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Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.
Jenkins, DJA, Kitts, D, Giovannucci, EL, Sahye-Pudaruth, S, Paquette, M, Blanco Mejia, S, Patel, D, Kavanagh, M, Tsirakis, T, Kendall, CWC, et al
The American journal of clinical nutrition. 2020;112(6):1642-1652
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Oxidative damage is a shared characteristic in chronic diseases such as cardiovascular disease (CVD), diabetes, cancer and ageing. Antioxidants mitigate the impact of oxidants and have been widely investigated in ageing and disease. However, the evidence for supplementary antioxidants has been mixed and some authorities have advised against the use of certain single nutrients for the prevention of CVD or cancer. This systematic review and meta-analysis focused on selenium due to its vital role in the antioxidant system and associations of low selenium blood levels with increased risk of CVD, cancers and death. The study included 43 randomised controlled trials (RCTs) evaluating the effect of supplemental selenium and antioxidants with or without selenium and their impact on CVD risk, cancer and all-cause mortality. Overall supplemental selenium or antioxidants alone did not seem to be associated with CVD outcomes, cancer, CVD and cancer mortality, or all-cause mortality. On close examination, a decreased risk was seen for CVD mortality when antioxidants were combined with selenium, whilst antioxidant mixtures without selenium demonstrated an increased risk in all-cause mortality. The findings did not seem to be influenced by dietary selenium intake. The authors suggested that inclusion of selenium as part of an antioxidant mix could be key for an antioxidant associated risk reduction. However, in the absence of further long term studies, a balanced antioxidant-rich diet was advocated as the safest approach. In clinical practice, where antioxidant support beyond diet is warranted, supplemental antioxidant use should be concurrent with adequate selenium supplementation, with dose benefits of 50-200mcg observed.
Abstract
BACKGROUND Antioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were antioxidant mixtures associated with reduced all-cause mortality. OBJECTIVE We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality. METHODS We identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS The meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002). CONCLUSION The addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42019138268.
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Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments.
Zuo, L, Prather, ER, Stetskiv, M, Garrison, DE, Meade, JR, Peace, TI, Zhou, T
International journal of molecular sciences. 2019;20(18)
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Reactive oxygen species (ROS) are produced during normal metabolic processes or can be induced by environmental factors. High levels of ROS in the cell can lead to oxidation causing cellular damage and a subsequent increase in inflammation, which is a significant contributor to disease. Age-associated increases in such chronic, low-grade inflammation is also referred to as inflammaging. This review summarizes how inflammaging plays a role in various age-related health conditions. Described are the mechanisms of how ROS and the age-related decline in cellular turn-over and immune activation contribute to the pathology of cardiovascular disease, cancer, neurodegeneration concerning Alzheimer’s and Parkinson’s disease, diabetes and rheumatoid arthritis. Furthermore, the authors discuss potential treatments that could assist in the management of such inflammaging-related diseases. These include vaccines to stimulate immune activity, stem cell intervention, drugs like metformin, nutritional and nutraceutical supplements like zinc, vitamin E, vitamins C, D, carotenoids, polyphenols and flavonoids like resveratrol, red algae extract and melatonin. Addressed are also general dietary concepts like calorie restriction, the benefits of the Mediterranean diet or a whole foods diet, and the potential of specific plant derived compounds like baicalin and sulforaphanes. The authors also briefly highlight the importance of the gut microbiome, as a poor gut microbiota has been associated with unfavourable age-related immune alterations and overall inflammaging. This review provides a comprehensive resource, detailing the effects and mechanisms of oxidative damage and its contribution to age-related diseases, including a list of interventions to consider when navigating the impact and risks associated with inflammaging.
Abstract
It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed in the elderly population. Inflammaging is associated with over-abundance of reactive oxygen species in the cell, which can lead to oxidation and damage of cellular components, increased inflammation, and activation of cell death pathways. This review focuses on inflammaging and its contribution to various age-related diseases such as cardiovascular disease, cancer, neurodegenerative diseases, chronic obstructive pulmonary disease, diabetes, and rheumatoid arthritis. Recently published mechanistic details of the roles of reactive oxygen species in inflammaging and various diseases will also be discussed. Advancements in potential treatments to ameliorate inflammaging, oxidative stress, and consequently, reduce the morbidity of multiple disease states will be explored.
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Changes in LDL Oxidative Status and Oxidative and Inflammatory Gene Expression after Red Wine Intake in Healthy People: A Randomized Trial.
Di Renzo, L, Marsella, LT, Carraro, A, Valente, R, Gualtieri, P, Gratteri, S, Tomasi, D, Gaiotti, F, De Lorenzo, A
Mediators of inflammation. 2015;2015:317348
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It is recognised that inflammation and oxidative stress may play a role in the development of heart disease. Red wine has previously been shown to lower inflammation and improve antioxidant status. This small, randomised, crossover trial aims to investigate if resveratrol in red wine causes these effects. The trial involved twenty-four healthy adults who took part in the four intervention arms, with a three week washout period in between. Blood markers and genomic information were measured at (1) baseline and after each intervention: (2) a high-fat McDonald’s meal (McDM), (3) McDM + red wine and (4) just red wine. While eating McDM alone raised markers of oxidative stress, having red wine with McDM lowered markers. The authors concluded that having red wine with a meal could reduce the levels of inflammation and oxidative stress normally seen after eating. It was suggested that moderate red wine consumption (2 drinks a day for men and 1 drink a day for women) could potentially lower the risk of heart disease, but longer term studies are needed before definite conclusions can be drawn.
Abstract
Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. Micronutrients modulate immune system and exert a protective action by reducing low density lipoproteins (LDL) oxidation via induction of antioxidant enzymes. We evaluated the gene expression of oxidative stress (HOSp), inflammasome (HIp), and human drug metabolism pathways (HDM) and ox-LDL level at baseline and after the intake of red wine naturally enriched with resveratrol (NPVRW), in association with or without a McDonald's meal (McDM). The ox-LDL levels significantly increase comparing baseline (B) versus McDM and decreased comparing McDM versus McDM + NPVRW (P ≤ 0.05). Percentages of significant genes expressed after each nutritional intervention were the following: (1) B versus McDM, 2.88% HOSp, 2.40% of HIp, and 3.37% of HDMp; (2) B versus McDM + NPVRW, 1.44% of HOSp, 4.81% of HIp, and 0.96% of HDMp; (3) McDM versus McDM + NPVRW, 2.40% of HOSp, 2.40% of HIp, and 5.77% of HDMp; (4) B versus NPVRW, 4.80% HOSp, 3.85% HIp, and 3.85% HDMp. NPVRW intake reduced postprandial ox-LDL and the expression of inflammation and oxidative stress related genes. Chronic studies on larger population are necessary before definitive conclusions.