https://zerospike.org/wp-content/uploads/2022/04/The_Therapeutic_Use_of_N_Acetylcysteine_NAC_in_Medicine_by_Richard.pdf The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine
An AMAZING comprehensive book on NAC:
“I work in the field of autism where effective treatments are few and treatment targets are still ill defined. One principle when looking for a potential effective treatment, especially for children, is to assure safety of the treatment because the young body is vulnerable and because the treatment, if effective, could be required lifelong. My journey into treating children with autism led me to an interest in metabolic disorders that affect the nervous system…” (Richard Eugene Frye, MD, PhD Editor)
Part I Introduction
1 History of N-Acetylcysteine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Leonore A. Herzenberg Part II The Basic Science of N-Acetylcysteine (NAC)
2 Neurotransmitter Systems: Glutamate . . . . . . . . . . . . . . . . . . . . . . . . . . 19 M. Foster Olive, Gregory Powell, Erin McClure, and Cassandra D. Gipson
3 Neurotransmitter Systems: Dopamine . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Nihit Kumar
4 Oxidative Stress in Psychiatric Disorders . . . . . . . . . . . . . . . . . . . . . . . . 53 Lawrence Fung and Antonio Hardan
5 Mitochondrial Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 Shannon Rose and Sirish C. Bennuri
6 Apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Sirish C. Bennuri, Shannon Rose, and Richard Eugene Frye
7 Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Rabindra Tirouvanziam Part III The Clinical Use of N-Acetylcysteine (NAC)
8 Clinical Trials on N-Acetylcysteine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Richard Eugene Frye
9 N-Acetylcysteine in the Poisoned Patient . . . . . . . . . . . . . . . . . . . . . . . . 147 Angela L. Chiew and Geoffrey K. Isbister
10 The Use of N-Acetylcysteine as a Chelator for Metal Toxicity . . . . . . . .169 Daniel A. Rossignol x
11 Application of N-Acetylcysteine in Neurological Disorders . . . . . . . . . 181 Reza Bavrsad Shahripour, Ana Hossein Zadeh Maleki, and Andrei V. Alexandrov
12 Application of N-Acetylcysteine in Psychiatric Disorders . . . . . . . . . . . 203 John Slattery and Richard Eugene Frye
13 Clinical Treatment of Addictive Disorders with N-Acetylcysteine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219 Gregory Powell, Erin A. McClure, M. Foster Olive, and Cassandra D. Gipson
14 The Clinical Use of N-Acetylcysteine for the Treatment and Protection Against Renal Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 Richard Eugene Frye
15 Application of N-Acetylcysteine in Pulmonary Disorders. . . . . . . . . . . 255 Carol Conrad
16 The Clinical Use of N-Acetylcysteine in Cardiology . . . . . . . . . . . . . . . 277 John P. Marenco and Richard Eugene Frye
17 The Clinical Use of N-Acetylcysteine in Gastrointestinal Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289 Richard Eugene Frye
18 The Clinical Use of N-Acetylcysteine in Other Medical Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301 Richard Eugene Frye
19 The Physiological Effects of N-Acetylcysteine in Clinical Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 Richard Eugene Frye
20 Cysteine/Glutathione Deficiency: A Significant and Treatable Corollary of Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 Pietro Ghezzi, Kevin V. Lemley, James P. Andrus, Stephen C. De Rosa, Arne Holmgren, Dean Jones, Farook Jahoor, Richard Kopke, Ian Cotgreave, Teodoro Bottiglieri, Neil Kaplowitz, Hajime Nakamura, Frank Staal, Stephen W. Ela, Kondala R. Atkuri, Rabindra Tirouvanziam, Kartoosh Heydari, Bita Sahaf, Andrew Zolopa, Richard Eugene Frye, John J. Mantovani, Leonard A. Herzenberg, and Leonore A. Herzenberg
21 Pharmacology, Formulations, and Adverse Effects . . . . . . . . . . . . . . . . 387 Richard Eugene Frye, James P. Andrus, Kevin V. Lemley, Stephen C. De Rosa, Pietro Ghezzi, Arne Holmgren, Dean Jones, Farook Jahoor, Richard Kopke, Ian Cotgreave, Teodoro Bottiglieri, Neil Kaplowitz, Hajime Nakamura, Frank Staal, Stephen W. Ela, Kondala R. Atkuri, Rabindra Tirouvanziam, Kartoosh Heydari, Bita Sahaf, Andrew Zolopa, John J. Mantovani, Leonard A. Herzenberg, and Leonore A. Herzenberg
Some useful links to scientific articles about N-Acetyl Cysteine:
Prion disease / Amyloidosis
https://www.hindawi.com/journals/neuroscience/2019/7547382/ Effect of N-Acetyl Cysteine on Intracerebroventricular Colchicine Induced Cognitive Deficits, Beta Amyloid Pathology, and Glial Cells
In this study, enhancing the brain antioxidant capacity by NAC treatment was able to reverse the cognitive deficits. It is well-known that oxidative stress is responsible for changes in the neurons and behavioral deficits in AD (Alzheimer’s disease). In previous studies, NAC has reversed behavioral deficits observed in traumatic brain injury in several animal models due its antioxidant potential. NAC treatment in mice receiving ICV injections of BAP had improved learning and memory compared to vehicle-treated animals.
NAC is known to exert its neuroprotective potential through two well-known mechanisms, that is, restoration of glutathione pool and direct scavenging ability against reactive oxygen species. Activation of microglia is a hallmark of neuroinflammation, which enhances the production and release of reactive oxygen species. NAC, the antioxidant, is involved in detoxification of reactive oxygen species in the brain.
Conclusion:
It can be postulated that NAC might have reversed the effect of intraneuronal beta amyloid protein by acting on some downstream compensatory mechanism which needs to be explored.
NAC appears to work by preventing the formation of amyloid-producing proteins, which promote amyloid deposits linked to strokes
The finding is even more significant because it was conducted by researchers from Children’s Hospital of Philadelphia (CHOP), which is notoriously against most dietary supplements
The study by CHOP researchers suggests NAC may block the precipitation of amyloid plaque deposits, as well as help break up their formation (!!!!!), which could make a dramatic difference for those living with HCCAA. The study’s lead author, Dr. Hakon Hakonarson, director of CHOP’s Center for Applied Genomics, said in a news release:10
“Amyloids cannot precipitate without aggregating, so if we can prevent that aggregation with a drug [NAC] that is already available, then we could make an incredible difference in the lives of these patients.
Additionally, since we already have genetic testing available to identify these patients, we could conceivably give this treatment early in life and potentially prevent that first stroke from ever occurring.”
Also, regarding this:
https://www.sciencedirect.com/science/article/abs/pii/S0006291X1300466X?via%3Dihub Thymoquinone protects cultured rat primary neurons against amyloid β-induced neurotoxicity - PubMed (nih.gov)
Thymoquinone (TQ) is the main constituent of the oil extracted from Nigella sativa seeds, which is known to be the active constituent responsible for many of the seed antioxidant and anti-inflammatory effects.
The present study was designed to investigate whether TQ can protect against Alzheimer's amyloid-β peptide (Aβ) induced neurotoxicity in rat primary neurons.
Oxidative stress
https://www.tandfonline.com/doi/full/10.3109/15412555.2014.898040 Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine
https://www.tandfonline.com/doi/full/10.1080/10715762.2018.1468564 N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why
Radioprotective effects of N-acetylcysteine
https://www.sciencedirect.com/science/article/abs/pii/S096980432200238X Radioprotective effects of N-acetylcysteine on rats’ brainstem following megavoltage X-irradiations
https://www.sciencedirect.com/science/article/abs/pii/S0041134509014444 Effects of Radiation on Protein Oxidation and Lipid Peroxidation in the Brain Tissue
https://www.sciencedirect.com/science/article/abs/pii/S0006295207006545 Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats
C-19
https://www.tandfonline.com/doi/full/10.1080/23744235.2021.1945675 N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study
"Oral N-acetyl-cysteine administration (1200 mg/d) in patients with #COVID19 pneumonia reduces the risk for mechanical ventilation and mortality."
https://www.biorxiv.org/content/10.1101/2023.01.09.523209v2 Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern
Antioxidant drugs, such as N-acetyl cysteine (NAC), were effective against all variants both in human lung cells, and in a humanised mouse model. Our study supports the use of available antioxidant drugs, such as NAC, as a general and effective anti-COVID-19 approach.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172740/ Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases - PMC (nih.gov)
Oral and IV glutathione as well as glutathione precursors (N-acetyl-cysteine, alpha-lipoic acid) may, therefore, represent a novel treatment approach for blocking NFKappaB and addressing “cytokine storm syndrome” and respiratory distress in patients suffering with COVID 19 pneumonia. Zinc, vitamin C and NRF 2 activators may also be helpful in decreasing the inflammatory response and lowering cytokine production.
https://www.mdpi.com/1999-4915/13/3/425 The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
The combination of Bromelain and Acetylcysteine, BromAc, synergistically inhibited the infectivity of two SARS-CoV-2 strains cultured on Vero cells.
More recently, Acetylcysteine has been used in the development of therapies for respiratory infections such as influenza and COVID-19, where the integrity of the spike protein is vital for infection. A hypothesized mechanism of action could be the unfolding of the spike glycoprotein and the reduction of its disulfide bonds.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263077/ Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients
The hypothesis that glutathione deficiency is the most plausible explanation for serious manifestation & death in COVID-19 patients was proposed on the basis of an exhaustive literature analysis and observations. The hypothesis unravels the mysteries of epidemiological data on the risk factors determining serious manifestations of COVID-19 infection & the high risk of death & opens real opportunities for effective treatment & prevention of the disease.
Therefore, restoration of glutathione levels in COVID-19 patients would be a promising approach for the management of the novel coronavirus SARS-CoV-2. Notably, long-term oral administration of N-acetylcysteine has already been tested as an effective preventive measure against respiratory viral infections.
N-Acetylcysteine is widely available, safe, and cheap and could be used in an “off-label” manner.
Moreover, parenteral injection of NAC or reduced glutathione (GSH is more bioavailable than NAC) could be an efficient therapy for COVID-19 patients with serious illness. Horowitz et al.18 just published a paper confirming this hypothesis: the authors reported the efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia. Nonetheless, the proposed hypothesis has to be confirmed in larger epidemiological and experimental studies, and also, clinical trials are needed to objectively assess the efficacy of N-acetylcysteine and reduced glutathione for the treatment and prevention of COVID-19 infection.
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c753ec4c89190f3bad43ca/original/n-acetyl-cysteine-a-tool-to-perturb-sars-co-v-2-spike-protein-conformation.pdf N-acetyl cysteine: A tool to perturb SARS-CoV-2 spike protein conformation
Proteomics data showed that N-acetyl cysteine (NAC), an antioxidant and mucolytic agent been widely in use in clinical medicine, forms covalent conjugates with solvent accessible cysteine residues of spike protein that were disulfide bonded in the native state. In silico analysis indicated that this covalent conjugation perturbed the stereo specific orientations of the interacting key residues of spike protein that resulted in threefold weakening in the binding affinity of spike protein with ACE2 receptor. Antiviral assay using VeroE6 cells showed that NAC caused 54.3% inhibition in SARS-CoV-2 replication. Interestingly, almost all SARS-Cov-2 variants conserved cystine residues in the spike protein. Our observed results open avenues for exploring in vivo pharmaco-preventive and therapeutic potential of NAC for Coronavirus Disease 2019 (COVID-19).
And more…
https://link.springer.com/chapter/10.1007/978-981-10-5311-5_10 The Use of N-Acetylcysteine as a Chelator for Metal Toxicity
In a systematic review to identify studies, NAC was shown to chelate toxic metals in 33 animal studies. Metals that were removed in these studies included mercury, lead, cadmium, aluminum, arsenic, and gold.
https://pubmed.ncbi.nlm.nih.gov/30407312/ N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: A randomized controlled trial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036554/ Getting a Knack for NAC
https://nutritionofpower.com/nutrition/n-acetyl-cysteine-for-mucus-in-your-body/ N-Acetyl Cysteine for Mucus in your body - Proper Nutrition | NutritionOfPower.com
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320789/ Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases
https://www.webmd.com/vitamins-and-supplements/n-acetyl-cysteine-uses-and-risks N-Acetyl Cysteine (NAC): Uses and Risks
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241507/ A Review on Various Uses of N-Acetyl Cysteine
https://www.ncbi.nlm.nih.gov/books/NBK537183/ N-acetylcysteine (NAC)
N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990475/ Oxidative stress, inflammation, and cancer: How are they linked?
I literally just swallowed 1200 mg 30 seconds before this hit my inbox! 😁😁😁😁
Okay this is too weird, I just received my NAC from Amazon and was reading up about the benefits when you posted this!!! Thank you so much!!! You somehow read my mind!!