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Modulating the Gut Microbiome in Multiple Sclerosis Management: A Systematic Review of Current Interventions.
Tsogka, A, Kitsos, DK, Stavrogianni, K, Giannopapas, V, Chasiotis, A, Christouli, N, Tsivgoulis, G, Tzartos, JS, Giannopoulos, S
Journal of clinical medicine. 2023;12(24)
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Multiple sclerosis (MS) is an autoimmune disease caused by the altered immune system mistakenly attacking the central nervous system. While genetics play a leading causative role in the manifestation of this disease, other contributing environmental factors can also exist, such as a disruption in the intestinal microbial composition. Previous research has shown that the bidirectional communication between the brain's and gut's health, also known as the gut-brain axis, may contribute to the prognosis of MS. Modulating gut microbial composition can be a therapeutic strategy in MS patients to manage symptoms and prevent disease progression. This systematic review assessed different protocols for modulating gut microbial composition, including dietary modifications, probiotic use, intermittent fasting, and faecal microbial transplantation. The review included thirteen studies that compared the effects of the above gut microbial modulation intervention protocols in MS patients with healthy participants. While different dietary modification strategies improved MS symptoms, probiotic supplementations and intermittent fasting reduced inflammation, and faecal microbial transplantation showed promising positive effects in a few reports. Due to the methodological limitations of the included studies, further robust studies are required to evaluate the beneficial effects of gut microbial modulation strategies in reducing the symptoms of MS patients. However, healthcare professionals can use the results of this study to understand the benefits of gut microbial modulation in MS patients.
Abstract
This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.
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Absence of Effects of L-Arginine and L-Citrulline on Inflammatory Biomarkers and Oxidative Stress in Response to Physical Exercise: A Systematic Review with Meta-Analysis.
Porto, AA, Gonzaga, LA, Benjamim, CJR, Valenti, VE
Nutrients. 2023;15(8)
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L-citrulline is a non-essential amino acid that acts as a precursor to L-arginine. L-arginine is a semi-essential amino acid used for nitric oxide production which is crucial for maintaining physiological function and immune regulation. Previous research has shown that L-citrulline and L-arginine supplementation may offer antioxidant and anti-inflammatory benefits in reducing exercise-related oxidative stress and inflammation. This systematic review and meta-analysis included seven randomised controlled trials to investigate the effect of L-citrulline and L-arginine on antioxidants, oxidative stress, and inflammatory and anti-inflammatory markers. This systematic review and meta-analysis showed no significant improvements in oxidative stress and inflammation followed by the supplementation of L-citrulline and L-arginine before exercise. However, further robust studies that include different dosages and exercise intensities are required to assess the beneficial effects of L-citrulline and L-arginine supplements to support physical exercise-induced oxidative stress and inflammation due to the heterogeneity of the included studies. Healthcare professionals can use the results of this study to understand the potential benefits of L-citrulline and L-arginine supplementation in people prone to producing proinflammatory cytokines.
Abstract
The repercussions on oxidative and inflammatory stress markers under the effects of arginine and citrulline in response to exercise are not fully reached. We completed a systematic review to investigate the effects of L-Citrulline or L-Arginine on oxidative stress and inflammatory biomarkers following exercise. EMBASE, MEDLINE (PubMed), Cochrane Library, CINAHL, LILACS, and Web of Science databases were used to record the trials. This study includes randomized controlled trials (RCTs) and non-RCTs with subjects over 18 years old. Those under the intervention protocol consumed L-Citrulline or L-Arginine, and the controls ingested placebo. We recognized 1080 studies, but only 7 were included (7 studies in meta-analysis). We observed no difference between pre- vs. post-exercise for oxidative stress (subtotal = -0.21 [CI: -0.56, 0.14], p = 0.24, and heterogeneity = 0%. In the sub-group "L-Arginine" we found a subtotal = -0.29 [-0.71, 0.12], p = 0.16, and heterogeneity = 0%. For the "L-Citrulline" subgroup we observed a subtotal = 0.00 [-0.67, 0.67], p = 1.00, and heterogeneity was not applicable. No differences were observed between groups (p = 0.47), and I² = 0%) or in antioxidant activity (subtotal = -0.28 [-1.65, 1.08], p = 0.68, and heterogeneity = 0%). In the "L-Arginine" sub-group, we found a subtotal = -3.90 [-14.18, 6.38], p = 0.46, and heterogeneity was not applicable. For the "L-Citrulline" subgroup, we reported a subtotal = -0.22 [-1.60, 1.16], p = 0.75, and heterogeneity was not applicable. No differences were observed between groups (p = 0.49), and I² = 0%), inflammatory markers (subtotal = 8.38 [-0.02, 16.78], p = 0.05, and heterogeneity = 93%. Tests for subgroup differences were not applicable, and anti-inflammatory markers (subtotal = -0.38 [-1.15, 0.39], p = 0.34 and heterogeneity = 15%; testing for subgroup differences was not applicable). In conclusion, our systematic review and meta-analysis found that L-Citrulline and L-Arginine did not influence inflammatory biomarkers and oxidative stress after exercise.
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The Gut Microbiota (Microbiome) in Cardiovascular Disease and Its Therapeutic Regulation.
Rahman, MM, Islam, F, -Or-Rashid, MH, Mamun, AA, Rahaman, MS, Islam, MM, Meem, AFK, Sutradhar, PR, Mitra, S, Mimi, AA, et al
Frontiers in cellular and infection microbiology. 2022;12:903570
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Cardiovascular disease (CVD) accounts for 31% of all-cause mortality worldwide. Irregularities in the composition of intestinal microbial composition, genetic factors, nutrition, metabolic irregularities, and smoking are among the potential causes of CVD. Intestinal permeability and translocation of endotoxins and bacterial metabolites to systemic circulation may trigger an immune response and inflammation, which may increase the risk of CVD. Synthesis of bacterial metabolites such as trimethylamine N-oxide (TMAO) by choline-inducing gut bacteria and reduced consumption of dietary TMAO precursors may elevate the CVD risk. This review explores the latest research on the role of gut microbiota in the development of atherosclerosis and CVD, as well as potential strategies to prevent CVD by targeting TMAO-producing gut bacteria. Elevated levels of TMAO in the bloodstream can lead to the buildup of cholesterol and ultimately result in atherosclerosis. However, consuming probiotics and fibre-rich foods can help regulate gut bacteria, reduce inflammation, and improve lipid profiles, all of which contribute to better cardiovascular health. More future robust studies are required to examine the mechanistic insights and confirm whether TMAO can serve as a biomarker for preventing CVD through the therapeutic modulation of intestinal bacteria.
Abstract
In the last two decades, considerable interest has been shown in understanding the development of the gut microbiota and its internal and external effects on the intestine, as well as the risk factors for cardiovascular diseases (CVDs) such as metabolic syndrome. The intestinal microbiota plays a pivotal role in human health and disease. Recent studies revealed that the gut microbiota can affect the host body. CVDs are a leading cause of morbidity and mortality, and patients favor death over chronic kidney disease. For the function of gut microbiota in the host, molecules have to penetrate the intestinal epithelium or the surface cells of the host. Gut microbiota can utilize trimethylamine, N-oxide, short-chain fatty acids, and primary and secondary bile acid pathways. By affecting these living cells, the gut microbiota can cause heart failure, atherosclerosis, hypertension, myocardial fibrosis, myocardial infarction, and coronary artery disease. Previous studies of the gut microbiota and its relation to stroke pathogenesis and its consequences can provide new therapeutic prospects. This review highlights the interplay between the microbiota and its metabolites and addresses related interventions for the treatment of CVDs.
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A Review of Dietary (Phyto)Nutrients for Glutathione Support.
Minich, DM, Brown, BI
Nutrients. 2019;11(9)
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Glutathione is made up of 3 amino acids (cysteine, glutamic acid and glycine) and plays important roles in the body, including oxidative stress reduction, supporting the immune system and contributing to detoxification processes. Evidence suggests that it is an important marker and target for treatment in many chronic, age-related diseases. This review article explores the evidence of nutritional strategies to improve glutathione status. The authors examine the evidence for supplementation of the precursors of glutathione as well as with various forms of supplemental glutathione itself, and the impacts on glutathione status and clinical impacts. Crucially, the review article provides information on dietary sources of precursors of glutathione and glutathione itself, which will provide Nutrition Practitioners with compelling information for use in clinic. Lean protein, brassica vegetables, polyphenol-rich fruits and vegetables, green tea, herbs and spices and omega-3 rich foods are all discussed in detail.
Abstract
Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.
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Vitamin D Supplementation in Central Nervous System Demyelinating Disease-Enough Is Enough.
Häusler, D, Weber, MS
International journal of molecular sciences. 2019;20(1)
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Vitamin D is associated with a reduced risk and severity of multiple sclerosis (MS). However, whether supplementing vitamin D level alters disease severity, is a matter of ongoing debate. This review looks at both clinical and pre-clinical evidence for supplementing vitamin D in people with MS. In vitro experiments show that vitamin D and its metabolites can alter function of various immune cells, mostly via interaction with vitamin D receptors (VDR). Results from human clinical trials, however, are mixed. Preclinical evidence suggests that high dose vitamin D supplementation, when leading to hypercalcaemia, a potentially serious side effect of excessive vitamin D intake, may worsen MS. The authors also review research which suggests mechanisms by which sun exposure can improve MS symptoms independent of vitamin D production. The authors conclude that moderate sun exposure, combined with adequate dietary intake of vitamin D, and in conjunction with a regular assessment of vitamin D serum levels (to avoid hypercalcaemia), might be the best strategy for patients with MS.
Abstract
The exact cause of multiple sclerosis (MS) remains elusive. Various factors, however, have been identified that increase an individual's risk of developing this central nervous system (CNS) demyelinating disease and are associated with an acceleration in disease severity. Besides genetic determinants, environmental factors are now established that influence MS, which is of enormous interest, as some of these contributing factors are relatively easy to change. In this regard, a low vitamin D status is associated with an elevated relapse frequency and worsened disease course in patients with MS. The most important question, however, is whether this association is causal or related. That supplementing vitamin D in MS is of direct therapeutic benefit, is still a matter of debate. In this manuscript, we first review the potentially immune modulating mechanisms of vitamin D, followed by a summary of current and ongoing clinical trials intended to assess whether vitamin D supplementation positively influences the outcome of MS. Furthermore, we provide emerging evidence that excessive vitamin D treatment via the T cell-stimulating effect of secondary hypercalcemia, could have negative effects in CNS demyelinating disease. This jointly merges into the balancing concept of a therapeutic window of vitamin D in MS.