BENEFITS OF SUPPLEMENTING N-ACETYL L-CYSTEINE:

Improves mental health conditions and substance use disorder

• N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder
• https://onlinelibrary.wiley.com/doi/10.1111/jcpt.12370
• double-blind, two-centre, placebo-controlled, 10-week trial, patients with moderate-to-severe OCD were enrolled
• Patients were randomized into two parallel groups to receive fluvoxamine (200 mg daily) plus placebo or fluvoxamine (200 mg daily) plus NAC (2000 mg daily).
• A total of 44 patients (22 in each group) were visited to evaluate response to therapy using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at baseline, and at weeks 4, 8 and 10
• Repeated-measures ANOVA showed a significant effect for time × treatment interaction (Greenhouse–Geisser corrected: F = 5·14, d.f. = 1·64, P = 0·012) in the Y-BOCS total score and a significant effect for time × treatment interaction (Greenhouse–Geisser corrected: F = 5·44, d.f. = 1·54, P = 0·011) in the Y-BOCS obsession subscale between the two groups.
• N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis
• https://www.psychiatrist.com/jcp/n-acetylcysteine-depressive-symptoms-functionality/
• Five studies fulfilled our inclusion criteria for the meta-analysis, providing data on 574 participants, of whom 291 were randomized to receive N-acetylcysteine and 283 to placebo
• The follow-up varied from 12 to 24 weeks
• Two studies included subjects with bipolar disorder and current depressive symptoms, 1 included subjects with MDD in a current depressive episode, and 2 included subjects with depressive symptoms in the context of other psychiatric conditions
• Treatment with N-acetylcysteine improved depressive symptoms as assessed by Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale when compared to placebo (SMD = 0.37; 95% CI = 0.19 to 0.55; P < .001). Subjects receiving N-acetylcysteine had better depressive symptoms scores on the Clinical Global Impressions-Severity of Illness scale at follow-up than subjects on placebo (SMD = 0.22; 95% CI = 0.03 to 0.41; P < .001)
• Administration of N-acetylcysteine ameliorates depressive symptoms, improves functionality, and shows good tolerability.

Helps relieve symptoms of respiratory conditions

• Efficacy of Ascorbic Acid (Vitamin C) and/N-Acetylcysteine (NAC) Supplementation on Nutritional and Antioxidant Status of Male Chronic Obstructive Pulmonary Disease (COPD) Patients
• https://www.jstage.jst.go.jp/article/jnsv/62/1/62_54/_article
• A parallel and single blind randomised controlled clinical trial (RCT) was conducted at two medical centers in Kuala Lumpur, Malaysia. Seventy-nine subjects were recruited and randomly divided into four trial arms (i.e., NAC, vitamin C, NAC+vitamin C and control groups) for six mo.
• The primary outcome was changes in body mass index by estimating power of 90% and significance level of p<0.05. Repeated Measure ANOVA showed that there was a significant interaction effect on BMI (p=0.046) and carbohydrate intake (p=0.030), especially in the NAC group
• Plasma glutathione (GSH) increased significantly in all intervention groups, especially in vitamin C (p=0.005). A single supplementation of NAC or vitamin C improved nutritional and antioxidant status of subjects
• Safety of N-Acetylcysteine at High Doses in Chronic Respiratory Diseases
• https://link.springer.com/article/10.1007/s40264-020-01026-y
• The aim of this review was to evaluate the adverse effects profile of NAC at higher than the standard dose in chronic respiratory diseases to establish a risk–benefit ratio in increasing the daily dose; therefore, studies using NAC at a dose of at least 600 mg/day were selected.
• Forty-one articles where NAC has been used at 600 mg and above, up to 3000 mg/day, and with a specific report on safety, were considered. Most of the studies used oral NAC and were conducted on patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, bronchiectasis, chronic bronchitis and cystic fibrosis
• the safety profile was similar at both the high and standard doses with the oral formulation; gastrointestinal symptoms were reported but they were no more common than in the control group.

Boosts brain health by regulating glutamate and replenishing glutathione

• N-acetylcysteine protects memory decline induced by streptozotocin in mice
• https://www.sciencedirect.com/science/article/pii/S0009279716301491?via%3Dihub
• Recently we reported that the N-acetylcysteine (NAC) decreases brain acetylcholinesterase (AChE) activity in vitro
• Mice were divided into four groups: I) Sham, II) NAC, III) STZ and IV) NAC + STZ. Animals were daily treated with NAC (50 mg/kg/day, p.o.) for nine consecutive days and with STZ (2.5 mg/kg i.c.v.) at the first and third days
• On the tenth day animals were euthanized for AChE and butyrylcholinesterase (BChE) activities and ACh, energy-rich phosphate and brain glucose uptake levels evaluations. A learning and memory impairment was observed in SDPA and MWM in those animals that receive STZ. Nevertheless, the same was not observed in those animals that also received NAC
• Brain cortex and hippocampus AChE and hippocampus BChE activities increase induced by STZ were also prevented by NAC treatment. The STZ induced a brain energy metabolism imbalance, decreasing adenosine triphosphate and increasing adenosine levels.
• The glucose uptake decrease in hippocampus was prevented by NAC
• NAC treatment prevented the cognitive disturbance, by restoring the cholinergic system and brain energy metabolism disorders

Improves fertility in men

• Effects of N-acetyl-cysteine supplementation on sperm quality, chromatin integrity and level of oxidative stress in infertile men
• https://rbej.biomedcentral.com/articles/10.1186/s12958-019-0468-9
• The patients consisted of 50 infertile men with asthenoteratozoospermia who received NAC (600 mg/d) orally for 3 months
• After NAC treatment, patients’ sperm count and motility increased significantly whereas abnormal morphology, DNA fragmentation and protamine deficiency showed significant decreases compared to pre-treatment levels
• Hormonal profile improvement was associated with lowered FSH and LH levels and increased amount of testosterone (P < 0.05). TAC significantly increased and MDA decreased with an inverse significant correlation between TAC and MDA (P < 0.05).
• A Preliminary Study: N-acetyl-L-cysteine Improves Semen Quality following Varicocelectomy
• https://www.ijfs.ir/article_45368.html
• Trial included 35 infertile men with varicocele randomly divided into control (n=20) and NAC (n=15) groups
• three months after varicocelectomy.
• Percentage of abnormal semen parameters, protamine deficiency, DNA fragmentation and oxidative stress were significantly decreased in both groups compared to before surgery
• NAC improved chromatin integrity and pregnancy rate when administered as adjunct therapy post-varico- celectomy.

Stabilizes blood sugar by decreasing inflammation in fat cells

• N-acetylcysteine Protects Mice from High Fat Diet-induced Metabolic Disorders
• https://link.springer.com/article/10.1007/s11095-016-1941-1
• Six-week-old male C57BL/6 mice fed a chow or high-fat diet (HFD) were treated with NAC (2 g/L) in drinking water for 11 weeks
• NAC supplementation inhibited the increase of fat mass and the development of obesity when mice were fed an HFD. NAC treatment significantly lowered HFD-induced macrophage infiltration, and enhanced adiponectin gene expression, resulting in reduced hyperglycemia and hyperinsulinemia, and improvement of insulin resistance
• NAC oral administration suppressed hepatic lipid accumulation, as evidenced by lower levels of triglyceride and cholesterol in the liver.

Reduces heart disease risk by preventing oxidative damage

• Associations between dietary antioxidant intakes and cardiovascular disease
• https://www.nature.com/articles/s41598-022-05632-x?utm_medium=affiliate&utm_source=commission_junction&utm_campaign=CONR_PF018_ECOM_GL_PHSS_ALWYS_DEEPLINK&utm_content=textlink&utm_term=PID100090071&CJEVENT=4332113af37511ee82e900700a1cb828
• Eligible adults (n = 5102) aged ≥ 30 years, were selected from the participants of the Tehran lipid and glucose study with an average follow-up of 5.3 years.
• This study was conducted on 2253 men and 2849 women aged 47.0 ± 11.6 and 45.6 ± 10.5 years, respectively. The main sources of dietary vitamins A, E, and C and zinc were fruits, vegetables, and legumes. Risk of CVD decreased from quartile 1 to quartile 4 for vitamin E intake (HR 1.00, 0.91, 0.77, and 0.57; Ptrend = 0.03)
• an inverse association between vitamin E intake and the risk of CVD, emphasizing the potential protective role of fruit and vegetable in the prevention of CVD.
• N-Acetylcysteine for Cardiac Protection During Coronary Artery Reperfusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
• https://www.frontiersin.org/articles/10.3389/fcvm.2021.752939/full
• 787 publications reviewed, 28 RCTs were identified, with a summary of 2,174 patients
• A meta-analysis using the random effects model indicated that NAC administration during or prior to the reperfusion procedures resulted in a trend toward a reduction in the level of serum cardiac troponin (cTn) [95% CI, standardized mean difference (SMD) −0.80 (−1.75; 0.15), p = 0.088, n = 262 for control, 277 for NAC group], and in the incidence of postoperative atrial fibrillation [95% CI, relative risk (RR) 0.57 (0.30; 1.06), p = 0.071, n = 484 for control, 490 for NAC group]
• Among the nine trials that measured ROS, seven showed a correlation between the reduction of lipid peroxidation and improved clinical outcomes. These lines of evidence support the potential benefit of NAC as an adjuvant therapy for cardiac protection against reperfusion injury.

Boost glutathione levels, improves immune function

• Glutathione Fine-Tunes the Innate Immune Response toward Antiviral Pathways in a Macrophage Cell Line Independently of Its Antioxidant Properties
• https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01239/full
• a 24-h BSO pretreatment decreased glutathione (GSH + GSSG) levels by 99%, and addition of LPS had no effect up to 2 h later. Although LPS induced an oxidative burst in terms of increased ROS production detectable by EPR, this did not affect GSH or GSSG levels significantly. BSO, alone or with LPS, was not toxic to the cells as detected by CellTiter-Blue^® Assay (viability, mean ± SD from five biological replicates: control, 100 ± 1%; BSO, 98 ± 2%; BSO + LPS, 95 ± 1%).