Written by Taylor Woosley, Staff Writer. 4-week supplementation of 600 mg/day of NAC significantly reduced IL-6, hs-CRP, insulin, and fasting blood sugar levels compared to placebo. 

weight controlObesity rates are rising worldwide, and its management is challenging because of the complex etiology of obesity, with many factors involved in its development such as unbalanced diets, sedentary lifestyle, genetic factors, and social and environmental factors1. Obesity is complicated by other diseases such as type 2 diabetes mellitus (T2DM), hepatic steatosis, cardiovascular diseases, stroke, dyslipidemia, hypertension, and certain types of cancer, all of which can lead to an increased risk of mortality2. Reactive oxygen species (ROS) play an important role in the development of obesity and its metabolic complications and, in high levels, they may damage DNA, lipids and proteins, resulting in injury to tissues and cell death3.

N-acetylcysteine (NAC) is a common thiol antioxidant that is converted to L-cysteine and glutathione for protein synthesis and cellular redox maintenance4. NAC modulates oxidative stress, along with other pathophysiologic processes implicated in disease, including mitochondrial dysfunction, apoptosis, and inflammation5. Additionally, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α)6.

Sohouli et al. conducted a double-blind, randomized controlled trial (RCT) to analyze the effects of NAC on anthropometric indices, inflammatory factors, insulin resistance, and senescence (cells loss of proliferative capacity) of visceral adipose tissue of obese participants. Study inclusion consisted of obese men and women with a BMI ≥35 kg/m2, aged 25-50 years, who were candidates for bariatric surgery. 40 participants with obesity were randomized to consume either NAC (n=20) or a placebo (n=20) for 4 weeks at lunch time. Subjects in the NAC group consumed 600 mg/day of NAC, while those in the control received 600 mg/day of a placebo containing starch powder. All participants were given dietary recommendations to adjust total energy intake per day based on energy intake calculated based on age, gender, and body mass index (BMI).

Primary study outcomes were SA-β-gal test (a marker for senescence) and significant changes in the expression of the genes for TNF-α and IL-6. Secondary outcome measures included changes in BMI, waist circumference (WC), fasting blood sugar (FBS), insulin, HOMA-IR, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and hs-CRP. SA-β-gal activity was measured by harvesting paired visceral adipose tissue during bariatric surgery using the Senescence Cells Histochemical Staining Kit. Anthropometric factors were measured before and after study conclusion. Dietary intake was assessed using a 24-hour dietary recall questionnaire.

An independent t-test was used to compare the mean of the quantitative variables and the mean of their changes between the two groups at the beginning and end of the study. Furthermore, a paired t-test was utilized to compare the mean of quantitative variables between before and after the intervention for each group. There was no significant difference between the two groups regarding sex, weight, BMI, WC, physical activity, multivitamin consumption, drug use, marital status, and education level, except for HOMA-IR. Significant findings of the study are as follows:

  • Real-time PCR data and analysis of expression fold change show that the level of IL-6 (P 0.014; fold change: 0.02) and P16 (P 0.047; fold change: 0.23) gene expression in the intervention group with NAC was significantly lower than the placebo group.
  • 4-week administration of NAC significantly reduced FBS, HOMA-IR, insulin, IL-6, and hs-CRP levels compared to placebo.
  • No significant changes were noted between groups regarding weight, BMI, WC, TC, TG, LDL, HDL, and TNF-α.

Results of the study show that NAC supplementation significantly reduced senescence activity, IL-6, insulin, and hs-CRP concentrations compared to placebo. Further research should continue to explore the use of NAC to reduce inflammation and oxidative stress present in obesity. Study limitations include the short study duration, the inability to assess obesity-related hormones and body fat percentage, and the lack of performing immunohistochemistry to evaluate inflammatory changes in fat tissue.

Source: Sohouli, Mohammad Hassan, Ghazaleh Eslamian, Nasser Malekpour Alamdari, Maryam Abbasi, Sepideh Fazeli Taherian, Diba Behtaj, and Hamid Zand. “Effects of N-acetylcysteine on aging cell and obesity complications in obese adults: a randomized, double-blind clinical trial.” Frontiers in Nutrition 10 (2023).

© 2023 Sohouli, Eslamian, Malekpour Alamdari, Abbasi, Fazeli Taherian, Behtaj and Zand. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the
original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these
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Posted November 7, 2023.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

  1. Cuevas-Sierra A, Ramos-Lopez O, Riezu-Boj JI, Milagro FI, Martinez JA. Diet, Gut Microbiota, and Obesity: Links with Host Genetics and Epigenetics and Potential Applications. Advances in nutrition (Bethesda, Md). Jan 1 2019;10(suppl_1):S17-s30. doi:10.1093/advances/nmy078
  2. Mayoral LP, Andrade GM, Mayoral EP, et al. Obesity subtypes, related biomarkers & heterogeneity. Indian J Med Res. Jan 2020;151(1):11-21. doi:10.4103/ijmr.IJMR_1768_17
  3. Pérez-Torres I, Castrejón-Téllez V, Soto ME, Rubio-Ruiz ME, Manzano-Pech L, Guarner-Lans V. Oxidative Stress, Plant Natural Antioxidants, and Obesity. Int J Mol Sci. Feb 11 2021;22(4)doi:10.3390/ijms22041786
  4. Gusarov I, Shamovsky I, Pani B, et al. Dietary thiols accelerate aging of C. elegans. Nat Commun. Jul 15 2021;12(1):4336. doi:10.1038/s41467-021-24634-3
  5. Raghu G, Berk M, Campochiaro PA, et al. The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress. Curr Neuropharmacol. 2021;19(8):1202-1224. doi:10.2174/1570159×19666201230144109
  6. Dludla PV, Nkambule BB, Mazibuko-Mbeje SE, et al. N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature. Antioxidants (Basel, Switzerland). Dec 16 2020;9(12)doi:10.3390/antiox9121283