The Biological Relevance of Direct Antioxidant Effects of Polyphenols for Cardiovascular Health in Humans Is Not Established
TL;DR: Overall, although some polyphenol-rich foods exert beneficial effects on some biomarkers of cardiovascular health, there is no evidence that this is caused by improvements in antioxidant function biomarkers (oxidative damage or antioxidant capacity).
Abstract: Human studies provide evidence for beneficial effects of polyphenol-rich foods on cardiovascular health The antioxidant activity of polyphenols potentially explains these effects, but is the antioxidant activity a reliable predictor for these effects? An International Life Sciences Institute Europe working group addressed this question and explored the potential of antioxidant claims for polyphenols in relation to cardiovascular health by using the so-called Process for the Assessment of Scientific Support for Claims on Foods project criteria In this process, analytical aspects of polyphenols, their occurrence in foods, dietary intake, and bioavailability were reviewed Human studies on polyphenols and cardiovascular health were reviewed together with methods for biomarkers of oxidative damage and total antioxidant capacity (TAC) In retrospective studies, F2-isoprostanes and oxidized LDL, the most reliable biomarkers of lipid peroxidation, and measures for TAC showed the expected differences between cardiovascular disease patients and healthy controls, but prospective studies are lacking, and a causal relationship between these biomarkers and cardiovascular health could not be established Therefore, the physiological relevance of a potential change in these biomarkers is unclear We found limited evidence that some types of polyphenol-rich products modify these biomarkers in humans A direct antioxidant effect of polyphenols in vivo is questionable, however, because concentrations in blood are low compared with other antioxidants and extensive metabolism following ingestion lowers their antioxidant activity Therefore, the biological relevance of direct antioxidant effects of polyphenols for cardiovascular health could not be established Overall, although some polyphenol-rich foods exert beneficial effects on some biomarkers of cardiovascular health, there is no evidence that this is caused by improvements in antioxidant function biomarkers (oxidative damage or antioxidant capacity)
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TL;DR: The interactions between phenolic compounds and lipids, carbohydrates and proteins and their impact on polyphenol activity are reviewed.
763 citations
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...It is increasingly emphasized that there are multiple bioactivities of polyphenols in the human organism that are important to understand, such as the role of their metabolites, the effects on the modulations of enzymes (Hollman et al., 2011) and interactions with other macromolecules (Le Bourvellec & Renard, 2012)....
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...On the other hand, some activities of polyphenols are being reassessed, such as their direct antioxidant activities inside the organism and the biological relevance of antioxidant activities in cardiovascular disease protection (Hollman et al., 2011)....
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TL;DR: The potential for the Mediterranean diet to act as a key player in cardiovascular disease prevention, and attempt to identify certain aspects of the diet that are particularly beneficial for cardioprotection are highlighted.
578 citations
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...While solid evidence establishes the antioxidant properties of fruit and vegetables (65) and the health benefits of increased flavonol intake (66), alternative mechanisms have been proposed (67) and could include the effects of nitric oxide (NO) species or concomitant weight loss associated with diets high in fruits and vegetables....
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TL;DR: The clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.
Abstract: Oxidative stress is the result of the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1) ROS in leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced modifications of lipids, DNA, and proteins, (3) enzymatic players of redox status, and (4) total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.
505 citations
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...From the mentioned above limitations and potential confounding, it appears that a clear association between increase in NEAC and health benefit is difficult to evaluate [405, 406]....
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...The latter reports onantioxidants’ reductive capacity, including its metal reducing power, and could be considered an “indirect assay,” whereas the former is a “direct assay” (competitive) inwhich the inhibitionof the oxidation of an indicator substance is determined as a measure of the antioxidant capacity [406, 407]....
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...In these assays, it is assumed that antioxidant activity is equal to reducing capacity [406]....
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...As previously pointed out, in NEAC assays the contribution of the antioxidant enzymes is neglected [405, 406]....
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TL;DR: Current concepts in the meaning of obesity as a state of chronic oxidative stress and the potential interventions to improve redox balance are described.
Abstract: Obesity represents a major risk factor for a plethora of severe diseases, including diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. It is often accompanied by an increased risk of mortality and, in the case of non-fatal health problems, the quality of life is impaired because of associated conditions, including sleep apnea, respiratory problems, osteoarthritis, and infertility. Recent evidence suggests that oxidative stress may be the mechanistic link between obesity and related complications. In obese patients, antioxidant defenses are lower than normal weight counterparts and their levels inversely correlate with central adiposity; obesity is also characterized by enhanced levels of reactive oxygen or nitrogen species. Inadequacy of antioxidant defenses probably relies on different factors: obese individuals may have a lower intake of antioxidant- and phytochemical-rich foods, such as fruits, vegetables, and legumes; otherwise, consumption of antioxidant nutrients is normal, but obese individuals may have an increased utilization of these molecules, likewise to that reported in diabetic patients and smokers. Also inadequate physical activity may account for a decreased antioxidant state. In this review, we describe current concepts in the meaning of obesity as a state of chronic oxidative stress and the potential interventions to improve redox balance.
371 citations
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...Nonetheless, human prospective studies are lacking and a causal relationship between polyphenols, obesity and chronic diseases cannot be established [203]....
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TL;DR: The intestinal microbiota is a key factor in mediating the physiological functions of dietary polyphenols, resulting in health promotion by the activation of short chain fatty acids excretion and intestinal immune function.
Abstract: Polyphenols are categorized as plant secondary metabolites, and they have attracted much attention in relation to human health and the prevention of chronic diseases. In recent years, a considerable number of studies have been published concerning their physiological function in the digestive tract, such as their prebiotic properties and their modification of intestinal microbiota. It has also been suggested that several hydrolyzed and/or fission products, derived from the catabolism of polyphenols by intestinal bacteria, exert their physiological functions in target sites after transportation into the body. Thus, this review article focuses on the role of intestinal microbiota in the bioavailability and physiological function of dietary polyphenols. Monomeric polyphenols, such as flavonoids and oligomeric polyphenols, such as proanthocyanidins, are usually catabolized to chain fission products by intestinal bacteria in the colon. Gallic acid and ellagic acid derived from the hydrolysis of gallotannin, and ellagitannin are also subjected to intestinal catabolism. These catabolites may play a large role in the physiological functions of dietary polyphenols. They may also affect the microbiome, resulting in health promotion by the activation of short chain fatty acids (SCFA) excretion and intestinal immune function. The intestinal microbiota is a key factor in mediating the physiological functions of dietary polyphenols.
355 citations
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...[14] suggested that antioxidant function may not explain the major vascular effects of dietary flavonoids....
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Abstract: Several details of the assay of total phenolic substances have been investigated and an improved procedure developed. The improvements include the use of Folin-Ciocalteu reagent rather than the Folin-Denis reagent, gallic acid as a reference standard, and a more reproducible time-temperature color development period. The values obtained are less subject to variation and interference from several nonphenols, yet are directly comparable to the "tannin" values obtained by the previously standard method.
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