NAC, N-Acetyl Cysteine, Health Benefits, Respiratory Health, Immunity, Inflammation
Most of the time with teas, herbs, wild foraged plants, and mushrooms, we’re focused on many different types of naturally occurring compounds found within them that affect our health and longevity. Many of those compounds, whether they be beta-glucans from mushrooms, or plant flavanols and antioxidants like quercetin, are not considered essential nutrients despite the research-backed impact they have on our bodies in both times of health and sickness.
Before we get into the nitty gritty details, here is the quick and dirty list of health benefits of NAC.
You can also find our NAC capsules here.
Health Benefits and Possible Benefits of N-Acetyl Cysteine:
-regulates chronic and acute inflammation
-helps the body to detox harmful and carcinogenic compounds
-replenishes the incredibly important, naturally occurring anti-oxidant glutathione
-helps to build DNA, proteins, and important cellular components
-supports the liver and is used to treat and prevent fatty liver disease
-plays a major role in supporting respiratory ailments like asthma, pneumonia, COPD, cystic and pulmonary fibrosis, bronchitus etc
-helps to detoxify the kidneys
-is given to patients who clinically overdose on acetaminophen to prevent serious organ damage
-helps to regulate levels of glutamate in the brain, and because of this, is being researched for helping to treat behavioral disorders like ocd, addiction, withdrawal, and even schizophrenic disorders (which have classically dysregulated levels of glutamate).
-can improve muscle performance
-is being researched for neurodegenerative diseases like parkinsons disease, ulcerative colitis, and many other conditions
I know that list sounds almost too good to be true, but this isn’t coconut oil or turmeric or whatever is popular this year, this is a super important compound that’s already in our bodies and needs to be maintained, and, there is SO MUCH research about this compound compared to other things like chaga mushroom that really aren’t super established in the actual treatment of actual conditions. (no hate on chaga mushroom or any other mushrooms, I just can’t stand the lies and hype that some people attach to it).
What is N-Acetyl Cysteine?
NAC, or n-acetyl l-cysteine is a very different story. It’s an amino acid that is considered “semi-essential” because it’s something our bodies have the ability to make out of our other amino acids in their endless cycles of breaking down and being rebuilt to keep all the systems of our bodies running.
Many people are aware of vitamins and minerals, and even the importance of getting blood labs done to measure the amounts of these things in our bodies, but very few people are aware that there are blood tests for various amino acids and other biomarkers that even the average doctor may not be aware of. Check out the Organic Acids Test here. I am not affiliated with them in any way, but this kind of testing is 100% going to make its way into “mainstream” healthcare.
What does N-Acetyl Cysteine do?
NAC replenishes our own, endogenous (naturally produced in our body) “master” antioxidant that regulates inflammation all throughout the body. More people these days have heard of Glutathione and its importance would be impossible to overstate. We’ll get into all the things it actually does in a bit, but first it’s important to understand the precarious situation that glutathione is in.
The trouble is that it’s easily depleted. Even by things like aspirin, too much monster energy drink, environmental toxins, age, chronic inflammation, poor diet, lack of exercise, we have created a toxic world to the point where our buildings are toxic, the walls, the floor, even the furniture, the air, cars themselves in many ways, toxic jobs + chronic stress and fatigue, the food and drink especially, not to mention that approximately 66% of Americans are on prescription drugs (THAT WE KNOW OF). All of these things combined are overwhelming our bodies’ natural ability to defend itself.
So what happens when glutathione gets low? Like many vitamins and minerals, glutathione has a dynamic / competitive relationship to other amino acids. When glutathione is low, homocysteine and pyroglutamic acid will surely be high (both inflammatory biomarkers). Another toxic compound called 5-oxoproline can also build up in excessive amounts, and all of this can even lead to metabolic-acidosis in some unlucky people.
A “normal” person having low levels of glutathione is very different from the few unlucky people have a genetic deficiency. Glutathione synthetase deficiency is a terrible sounding birthright that results in: “Anemia, the buildup of too much acid in the body (metabolic acidosis), frequent infections, and symptoms caused by problems in the brain including seizures, intellectual disability, and loss of coordination (ataxia).”
Is There Such a Thing as Too Much Glutathione?
Yes, there is. Too much glutathione has been linked to low levels of zinc, bloating, rashes, and cramping. In general, the first and foremost side effect to consider is the fact that it speeds up the flushing of compounds out of the body through the liver. This is akin to too much coffee or alcohol (both potent diuretics, meaning to speed up the flow of urine). Zinc is water soluble and also easily depleted. Dandelion root and milk thistle can result in similar depletions of water soluble vitamins and minerals as well lower the amount of absorption of any medication you might be taking. This is an especially important side effect to be mindful of. In fact, even CBD can result in this because it upregulates something called NRF2 which also regulates many of the same things as glutathione. If you are taking something EXTREMELY important like cancer medication, then you should not be taking CBD, milk thistle, dandelion root, NAC, or anything else which can prevent you from absorbing a medication. At the very least these things need to be discussed with a doctor.
N-Acetyl Cysteine Scientific Research:
A Review on Various Uses of N-Acetyl Cysteine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241507/
N-acetyl cysteine (NAC), as a nutritional supplement, is a greatly applied antioxidant in vivo and in vitro. NAC is a precursor of L-cysteine that results in glutathione elevation biosynthesis. It acts directly as a scavenger of free radicals, especially oxygen radicals. NAC is a powerful antioxidant. It is also recommended as a potential treatment option for different disorders resulted from generation of free oxygen radicals. Additionally, it is a protected and endured mucolytic drug that mellows tenacious mucous discharges. It has been used for treatment of various diseases in a direct action or in a combination with some other medications. This paper presents a review on various applications of NAC in treatment of several diseases.
Glutathione as a Redox Biomarker in Mitochondrial Disease—Implications for Therapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447941/
Technical advances in the ability to measure mitochondrial dysfunction are providing new insights into mitochondrial disease pathogenesis, along with new tools to objectively evaluate the clinical status of mitochondrial disease patients. Glutathione (l-ϒ-glutamyl-l-cysteinylglycine) is the most abundant intracellular thiol, and the intracellular redox state, as reflected by levels of oxidized (GSSG) and reduced (GSH) glutathione, as well as the GSH/GSSG ratio, is considered to be an important indication of cellular health. The ability to quantify mitochondrial dysfunction in an affected patient will not only help with routine care, but also improve rational clinical trial design aimed at developing new therapies. Indeed, because multiple disorders have been associated with either primary or secondary deficiency of the mitochondrial electron transport chain and redox imbalance, developing mitochondrial therapies that have the potential to improve the intracellular glutathione status has been a focus of several clinical trials over the past few years. This review will also discuss potential therapies to increase intracellular glutathione with a focus on EPI-743 (α-tocotrienol quinone), a compound that appears to have the ability to modulate the activity of oxidoreductases, in particular NAD(P)H:quinone oxidoreductase 1.
Therapeutic role of N-acetyl cysteine (NAC) for the treatment and/or management of SARS-CoV-2-induced lung damage in hamster model
https://www.sciencedirect.com/science/article/pii/S0014299922006537
Oxidative stress by reactive oxygen species (ROS) has been hypothesized to be the major mediator of SARS-CoV-2-induced pathogenesis. During infection, the redox homeostasis of cells is altered as a consequence of virus-induced cellular stress and inflammation. In such scenario, high levels of ROS bring about the production of pro-inflammatory molecules like IL-6, IL-1β, etc. that are believed to be the mediators of severe COVID-19 pathology. Based on the known antioxidant, anti-inflammatory, mucolytic and antiviral properties of NAC, it has been hypothesized that NAC will have beneficial effects in COVID-19 patients. In the current study efforts have been made to evaluate the protective effect of NAC in combination with remdesivir against SARS-CoV-2 induced lung damage in the hamster model. The SARS-CoV-2 infected animals were administered with high (500 mg/kg/day) and low (150 mg/kg/day) doses of NAC intraperitoneally with and without remdesivir. Lung viral load, pathology score and expression of inflammatory molecules were checked by using standard techniques. The findings of this study show that high doses of NAC alone can significantly suppress the SARS-CoV-2 mediated severe lung damage (2 fold), but on the contrary, it fails to restrict viral load. Moreover, high doses of NAC with and without remdesivir significantly suppressed the expression of pro-inflammatory genes including IL-6 (4.16 fold), IL-1β (1.96 fold), and TNF-α (5.55 fold) in lung tissues. Together, results of this study may guide future preclinical and clinical attempts to evaluate the efficacy of different doses and routes of NAC administration with or without other drugs against SARS-CoV-2 infection.
N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions
https://www.sciencedirect.com/science/article/pii/S1876034122003021
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19) and can be associated with serious complications, including acute respiratory distress syndrome. This condition is accompanied by a massive release of cytokines, also denominated cytokine storm, development of systemic oxidative stress and a prothrombotic state. In this context, it has been proposed a role for acetylcysteine (NAC) in the management of patients with COVID-19. NAC is a molecule classically known for its mucolytic effect, but it also has direct and indirect antioxidant activity as a precursor of reduced glutathione. Other effects of NAC have also been described, such as modulating the immune and inflammatory response, counteracting the thrombotic state, and having an antiviral effect. The pharmacological activities of NAC and its effects on the mechanisms of disease progression make it a potential therapeutic agent for COVID-19. NAC is safe, tolerable, affordable, and easily available. Moreover, the antioxidant effects of the molecule may even prevent infection and play an important role as a complement to vaccination. Although the clinical efficacy and dosing regimens of NAC have been evaluated in the clinical setting with small series of patients, the results are promising. In this article, we review the pathogenesis of SARS-CoV-2 infection and the current knowledge of the mechanisms of action of NAC across disease stages. We also propose NAC posology strategies to manage COVID-19 patients in different clinical scenarios.
Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine
https://www.sciencedirect.com/science/article/pii/S1521661620306513
Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting of controlled clinical trials.
N Acetylcysteine
https://www.ncbi.nlm.nih.gov/books/NBK537183/
N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity. NAC has FDA approval for the treatment of potentially hepatotoxic doses of acetaminophen (APAP), and it is almost 100% effective if given within 8 hours post-ingestion. It is also approved for use in conditions with abnormal, viscid or inspissated mucous secretions such as pneumonia, bronchitis, tracheobronchitis, cystic fibrosis, tracheostomy patients, postoperative pulmonary complications, posttraumatic chest conditions and before diagnostic bronchoscopy to help with mucous plugging. Off-label indications include acute hepatic failure, prevention of contrast-induced nephropathy and topical treatment of keratoconjunctivitis sicca. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, monitoring, and toxicity of NAC, so providers can direct patient therapy to optimal outcomes where NAC is indicated.
N-acetylcysteine enhances T cell functions and T cell growth in culture
https://pubmed.ncbi.nlm.nih.gov/8443125/
N-Acetylcysteine (NAC) is highly nontoxic for peripheral blood T cells and immunostimulatory enhancing T cell functions such as mitogenesis, interleukin-2 (IL-2) production, and growth in culture. NAC has been proposed for the treatment of AIDS based on its inhibition of human immunodeficiency virus (HIV) replication in cultured cells. Therefore its effect on normal T cells from 10 young donors and one elderly donor has been investigated as a prelude to clinical consideration. T cell function was evaluated in the presence and absence of accessory cells. With concanavalin A and anti-CD3 activation, NAC enhanced mitogenesis by approximately 2- to 2.5-fold at 5-10 mM. Mitogenesis of purified T cells with anti-CD2 was not affected by NAC; in the presence of accessory cells, NAC enhanced mitogenesis by approximately 2-fold at 1-10 mM. Importantly, NAC levels above 10 mM completely inhibited activation of peripheral blood mononuclear cells by anti-CD2. IL-2 secreted by T cells was also enhanced by NAC, approximately 1.5-fold, but IL-2 secreted by cells from old donors was enhanced by 3-fold. In cultures of peripheral blood T cells, NAC (10 mM) stimulated growth by at least 4- to 6-fold after two passages. These results show that NAC, nontoxic even at 20 mM, is an effective enhancer of T cell function and a remarkable enhancer of growth. Results from other laboratories show that NAC, which increases glutathione levels, suppresses HIV replication presumably via suppression of the activation of transcriptional factor NF-kappa B.(ABSTRACT TRUNCATED AT 250 WORDS)
N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling
https://pubmed.ncbi.nlm.nih.gov/36604630/
Compared with the untreated control, treatment with 500 µM NAC greatly promoted the proliferation of TSPCs and significantly mitigated hydrogen peroxide-induced ROS production and cytotoxicity in vitro. NAC treatment significantly increased the relative protein expression of collagen type 1 alpha 1 (COL1A1), tenascin C (TNC), scleraxis (SCX), and tenomodulin (TNMD) in TPSCs. Bioinformatics analyses revealed that NAC modulated transcriptomes, particularly in the integrin-related phosphoinositide 3-kinase (PI3K)/AKT signaling, and Western blotting revealed that NAC enhanced integrin α5β1 expression and PI3K/AKT activation in TSPCs. Finally, NAC treatment mitigated the tendon injury, but enhanced the protein expression of SCX, TNC, TNMD, and COLIA1 in the injured tissue regions of the rats.
Conclusion: NAC treatment promoted the survival and differentiation of TSPCs to facilitate tendon repair after tendon injury in rats. Thus, NAC may be valuable for the treatment of tendon injury.
N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus
https://pubmed.ncbi.nlm.nih.gov/19732754/
The antioxidant N-acetyl-L-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15 mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24 h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-kappaB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-kappaB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. The combination of BAY 11-7085 and SB203580 resulted in increased inhibitory effects on virus replication and production of pro-inflammatory molecules relative to either single treatment. NAC inhibits H5N1 replication and H5N1-induced production of pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.
N-acetylcysteine for treating cocaine addiction - A systematic review
https://pubmed.ncbi.nlm.nih.gov/28213190/
The aim of this paper is to extensively review the current literature available on N-acetylcysteine (NAC) treatment for cocaine dependence (clinical and experimental studies). We screened all articles published before February 2016 reporting on the use of NAC as a pharmacological intervention for cocaine dependence or discussed its potential as a therapeutic approach for cocaine dependence. We described our results qualitatively. 21 studies matched our search criteria: 6 clinical trials and 15 animal studies. Four clinical studies showed NAC's capacity to reduce craving, desire to use cocaine, cocaine-cue viewing-time and cocaine-related spending. Studies in animal models also support this reinstatement prevention application of NAC. NAC reverses the disruption of glutamate homeostasis caused by long-term cocaine use restoring function of the cystine-glutamate exchanger in glial cells and reversing the downregulated GLT-1 receptor. Current data suggest promising potential for NAC as an anti-relapse agent, as a double-blind placebo trial was mainly negative, except in the subgroup of patients who were already abstinent. An optimal dose for relapse prevention may be one that restores extrasynaptic glutamate to physiological levels and predominantly activates mGluR2 and 3, but not mGluR5 receptors, which are linked to relapse. NAC may be better suited for avoiding relapse in already abstinent subjects.
Click Here to View the Many Studies on NAC and OCD Disorder:
https://search.nih.gov/search?affiliate=nih&query=NAC+ocd
N-acetylcysteine improves liver function in patients with non-alcoholic Fatty liver disease
https://pubmed.ncbi.nlm.nih.gov/22308119/
Background and aims: Non-alcoholic fatty liver change is a common disease of the liver in which oxidative stress plays a basic role. Studies are largely focused on protecting the liver by means of anti-oxidative material. The aim of this study is to evaluate the role of N- acetylcysteine in the process of liver injury.
Methods: Thirty patients with non-alcoholic fatty liver steatosis were randomly selected to receive either N-acetylcysteine or vitamin C. Liver function tests (alanine aminotransfrase, aspartate aminotransfrase and alkaline phosphatase) were measured as well as the grade of steatosis, the pattern of its echogenicity, the span of the liver and the spleen and the portal vein diameter before the intervention. Patients were followed up using the same method of evaluation repeated in the first, second and third months.
Results: The mean age (SD) was 40.1(12.4) in patients receiving NAC and 46(10.4) years in patients receiving vitamin C (P = 0.137). NAC resulted in a significant decrease of serum alanine aminotransfrase after three months, compared to vitamin C. This effect was independent of the grade of steatosis in the initial diagnosis. NAC was able to significantly decrease the span of the spleen.
Conclusions: N-acetylcysteine can improve liver function in patients with non-alcoholic fatty liver disease. Better results may be achievable in a longer follow up.
A dual effect of N-acetylcysteine on acute ethanol-induced liver damage in mice
https://pubmed.ncbi.nlm.nih.gov/16439183/
Reactive oxygen species (ROS) have been associated with acute ethanol-induced liver damage. N-acetylcysteine (NAC) is a glutathione (GSH) precursor and direct antioxidant. In this study, we investigated the effects of NAC on acute ethanol-induced liver damage. Female ICR mice were administered by gavage with a single dose of ethanol (6g/kg). NAC was administered in two different modes. In mode A, mice were injected with different doses of NAC at 30min before ethanol. In mode B, mice were injected with different doses of NAC at 4h after ethanol. Acute ethanol-induced liver damage was estimated by measuring serum alanine aminotransferase (ALT) activity and histopathological changes. Result showed that a single dose of ethanol (6g/kg) caused a significant increase in serum ALT activity, followed by microvesicular steatosis and necrosis in mouse liver. Pretreatment with NAC significantly protected against acute ethanol-induced liver damage in a dose-independent manner. Correspondingly, pretreatment with NAC significantly attenuated acute ethanol-induced lipid peroxidation and GSH depletion and inhibited hepatic TNF-alpha mRNA expression. By contrast, post-treatment with NAC aggravated ethanol-induced hepatic lipid peroxidation and worsened acute ethanol-induced liver damage in a dose-dependent manner. Taken together, NAC has a dual effect on acute ethanol-induced liver damage. Pretreatment with NAC prevent from acute ethanol-induced liver damage via counteracting ethanol-induced oxidative stress. When administered after ethanol, NAC might behave as a pro-oxidant and aggravate acute ethanol-induced liver damage.
N-acetylcysteine inhibits muscle fatigue in humans
https://pubmed.ncbi.nlm.nih.gov/7989604/
N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively inhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experiments test the hypothesis that NAC pretreatment can inhibit acute muscular fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in water by intravenous infusion. The subject then sat in a chair with surface electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimulated to contract electrically (40-55 mA, 0.2-ms pulses) and force production was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions (MVC) of ankle dorsiflexor muscle groups and during electrical stimulation of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1). Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subsequently were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did not alter the function of unfatigued muscle; MVC performance and the force-frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force output by approximately 15% (P < 0.0001), an effect that was evident after 3 min of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue. N-acetylcysteine pretreatment can improve performance of human limb muscle during fatiguing exercise, suggesting that oxidative stress plays a causal role in the fatigue process and identifying antioxidant therapy as a novel intervention that may be useful clinically.
Rhinovirus (RV)-Induced Interleukin-8 (IL-8) Production in Respiratory Epithelial Cells is Mediated by H2O2 and is Inhibited by N-Acetyl Cysteine (NAC) † 690
https://www.nature.com/articles/pr1997869
A direct correlation has been reported between the severity of common cold symptoms and the concentration of IL-8 in nasal secretions from volunteers with experimental RV colds. The purpose of these studies was to examine the mechanism by which RV infection stimulates IL-8 elaboration. All studies were done in a transformed respiratory epithelial cell line (BEAS-2b). Increased fluorescence staining of carbonyl groups and activation of dichlorofluorescein diacetate was seen in RV-challenged cells suggesting an increase in oxidative stress. Quantitative measurement of H2O2 with a colorimetric assay revealed H2O2 concentrations of 4.74 ± 2.04 μM and.40 ±.49 μM in media from challenged and control cells four hours after virus challenge, respectively (p<0.01). Stimulation of BEAS-2b cells with H2O2 resulted in elaboration of IL-8. Treatment of BEAS-2b cells with NAC significantly inhibited RV-induced IL-8 elaboration. IL-8 concentrations in supernatant media were 183 ± 64 pg/ml and 44 ± 4 six hours after virus challenge in treated (20 mM NAC) and untreated cells, respectively. In spite of the effect of NAC on IL-8 elaboration, RV stimulated increases in H2O2 concentration were not affected by NAC. These results demonstrate that H2O2 is produced in respiratory epithelial cells in response to RV infection and is a potential mediator of RV-induced IL-8 elaboration. NAC inhibits RV-induced IL-8 by a mechanism other than inhibition of H2O2 production.
Clearance of mixed biofilms of Streptococcus pneumoniae and methicillin-susceptible/resistant Staphylococcus aureus by antioxidants N-acetyl-L-cysteine and cysteamine
https://www.nature.com/articles/s41598-022-10609-x
Biofilm-associated infections are of great concern because they are associated with antibiotic resistance and immune evasion. Co-colonization by Staphylococcus aureus and Streptococcus pneumoniae is possible and a threat in clinical practice. We investigated the interaction between S. aureus and S. pneumoniae in mixed biofilms and tested new antibiofilm therapies with antioxidants N-acetyl-L-cysteine (NAC) and cysteamine (Cys). We developed two in vitro S. aureus–S. pneumoniae mixed biofilms in 96-well polystyrene microtiter plates and we treated in vitro biofilms with Cys and NAC analyzing their effect by CV staining and viable plate counting. S. pneumoniae needed a higher proportion of cells in the inoculum and planktonic culture to reach a similar population rate in the mixed biofilm. We demonstrated the effect of Cys in preventing S. aureus biofilms and S. aureus–S. pneumoniae mixed biofilms. Moreover, administration of 5 mg/ml of NAC nearly eradicated the S. pneumoniae population and killed nearly 94% of MSSA cells and 99% of MRSA cells in the mixed biofilms. The methicillin resistance background did not change the antioxidants effect in S. aureus. These results identify NAC and Cys as promising repurposed drug candidates for the prevention and treatment of mixed biofilms by S. pneumoniae and S. aureus.
Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model
https://www.nature.com/articles/s41598-019-55297-2
The number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reactive oxygen species (ROS) in chondrocytes in vivo, resulting in chondrocyte apoptosis and leading to osteoarthritis development in a rat model. We demonstrate that mechanical stress induces ROS accumulation and inflammatory cytokine expression in cultured chondrocytes in vitro and that both are inhibited by treatment with the anti-oxidant N-acetyl cysteine (NAC). In vivo, osteoarthritis development in a rat osteoarthritis model was also significantly inhibited by oral administration of NAC. MMP13 expression and down-regulation of type II collagen in chondrocytes, both of which indicate osteoarthritis, as well as chondrocyte apoptosis in osteoarthritis rats were inhibited by NAC. Interestingly, osteoarthritis development in sham-operated control sides, likely due to disruption of normal weight-bearing activity on the control side, was also significantly inhibited by NAC. We conclude that osteoarthritis development in rats is significantly antagonized by oral NAC administration. Currently, no oral medication is available to prevent osteoarthritis development. Our work suggests that NAC may represent such a reagent and serve as osteoarthritis treatment.
The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after hematopoietic stem cell transplantation
https://www.nature.com/articles/s41598-018-26033-z
Busulphan (Bu) is a myeloablative drug used for conditioning prior to hematopoietic stem cell transplantation. Bu is predominantly metabolized through glutathione conjugation, a reaction that consumes the hepatic glutathione. N-acetyl-l-cysteine (NAC) is a glutathione precursor used in the treatment of acetaminophen hepatotoxicity. NAC does not interfere with the busulphan myeloablative effect. We investigated the effect of NAC concomitant treatment during busulphan conditioning on the liver enzymes as well as the clinical outcome. Prophylactic NAC treatment was given to 54 patients upon the start of busulphan conditioning. These patients were compared with 54 historical matched controls who did not receive NAC treatment. In patients treated with NAC, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly (P < 0.05) decreased after conditioning compared to their start values. Within the NAC-group, liver enzymes were normalized in those patients (30%) who had significantly high start values. No significant decrease in enzyme levels was observed in the control group. Furthermore, NAC affected neither Bu kinetics nor clinical outcome (sinusoidal obstruction syndrome incidence, graft-versus-host disease and/or graft failure). In conclusion: NAC is a potential prophylactic treatment for hepatotoxicity during busulphan conditioning. NAC therapy did not alter busulphan kinetics or affect clinical outcome.
Premature senescence of endothelial cells upon chronic exposure to TNFα can be prevented by N-acetyl cysteine and plumericin
https://www.nature.com/articles/srep39501
Cellular senescence is characterized by a permanent cell-cycle arrest and a pro-inflammatory secretory phenotype, and can be induced by a variety of stimuli, including ionizing radiation, oxidative stress, and inflammation. In endothelial cells, this phenomenon might contribute to vascular disease. Plasma levels of the inflammatory cytokine tumor necrosis factor alpha (TNFα) are increased in age-related and chronic conditions such as atherosclerosis, rheumatoid arthritis, psoriasis, and Crohn’s disease. Although TNFα is a known activator of the central inflammatory mediator NF-κB, and can induce the intracellular generation of reactive oxygen species (ROS), the question whether TNFα can induce senescence has not been answered conclusively. Here, we investigated the effect of prolonged TNFα exposure on the fate of endothelial cells and found that such treatment induced premature senescence. Induction of endothelial senescence was prevented by the anti-oxidant N-acetyl cysteine, as well as by plumericin and PHA-408, inhibitors of the NF-κB pathway. Our results indicated that prolonged TNFα exposure could have detrimental consequences to endothelial cells by causing senescence and, therefore, chronically increased TNFα levels might possibly contribute to the pathology of chronic inflammatory diseases by driving premature endothelial senescence.
Protective Effects of N-acetyl-L-cysteine on the Reduction of Dopamine Transporters in the Striatum of Monkeys Treated with Methamphetamine
https://www.nature.com/articles/1300512
Several lines of evidence suggest that oxidative stress might contribute to neurotoxicity in the dopaminergic nerve terminals after administration of methamphetamine (MAP). We undertook the present study to determine whether intravenous administration of N-acetyl-L-cysteine (NAC), a potent antioxidant drug, could attenuate the reduction of dopamine transporter (DAT) in the striatum of monkey brain after administration of MAP. Positron emission tomography studies demonstrated that repeated administration of MAP (2 mg/kg as a salt, four times at 2-h intervals) significantly decreased the accumulation of radioactivity in the striatum after intravenous administration of [11C]β-CFT. In contrast, the binding of [11C]SCH 23390 to dopamine D1 receptors in the monkey striatum was not altered after the administration of MAP. A bolus injection of NAC (150 mg/kg, i.v.) 30 min before MAP administration and a subsequent continuous infusion of NAC (12 mg/kg/h, i.v.) over 8.5 h significantly attenuated the reduction of DAT in the monkey striatum 3 weeks after the administration of MAP. These results suggest that NAC could attenuate the reduction of DAT in the monkey striatum after repeated administration of MAP. Therefore, it is likely that NAC would be a suitable drug for treatment of neurotoxicity in dopaminergic nerve terminals related to chronic use of MAP in humans.
Repeated N-Acetyl Cysteine Reduces Cocaine Seeking in Rodents and Craving in Cocaine-Dependent Humans
https://www.nature.com/articles/npp2010226
Addiction is a chronic relapsing disorder hypothesized to be produced by drug-induced plasticity that renders individuals vulnerable to craving-inducing stimuli such as re-exposure to the drug of abuse. Drug-induced plasticity that may result in the addiction phenotype includes increased excitatory signaling within corticostriatal pathways that correlates with craving in humans and is necessary for reinstatement in rodents. Reduced cystine–glutamate exchange by system xc– appears to contribute to heightened excitatory signaling within the striatum, thereby posing this as a novel target in the treatment of addiction. In the present report, we examined the impact of repeated N-acetyl cysteine, which is commonly used to activate cystine–glutamate exchange, on reinstatement in rodents in a preclinical study and on craving in cocaine-dependent humans in a preliminary, proof-of-concept clinical experiment. Interestingly, repeated administration (7 days) of N-acetyl cysteine (60 mg/kg, IP) produced a significant reduction in cocaine (10 mg/kg, IP)-induced reinstatement, even though rats (N=10–12/group) were tested 24 h after the last administration of N-acetyl cysteine. The reduction in behavior despite the absence of the N-acetyl cysteine indicates that repeated N-acetyl cysteine may have altered drug-induced plasticity that underlies drug-seeking behavior. In parallel, our preliminary clinical data indicate that repeated administration (4 days) of N-acetyl cysteine (1200–2400 mg/day) to cocaine-dependent human subjects (N=4 per group) produced a significant reduction in craving following an experimenter-delivered IV injection of cocaine (20 mg/70 kg/60 s). Collectively, these data demonstrate that N-acetyl cysteine diminishes the motivational qualities of a cocaine challenge injection possibly by altering pathogenic drug-induced plasticity.
Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients
https://www.nature.com/articles/1301624
In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls (p=0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p=0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.
We hope you enjoyed this introduction to NAC and some of its known and possible qualities. As always, please do your own research and be mindful that taking supplements and naturally occurring plants and herbs still come with risks that we are responsible to understand.
The above statements are for informational purposes only. Our NAC supplements are not intended to treat, cure, or prevent any disease.
