In 2022, the Accelerating Innovations for Mothers (AIM) project identified L‐arginine as one of five high‐potential medicines under investigation for pre‐eclampsia prevention . More trials are needed to determine the optimal dose and time to commence supplementation and support clinical decision‐making. Meta‐analyses were conducted separately for prevention or treatment trials, using random‐effects models. Recent studies, mostly in animals, have examined the effects of these fatty acids and dietary hempseed itself on platelet aggregation, ischemic heart disease and other aspects of our cardiovascular health. After 6 months of treatment there were 12 clinical events in the L-arginine group verses 7 in the placebo group. Post treatment results revealed L-arginine supplementation had no effect on maximal oxygen consumption or ventilator threshold. Furthermore, flow-mediated dilation and systemic NO production were not improved by L-arginine supplementation. This reviewarticle focuses on the relevance of L-ARG in the prevention and treatment of a variety of illnesses. L-ARG is an important semi-essential alpha-amino acidthat serves as a natural precursor for the synthesis of nitric oxide (NO). WebMD does not provide medical advice, diagnosis or treatment. I went to the Podiatrist she said it’s not typical for fungal and looks like Reynards disease. Seventeen healthy males participated in a randomized, double-blind, placebo-controlled study.A score of less than 26 on the total FSFI is an indication of sexual dysfunction.20 Higher scores on both the total FSFI and subscales indicate better sexual functioning.Although clinical studies in the mid-1990s were not in agreement on the benefits of arginine supplementation in pulmonary hypertension 78-81, recent studies have more consistently supported the beneficial effects of arginine/citrulline in adults with cardiovascular problems 76, 82.There were no significant differences in the basic characteristics of the included studies.A 2008 double-blind, randomized trial comparing relaxation versus lifestyle modification found that both groups had similar reductions in systolic blood pressure; however, significantly more participants in the relaxation response group eliminated an antihypertensive medication while maintaining adequate blood pressure control .(A) Forest plot stratified by intervention settings for systolic blood pressure (SBP).A plethora of studies has demonstrated that the culture of T cells under limiting arginine concentrations impairs their function via downregulation of the CD3ζ subunit of the T cell receptor (TCR) complex (Fig. 3). Acute and chronic administration of L-arginine has been shown to improve endothelial function in animal models of hypercholesterolemia and atherosclerosis. The present study aimed to evaluate the effect of supplementation with Gln/Arg/HMB in patients undergoing heart surgery. In some medical conditions, supplementation with a combination of l-glutamine (Gln), β-hydroxy-β-methylbutyrate (HMB), and l-arginine (Arg) had promising effects on improving recovery. Subjects underwent continuous monitoring of BP and heart rate (HR) as well as intermittent determination of mixed expired NO concentration and plasma L-arginine and L-citrulline levels. Consistent with previous reviews, we found that L‐arginine may be promising for preventing pre‐eclampsia 26, 27. We also included only studies in which the treatment and control groups were from the same population to avoid bias. We found no association of L‐arginine with admission to NICU, mean gestational age at birth, neonatal mortality or stillbirth from low‐ or very low‐certainty evidence in women with pre‐eclampsia (Figure 4, Figure S4, Appendix S4). We found no association of L‐arginine with caesarean section or mean diastolic BP from very low certainty evidence in women with pre‐eclampsia (Figure 3, Appendix S4). Several non-canonical mechanisms have been proposed to explain the beneficial cardiac effects of empagliflozin, including an inhibitory action on NHE1, thereby causing a reduction in intracellular Na+ (Na+i) 96,97. Moreover, in the current update of the American Council of Cardiologists consensus practice guidelines, gliflozins are indicated as add-on therapy to Angiotensin Receptor Neprilysin Inhibitors (ARNI)/Angiotensin Converting Enzyme Inhibitors (ACEI)/Angiotensin Receptor Blockers (ARB) and evidence-based Beta Blocker (BB) with diuretic agents, especially in patients belonging to New York Heart Association (NYHA) class II-IV and meeting GFR criteria . Among these findings, a substantial improvement of different cardiovascular outcomes emerged, suggesting their potential use even in other cardiovascular conditions. Four out of 5 study patients were categorized as major or extreme severity of illness and risk of mortality; however, only 28.9% of patients had a diagnosis of malnutrition, most likely due to variation in coding.On the other, there are some papers suggesting that L-arginine is most effective when combined with other compounds in the nitric oxide synthesis pathway, like citrulline or other amino acids.This study involves human participants and was approved by Ethics Committee of Renji Hospital and Swedish Ethical Review Authority.Finally, the study is an additional example for the benefit of absolute quantitative numbers obtained from MRI data.Along similar lines, activated Arg2−/− mouse T cells present enhanced in vitro survival and increased intracellular arginine levels—the latter being indicative of reduced arginase activity in these cells .Perfusion Index-blood flow (PI-BF) levels also increased, indicating the effect of L-arginine even when added to the biscuits.In parallel to a need for a better understanding of arginine metabolism in other immune cell lineages, some aspects of arginine relevance for immune cell biology remain unaddressed.ED is a disorder common in men and has extremely serious negative effects on the quality of life of men worldwide (27). Taken together, these observations suggest that the intracellular arginine concentration and its regulation by Arg2 dictate Treg expansion and survival in different microenvironments, and unveil Arg2 as a putative therapeutic target in both autoimmune and neoplastic diseases. Notably, pharmacological inhibition of arginases increases in vitro activation and survival of human T cells, which express ARG2 but not ARG1 . Mounting evidence suggests that the intracellular metabolism of arginine profoundly alters T cell function. PRMTs regulate transcription, splicing, RNA biology, the DNA damage response and cell metabolism; these fundamental processes are altered in many diseases. I think, because of the financial problems we don´t will have a well performed double blinded long-term study in the future. L-Arginine supplement was used in sport, but its positive effects on it are not sure1. For this issue it is necessary to perform long-term studies. Schachter, A., Goldman, J. A., and Zukerman, Z. Treatment of oligospermia with the amino acid arginine. Elam, R. P., Hardin, D. H., Sutton, R. A., and Hagen, L. Effects of arginine and ornithine on strength, lean body mass and urinary hydroxyproline in adult males. Morgante, G., Scolaro, V., Tosti, C., Di, Sabatino A., Piomboni, P., and De, Leo, V. Treatment with carnitine, acetyl carnitine, L-arginine and ginseng improves sperm motility and sexual health in men with asthenopermia. L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency Regardless of the physiologic, pathologic and species differences in these animals, intravenous supplementation of arginine increased plasma arginine levels, but it returned to the baseline with 4-5 hours after administration. Arginine exposure and clearance after supplementation are influenced by the patients’ age and the types and stages of the targeted diseases. In 2016, El-Hattab et al. reported a controlled crossover study of 5 pediatric patients with MELAS syndrome, with five healthy pediatric participants serving as controls, given citrulline and arginine. Flow chart of the study. Informed consent was obtained by all patients before testing, and the experimental protocol was approved by the Ethical Committee of Campania Nord. ROS generation was quantified using MitoSOX™ Red (Molecular Probes Inc, M36008), incubating cells for 10 min at 37°C and 5% CO2, as we previously described (6, 40). The dose of L-Arginine was based on previously published clinical trials (33, 34). Restoring metabolism of myeloid cells reverses cognitive decline in ageing. By metabolizing L-arginine, arginases compete with nitric oxide synthase (NOS), including endothelial, inducible, and neuronal NOS (eNOS, iNOS and nNOS, respectively), for their common substrate L-arginine, leading to decreased NO production in endothelial cells, macrophages and in the neural tissue 18–20. Ast, J., Jablecka, A., Bogdanski, P., Smolarek, I., Krauss, H., and Chmara, E. Evaluation of the antihypertensive effect of L-arginine supplementation in patients with mild hypertension assessed with ambulatory blood pressure monitoring. Oka, R. K., Szuba, A., Giacomini, J. C., and Cooke, J. P. A pilot study of L-arginine supplementation on functional capacity in peripheral arterial disease. Dietary supplementation with L-arginine fails to restore endothelial function in forearm resistance arteries of patients with severe heart failure. Arginine Supplementation in Cardiovascular Disorders Animal experimentation revealed that arginine administration prevents thymic involution after surgery and increases lymphocyte counts 27, 28. In this respect, a growing body of evidence indicates that over the course of immune system evolution, arginine has been selected as a metabolic node for the regulation of immune responses . Moreover, it has been hypothesized that the positively charged guanidium group interferes with the incorporation of arginine into the hydrophobic interior of proteins, exerting an evolutionary selective pressure against the incorporation of arginine into bigger and more complex proteins . The pKa value of 13.8 ± 0.1 of arginine’s guanidinium group implies that the arginine side chain remains protonated throughout all physiologic conditions, therefore, operating as a positively charged, basic amino acid. However, in this study, there was no significant statistical significance in IIEF scores (erectile domain), overall satisfaction, intercourse satisfaction, sexual desire, and IIEF-5, which may be related to the low dose of oral PAL. No adverse events were reported in any of the three studies. Therefore, more and better designed clinical trials are needed for further investigation. Another study with an international basis of patient information found that the prevalence of CAM use among people with CVD ranged from 4% to 61% (biologically-based therapies 22%–68%, herbal medicine 2%–46%, vitamins/minerals/dietary supplements 3%–54%, and mind-body therapies 2–57%) . Herbal products (echinacea, garlic, ginseng, ginkgo biloba, and glucosamine) and mind-body therapies (deep-breathing exercises and meditation) were used by 18% and 17% of patients, respectively, and constituted the most commonly used therapies . Cardiovascular disease (CVD) is the leading cause of mortality in the United States for both men and women . Additionally, the lack of a uniform definition of CAM and the huge diversity of the different methods, therapies, and dogmas of CAM make the studies difficult to compare . Another potential confounder is that traditional outcome measures may not capture the full effect of treatment, since many such therapies do not have well-recognized and understood physiologic mechanisms of action (i.e., qi or chi in Chinese medicine). Because of low-cost, low-risk, and nondrug intervention, the European Society of Cardiology recommended that exercise training should be provided by cardiac rehabilitation programs in patients with non-ST elevation acute coronary syndrome in 2015 . Exercise increases thioredoxin reductase 1 and decreases thioredoxin-interacting protein (TXNIP) in blood mononuclear cells and skeletal muscles, which promote antioxidant ability and eliminate free radical 104, 105. Through activating AMPK, exercise training increases sirt3 and PPARγ and the targets SOD1, SOD2, GPX1, and catalase, thus resulting in less ROS production and more ROS clearance in skeletal muscles . That means, all the proteins taking part in oxidative stress tend to recover to normal levels after exercise treatment . All studies retrieved from the electronic databases and reference lists were entered into endnote software (EndNote X6; Thomson Corporation) and duplicate studies were removed. The two reviewers also performed screening of the reference lists of relevant review articles and original papers that were selected for full-text review to identify potential eligible studies. Participants, interventions, comparisons, outcomes and study design are shown in Table 1. The present study was not prospectively registered. Thus, there is a demand to identify viable, anti-lipid agents that are able to pose cardio-protective effects without inducing any side effects. What role does lifestyle play alongside supplementation? Prescription phosphodiesterase‑5 inhibitors have robust efficacy data across a wide severity spectrum of erectile dysfunction. Interactions with anticoagulants (e.g., warfarin) have been observed when supplements contain high levels of vitamin K or flavonoids. Most over‑the‑counter male enhancement supplements are well tolerated at recommended doses, but adverse effects can occur. Ginseng also increases hypoglycemia with antidiabetes drugs, leads to falsely increased levels of digoxin, and decreases effectiveness of warfarin . For instance, garlic may interact with aspirin, clopidogrel, warfarin, or heparinoids to increase bleeding risk . The general public regards biologically-based therapies as safe, natural, and as having fewer side effects than conventional medications (29%–60% of CAM users) 6, 37. A new dietary supplement may be introduced and marketed rapidly despite containing new, experimental, or unregulated herbal ingredients, and many supplements contain ingredients or contaminants with adverse effects or interactions . Most patients believe that the government oversees the safety of CAM; however, the only requirement is for the manufacturer to send a copy of the product label to the FDA . Arginine supplementation improves exercise tolerance in db/db mice The mechanisms may be partial that exercise training leads to increased blood flow and shear stress, contributing to endothelial NOS (eNOS) expression, NO release, and artery relaxation. The endothelium is a single layer of cells in the intima of vessels separating blood from the tissue. Known as an endothelial-derived relaxing factor, NO contributes to not only endothelial-dependent relaxation (EDR) but also to the maintenance of endothelial function . However, studies showed that the strenuous short-term exercise activated platelets and promoted aggregation of platelets, thus increasing the risk of MI or cardiac arrest. This study found that arginine supplementation had no effect on endothelial function in younger, healthy men.On these ground, we sought to evaluate the effects of Arg supplementation on DC onset and progression, determining its impact on mitochondrial homeostasis in diabetic heart during the early stage of DC.PRMTs methylate arginine residues and other factors.NO is biosynthesized endogenously from Arg, O2, and nicotinamide adenine dinucleotide phosphate (NADPH) by three isoforms of nitric oxide synthase, which are termed endothelial (eNOS), neuronal (nNOS), and inducible (iNOS).In 2013, the Food and Drug Administration (FDA) of the United States approved canagliflozin as the first SGLT2 inhibitor as antihyperglycemic agent for patients with T2DM, followed by empagliflozin and dapagliflozin in 2014, and ertugliflozin in 2017 .However, prolonged supplementation with L-arginine generally has not been found to effectively treat cardiovascular related abnormalities, and under some conditions it has been found to be harmful.Individuals with specific health concerns, such as low blood pressure or heart disease, should seek medical supervision before including L-Arginine in their routine.Quyyumi, A. A. Does acute improvement of endothelial dysfunction in coronary artery disease improve myocardial ischemia?The intake of 2 g of L-arginine per day, for 45 days, could improve the lipid profile and FBS in male athletes, but has no effect on systolic and diastolic blood pressure.Suliburska et al. (2014) conducted a study on the effects of L-arginine supplementation (3 × 9 g/day for 6 months) on mineral concentration, lipid serum levels, glucose, fat content, and insulin resistance in patients with obesity. The assessment of ED in the clinical practice and in clinical trials is based on the administration of different questionnaires specifically validated for the evaluation and/or grading of ED; the aforementioned trials, designed for evaluating the effect of l-ARG supplementation, used standardized O’Leary and KEED questionnaires, addressing the overall sexual function by including erectile and ejaculatory function evaluated during both sexual activity with the partner and masturbatory activity. The discrepancies between the results of the various studies might be related not only to the dose of l-ARG or the period of l-ARG supplementation, as well as the population cohort and the study design, but also to the methodology used for the assessment of ED, which was relevantly different among the studies. In particular, one randomized, double-blind, placebo-controlled clinical trial demonstrated that daily oral administration of equal-lower doses (5 g/day) of l-ARG for a shorter period (1 month) compared to the current study significantly increased IIEF-6 score in 34 diabetic middle-aged men affected by mild–moderate ED of unknown etiology . Benetos A, Petrovic M, Strandberg T. Hypertension management in older and frail older patients. PM is the guarantor of this work and, as such, had full access to all the data in the study and takes full responsibility for the integrity of the data and the accuracy of the data analysis. We tested this hypothesis in a clinical trial. Comorbidities such as hypertension are known to play a key role in increasing the risk of mortality, hospitalization, disability and cognitive impairment. Once inside cells, there are multiple pathways for Arg degradation to produce NO, ornithine, urea, polyamines, proline, glutamate, creatine, and/or agmatine (Wu and Morris 1998). Arg transport by cells involves the system y+ (a high-affinity, Na+-independent transporter) and Na-dependent transporters (e.g., b0,+, B0,+, and y+L) in a cell-specific manner (Grillo et al. 2008). Animals (Wu et al. 2004c) and humans (Moinard et al. 2008) with functional kidneys have high rates of Arg synthesis from endogenous and exogenous citrulline. In total, 631 participants were enrolled in the selected articles, out of which 359 individuals were allocated to l-arginine supplementation group and 272 subjects to the control group. Therefore, we conducted a meta-analysis of those randomised controlled trials (RCT) to examine the efficacy of l-arginine supplementation as a lipid-lowering agent. For instance, some trials report that l-arginine supplementation induced a reduction in circulating concentrations of lipid parameters(Reference Dashtabi, Mazloom and Fararouei20–Reference Bahrami, Mozaffari-Khosravi and Zavar-Reza23), while others report no significant effect(Reference Suliburska, Bogdanski and Szulinska18, Reference Bogdanski, Suliburska and Grabanska24–Reference Clarkson, Adams and Powe30). The above studies also show that when supplementation with L-arginine healthy animals, does not appear to have side effects. Also, both studies showed that L-arginine supplementation after injection of alloxan did not affect hyperglycemia. Both of these studies clearly showed that TBARS, a byproduct of lipid peroxidation, is elevated in diabetes, and L-arginine supplementation significantly lowers it. Another study, conducted by Ortiz et al. (2013), investigated the physiology of mitochondria and their production of NO in cortex cells of rats with induced diabetes and the effect of L-arginine administration on these cells. Fu et al. (2005) performing a study on Zucker rats with diabetes demonstrated that a number of parameters improves after L-arginine supplementation. For example, oral supplementation of L‐arginine was used in combination with various other metabolites/salts in several studies that may cause synergistic or antagonistic effects (McConell, 2007).The most commonly observed side effects included mild gastrointestinal discomfort and headache, but these were similar between the two active treatments, indicating no major safety concerns specific to IBA .Supplementation with citrulline resulted in more significant increases in nitric oxide production rate, arginine and citrulline flux, and plasma arginine and citrulline concentrations.Differences in the patient populations may have contributed to the different results regarding plasma arginine.Although we pre-specified subgroup analyses, we underscored that (i) NOx and ADMA subgroup meta-analyses were based on few studies, and (ii) distinct sample sets of individuals precluded us from exploring subgroup estimates of blood flow.HRR refers to the declining rate of heart rate and is recognized as an indicator of cardiac prognosis .31) L-Arginine significantly improves the function of the kidneys and helps to prevent age-related degradation of the kidneys. One important finding is that these effects may indeed vary as a function of the amount of arginine, its form and notably the metabolic status of the population. Cardiac function (based on echocardiography and six-minute walk test), blood pressure, and quality of life (based on the Minnesota living with heart failure questionnaire) were assessed. Although our study focuses on a different clinical setting, these findings suggest the need for further research to ensure patient safety before L-arginine can be recommended post-CABG. Previous studies, such as the RCT in post-infarction patients , have raised concerns about increased mortality with L-arginine use in such populations. Baseline corrected plasma L-arginine concentrations measured after oral or intravenous L-arginine administrations showed a bi-phasic elimination pattern . Infectious conditions such as endotoxemic sepsis can severely reduce citrulline bioavailability, although arginine pharmacokinetics remains largely unaltered . Higher clearance of arginine in intravenously administered animals was observed in pregnant, neonatal, and lean animals when compared to that of their counterparts–non-pregnant, adult and obese animals, respectively. Determination of optimized L-citrulline dosing was outside the study scope, and the study revealed that controls for baseline citrulline concentrations are of potential consequence in future studies. In 2006, Smith et al. reported a randomized, placebo-controlled trial of 40 children undergoing surgery with cardiopulmonary bypass given oral L-citrulline supplementation in preventing postoperative pulmonary hypertension. Arginase As a free amino acid, arginine serves as the substrate for different nitrogen-containing compounds. One such amino acid is arginine, a proteinogenic α-amino acid that is encrypted in mRNA molecules for protein synthesis. In addition to being a building block for protein synthesis, arginine serves as a substrate for distinct metabolic pathways that profoundly affect immune cell biology; especially macrophage, dendritic cell and T cell immunobiology. A growing body of evidence indicates that, over the course of evolution of the immune system, arginine has been selected as a node for the regulation of immune responses. Osteoclastogenesis was significantly inhibited by L-arginine in a dose-dependent manner in WT and hTNFtg+/− cells (online supplemental figure S3C, D). To delineate whether L-arginine acts directly on osteoclasts, we isolated bone marrow cells from hTNFtg+/− and littermate control mice, and performed MCSF/RANKL-mediated osteoclast differentiation assays with or without L-arginine (online supplemental figure S3A). ΜCT analysis of tibial and vertebral bones showed that L-arginine treatment ameliorated bone loss with significant increases in bone volume and trabecular numbers (figure 1I,J, online supplemental figure S2D, E). We hypothesised that longer-term L-arginine treatment may have a better outcome. These results indicate that a moderate increase in L-arginine significantly lowered blood pressure and affected renal function and carbohydrate metabolism in healthy volunteers.Studies often show various, contradictory results, especially concerning the effects on lipid profile.PM is the guarantor of this work and, as such, had full access to all the data in the study and takes full responsibility for the integrity of the data and the accuracy of the data analysis.In vitro activation with phorbol myristate acetate (PMA), which bypasses the requirement for TCR signaling, does not suffice to rescue poor T cell proliferation in arginine-depleted conditions .Of note, these functions of ARG2 including activation of S6K1, p38MAPK, and p66shc appear to be independent of its L-arginine-urea hydrolase activity, but rely on its C-terminal 57, 69.Hence, the specific effects of L-arginine on osteoclast formation and purine metabolism might result from the overall combination of Arg-1 catalytic downstream metabolites.In this randomized crossover trial in 44 young men, supplementing with arginine and citrulline malate did not improve anaerobic exercise performance. Consulting a healthcare professional before starting supplementation is advised for those with pre-existing medical conditions. Gastrointestinal symptoms, such as nausea, diarrhea, abdominal pain, and bloating, are the most frequently reported side effects of L-Arginine. While experiencing any observable reactions, seek qualified clinical advice before continuing dosage plans engaged. The best time to initiate supplementation exists during mealtimes, embracing prior usage tips for compelling outcomes. Dietary intakes of the participants across tertiles of total L-arginine are presented in Table 2. Risk factors for which there were significant differences between participants with and without CHD were age, smoking status, anthropometric measures, blood pressure, lipid profiles, and serum creatinine. Mean dietary intakes of total L-arginine, plant-derived and animal-derived L-arginine was 4.0 ± 1.5, 2.2 ± 0.8 and 1.8 ± 0.9 g/d, respectively. Quality assessment of included studiesFurthermore, individuals show variability in autonomic recovery post-exercise, particularly in their heart rate recovery (HRR) and blood pressure (BP) responses.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Summary of clinical studies evaluating the efficacy and onset of action of ibuprofen arginine (IBA)After arginine enters mammalian cells through the membrane-bound transporters CAT1 and CAT2B, it is metabolized by one of the NOS enzymes.A thorough and extensive search of medical databases, including MEDLINE, PubMed, Embase, Web of Science, Scopus, Cochrane library, and Google Scholar, was conducted to find relevant RCTs reporting on the impact of L-arginine on inflammatory and cardiac markers in subjects undergoing CABG surgery.Further support for this approach may be seen in smooth muscle cells, where heightened arginine catabolic processes could result in increased production of collagen and enhanced cell proliferation attributable to the metabolism of ornithine into proline and polyamines, respectively.This, taken together with the short equilibration half-life between l-arginine plasma concentration and the effect, suggests a direct vasodilator action of l-arginine within the vasculature. There has been concern about arginine supplements and food sources leading to herpes outbreaks. L-arginine works best in combination with L-citrulline and L-taurine. L-Arginine’s role in nitric oxide production can also contribute to maintaining the integrity of the gastrointestinal lining, which is essential for preventing conditions such as leaky gut syndrome. Studies on multiple animal models and in a limited number of human subjects have shown that L-arginine can stimulate the development of brown adipose tissue mitochondria and induce the regulation of gene expression38. There is evidence that long-term L-arginine intake can increase insulin sensitivity and improve the glycemic indices29. Baseline and after intervention values of FBS, blood pressure and lipid profile are presented in (Table 3). Blood pressure was measured three times in every session after a 15 minute rest sitting down by mercury sphygmomanometer and the average blood pressure obtained was recorded at each stage. Participants with any of the aforementioned diseases were excluded from this study. Embla Arginine products contain Banaba Root, Chromium, Vanadium, B-Vitamins, Choline and Curcumin that help the body to repair damaged Endothelial cells. That combination is a recipe for cardiovascular problems. It signals the elastic interna to relax each time the heart beats. Endothelial cells are the layer above that protect that muscle. Details of data extraction from studies are presented in Table 1. These studies included one meta-analysis, one randomized controlled trials and two randomized, double-blinded, crossover studies. Only four studies met inclusion criteria and were included in this review topic. L-Arginine Relaxes Smooth Muscle of Isolated Large Arteries and Dilates Arterioles With its unique blend of ingredients and proven benefits, Cardio Miracle has the potential to be a game-changer in the realm of cardiovascular supplements. These antioxidants help combat oxidative stress and inflammation, both of which can impair nitric oxide signaling. It contains flavonoids and antioxidants that help protect blood vessels from damage and improve circulation. Before delving into the intricacies of Cardio Miracle, it’s crucial to grasp the significance of nitric oxide (NO) in the body. In the quest for better cardiovascular health, many individuals find themselves navigating through a sea of supplements, each promising miraculous results. Lastly, 2 (9.52%) patients with mild–moderate ED worsened to moderate ED and 2 (14.29%) patients with mild ED worsened to mild–moderate ED; 1 (7.14%) patient with mild ED dropped out at T1.Subjects under 18, those without the ability to understand informed consent and subjects diagnosed with cardiovascular disease during initial assessments were excluded.A previous study demonstrated that administration of l‐Arg meaningfully diminished the levels of IL‐2, IL‐6, and IFN‐γ which are considered noteworthy pro‐inflammatory cytokines .Hence, a constant need to search for novel or complementary targets to decrease the burden of stroke.Additional studies are required to elucidate the basis for the apparent discrepancies in results of these two studies.Proline, polyamines and NO play important roles in renal function, but high concentrations of these substances also contribute to renal injury and fibrosis (Satriano 2007).Either a fixed-effects or, in the presence of heterogeneity, a random-effects model was used to calculate the combined treatment effect.Corelease of nitric oxide and prostaglandins mediates flow-dependent dilation of rat gracilis muscle arterioles. All subjects underwent body composition analysis, 24 h blood pressure monitoring and pulse wave analysis at enrollment and at six months. The most commonly observed side effects included mild gastrointestinal discomfort and headache, but these were similar between the two active treatments, indicating no major safety concerns specific to IBA . In terms of overall efficacy, both IBA and ibuprofen achieved similar levels of peak pain relief, suggesting that while the speed of action differed, their maximum analgesic effects were comparable. The study demonstrated that both IBA and ibuprofen were significantly more effective in reducing menstrual pain compared to placebo. Each participant underwent three treatment periods, receiving a single or double dose of IBA, ibuprofen or placebo in a random sequence. The main findings in changes of the biomarkers, namely increase of SDMA and reduction of hArg in plasma, show a high degree of similarity in responses to treatment for both empagliflozin and dapagliflozin. In plasma hArg was significantly reduced and SDMA increased after treatment with both SGLT-2 inhibitors. ClR of Arg was not significantly altered in the empagliflozin study. Similarly to Ae, ClR of hArg was not significantly altered in the empagliflozin study. To clarify this issue, we conducted a clinical study to investigate the plasma concentration of ADMA in 30 patients who underwent PCI with stent implantation.Biochemical investigations included measurement of circulating NOx, malondialdehyde (MDA), and lipid profile markers, as well as dimethylarginine dimethylaminohydrolase (DDAH) and ACE activities.Benefits of EN include maintenance of gut integrity, modulation of the systemic immune response, and the attenuation of disease severity .Briefly, the free arginine pool is derived from diet, endogenous synthesis and turnover of cellular protein (Figure 1) (Morris, 2004; Wu and Morris, 2004).Life Extension offers a balanced formula with added Vitamin C, supporting heart health, nitric oxide production, and immune function.Eighteen local domestic rabbits (male) were introduced and allocated into 3 groups (6 rabbits per group) and the duration of the study was 12 weeks.Various studies show that the duration of physical activity but not intensity is the primary factor leading to benefits for humans . But too much cholesterol will become risk factors for human diseases like heart disease, stroke, and atherosclerosis . Various studies show an obvious dose-response relationship between increased physical activity and decreased occurrence rate of CVD including reduced blood pressure, body weight, ox-LDL, and elevated glucose tolerance. High glucose links to dysfunctions of glucose uptake and catabolism and induces high oxidative stress, dysfunction of endothelial cells. Although our analysis is exploratory, the upregulation in benzoate analytes suggests that the microbiome and gut permeability may be critical in determining responder versus nonresponder status after arginine supplementation. Responders had higher levels of methyl-4-hydroxybenzoate sulfate and X at 0 h and 1.5 h in both the arginine and placebo supplement groups. Interestingly, 3-methyladipate was elevated in responders 1.5 h after arginine supplementation, and may represent the mobilization of fatty acids for skeletal muscle uptake. As known endothelial dysfunction is an early pathophysiological feature and an independent predictor cardiovascular disease. Effects of treatment with SGLT-2 inhibitors on arginine-related cardiovascular and renal biomarkers. In the dapagliflozin group a ClR reduction of ADMA by verum treatment in comparison to placebo is indicated by the linear mixed effects model, however, this is not congruent with the other analysis performed in the present study. The proposed potential mechanisms for L-carnitine’s cardiovascular benefits have been the focus of much research. Many trials and meta-analyses have purported to show that L-carnitine supplementation can reduce mortality and arrhythmia events. Fish odor syndrome is a syndrome in which a lack of, or diminished, flavin-dependent monooxygenase (FMO3) activity (which converts TMA to TMAO) leads to the accumulation of TMA in the blood . The majority of users who report gastrointestinal side effects reported that they are dose-dependent . Moreover, infused arginine—but not enteral arginine—acts as a secretagogue, stimulating the secretion of anabolic hormones, such as insulin, glucagon, prolactin, somatostatin, pancreatic polypeptide from the pancreas, and adrenal catecholamines 19–21. Arginine also regulates its synthesis via allosteric activation of the synthesis of N-acetylglutamate , a cofactor subsequently required for glutamine metabolization into arginine. Besides protein anabolism and ammonia detoxification, arginine regulates a plethora of biological processes, such as vasodilation, calcium signaling, regeneration of adenosine triphosphate, neurotransmission, cell proliferation, and immunity 2, 3. The dependence on dietary arginine provision during periods of increased demand for this amino acid consequently accounts for the conditional essentiality of arginine . To identify duplicates and any potential missing studies, all titles and abstracts from the search were cross-referenced. A systematic search of the scientific literature was performed to investigate the effect of Arg supplementation on sports performance. These positive effects related with strength could be explained because of Arg enhance GH-releasing hormone, suppresses the endogenous GH-inhibiting hormone and increases insulin-like growth factor 1 (IGF-1) 37,38. Citrulline, an alpha-amino acid that is metabolized to L-arginine, when given orally, is more effective than L-arginine in improving arginine plasma concentration because it is not the substrate of hepatic or intestinal arginases . For the last two decades, supplemental arginine was useful in improving clinical outcomes in children with UCD 26, 27. Published literature shows that supplemental arginine can replenish NO deficiency and thus can improve blood circulation in the cerebral microvasculature 22, 23. Health Coaching Patients assigned to empagliflozin had a greater likelihood (20–40%) of improvement in New York Heart Association (NYHA) functional class and were less likely to experience worsening of their NYHA class 37,38. Other cardiovascular benefits of SGLT2 inhibitors substantiated by these trials include a decreased incidence of atrial/ventricular arrhythmia and anemia 23,24. Dapagliflozin met the primary safety endpoint of non-inferiority for major adverse cardiovascular events (MACE) and achieved a statistically-significant reduction in the composite endpoint of hospitalization for HF or cardiovascular death . To specifically explore the effects of SGLT2 inhibitors on HF, several randomized controlled trials have been completed. The key secondary endpoint was the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke plus hospitalization for unstable angina. In the following, we consider the role of arginine in the synthesis of other essential metabolites. How different cell types balance their use of arginine between protein synthesis and the support of these additional uses is poorly understood. However, unlike glutamine, serine, and glycine, arginine is semi-essential (Morris, 2016). In contrast, the role of arginine as a molecular precursor has been underappreciated. Only English language publications were retrieved that provided quantitative statistical analysis of outcomes on blood pressure and immune function. However, there is much discrepancy in the literature when it comes to randomized controlled studies, and so this umbrella review of published meta-analyses was performed to examine the efficacy of l-arginine's role as a therapeutic agent. However, the use of distinct l-arginine sources, intervened populations, and treatment regimens may have yielded confusion about their efficacy. L-Arginine supplementation is a potential therapy for treating cardiovascular and metabolic diseases. Seventy-five patients assigned to receive L-arginine and 35 to receive placebo successfully completed the study protocol (Fig. 1). Before starting and at the end of the 3-week treatment with L-arginine or placebo the patients performed a 6MWT and underwent BRPE scale evaluation (described below). L-arginine is a semiessential amino acid involved in a number of biologic processes; among these, L-arginine is the substrate used by nitric oxide synthase to produce NO, which is a fundamental endothelial relaxation factor driving cardiovascular homeostasis (Gambardella et al., 2020a). For instance, L-arginine along with its downstream metabolites may control apoptosis and efferocytosis, interfering with the cell fate.54 55 Nevertheless, it would require further studies to analyse L-arginine effect on osteoclast in non-inflammatory conditions. Moreover, with the two strains of Arg-1 deficient cells, we demonstrated that Arg-1 mediates the inhibition on osteoclastogenesis by L-arginine. L-arginine was sufficient to interfere with the TNFα-cJun-Arg1 axis, resulting in reduced c-Jun production and increased Arg1 expression, hence decreasing osteoclastogenesis. These results indicated that the effect of L-arginine on osteoclastogenesis might be due to an autoregulatory mechanism of L-arginine to determine osteoclast fate,37 where the affinity and the catalytic efficiency of the key enzymes, arginases and NOSs, depend on the concentration of L-arginine.38–40 Moreover, L-arginine reduced osteoclastogenesis in cells from WT and hTNFtg mice, as well as from synovial inflammatory macrophages. Studies show that taking l-arginine during pregnancy may help prevent preeclampsia, lower your blood pressure, and help with your baby's growth. L-arginine may interact with certain medications that lower blood pressure. In clinical trials, l-arginine has been used safely with minor side effects for up to three months. Because authors were employees or received direct or indirect payment from the study sponsor for this work, potential biases were minimized by presenting both significant and non-significant results. Further, because the study did not include chart review, the administration, adequacy, and timing of nutrition provided, as well as the total dose of antidiarrheals and the magnitude and severity of diarrhea could not be accounted for. Study limitations reflecting our use of observational administrative data include reliance upon diagnoses and procedure coding (e.g., codes do not differentiate between diagnoses on admission vs clinical outcomes). In association with immune dysfunction, inflammation, and oxidative stress, the body’s response to critical illness and injury involves trace elements and select vitamins. European guidelines on surgical nutrition also include nucleotides on the list of EN immunonutrients suggested for malnourished patients having major cancer surgery . A random-effects model was used to estimate the weighted mean difference (WMD) and 95% CI. Moreover, the durations of these studies have been limited, for the most part, to only 3 days to 6 weeks in length. Superoxide anions can scavenge NO to form peroxynitite and also lead to the production of other reactive oxygen species 5,6. This uncoupling is primarily caused by a reduction in intracellular tetrahydrobiopterin availability secondary to oxidative stress, elevated levels of homocysteine, aging and inadequate nutrition 65,66. Group Leader Position in Nutrition and Health In states ofhypertension, diabetes, hypercholesterolemia and vascular inflammation a disorder occurs in the metabolic pathway of thesynthesis of NO from L-Arg which all together bring alterations of blood vessels. As a free radical, NO issynthesized in all mammalian cells by L-Arg with the activity of NO synthase (NOS). Consequently, this suppression of the NF‐κB signaling pathway is responsible for the anti‐inflammatory effect, effectively countering the pro‐inflammatory effects of NF‐κB. Polyamines are among the most nitrogen rich and highly charged aliphatic compounds that exist in the human body. Briefly, NO is a vasodilator in smooth muscle cells, it works as a retrograde neurotransmitter in synapses, and NO is secreted by myeloid cells to kill microbial pathogens (Keshet and Erez, 2018). As one of the most important messenger molecules in biology, the full description of NO’s function can be found in other literature (Lundberg and Weitzberg, 2022). Cancer cells take advantage of the creatine shuttle for their own proliferation and survival (Kazak and Cohen, 2020). Creatine-P, in turn, rapidly diffuses throughout the cytosol, where it donates its phosphate group back to ADP by cytosolic creatine kinase (CKM) to replenish the local ATP levels at sites of high ATP utilization. In addition, both control and experimental group’s SMD were subtracted to obtain the net treatment effect and pooled SD of changes scores were used to calculate variance. In order to compare the ingestion of Arg vs. placebo, the number of participants, the standardized mean difference (SMD), and the standard error of the SMD were performed for each trial. Indicate low risk of bias; indicate unknown risk of bias; indicate high risk of bias. Isocaloric diets were provided to participants for consumption for 3 d for each supplementation period. Peripheral arterial tonometry (PAT) was performed after the 1.5 h blood draw and questionnaire administration. Blood samples were collected at baseline (fasting), 1.5 h, 3.0 h, and 24 h after supplementation. For each participant, each supplement (or period) blood sampling started at the same time. L-arginine appears to exert no effect in subjects with low ADMA levels, whereas in subjects with high ADMA levels, L-arginine restores the L-arginine/ADMA ratio to normal levels and thereby normalizes endothelial function. Recently it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of L-arginine metabolism by NO synthase, may determine a subject's response to L-arginine supplementation. In several controlled clinical trials, long-term administration of L-arginine has been shown to improve the symptoms of cardiovascular disease. L-arginine plasma levels are not significantly reduced in most disease conditions, except end-stage renal failure during hemodialysis treatment. Animal experiments and clinical trials are needed to improve knowledge on the physiology of L-homoarginine and differentiate its role as marker and mediator in cardiovascular disease. L-arginine content of food items (mg/100 g of foods), were multiplied by the amount of daily intake of food items; dietary total intake of the participants was estimated by summing up of the obtained values. A validated 168-item food frequency questionnaire (FFQ) was used to assess typical food intake, and total L-arginine intake as well as L-arginine from animal and plant sources, over the previous year. Fasting blood samples were taken after 12–14 h from all study participants at baseline and follow-up phase. For blood pressure (BP) measurements, after a 15-minute rest in the sitting position, two measurements of BP were taken on the right arm, during a standardized mercury sphygmomanometer; the mean of the two measurements was considered as the participant’s BP. 23) L-Arginine improves peripheral vascular disease. 19) L-Arginine reduces blood clots and strokes. 17) L-Arginine improves walking distance in peripheral vascular disease. NOS oxidizes arginine to citrulline and NO, and ARG hydrolyzes arginine into ornithine and urea. Therefore, overall arginine metabolism depends on the activity of the NOS and ARG enzyme families. We and others have also found that increased arginine metabolism in melanoma tumors and their microenvironment mediates a previously unappreciated system that is fundamental to sustaining the growth of many cancers while specifically causing immunosuppression (11–14). The third NOS, endothelial NOS, regulates NO production in endothelia and is responsible for vascular relaxation (9). Among others, in CABG patients but more so in valve replacement patients, the level of ADMA was high and correlated with hypertrophy of the left ventricle and other parts of the heart. We extended our interest to patients who underwent CABG surgery with or without CPB and measured and compared serum levels of ADMA, SDMA, and L-Arg from coronary sinus (CS) and from peripheral veins (Cziraki et al., 2011). We suggest that this is due to reduced cellular uptake of L-Arg (Bae et al., 2005) and/or increased proteolysis (Chia et al., 2009) resulting in release of free amino acids, such as L-Arg and methylated-arginines. Thus in order to see the importance of L-arginine and its derivatives we measured the plasma level of L-Arg, ADMA, and SDMA (Figure 4) immediately after PCI (Ajtay et al., 2010). The patients/participants or their legal representatives provided a written informed consent to participate in this study. In conclusion, to the best of our knowledge, our study is the first to demonstrate that oral L-Arginine supplementation significantly improves cognitive impairment in hypertensive older adults. We found that the co-treatment of HUVECs with Ang II and L-Arginine significantly attenuated mitochondrial ROS production compared to Ang II alone (Figure 3). The long term mono supplementation with high doses of L-arginine can exert detrimental effects (Huang et al.). A reduced NO formation by insufficient supply of L-arginine leads to an endothelial dysfunction that compromises the endogenous supply of energetic resources to enable regeneration (Curis et al., 2005; El Assar et al., 2016; Jankovic et al., 2017). Nucleotides support replication of rapidly dividing cells (i.e., lymphocytes) by providing a source of purine and pyrimidine bases for DNA/RNA production, and in pre-clinical studies have been shown to help clear pathogens through the action of macrophages and natural killer cells 20, 52. In the current study, all patients received about 1 liter of formula per day with the difference in supplemental L-arginine being approximately 7.7g/L between HAF and LAF. The median 7 days study patients received HAF or LAF is comparable to an 8–9 day mean observed in a multi-center trial comparing immunonutrition containing L-arginine, n-3 fatty acids, and nucleotides with standard formula . 3) In VSMC, enhanced Arg-I or Arg-II activity promotes cell proliferation and collagen production through their downstream metabolites derived from L-arginine, polyamine and L-proline, respectively. The role of Arg-II in vascular diseases is further confirmed by a study showing that endothelial specific Arg-II transgenic mice on ApoE−/− background reveal accelerated atherosclerosis 28•. Our recent study demonstrates a positive cross talk between S6K1 and Arg-II in endothelial cells, which is importantly involved in vascular endothelial aging, endothelial-monocyte interaction due to enhanced endothelial expression of adhesion molecules VCAM-1 and ICAM-1 through uncoupling of eNOS. Other important regulatory signals for arginases are the small G-protein RhoA and its downstream kinase ROCK 23, 53, p38mapk as well as S6K1 as demonstrated by our most recent studies 13•, 14••. Together, these examples demonstrate that dietary Arg supplementation has remarkably positive effects on numerous physiological systems in mammals. In young men under stressful conditions, Arg supplementation enhanced neuroendocrine and cardiovascular health as well as mood (6). It also had positive effects on immune, muscle, brain function, metabolism, and tissue repair. While Arg affects most physiological systems in mammals, its effects on reproduction are remarkable and have far-reaching consequences. L-arginine (Arg) is a dietary amino acid that is, like others, incorporated into proteins. Taken together, our data indicate that L-arginine potentiates the response to CR independently of age, sex, baseline functional capacity, and comorbid conditions. We hypothesized that L-arginine could enhance physical capacities in patients who underwent CR after AMI. L-arginine inhibits arthritis and bone loss by reprogramming osteoclast metabolism. Supplementation with l-arginine, an amino acid naturally found in many protein-rich foods, has previously been shown to alleviate experimental arthritis, but its influence on inflammatory bone loss and the underlying mechanisms were unclear. Gatsiou, A., Stellos, K. RNA modifications in cardiovascular health and disease. L-arginine (2-Amino-5-guanidinovaleric acid-Arg) is a conditionally essential amino-acid, that is mainly formed in the urea cycle . The review explores l-arginine pharmacodynamics, pharmacokinetic aspects, and molecular mechanisms in prediabetes and past or ongoing trials about the role of this molecule in prediabetes. Our review aims to summarize the current literature on the role of l-arginine in prediabetes as a therapeutic agent for this condition and as a preventive strategy against progression to diabetes. Regarding vitamin D, several studies have been conducted, and recently, two meta-analyses were published, demonstrating a reduction in the development of new-onset diabetes in individuals with prediabetes treated with vitamin D supplementation. Whether L-arginine supplementation under the condition of "relative L-arginine deficiency" causes detrimental effects due to production of other undesired metabolites from L-arginine via arginase such as urea and L-ornithine which is further metabolized to polyamines, is not fully clear 18, 21, 22. These results have challenged the hypothesis whether L-arginine deficiency exists under disease conditions and whether arginase impairs endothelial function through depleting L-arginine bioavailability for endothelial NO production. The impact of L-arginine supplementation, particularly chronic supplementation for treatment of cardiovascular diseases seems detrimental. No effect or no sustained effects on endothelial function 33–35, and even harmful effects on atherosclerotic lesion formation in Apolipoprotein E (ApoE)/iNOS double knockout mice have been reported with L-arginine supplementation . Though several groups demonstrated that supplementation of L-arginine improved endothelium-dependent vasodilation in disease animal models or patients with cardiovascular diseases 31, 32, numerous studies with supplemental L-arginine therapy either in animal models or humans do not show consistent results. This study used real-world data in a heterogeneous patient cohort from multiple US hospitals to examine differences in association between ICU LOS and the receipt of different isocaloric and isoproteic immunonutrition formulas containing either higher or lower amounts of L-arginine and other ingredient differences. Although similarly designed for nutrition and tolerance in critically ill patients, immunonutrition formulas differ in amount and type of immunonutrients, i.e., arginine and other micro and macronutrients 17, 27, 28. Recent work showed that critically ill patients who received standard high-protein EN were older, were less likely to be surgical or trauma patients, had shorter LOS, and had higher total cost per day in adjusted analyses compared to patients that received arginine-supplemented enteral immunonutrition . Higher arginine immunonutrition formula may play a role in improving health outcomes in primarily surgical critically ill patients. Arg indirectly is involved in cell signaling by being metabolized to NO, which has numerous tissue effects including vasodilation.Cardiovascular Reviews （CR） publishes peer-reviewed research articles across basic, translational, and clinical cardiovascular medicine.ADMA is synthesized by protein arginine methyltransferase type I (PRMT-1) (Boger, 2005).In general, administration of the inhibitors resulted in improvement of pathological features, usually ascribed to increased NO production and activity of NO-dependent processes.(A) Forest plot stratified by intervention duration for systolic blood pressure (SBP).Eligibility criteria included randomized clinical trials and interventions based on oral supplementation of l-arginine with a minimum duration of three days; comparison groups consisted of individuals with the same disease condition receiving an oral placebo substance.1991 The effects of increase testicular temperature on spermatogenesis in the stallion J Reprod Fertil Suppl –134. In addition, biochemical markers have great variability depending on the measurement technique, time of the day, and type of patients, etc. . In this regard, we point out that trials herein summarized often evaluated physiological or clinical outcomes without assessing whether the expected biochemical effect was triggered (increase in bioactive NO). Sensitivity analyses for studies with a minimum duration of four weeks and studies in which participants did not use antihypertensive medications yielded similar results. So abnormality in platelet activation leads to a variety of atherosclerotic diseases mainly through excess thrombosis in small arteries like coronary arteries and blood vessels of the brain . Through forming thrombus, the platelets exert primary function of maintaining hemostasis of blood flow. Moderate-intensity exercise causes a vasodilatory response and decreases the vasoconstricting response and lipid in rat aortas, which exhibits a decrease in diastolic blood pressure 46, 47. There were significant changes, reduction of 4.8 mmHg for systolic blood pressure (SBP) and 3.2 mmHg for diastolic blood pressure (DBP). Exercise always leads to a postexercise hypotension, and both normotensive and hypertensive persons experience a transient reduction in blood pressure. However, enhanced oxidative stress present in congestive heart failure can reduce DDAH and increase PRMT 1 activity thus resulting in elevated ADMA serum concentration (Searles, 2002). ADMA plays an important role in the control of coronary vascular function. For that reason, ADMA may be useful as a diagnostic tool and as a risk marker (Vallance et al., 1992). On the basis of these findings it can be proposed that endogenous MLAs are regulators of NO-mediated dilations both by inhibiting NOS and via superoxide production interfering with NO. Figure 1. Schematic illustration of pathways for nitric oxide production and arginine catabolism. The peripheral blood samples also showed elevated ADMA level during CPB, whereas ADMA level did not changed during OPCABG. We collected intraoperative samples in which ADMA increased in the CPB patients for off-pump off pump CABG (OPCABG) and CPB patients (Figure 5). Akila et al. reported that coronary artery bypass grafting (CABG) can be executed with extracorporeal perfusion with cardiopulmonary bypass, which results in global ischemia in the affected area of the heart. Indeed, in 2023, a collaborative study between research groups from the Netherlands and Greece has generated a novel global SGLT2 knock-out mouse demonstrating that the beneficial cardiovascular effects of empagliflozin are independent of SGLT2 , at least in a model of cardiac ischemia/reperfusion injury. In the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic HF, SGLT2 inhibitors dapagliflozin and empagliflozin are recommended in all patients affected by HFrEF already in treatment with ARNI/ACEI/ARB, beta blockers, and Mineralocorticoid Receptor Antagonists, to reduce cardiovascular death and worsening HF. Nevertheless, further data are needed to better clarify their precise mechanism of action and off-target effects (see the section below) as well as to assess their efficacy and safety in other clinical conditions. Thus, the cardioprotective effects of SGLT2 inhibitors are also being investigated in other settings; in fact, in a variety of preclinical studies gliflozins have been shown to reduce acute myocardial ischemia/reperfusion injury 63,64. The arginine metabolism as a target for cardioprotection in patients with ST-segment elevation myocardial infarction (STEMI) remains insufficiently understood. L‐arginine could have a potentially beneficial role in CHF, acting through the nitric oxide (NO)‐L‐arginine pathway or by growth hormone increment. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. Arginine de novo and nitric oxide production in disease states. In this context, we posited that L-Arginine treatment could improve cognitive impairment in frail older adults for its beneficial action on endothelial dysfunction. We also observed that L-arginine significantly increased the efficiency of ATP synthesis in osteoclasts by switching the respiratory dependence from glycolysis to oxidative phosphorylation. L-arginine is converted into 2-oxoglutarate (also known as α-ketoglutarate) as a glucose precursor, which then directly participates in the energy metabolism through OXPHOS.51 Moreover, it is likely that inosine that is altered in our models, might be an alternative carbon source and energy provider for osteoclasts.52 Reprogramming of the energy metabolism of immune cells influences cell fate and function of immune cells. L-arginine mitigated osteoclastogenesis induced by TNFα, which boosts RANKL-induced NF-κB and MAPK-AP-1 activation and thereby promotes NFATc1-mediated osteoclastogenesis.5 41 In macrophages and osteoclasts, L-arginine and TNFα signalling seems interconnected. The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. Ohtsuka Y, Nakaya J. Effect of oral administration of L-arginine on senile dementia. Interaction of L-arginine and phosphodiesterase inhibitors in vasodilation of the porcine internal mammary artery. Clarkson P, Adams MR, Powe AJ, et al. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. Creager MA, Gallagher SJ, Girerd XJ, et al. L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. Most of the known cardiovascular effects of L-arginine are exerted via its conversion to nitric oxide by nitric oxide synthase. In this context, Porto et al. (2021) conducted a systematic review of the effects of L-arginine supplementation on hypertensive adults post-exercise, involving a sample of 60 individuals. This study highlights a particular context in which L-arginine supplementation might not provide the expected benefits. In conclusion, the effects of L-arginine supplementation on human physiology appear to be multicausal and dose-related. Evidences indicate that exercise reduces ROS, improves endothelial function, and increases levels of elastin, fibrillin, and NO. In renovascular hypertensive rats, ROS released by vascular endothelial cells impairs EDR by decreasing NO production and facilitating vasoconstriction. ROS overproduction, decreased antioxidant enzymes, and the downstream targets damage the subcellular organelles, thus impairing the cardiovascular system. Exercise training has beneficial roles in autonomic function, as indicated by improved heart rate recovery (HRR) and heart rate variability (HRV) in various populations, such as in sedentary individuals and chronic heart failure patients . Nascimentoet al. showed that L-arginine supplementation in overweight men for 7 days reduced LDL and increased HDL, results that agree with the results of our study. Lekakis and colleagues found similar results where a daily 6 g oral dose of L-arginine did not have a significant effect on blood pressure of patients with essential hypertension23. In a study conducted by Natarajanet al., supplementation with L-arginine improves glycemic sensitivity in patients with diabetes30. The results showed that L-arginine supplementation significantly decreased the levels of FBS, triglycerides, LDL and cholesterol and a significant increase in HDL levels compared to the control group (P0.05) (Table 3). The levels of total cholesterol, triglycerides, C-reactive protein, serum creatinine, body mass index, body area index were determined. The 1st group made up 29 patients with hypertension combined with rheumatoid arthritis, 2nd group – 20 patients with rheumatoid arthritis, 3rd group – 20 patients with hypertension. Written informed consent was obtained from each patient before study inclusion. The datasets used and analysed during the current study are available from the corresponding author on reasonable request. In the open-label trials, the definition of a stroke-like episode relied primarily on clinical symptoms alone4,9,10 (e.g., headaches, nausea, and vomiting) without supporting evidence from neuroimaging or EEG. Deterioration in clinical status also occurred in 1 patient, which was attributed by the authors to the patient being prone to seizures. While AED use was not reported in 2 of the 3 open-label trials,4,10 AEDs were prescribed simultaneously in 7 of 9 patients who responded in the case reports. Fifteen patients (31%) had a positive response, with the severity or frequency of stroke-like episodes reduced. All patients reported by Koga et al.18 had been prescribed at least 1 AED. Sullivan, K. J., Kissoon, N., Sandler, E., Gauger, C., Froyen, M., Duckworth, L., Brown, M., and Murphy, S. Effect of oral arginine supplementation on exhaled nitric oxide concentration in sickle cell anemia and acute chest syndrome. Doutreleau, S., Rouyer, O., Di, Marco P., Lonsdorfer, E., Richard, R., Piquard, F., and Geny, B. L-arginine supplementation improves exercise capacity after a heart transplant. Huang, C. C., Lin, T. J., Lu, Y. F., Chen, C. C., Huang, C. Y., and Lin, W. T. Protective effects of L-arginine supplementation against exhaustive exercise-induced oxidative stress in young rat tissues. The elevated circulating concentrations of arginine generally returned to baseline levels within 4-5 h after administration, with the rates varying with the age and physiological status of the animals. Anticipating the future use of arginine to enhance fetal and neonatal growth as well as to treat diabetes and obesity, we performed studies in pigs, rats, and sheep to determine the pharmacokinetics of orally or i.v. Adhesion was reduced following L-arginine compared to placebo (42 92 vs. 50 91%, PB 0.01). A clean and streamlined supplement design informed our ratings of the L-arginine based nitric oxide supplements. Additionally, it also can help people who are looking to decrease their risk factors for heart disease. It also helps improve your body’s ability to process carbohydrates, which becomes impaired in metabolic syndrome and in people who are overweight or obese, and is an independent risk factor for heart disease. Havasu Nutrition L-Arginine pairs the nitric oxide boosting capabilities of L-arginine with widely-known nitric oxide boosters found in beet root extract.