NAC as a chelator for heavy metals and nanoparticles
Hindawi Journal of Nutrition and Metabolism
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https://downloads.hindawi.com/journals/jnme/2021/9949453.pdf N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)
Abstract
Objective. To review the clinical usefulness of N-acetylcysteine (NAC) as treatment or adjunctive therapy in a number of medical conditions. Use in Tylenol overdose, cystic fibrosis, and chronic obstructive lung disease has been well documented, but there is emerging evidence many other conditions would benefit from this safe, simple, and inexpensive intervention. Quality of Evidence. PubMed, several books, and conference proceedings were searched for articles on NAC and health conditions listed above reviewing supportive evidence. This study uses a traditional integrated review format, and clinically relevant information is assessed using the American Family Physician Evidence-Based Medicine Toolkit. A table summarizing the potential mechanisms of action for N-acetylcysteine in these conditions is presented. Main Message. N-acetylcysteine may be useful as an adjuvant in treating various medical conditions, especially chronic diseases. These conditions include polycystic ovary disease, male infertility, sleep apnea, acquired immune deficiency syndrome, influenza, parkinsonism, multiple sclerosis, peripheral neuropathy, stroke outcomes, diabetic neuropathy, Crohn’s disease, ulcerative colitis, schizophrenia, bipolar illness, and obsessive compulsive disorder;
it can also be useful as a chelator for heavy metals and nanoparticles.
There are also a number of other conditions that may show benefit; however, the evidence is not as robust.
Conclusion. The use of N-acetylcysteine should be considered in a number of conditions as our population ages and levels of glutathione drop. Supplementation may contribute to reducing morbidity and mortality in some chronic conditions as outlined in the article.
8.6. Use as Chelator for Metal Toxicity (LOE = A, B)
N-acetylcysteine has been shown to chelate toxic metals in animal studies as well as in human studies with little or no effect on essential metals. Mercury, lead, gold, and arsenic have been removed in humans although the studies are limited. The evidence for removal of lead is more robust because of a double-blind placebo-controlled trial [142]. Metal on metal hip prosthesis often results in increased chromium in the blood and NAC has been helpful in reducing levels safely [143]. Adverse effects of arsenic-induced hepatotoxicity in rats were countered by NAC [144]. In a case report of acute ingestion of a potentially lethal overdose of sodium arsenate ant poison, intravenous NAC reversed the clinical outcome of expected death [145].
8.7. Nanoparticle-Induced Reduction of Deoxyribonucleic Acid Methylation (LOE = B)
There has been increasing concern with the toxicity of nanoparticles causing cellular damage by increasing reactive oxygen species as an epigenetic mechanism decreasing deoxyribonucleic acid (DNA) methylation. Preclinical studies show that NAC reverses and prevents the oxidative damage caused by engineered nanoparticles [146].
1. Introduction
N-acetylcysteine (NAC) is a sulfhydryl-containing compound, with mucolytic properties, originally patented in 1960, and its use in medicine was first reported in 1967 [1]. Its chemical structure and nomenclature are depicted in Figure 1. Clinically it has been used in cystic fibrosis since 1969 [2]. Since then, NAC use has been expanded to acetaminophen overdose and chronic obstructive lung disease and its role is ever expanding clinically.
The properties of NAC include enhancing glutathione S-transferase activity, repleting glutathione, scavenging free radicals, and stabilizing protein structures by crosslinking cysteine disulfide molecules along with its antioxidant, anti-inflammatory, and mucolytic properties. A more complete list of mechanisms of action is given in Table 1.
An overview of the use of NAC in clinically relevant disorders is depicted in Figure 2.
2.1. N-Acetylcysteine in Lung Disorders
2.2. Cystic Fibrosis (LOE = A)
2.3. Chronic Obstructive Lung Disease and Chronic Bronchitis (LOE = A,C)
2.4. Asthma and Allergy (LOE = B)
2.5. Bronchiectasis (LOE = A)
2.6. Bronchiolitis (LOE = A)
2.7. Idiopathic Pulmonary Fibrosis (LOE = A)
3. Liver and Bowel Diseases
3.1. Acetaminophen Overdose (LOE = A)
3.2. Non-Acetaminophen-Induced Acute Liver Failure (LOE = A)
3.3. Hepatocarcinoma (LOE = B)
3.4. Crohn’s Disease (LOE = A)
3.5. Ulcerative Colitis (LOE = A)
3.6. Systemic Lupus Erythematosus (LOE = A)
4. Metabolic Syndrome including Nonalcoholic Fatty Liver Disease, Diabetes, and Polycystic Ovary
4.1. Nonalcoholic Fatty Liver Disease (LOE = B)
4.2. Diabetes
4.3. Diabetic Neuropathy, Retinopathy, and Nephropathy (LOE = A)
4.4. Polycystic Ovary Disease, Chorioamnionitis, and Recurrent Pregnancy Loss (LOE = A, B)
4.5. Male Fertility (LOE = A)
4.6. Hypertension (LOE = B)
4.6.1. Pulmonary Hypertension
4.7. Chemotherapy
4.8. Breast Cancer, Prostate Cancer, Lung Cancer, Glioblastoma, and Chronic Lymphocytic Leukemia
4.9. Sleep Apnea (LOE = B)
5. Infectious Disease
5.1. Overview
5.2. Acquired Immune Deficiency Syndrome (LOE = A)
5.3. Tuberculosis (LOE = A)
5.4. Influenza, Respiratory Syncytial Virus, and SARS-CoV-2 (LOE = A, B)
5.5. H. pylori (LOE = B)
6. Neurodegenerative Disorders
6.1. Overview
6.2. Parkinson’s Disease (LOE = B)
6.3. Dementia (LOE = B)
6.4. Neuropathic Pain (LOE = A, B)
6.5. Stroke (LOE = A)
6.6. Multiple Sclerosis (LOE = B)
7. Eye Conditions
7.1. Age-Related Macular Degeneration
7.2. Glaucoma (LOE = B)
7.3. Sjogren’s Syndrome (Dry Eyes) (LOE = A)
8. Psychiatric Conditions
There may be therapeutic benefit with NAC on schizophrenia, bipolar illness, and obsessive-compulsive disorder as well as other impulsive or compulsive behaviors such as seen in gambling, substance misuse, pathological nail biting, and trichotillomania.
8.1. Schizophrenia (LOE = A)
8.2. Obsessive Compulsive Disorder (LOE = A)
8.3. Bipolar Illness (LOE = A)
8.4. Trichotillomania, Pathologic Nail Biting, and Skin Picking (LOE = A, B)
8.5. Addiction Behavior (LOE = B)
8.6. Use as Chelator for Metal Toxicity (LOE = A, B)
8.7. Nanoparticle-Induced Reduction of Deoxyribonucleic Acid Methylation (LOE = B)
8.8. Side Effects
One of the properties of NAC is that it has an unpleasant smell and taste but is generally well tolerated in oral doses below 1200 mg/day. It may also cause some nausea vomiting and diarrhea. Vomiting after intravenous use has been reported in about 11% at doses of 150 mg/kg and one anaphylactic reaction has been reported [147]. N-acetylcysteine has anticoagulant and platelet inhibiting properties and the use in patients with bleeding disorders or blood thinners may be relatively counter indicated [148]. The use of NAC with patients on nitroglycerine should be cautioned, since it may cause hypotension [149]. Other rarer side effects may include stomatitis, drowsiness, rhinorrhea, and hemoptysis [127].
8.9. Dosing of NAC
N-acetylcysteine dosing varies significantly with various clinical studies and doses of 1200 mg daily or more are usually required to be clinically relevant. Studies in metabolic diseases show that 5–600 mg orally per day may be sufficient to ameliorate fatty liver disease. For Crohn’s disease and ulcerative colitis, doses of 800 mg per day seemed sufficient. Doses as high as 1250 mg orally three times a day have been used safely in MS and showed benefit in reducing fatigue. Doses of 8000 mg/day orally did not cause clinically significant reactions in HIV patients [150]. Clearly dosing is still debated and much needs to be learned in this area.
9. Discussion and Conclusion
N-acetylcysteine appears to be well tolerated with minimal side effects when used as a supplement or in treatment of various disorders. As stated above, the dosage required for this medication is not always clear, and there is much work needed to provide this information. A number of mechanisms of its actions are listed in Table 1. These actions provide reasoning for some of the results that are seen in so many different conditions. Many other conditions not listed in this document are emerging as understanding about NAC grows. As seen with other antioxidants in the past, there is some caution as expressed above with lung cancer models, where there may be an increase in proliferation as a result of p53 inhibition or likewise a possible increase in pulmonary hypertension.
As seen above, benefit has been shown with pulmonary, psychiatric, neurologic, metabolic, and infectious diseases, fertility issues, and some cancers. For most of these conditions, NAC can be used as an adjuvant, which may improve quality of life, morbidity, and mortality.
The use in metal toxicity and recent evidence in protecting DNA are also important. Much needs to be learned and more in vivo studies need to be performed to give us more confidence in using this simple compound.
Glycine & NAC: A Winning Combo
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002905/ Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial
Abstract
This study found that compared to healthy young adults, older humans have severely elevated oxidative stress, glutathione deficiency, impaired mitochondrial function, increased inflammation, insulin resistance and endothelial dysfunction, and lower muscle strength and mental cognition. We tested and found that supplementing GlyNAC (combination of glycine and N‐acetylcysteine) improved all these defects, and that stopping GlyNAC resulted in a loss of benefits. The results of this trial suggests that GlyNAC supplementation could be a simple, safe and effective nutritional strategy to boost cellular defenses to protect against oxidative stress, correct mitochondrial defects to improve energy availability, increase muscle strength and cognition, and thereby promote healthy aging in humans.
https://www.youtube.com/watch?v=XR7iVMo4nWc NAC, Glutathione & Aging: New Study is Impressive
https://todayspractitioner.com/aging/glycine-nac-a-winning-combo-for-longevity/#.ZGP8xxHMKUk