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      Efficacy of Nutritional Interventions on Inflammatory Markers in Haemodialysis Patients: A Systematic Review and Limited Meta-Analysis

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          Abstract

          Low-grade chronic inflammation is prevalent in patients undergoing haemodialysis (HD) treatment and is linked to the development of premature atherosclerosis and mortality. The non-pharmacological approach to treat inflammation in HD patients through nutritional intervention is well cited. We aimed to assess the efficacy of different nutritional interventions at improving inflammatory outcomes in HD patients, based on markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). We searched PubMed, Cochrane Library, and Embase for randomized controlled trials (RCT) published before June 2017. Inclusion criteria included RCTs on adult patients on maintenance HD treatment with duration of nutritional interventions for a minimum 4 weeks. Risk of bias was assessed using the Jadad score. In total, 46 RCTs experimenting different nutritional interventions were included in the review and categorized into polyphenols rich foods, omega-3 fatty acids, antioxidants, vitamin D, fibres, and probiotics. Meta-analyses indicated significant reduction in CRP levels by omega-3 fatty acids (Random model effect: −0.667 mg/L, p < 0.001) and vitamin E (fixed model effect: −0.257 mg/L, p = 0.005). Evidence for other groups of nutritional interventions was inconclusive. In conclusion, our meta-analysis provided evidence that omega-3 fatty acids and vitamin E could improve inflammatory outcomes in HD patients.

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          Origin and physiological roles of inflammation.

          Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation - infection and tissue injury - are at one end of a large range of adverse conditions that induce inflammation, and they trigger the recruitment of leukocytes and plasma proteins to the affected tissue site. Tissue stress or malfunction similarly induces an adaptive response, which is referred to here as para-inflammation. This response relies mainly on tissue-resident macrophages and is intermediate between the basal homeostatic state and a classic inflammatory response. Para-inflammation is probably responsible for the chronic inflammatory conditions that are associated with modern human diseases.
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            Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential.

            Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.
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              NF-kappaB in renal inflammation.

              The NF-kappaB family of transcription factors regulates the induction and resolution of inflammation. Two main pathways, classical and alternative, control the nuclear translocation of NF-kappaB. Classical NF-kappaB activation is usually a rapid and transient response to a wide range of stimuli whose main effector is RelA/p50. The alternative NF-kappaB pathway is a more delayed response to a smaller range of stimuli resulting in DNA binding of RelB/p52 complexes. Additional complexity in this system involves the posttranslational modification of NF-kappaB proteins and an ever-increasing range of co-activators, co-repressors, and NF-kappaB complex proteins. Collectively, NF-kappaB regulates the expression of numerous genes that play a key role in the inflammatory response during human and experimental kidney injury. Multiple stimuli activate NF-kappaB through the classical pathway in somatic renal cells, and noncanonical pathway activation by TWEAK occurs in acute kidney injury. Under most test conditions, specific NF-kappaB inhibitors tend to reduce inflammation in experimental kidney injury but not always. Although many drugs in current use clinically influence NF-kappaB activation, there are no data regarding specific NF-kappaB inhibition in human kidney disease.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                23 March 2018
                April 2018
                : 10
                : 4
                : 397
                Affiliations
                [1 ]Dietetics Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia; khorbanhock@ 123456gmail.com (B.-H.K.); sreelakshmiprem07@ 123456gmail.com (S.S.N.); sham_0901@ 123456yahoo.com (S.S.)
                [2 ]Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; halimgafor@ 123456gmail.com
                [3 ]Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia; zulfitri@ 123456upm.edu.my
                [4 ]Department of Nutrition & Food Sciences, College of Liberal Arts & Sciences, Wayne State University, Detroit, MI 48202, USA; aa0987@ 123456wayne.edu
                [5 ]Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, 43126 Parma, Italy; alice.sabatino86@ 123456gmail.com (A.S.); enrico.fiaccadori@ 123456unipr.it (E.F.)
                [6 ]Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; karuthan@ 123456gmail.com
                [7 ]School of BioSciences, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Malaysia
                Author notes
                Author information
                https://orcid.org/0000-0002-4017-107X
                https://orcid.org/0000-0003-2098-7597
                Article
                nutrients-10-00397
                10.3390/nu10040397
                5946182
                29570616
                db62c14b-8078-408a-8baa-3b53939c53c8
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 February 2018
                : 21 March 2018
                Categories
                Review

                Nutrition & Dietetics
                haemodialysis,nutrition,inflammation,antioxidants,omega-3 fatty acids,polyphenols,fibres,systematic review,meta-analysis

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