society that places a high emphasis on procreation. It is estimated that nearly 72.4 million couples worldwide have fertility problems.
Male-induced infertility, also known as idiopathic infertile, is a multifactorial disease influenced by genetic, environmental, and hormonal factors, thought to be caused by changes in sperm concentration, motility or morphology, which accounts for 40% to 50% of infertility cases, and affects about 7% of men.
A systematic literature review and meta-analysis (3 randomized controlled trials, 431 participants in male idiopathic infertility) showed that oral acetylcysteine helped improve sperm concentration, ejaculate volume, sperm motility, and normal morphology compared with placebo morphology). Note 1
However, in terms of serum hormones, there were no significant differences in serum testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin levels in the acetylcysteine group compared to the placebo group.
*Conclusion: For male idiopathic infertility, oral acetylcysteine may bring positive help, but limited by the small sample size, more studies are needed to further validate
5. Beneficial for acute respiratory distress syndrome
Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung injury that is an acute response to multiple precipitating factors and etiologies, resulting in bilateral lung opacity and hypoxaemia on imaging. It presents with increased pulmonary vascular permeability, pulmonary hypoxia, pulmonary stiffness, and the need for mechanical ventilation support.
It was first defined in 1994 by the US-European Consensus Conference (AECC) as acute hypoxaemia (oxygenation index [PaO2/FIO2]≤200 mm Hg) with bilateral lamination infiltrates, pulmonary artery wedge pressure ≤ 18 mmHg, or no left atrial hypertension.
A meta-analysis (5 randomized controlled trials of 183 patients with acute acute respiratory distress syndrome) noted that acetylcysteine treatment (intravenously) did not significantly reduce short-term mortality, 30-day mortality, or the PaO2/FiO2 ratio compared with controls, but did help reduce length of stay in intensive care units. Note 2
*Conclusion: Although acetylcysteine therapy can help shorten the length of stay in intensive care units for acute respiratory distress syndrome, its clinical benefits are limited and need to be further verified by more studies
6. Beneficial for obsessive-compulsive disorder
Obsessive compulsive disorder is a debilitating neuropsychiatric disorder with a lifetime prevalence of 2 to 3 percent, making it one of the ten leading causes of disability in the world.
People with OCD experience repetitive, intrusive thoughts (obsessive thinking) or repetitive, stereotyped behaviors (obsessive-compulsive behaviors) that last at least an hour a day and significantly interfere with an individual’s normal level of functioning, impairing the individual’s attention and concentration.
A systematic review (5 randomized placebo-controlled trials associated with OCD, 3 case reports and 2 case series) noted that acetylcysteine (N-acetylcysteine) add-on therapy had a positive effect on disease improvement. Note 3
*Conclusion: Acetylcysteine add-on therapy may be of positive benefit in improving OCD, but due to the low quality and heterogeneity of the available evidence, more studies are needed to further validate
7. Beneficial schizophrenia
Schizophrenia, also known as schizophrenia, is a heterogeneous disorder that accounts for about 1% of the population, characterized by disorganized thinking, occasional non-logical thinking, lack of reasoning, and distortion of reality, and the disorder usually appears in late adolescence or early adulthood.
Symptoms can be divided into: positive symptoms (delusions, hallucinations, speech disturbances, and bizarre behavior), negative symptoms (decreased communication, volition, emotional flattening, and anhedonia), and cognitive symptoms (deficits in executive function, declarative memory, working memory, and language function).
A meta-analysis (7 randomized controlled trials, 440 people with schizophrenia) suggested that acetylcysteine as an adjunct to antipsychotics improved negative and total PANS (Positive And Negative Syndrome Scale) scores in schizophrenia after 24 weeks (or more) of treatment, and improved cognitive performance in working memory. Note 4
*Conclusion: N-acetylcysteine may be an adjunct to standard care for schizophrenia, possibly for symptom improvement
8. Beneficial non-acetaminophen-induced acute liver failure
Acute liver failure is defined as a change in coagulopathy in the absence of evidence of liver cells lasting days or weeks and without evidence of cirrhosis. Causes include the effects of a variety of factors including viruses, toxins, and drugs.
Although it has high morbidity and mortality, overall survival has improved through advances in enhanced care management and emergency liver transplantation.
A systematic literature review and meta-analysis (7 randomized controlled trials and retrospective studies of 883 patients with non-paracetamol-related acute liver failure) noted that acetylcysteine significantly improved overall survival, post-transplant survival, and transplant-free survival, while reducing total length of hospital stay. Note 5
*Conclusion: For acute liver failure associated with non-paracetamol, acetylcysteine may provide positive help, but limited by the small sample size, more studies are needed to further validate
Are there any side effects of acetylcysteine?
Oral acetylcysteine is probably safe for most adults.
However, side effects or adverse effects that have been reported include nausea, vomiting, diarrhea, bronchospasm, unpleasant odor, fever, coughing up blood, increased bronchial secretions, runny nose, nasal congestion, swelling and ulceration in the mouth, wheezing, shortness of breath, or constipation.
Rarer serious side effects are: difficulty breathing or swallowing, rash, fever, headache, drowsiness, low blood pressure, chest tightness, bronchial strictures, hives, reddening of the skin (especially around the ears), swelling inside the face or nose, unusual fatigue, bleeding, liver problems etc.
*(If any of the above side effects occur, please stop the drug immediately and seek medical attention urgently)
Safety precautions (6 contraindications for use)
1. Unless prescribed by a doctor, pregnant women, lactating women, and children should avoid use (due to unknown safety)
2. Patients with a history of related drug allergies should not use it
3. Do not use for asthma patients, as it may cause bronchospasm
4. Do not use for patients with abnormal coagulation function or taking anticoagulants, which may increase the risk of bruising and bleeding, because acetylcysteine has anticoagulant effects
5. Stop taking at least 2 weeks before the scheduled surgery, because acetylcysteine has anticoagulant effect
6. NAC may inhibit diamine oxidase activity, diamine oxidase is the main enzyme responsible for intestinal biogenic amine catabolism, in the case of reduced diamine oxidase activity, ingesting foods containing large amounts of biogenic amines will lead to histamine accumulation, resulting in symptoms of histamine intolerance, including: food allergies, skin reactions, flushing, asthma, gastrointestinal problems and other symptoms