Acute high-dose MitoQ does not increase urinary kidney injury markers in healthy adults: a randomized crossover trial.

Several human studies have used the mitochondrial antioxidant MitoQ. Recent in vitro data indicating that MitoQ may induce nephrotoxicity caused concern regarding the safety of MitoQ on the kidneys, but the doses were supraphysiological. Therefore, we sought to determine whether acute MitoQ elicits changes in urinary biomarkers associated with tubular injury in healthy adults with our hypothesis being there would be no changes. Using a randomized crossover design, 32 healthy adults (16 females and 16 males, 29 ± 11 yr old) consumed MitoQ (100-160 mg based on body mass) or placebo capsules. We obtained serum samples and a 4- to 6-h postcapsule consumption urine sample. We assessed creatinine clearance and urine kidney injury biomarkers including the chitinase 3-like-1 gene product YKL-40, kidney-injury marker-1, monocyte chemoattractant protein-1, epidermal growth factor, neutrophil gelatinase-associated lipocalin, interleukin-18, and uromodulin using multiplex assays. We used t tests, Wilcoxon tests, and Hotelling's T2 to assess global differences in urinary kidney injury markers between conditions. Acute MitoQ supplementation did not influence urine flow rate (P = 0.086, rrb = 0.39), creatinine clearance (P = 0.085, rrb = 0.42), or urinary kidney injury markers (T22,8 = 30.6, P = 0.121, univariate ps > 0.064). Using exploratory univariate analysis, MitoQ did not alter individual injury markers compared with placebo (e.g., placebo vs. MitoQ: YKL-40, 507 ± 241 vs. 442 ± 236 pg/min, P = 0.241; kidney injury molecule-1, 84.1 ± 43.2 vs. 76.2 ± 51.2 pg/min, P = 0.890; and neutrophil gelatinase-associated lipocalin, 10.8 ± 10.1 vs. 9.83 ± 8.06 ng/min, P = 0.609). In conclusion, although longer-term surveillance and data are needed in clinical populations, our findings suggest that acute high-dose MitoQ had no effect on urinary kidney injury markers in healthy adults.NEW & NOTEWORTHY We found acute high-dose mitochondria-targeted antioxidant (MitoQ) supplementation was not nephrotoxic and had no effect on markers of acute kidney injury in healthy adults. These findings can help bolster further confidence in the safety of MitoQ, particularly for future investigations seeking to examine the role of mitochondrial oxidative stress, via acute MitoQ supplementation, on various physiological outcomes.

Association between dietary antioxidants intake and the risk of type 2 diabetes mellitus in a prospective cohort study: Tehran Lipid and Glucose Study.

The present prospective cohort study aimed to determine whether dietary antioxidants were associated with incident type 2 diabetes mellitus (T2DM). Another objective was to find out whether such associations could be modified by the BMI status. A total of 2188 Tehranian adults aged 21-84 years, free of T2DM with the validated FFQ, was entered in the study. Multivariable Cox proportional hazards models adjusting for confounders were used to assess the association between dietary antioxidants and incident T2DM in total population, as well as in subjects with various BMI statuses. During 8·9 (8·1-9·6) years of follow-up, dietary vitamin E significantly decreased the incident T2DM, after adjustment for confounders. However, other dietary antioxidants were not shown to be significantly associated with incident T2DM. The interaction between dietary vitamin E, Mg and BMI status was found to influence the risk of T2DM (Pfor interaction < 0·05). After stratification of subjects based on BMI status, it was found that vitamin E and Mg decreased the risk of T2DM only among normal-weight individual. Also, an inverse association was found among dietary vitamin C, dietary Zn and the risk of T2DM in individuals with normal weight but not in overweight and obese individuals; however, the interaction test tended to be significant for these dietary variables. Dietary antioxidants including vitamin E, vitamin C, Zn and Mg when accompanied by healthy weight, may bring benefits to the prevention of T2DM.

Inhibition of MMP-2 and MMP-9 by Dietary Antioxidants in THP-1 Macrophages and Sera from Patients with Breast Cancer.

Polyphenols, the main antioxidants of diet, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of four polyphenolic compounds on ROS production and on the levels of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of breast cancer. THP-1 differentiated macrophages were activated by LPS and simultaneously treated with different doses of a green tea extract (GTE), resveratrol (RSV), curcumin (CRC) and an olive fruit extract (oliplus). By using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, we found that all of the tested compounds showed antioxidant activity in vitro. In addition, GTE, RSV and CRC were able to counteract ROS production induced by H2O2 in THP-1 cells. As assessed by a zymographic analysis of THP-1 supernatants and by an "in-gel zymography" of a pool of sera from patients with breast cancer, the antioxidant compounds used in this study inhibited both the activity and expression of MMP-2 and MMP-9 through different mechanisms related to their structures and to their ability to scavenge ROS. The results of this study suggest that the used antioxidants could be promising agents for the prevention and complementary treatment of breast cancer and other diseases in which MMPs play a pivotal role.

Dietary antioxidants and flavonoids intake, and their association with inflammation and oxidative stress parameters in asthmatic women: a case-control study.

Asthma is more prevalent and severe in women, especially after puberty. Studies suggest a potential link between dietary antioxidants, inflammation, and oxidative stress. This study aimed to compare the dietary intake of antioxidants in asthmatic and healthy women, evaluating their potential associations with inflammation and oxidative stress. This study analyzed 30 asthmatic and 30 healthy women's lung function, anthropometry, biochemical parameters, and dietary antioxidant intake using a 161-itemized semi-quantitative food frequency questionnaire. Additionally, the study explored connections between serum inflammatory markers and oxidative stress indicators in relation to dietary intake of antioxidant nutrients and flavonoids. Asthmatic women exhibited higher serum IL-6 levels and lower total antioxidant status compared to healthy controls. Nevertheless, no significant differences were observed in dietary antioxidant micronutrient intake. Healthy controls demonstrated a notably higher intake of anthocyanidins compared to asthmatic women. Furthermore, the study identified a negative correlation between flavonol intake and serum total oxidant status, as well as between flavan-3-ols intake and serum oxidative stress index. Dietary differences in flavonoid and flavonoid-rich foods intake among asthmatic women may affect their serum IL-6 levels and oxidative stress. Promoting a diverse diet rich in flavonoids could benefit women with asthma by mitigating inflammation and oxidative stress.

Bone mineral density is associated with composite dietary antioxidant index among US adults: results from NHANES.

This cross-sectional study investigated the relationship between composite dietary antioxidant index (CDAI) and individual dietary antioxidant intakes, including vitamins A, C, and E, zinc, selenium, and carotenoids, and bone mineral density (BMD) in the US population aged 20 years older. We found a positive correlation between CDAI and femoral BMD. Moreover, higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. INTRODUCTION: While individual dietary antioxidants have shown beneficial effects on bone metabolism, the diverse and potentially interacting nature of dietary components may limit the accuracy of evaluating their impact on bone health. Thus, this study aims to investigate the association between CDAI and BMD. Additionally, we explore the relationship between the intake of individual components of the CDAI and BMD. METHODS: The CDAI is a novel index evaluating total dietary antioxidant intake, considering vitamins A, C, and E, zinc, selenium, and carotenoids. A cross-sectional analysis was conducted using data from participants aged ≥ 20 in the National Health and Nutrition Examination Survey (2005-2010, 2013-2014, and 2017-2018). We utilized multivariate linear regression models to examine the relationship between CDAI, individual dietary antioxidants, including vitamins A, C, and E, zinc, selenium, carotenoids, and femoral BMD. RESULTS: The final analysis included 10,584 participants with a mean age of 50.73 ± 16.65 years. After multivariate adjustment, the second to fourth quartiles of CDAI (- 2.00-0.04, 0.04-2.54, and 2.54-70.78) exhibited higher femoral BMD compared to the first quartile of CADI (- 7.34 to - 2.00). Multiple regression analysis revealed that higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. CONCLUSIONS: CDAI serves as a comprehensive tool for evaluating the overall antioxidant capacity of antioxidants in diets. Additionally, our study shows a positive correlation between CDAI and BMD, which indicates that the combined intake of dietary antioxidants may help reduce the risk of osteoporosis in adults.

Integument colouration and circulating carotenoids in relation to urbanisation in Eurasian kestrels (Falco tinnunculus).

Urbanisation is one of the biggest environmental challenges of our time, yet we still lack an integrative understanding of how cities affect behaviour, physiology and parasite susceptibility of free-living organisms. In this study, we focus on carotenoids, strictly dietary micronutrients that can either be used as yellow-red pigments, for integument colouration (signalling function), or as antioxidants, to strengthen the immune system (physiological function) in an urban predator, the Eurasian kestrel (Falco tinnunculus). Kestrels are specialised vole hunters but shift to avian prey in cities where diurnal rodents are not sufficiently available. This different foraging strategy might determine the quantity of carotenoids available. We measured integument colouration, circulating carotenoids in the blood and ectoparasite burden in kestrels along an urban gradient. Our results showed that nestlings that were raised in more urbanised areas displayed, unrelated to their ectoparasite burden, a paler integument colouration. Paler colours were furthermore associated with a lower concentration of circulating carotenoids. These findings support the hypothesis that the entire urban food web is carotenoid deprived and only prey of low quality with low carotenoid content is available (e.g. fewer carotenoids in urban trees, insects, small birds and finally kestrels). The alternative hypothesis that nestlings allocate carotenoids to reduce physiological stress and/or to cope with parasites rather than invest into colouration could not be supported. Our study adds to existing evidence that urban stressors negatively affect carotenoid production in urban areas, a deficiency that dissipate into higher trophic levels.

Association between an oxidative balance score and mortality: a prospective analysis in the SUN cohort.

PURPOSE: We aimed to prospectively investigate the association of an overall oxidative balance score (OBS) with all-cause death and cause-specific mortality among participants in the Seguimiento Universidad de Navarra (SUN) Study, a Mediterranean cohort of Spanish graduates. METHODS: Using baseline information on 12 a priori selected dietary and non-dietary lifestyle pro- and antioxidants exposures-vitamins C and E, ß-carotenes, selenium, zinc, heme iron, polyphenols, total antioxidant capacity, body mass index, alcohol, smoking, and physical activity-we constructed an equally weighted OBS categorized into quartiles, with higher scores representing greater antioxidant balance. Cox proportional hazards models were fitted to evaluate the association between the OBS and mortality. RESULTS: A total of 18,561 participants (mean [SD] age, 38.5 [12.4] years; 40.8% males) were included in the analysis. During a median follow-up of 12.2 years (interquartile range 8.3-14.9), 421 deaths were identified, including 80 deaths from cardiovascular disease (CVD), 215 from cancer, and 126 from other causes. After adjustment for potential confounders, the hazard ratios and 95% confidence interval (CIs) between the highest quartile (predominance of antioxidants) vs. the lowest quartile (reference category) were 0.35 (95% CI 0.22-0.54, P-trend < 0.001) for all-cause mortality, 0.18 (95% CI 0.06-0.51, P-trend = 0.001) for CVD mortality, 0.35 (95% CI 0.19-0.65, P-trend = 0.002) for cancer mortality, and 0.45 (95% CI 0.20-1.02, P-trend = 0.054) for other-cause mortality. CONCLUSION: Our findings suggest a strong inverse association between the OBS and all-cause, CVD, and cancer mortality. Individuals exposed to both antioxidant dietary and lifestyle factors may potentially experience the lowest mortality risk. STUDY REGISTRY NUMBER: Dynamic Mediterranean Prospective Cohort: the SUN Project; NCT02669602. https://clinicaltrials.gov/ct2/show/NCT02669602 . https://proyectosun.es.

Antioxidants in brain tumors: current therapeutic significance and future prospects.

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progression by creating an energy crisis for preneoplastic cells, resulting in antiproliferative effects. These effects are referred to as chemopreventive effects mediated by an antioxidant mechanism. In addition, antioxidants minimize chemotherapy-induced nonspecific organ toxicity and prolong survival. Antioxidants also support the prooxidant chemistry that demonstrate chemotherapeutic potential, particularly at high or pharmacological doses and trigger OS by promoting free radical production, which is essential for activating cell death pathways. A growing body of evidence also revealed the roles of exogenous antioxidants as adjuvants and their ability to reverse chemoresistance. In this review, we explain the influences of different exogenous and endogenous antioxidants on brain cancers with reference to their chemopreventive and chemotherapeutic roles. The role of antioxidants on metabolic reprogramming and their influence on downstream signaling events induced by tumor suppressor gene mutations are critically discussed. Finally, the review hypothesized that both pro- and antioxidant roles are involved in the anticancer mechanisms of the antioxidant molecules by killing neoplastic cells and inhibiting tumor recurrence followed by conventional cancer treatments. The requirements of pro- and antioxidant effects of exogenous antioxidants in brain tumor treatment under different conditions are critically discussed along with the reasons behind the conflicting outcomes in different reports. Finally, we also mention the influencing factors that regulate the pharmacology of the exogenous antioxidants in brain cancer treatment. In conclusion, to achieve consistent clinical outcomes with antioxidant treatments in brain cancers, rigorous mechanistic studies are required with respect to the types, forms, and stages of brain tumors. The concomitant treatment regimens also need adequate consideration.

Daily mocha coffee intake and psycho-cognitive status in non-demented non-smokers subjects with subcortical ischaemic vascular disease.

Coffee intake has been recently associated with better cognition and mood in mild vascular cognitive impairment (mVCI). As tobacco can reduce the caffeine half-life, we excluded smokers from the original sample. Hamilton Depression Rating Scale (HDRS), mini-mental state examination (MMSE), Stroop Colour-Word Interference Test (Stroop), activities of daily living (ADL0) and instrumental ADL were the outcome measures. Significant differences were observed in higher consumption groups (moderate intake for HDRS; high intake for MMSE and Stroop) compared to the other groups, as well as in age and education. With age, education and coffee used as independent predictors, and HDRS, Stroop and MMSE as dependent variables, a correlation was found between age and both MMSE and Stroop, as well as between education and MMSE and between HDRS and Stroop; coffee intake negatively correlated with HDRS and Stroop. Higher coffee consumption was associated with better psycho-cognitive status among non-smokers with mVCI.

Dietary antioxidants and fibre intake and depressive symptoms in Iranian adolescent girls.

OBJECTIVE: To investigate the cross-sectional association between dietary intakes of antioxidants and fibre and depressive symptoms among Iranian adolescent girls. DESIGN: A cross-sectional population-based study. SETTING: Primary schools in two different cities located in northeastern Iran (Mashhad and Sabzevar). PARTICIPANTS: A total of 988 adolescent girls aged 12-18 years were included in the study. RESULTS: Subjects with no or minimal depression symptoms had significantly higher dietary intakes of α-carotene (P = 0·01), ß-carotene (P = 0·006), lutein (P = 0·03) and vitamin C (P = 0·04) when compared with subjects with mild-to-severe depression symptoms. Soluble dietary fibre and insoluble dietary fibre intakes were also significantly higher in healthy adolescents compared with those with depression symptoms (P < 0·001). In multivariate-adjusted model 2, the OR (95 % CI) of depressive symptoms were 0·61 (95 % CI 0·37, 1·01), 0·42 (95 % CI 0·26, 0·69), 0·50 (95 % CI 0·31, 0·79), 0·71 (95 % CI 0·44, 1·15), 0·51 (95 % CI 0·32, 0·82) and 0·42 (95 % CI 0·25, 0·68) for the highest v. lowest quartile of vitamin C, ß-carotene, α-carotene, lutein, soluble dietary fibre and insoluble dietary fibre cereal intakes, respectively. CONCLUSIONS: Dietary intake of some antioxidants and dietary fibre intake was inversely associated with depression symptoms among Iranian adolescent girls.

Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1.

Mechanical ventilation with hyperoxia is the major supportive measure to treat patients with acute lung injury and acute respiratory distress syndrome (ARDS). However, prolonged exposure to hyperoxia can induce oxidative inflammatory lung injury. Previously, we have shown that high levels of airway high-mobility group box 1 protein (HMGB1) mediate hyperoxia-induced acute lung injury (HALI). Using both ascorbic acid (AA, also known as vitamin C) and sulforaphane (SFN), an inducer of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), we tested the hypothesis that dietary antioxidants can mitigate HALI by ameliorating HMGB1-compromised macrophage function in phagocytosis by attenuating hyperoxia-induced extracellular HMGB1 accumulation. Our results indicated that SFN, which has been shown to attenute HALI in mice exposed to hyperoxia, dose-dependently restored hyperoxia-compromised macrophage function in phagocytosis (75.9 ± 3.5% in 0.33 µM SFN versus 50.7 ± 1.8% in dimethyl sulfoxide (DMSO) control, p < 0.05) by reducing oxidative stress and HMGB1 release from cultured macrophages (47.7 ± 14.7% in 0.33 µM SFN versus 93.1 ± 14.6% in DMSO control, p < 0.05). Previously, we have shown that AA enhances hyperoxic macrophage functions by reducing hyperoxia-induced HMGB1 release. Using a mouse model of HALI, we determined the effects of AA on hyperoxia-induced inflammatory lung injury. The i.p. administration of 50 mg/kg of AA to mice exposed to 72 h of ≥98% O2 significantly decreased hyperoxia-induced oxidative and nitrosative stress in mouse lungs. There was a significant decrease in the levels of airway HMGB1 (43.3 ± 12.2% in 50 mg/kg AA versus 96.7 ± 9.39% in hyperoxic control, p < 0.05), leukocyte infiltration (60.39 ± 4.137% leukocytes numbers in 50 mg/kg AA versus 100 ± 5.82% in hyperoxic control, p < 0.05) and improved lung integrity in mice treated with AA. Our study is the first to report that the dietary antioxidants, ascorbic acid and sulforaphane, ameliorate HALI and attenuate hyperoxia-induced macrophage dysfunction through an HMGB1-mediated pathway. Thus, dietary antioxidants could be used as potential treatments for oxidative-stress-induced acute inflammatory lung injury in patients receiving mechanical ventilation.

Reactive Oxygen Species in Venous Thrombosis.

Reactive oxygen species (ROS) have physiological roles as second messengers, but can also exert detrimental modifications on DNA, proteins and lipids if resulting from enhanced generation or reduced antioxidant defense (oxidative stress). Venous thrombus (DVT) formation and resolution are influenced by ROS through modulation of the coagulation, fibrinolysis, proteolysis and the complement system, as well as the regulation of effector cells such as platelets, endothelial cells, erythrocytes, neutrophils, mast cells, monocytes and fibroblasts. Many conditions that carry an elevated risk of venous thrombosis, such as the Antiphospholipid Syndrome, have alterations in their redox homeostasis. Dietary and pharmacological antioxidants can modulate several important processes involved in DVT formation, but their overall effect is unknown and there are no recommendations regarding their use. The development of novel antioxidant treatments that aim to abrogate the formation of DVT or promote its resolution will depend on the identification of targets that enable ROS modulation confined to their site of interest in order to prevent off-target effects on physiological redox mechanisms. Subgroups of patients with increased systemic oxidative stress might benefit from unspecific antioxidant treatment, but more clinical studies are needed to bring clarity to this issue.

The association between dietary antioxidants, oxidative stress markers, abdominal obesity and poly-cystic ovary syndrome: A case control study.

In this case-control study, 60 patients with Polycystic ovary syndrome (PCOS) referred to the Nursing and Midwifery Center of Khorramabad, were selected as the case group and 90 non-PCOS patients as the control group. Demographic information and anthropometric indices of each person were collected. The Food Frequency Questionnaire (FFQ) and International Physical Activity Questionnaire (IPAQ) were completed. After at least 12 h of fasting, 7 mL of blood samples were taken from the patients. There was no statistically significant difference observed in the mean of the total antioxidant capacity (TAC) between the two groups. However, a statistically significant difference was found between the two groups in terms of malondialdehyde (MDA) and some dietary antioxidants levels (mean in case group: vit C = 34/2 mg, vit E = 7/7 mg, Se = 84/6 µg, Zn = 7/5 mg, beta-carotene = 762/8 µg, mean in control group: vit C = 72/5 mg, vit E = 10/6 mg, Se = 91/0 µg, Zn = 10/6 mg, beta-carotene = 1609/5 µg).IMPACT STATEMENTWhat is already known on this subject? Polycystic ovary syndrome (PCOS) is one of the most common endocrine abnormalities and is considered as the main cause of infertility. Some studies have evaluated the link between dietary intakes and oxidative stress markers in PCOS patients. It is well known that about 40-50% of individuals with PCOS are obese and that leads to an increase in lipid catabolism and production of free radicals and oxidative stress.What the results of this study add? The aim of the present study was to compare the level of dietary antioxidants and oxidative stress markers including TAC, MDA and abdominal obesity prevalence in PCOS patients with healthy individuals.What the implications are of these findings for clinical practice and/or further research? We hope that our study can be influential in the field of PCOS. Furthermore, our findings have indicated a statistically significant difference between the two groups in terms of MDA and some dietary antioxidants levels. This result might be encouraging in using antioxidant in patients with PCOS.

Association between dietary total antioxidant capacity and hepatocellular ballooning in nonalcoholic steatohepatitis: a cross-sectional study.

PURPOSE: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, ballooning, and in some cases, fibrosis, which can progress to cirrhosis and carcinoma. The progression of NASH is closely related to oxidative stress. Dietary intake of antioxidants has been suggested in protection against oxidative damage and related clinical complications. Thus, we evaluated the potential association of dietary total antioxidant capacity (TAC) with disease severity in NASH patients, as well as with anthropometric and body composition markers and biochemical parameters. METHODS: Thirty-three outpatients with a mean age of 48.4 ± 1.9 years were evaluated. Dietary TAC was estimated from a quantitative food frequency questionnaire. NASH severity, determined by liver biopsy, lifestyle characteristics, occurrence of comorbidities, anthropometry, body composition, and biochemical parameters were assessed. RESULTS: NASH patients who had a higher dietary TAC had fewer ballooned hepatocytes compared to those with a lower TAC (p = 0.024). The patients with the highest dietary TAC had a reduction of approximately 20% in the risk of having many ballooned hepatocytes (OR 0.791; 95% CI 0.643-0.974; p = 0.027). There was no association of steatosis, lobular inflammation, and fibrosis with dietary TAC. The same occurred for lifestyle characteristics, occurrence of comorbidities, anthropometry, body composition, and biochemical parameters. CONCLUSION: Dietary TAC is higher in patients with lower hepatic injury (ballooning), suggesting a possible role of food intake naturally high in its antioxidant capacity in reducing free radical production and, consequently, oxidative stress.

Flavonoids Ability to Disrupt Inflammation Mediated by Lipid and Cholesterol Oxidation.

Flavonoids are plant secondary metabolites that act as protectants against harmful effects of UV-B radiation inasmuch as biotic stress, conferring at the same time pigmentation of fruits and leaves [67]. The term "flavonoid" refers to phenolics having a basic skeleton of diphenylpropane (C6-C3-C6), which consists of two aromatic rings linked through three carbons that usually form an oxygenated heterocycle [25, 52]. Flavonoids are broken down into several different sub-categories based on their chemical structure. The main subclasses commonly found in food items are: flavonols, flavones, flavanones, flavan-3-ols, proanthocyanidins, and anthocyanins [44, 67]. Figure 19.1 depicts the major classification of flavonoids according to their chemical structure. Their occurrence in food matrices has been extensively reviewed [39, 44], and has been subject of extensive research in the last decades. Table 19.1 contains a few examples of compounds from each of the subcategory, with the fruit (berry) in which they are commonly found. The monomeric unit of flavonoids can dimerize and polymerize to form other important high molecular weight molecules; this is the case of proanthocyanidins, that are polymers of flavan-3-ols or flavanols. Not only do these compounds act as plant protectants, but they can also be very beneficial to human health. Cohorts studies performed in the early '90 have shown that dietary consumption of flavonoids was inversely associated with morbidity and mortality from coronary heart disease [31, 32]. These findings have opened an intensive field of research on the effects of flavonoids and flavonoids-rich food extracts in cardiovascular diseases (CVD) progression, particularly in the modulating CVD-associated oxidative stress and inflammation. In this short review, we will summarize the current findings in flavonoids beneficial effects in preventing CVD through inhibition of initial stages of CVD progression. Given the magnitude of scientific literature in the field, we will focus on two strictly mechanistic aspects: inhibition of chemical-induced LDL oxidation, and the effect of flavonoids in the monocyte/macrophages activation pathways.

Environmental cues and dietary antioxidants affect breeding behavior and testosterone of male European starlings (Sturnus vulgaris).

Environmental cues, such as photoperiod, regulate the timing of major life-history events like breeding through direct neuroendocrine control. Less known is how supplementary environmental cues (e.g., nest sites, food availability) interact to influence key hormones and behaviors involved in reproduction, specifically in migratory species with gonadal recrudescence largely occurring at breeding sites. We investigated the behavioral and physiological responses of male European starlings to the sequential addition of nest boxes and nesting material, green herbs, and female conspecifics and how these responses depend on the availability of certain antioxidants (anthocyanins) in the diet. As expected, cloacal protuberance volume and plasma testosterone of males generally increased with photoperiod. More notably, testosterone levels peaked in males fed the high antioxidant diet when both nest box and herbal cues were present, while males fed the low antioxidant diet showed no or only a muted testosterone response to the sequential addition of these environmental cues; thus our results are in agreement with the oxidation handicap hypothesis. Males fed the high antioxidant diet maintained a constant frequency of breeding behaviors over time, whereas those fed the low antioxidant diet decreased breeding behaviors as environmental cues were sequentially added. Overall, sequential addition of the environmental cues modulated physiological and behavioral measures of reproductive condition, and dietary antioxidants were shown to be a key factor in affecting the degree of response to each of these cues. Our results highlight the importance of supplementary environmental cues and key resources such as dietary antioxidants in enhancing breeding condition of males, which conceivably aid in attraction of high quality females and reproductive success.

A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

OBJECTIVE: The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. RESULTS: Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. CONCLUSION: These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

Do Maternal Dietary Antioxidants Modify the Relationship Between Binge Drinking and Small for Gestational Age? Findings from a Longitudinal Cohort Study.

BACKGROUND: Vitamin C, vitamin E, and carotenoids are potent dietary antioxidants that have been shown to attenuate ethanol-induced harm in animal models of fetal alcohol spectrum disorders. A diet low in antioxidant-rich foods may induce a state of oxidative stress in the context of maternal alcohol consumption during pregnancy, potentially causing growth restriction in the developing fetus. METHODS: We conducted a secondary analysis of a longitudinal U.K. birth cohort. The sample comprised 9,699 women and their babies in Avon, U.K., with an estimated delivery date between April 1, 1991 and December 31, 1992. Alcohol consumption data were self-reported at 18 weeks' gestation via a postal questionnaire. Women reported any binge drinking (≥4 U.K. units/occasion) during the past month. Dietary data were self-reported at 32 weeks' gestation using a food frequency questionnaire. Estimated intakes of vitamins C and E and carotenoids were categorized into quartiles. Logistic regression models with interaction terms were used to investigate relationships between maternal binge drinking, dietary antioxidants, and fetal growth. Models were adjusted for maternal sociodemographic and lifestyle characteristics. Small for gestational age (SGA; <10th percentile) was defined using customized birth centiles. RESULTS: In the unadjusted models, binge drinking was associated with higher risk of SGA birth (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.10, 1.72, p = 0.005), and higher maternal intakes of vitamin C (OR = 0.90, 95% CI 0.84, 0.96, p = 0.002) and vitamin E (OR = 0.90, 95% CI 0.84, 0.95, p < 0.0001) were associated with lower risk of SGA birth. However, addition of potentially confounding variables attenuated these relationships. Likelihood ratio tests indicated that interaction terms were not significant for vitamin C (p = 0.116), vitamin E (p = 0.059), or carotenoid intakes (p = 0.174). CONCLUSIONS: There was no evidence of maternal intake of dietary antioxidants modifying the relationship between maternal binge drinking and SGA birth.

Serum antioxidant capacity, biochemical profile and body composition of breast cancer survivors in a randomized Mediterranean dietary intervention study.

PURPOSE: Increasing evidence suggests that Mediterranean Diet (MD) is correlated with reduced risk of breast cancer (BC) and cancer mortality, since it modifies patients' serum antioxidant capacity, body composition and biochemical parameters. The aim of the study was to investigate whether a dietary intervention based on MD has a beneficial effect on these factors. METHODS: In this intervention study, seventy female BC survivors were randomly assigned to (1) the intervention group (personalized dietary intervention based on MD) and (2) the control group (received the updated American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and ad libitum diet). Both groups were assessed twice [beginning, end of study (after 6 months)] regarding their anthropometric and biochemical parameters, serum vitamin C, vitamin A, a-tocopherol and CoQ10 levels, dietary intake and adherence to MD. An additional intermediate analysis was conducted on participants' body composition and biochemical profile. RESULTS: Concerning the intervention group, body weight, body fat mass, waist circumference, body mass index as well as HDL-cholesterol were significantly decreased (P < 0.2%). An increase was observed in the vitamin C levels in blood (P < 0.2%). In the control group, body weight, body fat mass and serum total cholesterol rose (P < 0.2%). At the end of the study the two groups were significantly different considering blood glucose, vitamin C, polyunsaturated fatty acids, vitamin A and a-tocopherol levels. CONCLUSIONS: This randomized dietary intervention based on MD managed to ameliorate serum antioxidant capacity, body composition, adherence to MD and glycemic profile of postmenopausal BC survivors.

Dietary Antioxidant Micronutrients and All-Cause Mortality: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

BACKGROUND: Oxidative stress, the imbalance between pro- and antioxidants, has been implicated in the etiology and pathophysiology of the incidence and mortality of many diseases. We aim to investigate the relations of dietary intakes of vitamin C and E and main carotenoids with all-cause mortality in Japanese men and women. METHODS: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk had 22,795 men and 35,539 women, aged 40-79 years at baseline (1988-1990), who completed a valid food frequency questionnaire and were followed up to the end of 2009. RESULTS: There were 6,179 deaths in men and 5,355 deaths in women during the median follow-up of 18.9 years for men and 19.4 years for women. Multivariate hazard ratios for the highest versus lowest quintile intakes in women were 0.83 (95% confidence interval [CI], 0.76-0.90; P for trend < 0.0001) for vitamin C, 0.85 (95% CI, 0.78-0.93; P for trend < 0.0001) for vitamin E, 0.88 (95% CI, 0.81-0.96; P for trend = 0.0006) for ß-carotene, and 0.90 (95% CI, 0.82-0.98; P for trend = 0.0002) for ß-cryptoxanthin. The joint effect of any two of these highly correlated micronutrients showed significant 12-17% reductions in risk in the high-intake group compared with the low-intake group in women. These significant associations were also observed in the highest quintile intakes of vitamin C, vitamin E, and ß-carotene in female non-smokers but were not observed in female smokers, male smokers, and non-smokers. CONCLUSIONS: Higher dietary intakes of antioxidant vitamins may reduce the risk of all-cause mortality in middle-aged Japanese women, especially female non-smokers.