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Hypertension is a leading cause of morbidity and mortality worldwide. Individuals with hypertension are at an increased risk for stroke, heart disease and kidney failure. Essential hypertension results from a combination of genetic and lifestyle factors. One such lifestyle factor is diet, and its role in the control of blood pressure has come under...
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Hypertension is a major health problem worldwide. Individuals with hypertension are at an increased risk for stroke, heart disease, and kidney failure. Although the etiology of essential hypertension has a genetic component, lifestyle factors such as diet play an important role. Insulin resistance is a common feature of hypertension in both humans...
Citations
... An increasing number of articles [3,5] confirm the efficacy of NAC use in the aforementioned disorders. Natural sources of cysteine include meat, fish, cereals, dairy, soybean, and egg products [6]. NAC is available in modest levels naturally in several fruits and vegetables as a dietary supplement [7]. ...
... The eye is extremely vulnerable to oxidative stress. Molecular oxygen can directly destroy or cause secondary reactions that might launch oxidative activities [6]. ...
This study aims to evaluate the therapeutic application of N-acetylcysteine (NAC) as a treatment or adjunct therapy for various medical conditions. While its efficacy in treating acetaminophen overdose, cystic fibrosis, and chronic obstructive pulmonary disease is well-established, emerging evidence suggests that NAC may also benefit a broader spectrum of illnesses due to its safety, simplicity, and affordability. A comprehensive review was conducted by searching PubMed, relevant books, and conference proceedings for publications discussing NAC about the specified health conditions. The clinically relevant data were analysed using the American Family Physician Evidence-Based Medicine Toolkit, following a standard integrated review methodology. NAC shows potential as an adjunctive treatment for a wide range of medical conditions, particularly chronic diseases. It may be beneficial for polycystic ovary syndrome, endometriosis, male infertility, cataracts, glaucoma, dry eye syndrome, parkinsonism, multiple sclerosis, Alzheimer’s disease, stroke outcomes, non-acetaminophen-induced acute liver failure, Crohn’s disease, ulcerative colitis, schizophrenia, bipolar disorder, and obsessive-compulsive disorder. Although evidence for some conditions is less robust, NAC's therapeutic potential warrants further investigation. Given the aging population and the decline in glutathione levels, the use of NAC should be considered across a variety of medical conditions. This paper suggests that NAC supplementation could play a significant role in reducing morbidity and mortality associated with numerous chronic diseases.
... Interestingly, all overlapped upstream regulators for the metabolomics profile, L-cysteine, agmatine, and betaine are related to hypertension ( Figure 6). [42][43][44][45] To further look at the metabolomic pathways in the kidney that are associated with SS hypertension, the integration of transcriptomics and metabolomics analysis identified multiple genes and metabolites related to the alteration of the TCA cycle, amino acid metabolism, and ROS metabolism in SS rats lacking K ir 5.1 (Figure 7). 37 ...
... This is also consistent with the upstream regulating effects of L-cysteine ( Figure 6), which not only affects taurine but also influences the homeostasis of glutathione and glutathione disulfide to reduce hypertension. 44 ...
... Nonetheless, a recent systematic review published in 2022 confirms the strong, but limited number of studies supporting CoQ10 supplementation in bipolar individuals. 14 N-ACETYLCYSTEINE N-acetylcysteine (NAC) is an antioxidant derived from the amino acid L-cysteine found in high concentrations in foods such as soybeans, quinoa, and whole wheat flour with promising antidepressant health implications for patients with BD. 21,22 Ingestion of NAC leads to increased production of glutathione, a major antioxidant important for reducing oxidative stress. 23 Recent studies exploring the mechanism of action of NAC reveal this substance may increase extracellular glutamate while inhibiting glutamate neurotransmission, thus producing antidepressant effects. ...
This narrative review analyzes the body of literature on known physiological mechanisms impacting bipolar disorder (BD) and how patient-centered nutrition in conjunction with prescribed medications may positively impact patient health outcomes. Additional topics include understanding the current state of research on nutrition and BD, impact of specific micronutrient imbalances on BD, dietary tendencies including current research on whole dietary patterns and potential applications for patients with BD. The totality of research included in this review indicate that inflammatory processes play a central role impacting health outcomes in patients with BD which can be addressed with not only medication, but also with targeted nutrition therapy.
... Another sulfur-containing amino acid, cysteine, functions as a precursor for hydrogen sulfide (H 2 S) and is an integral component of glutathione, which is a crucial antioxidant. Due to the interconnected roles of glutathione and H 2 S signaling in BP regulation [67,68], cysteine is recognized for its potential antihypertensive effects [69]. In a comparable manner, taurine, another amino acid containing sulfur, exhibits vasodilatory effects [70]. ...
... Recognized as a rate-limiting factor in the synthesis of glutathione [69], cysteine plays a crucial role in cellular processes. Experimental studies have employed cysteine supplementation to generate endogenous H 2 S [154]. ...
Amino acids are essential for normal pregnancy and fetal development. Disruptions in maternal amino acid metabolism have been associated with various adult diseases later in life, a phenomenon referred to as the developmental origins of health and disease (DOHaD). In this review, we examine the recent evidence highlighting the significant impact of amino acids on fetal programming, their influence on the modulation of gut microbiota, and their repercussions on offspring outcomes, particularly in the context of cardiovascular–kidney–metabolic (CKM) syndrome. Furthermore, we delve into experimental studies that have unveiled the protective effects of therapies targeting amino acids. These interventions have demonstrated the potential to reprogram traits associated with CKM in offspring. The discussion encompasses the challenges of translating the findings from animal studies to clinical applications, emphasizing the complexity of this process. Additionally, we propose potential solutions to overcome these challenges. Ultimately, as we move forward, future research endeavors should aim to pinpoint the most effective amino-acid-targeted therapies, determining the optimal dosage and mode of administration. This exploration is essential for maximizing the reprogramming effects, ultimately contributing to the enhancement of cardiovascular–kidney–metabolic health in offspring.
... Since then, NAC use has been expanded to acetaminophen overdose and chronic obstructive lung disease and its role is ever expanding clinically. Cysteine is found naturally in meat, fish, grains, dairy, soybean, and egg products [14]. As a nutritional supplement, NAC is found in small amounts naturally in some fruits and vegetables [15]. ...
Aim: The ameliorative effect of aqueous leaf extracts of Cola acuminata (ALECA) on mercury chloride (HgCl 2)-induced neurotoxicity in male Wistar rats was investigated. Methods: Thirty-six male Wistar rats weighing 120e150 g were randomly divided into six groups; group I received 0.5 ml normal saline; group II received 5 mg/kg body weight HgCl 2 ; group III received 5 mg/kg HgCl 2 150 mg/kg body weight ALECA; group IV received 5 mg/kg HgCl 2 300 mg/kg ALECA; group V received 5 mg/kg HgCl 2 50 mg/kg N-acetyl cysteine (NAC); and group VI: received 5 mg/kg HgCl 2 500 mg/kg body weight vitamin C. The animals were treated for 21 days through the oral route. The rats were subjected to open field tests and forelimb grip tests on days 14 and 21. The animals were then killed and brain tissues were collected, homogenized, and centrifuged for measurement of biochemical parameters: tumor necrosis factor alpha and nitric oxide. Results: The data obtained from the forelimb grip test showed that muscular strength was higher in the group given ALECA, NAC, and vitamin C when compared with the group given only HgCl 2 (P˂0.05). The data from the open field test also showed that locomotory activity and exploratory behavior are higher while anxiety levels are lower in the group treated with ALECA, NAC, and vitamin C when compared with the HgCl 2 group (P˂0.05). Also, the levels of tumor necrosis factor alpha and nitric oxide are lower in the group treated with ALECA when compared with the HgCl 2 group (P˂0.05). From the results, it was established that ALECA-treated groups compared favorably with the two reference drugs. Conclusions: These findings show the ameliorative effect of ALECA on mercury chloride induced neurotoxicity/ brain damage through modulation of inflammatory pathway.
... While there were no significant differences in blood pressure between the Ctrl and NAC groups at any time point, statistical testing found a trend towards lower blood pressure in the NAC group at 60 min reperfusion compared to baseline. This finding is in line with previous reports that NAC can have blood pressure lowering effects (63,64). Although not statistically significant in our data, hypotension may have biological consequences, including negative effects on arrhythmia incidence. ...
Background
Arrhythmias in the early phase of reperfusion after myocardial infarction (MI) are common, and can lead to hemodynamic instability or even cardiac arrest. Reactive oxygen species (ROS) are thought to play a key role in the underlying mechanisms, but evidence from large animal models is scarce, and effects of systemic antioxidative treatment remain contentious.
Methods
MI was induced in 7 male and 7 female pigs (Norwegian landrace, 35–40 kg) by clamping of the left anterior descending artery (LAD) during open thorax surgery. Ischemia was maintained for 90 min, before observation for 1 h after reperfusion. Pigs were randomized 1:1 in an operator-blinded fashion to receive either i.v. N-acetylcysteine (NAC) from 70 min of ischemia and onwards, or 0.9% NaCl as a control. Blood samples and tissue biopsies were collected at baseline, 60 min of ischemia, and 5 and 60 min of reperfusion. ECG and invasive blood pressure were monitored throughout.
Results
The protocol was completed in 11 pigs. Oxidative stress, as indicated by immunoblotting for Malondialdehyde in myocardial biopsies, was increased at 5 min of reperfusion compared to baseline, but not at 60 min of reperfusion, and not reduced with NAC. We found no significant differences in circulating biomarkers of myocardial necrosis, nor in the incidence of idioventricular rhythm (IVR), non-sustained ventricular tachycardia (NSVT), ventricular tachycardia (VT) or ventricular fibrillation (VF) between NAC-treated and control pigs during reperfusion.
Conclusion
Myocardial oxidation was increased early after reperfusion in a porcine model of MI, but systemic antioxidative treatment did not protect against reperfusion arrhythmias.
... These compound changes might provide its pathophysiological association with hypertension, insulin resistance, and dyslipidemia. It is also well-known that sulfur metabolism is involved in the metabolism of sulfur-containing amino acids such as cysteine and methionine to regulate the arterial blood pressure [68]. PICRUSt-COG analysis revealed that the microbial clusters of orthologs such as COG 4362 (Nitric Oxide Synthase) were significantly higher in BP than in the normal groups. ...
Background
The prevalence of hypertension in Qatar is 33 percent of the adult population. It is postulated that the salivary microbiome can regulate blood pressure (BP). However, limited investigations exist to prove this hypothesis. Therefore, we examined the difference in the salivary microbiome composition between hypertensive and normotensive Qatari subjects.
Methods
A total of 1190 Qatar Genome Project (QGP) participants (Mean age = 43 years) were included in this study. BP for all participants was classified into Normal (n = 357), Stage1 (n = 336), and Stage2: (n = 161) according to the American Heart Association guidelines. 16S-rRNA libraries were sequenced and analyzed using QIIME-pipeline, and PICRUST was used to predict functional metabolic routes. Machine Learning (ML) strategies were applied to identify salivary microbiome-based predictors of hypertension.
Results
Differential abundant analysis (DAA) revealed that Bacteroides and Atopobium were the significant members of the hypertensive groups. Alpha and beta diversity indices indicated dysbiosis between the normotensive and hypertensive groups. ML-based prediction models revealed that these markers could predict hypertension with an AUC (Area under the curve) of 0.89. Functional predictive analysis disclosed that Cysteine and Methionine metabolism and the sulphur metabolic pathways involving the renin-angiotensin system were significantly higher in the normotensive group. Therefore, members of Bacteroides and Atopobium can serve as predictors of hypertension. Likewise, Prevotella, Neisseria, and Haemophilus can be the protectors that regulate BP via nitric acid synthesis and regulation of the renin-angiotensin system.
Conclusion
It is one of the first studies to assess salivary microbiome and hypertension as disease models in a large cohort of the Qatari population. Further research is needed to confirm these findings and validate the mechanisms involved.
... Cisteína En mamíferos, la cisteína (Cys) es un aminoácido no esencial que contiene azufre y se produce endógenamente por el metabolismo de su precursor, el aminoácido esencial metionina (22). ...
... La cisteína participa tanto en la estructura como en la función de las proteínas y actúa de manera directa e indirecta para controlar el estrés oxidativo, incrementa la biodisponibilidad del NO y tiene un papel importante en el metabolismo de la insulina y la glucosa, además de mantener bajos los niveles de aldehídos reactivos y ayudar en la regulación de la presión arterial (22). Incluso se ha propuesto al H 2 S como probable responsable de la reducción de la presión arterial y los infartos que se ha observado con el consumo de una dieta rica en proteínas (23 Por otro lado, los niveles plasmáticos de cisteína total correlacionan consistentemente con el índice de masa corporal (IMC), la cantidad de masa grasa y el índice de cintura/cadera en algunos estudios en humanos (24). ...
Initially known for its deleterious health effects, hydrogen sulfide (H2S) has recently been recognized as a biologically important gas carrier, like nitric oxide and carbon monoxide. H2S is produced endogenously in mammalian cells by enzymatic and non-enzymatic pathways. When it is produced by the enzymatic pathway, its synthesis is carried out from the amino acid L-cysteine through the transsulfuration pathway. It can also be produced endogenously from exogenous compounds that function as H2S donors as, for example, the naturally occurring organic donors found in some plants. Currently, the role of H2S is well known as brain and cardiac protector, and its research as a therapeutic adjuvant in metabolic diseases such as obesity and type-2 diabetes is becoming increasingly important. The objective of this review is to examine how the contribution of donors and precursors of hydrogen sulfide by the diet impacts health and disease.
... Lower concentrations of both non-essential (arginine, proline, aspartic acid, glutamic acid, glycine, and serine) and essential (valine, lysine, and threonine) amino acids were found in this group, which is comparable to numerous studies in diseased populations such as those with hypertension (Wang et al. 2015), atherosclerosis (Tuel et al. 2009) and stroke (Jung et al. 2011). Arginine, glutamic acid (glutamate), and glycine modulate nitric oxide (NO) concentrations (Fig. 5), a potent vasodilator (Prasad et al. 1999;El Hafidi et al. 2006;Vasdev et al. 2009;Toba et al. 2010). Decreased synthesis and bioavailability of NO in early life has been implicated in the potential increased risk for future large artery stiffness and hypertension development in later life (Craig et al. 2020(Craig et al. , 2021. ...
Some individuals are susceptible to accelerated biological ageing, resulting in premature alterations in arterial structure and function. Identifying early-onset vascular ageing characterised by arterial stiffening is vital for intervention and preventive strategies. We stratified and phenotyped healthy children (5–9 yrs) and young adults (20–30 yrs) into their vascular ageing extremes established by carotid-femoral pulse wave velocity (cfPWV) percentiles (i.e., healthy vascular ageing (HVA) and early vascular ageing (EVA)). We compared anthropometric, cardiovascular, and metabolomic profiles and explored associations between cfPWV and urinary metabolites. Children and adults in the EVA groups displayed higher levels of adiposity, cardiovascular, and lifestyle risk factors (adults only) (all p ≤ 0.018). In adults, several urinary metabolites were lower in the EVA group (all q ≤ 0.039) when compared to the HVA group, with no differences observed in children. In multiple regression analysis (adults only), we found inverse associations between cfPWV with histidine (adj. R² = 0.038; β = –0.192; p = 0.013) and beta-alanine (adj. R² = 0.034; β = –0.181; p = 0.019) in the EVA group, but with arginine (adj. R² = 0.021; β = –0.160; p = 0.024) in the HVA group. The inverse associations of beta-alanine and histidine with cfPWV in the EVA group is suggestive that asymptomatic young adults who present with an altered metabolomic and less desired cardiovascular profile in combination with unfavourable lifestyle behaviours may be predisposed to early-onset vascular ageing. Taken together, screening on both a phenotypic and metabolic level may prove important in the early detection, prevention, and intervention of advanced biological ageing.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00726-023-03293-2.
... The proposed mechanism is that NAC can improve insulin sensitivity, reduce oxidative stress, minimize advanced glycation end products, increase glutathione accumulation, and modulate nitric oxide and other vasoactive mediators and thus, lower blood pressure 23 . Similar results are also shown by Hildebrandt W et al. and Vasdev S et al. 24,25 . In diabetic individuals, combining NAC with L-arginine increases nitric oxide synthesis and lowers systolic blood pressure 26 . ...