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19 Páginas.--1 Tabla.-- 2 Figuras, Purpose The objective of this study was to evaluate the capacity of modified phenols synthesized from hydroxytyrosol, a natural olive oil phenol, specifically those containing a selenium or sulphur group, to inhibit lipid peroxidation. Methods The compounds’ abilities to inhibit lipid peroxidation in liver microsomes obtained from vitamin E-deficient rats were compared to hydroxytyrosol. Results All synthetic compounds had a significant higher ability to inhibit lipid peroxidation than hydroxytyrosol. Selenium derivates displayed a higher antioxidant activity than sulphur derivatives. In addition, the antioxidant activity increased with a higher number of heteroatoms in the hydroxytyrosol molecular structure. Conclusion The study shows, for the first time, the ability of synthetic compounds, derived from the most active phenol present in olives in free form (hydroxytyrosol), and containing one or two atoms of sulphur or selenium, to inhibit the lipid peroxidation of vitamin E-deficient microsomes. The antioxidant activity of five thioureas, a disulfide, a thiol, three selenoureas, a diselenide, and a selenonium were evaluated and the results showed a higher inhibition of lipid peroxidation than the natural phenol. Selenium and sulphur derivatives of hydroxytyrosol are novel antioxidants with the potential to supplement the lack of vitamin E in the diet as natural alternatives for the prevention of diseases related to oxidative damage., The research of BDR and GD is funded by the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) division. This research was funded by the Spanish Ministry of Economy and Competitiveness and co-funded by the European Social Fund (ESF) (Project AGL2016-79088R). GRG wishes to thank the “Ramón y Cajal” Program (RYC-2012-10456 contract), co-funded by the ESF.

Flavan-3-ols and methylxanthines have potential beneficial effects on human health including reducing cardiovascular risk. We performed a randomized controlled crossover intervention trial to assess the acute effects of consumption of flavan-3-ol-enriched dark chocolate, compared with standard dark chocolate and white chocolate, on the human metabolome. We assessed the metabolome in urine and blood plasma samples collected before and at 2 and 6 h after consumption of chocolates in 42 healthy volunteers using a nontargeted metabolomics approach. Plasma samples were assessed and showed differentiation between time points with no further separation among the three chocolate treatments. Multivariate statistics applied to urine samples could readily separate the postprandial time points and distinguish between the treatments. Most of the markers responsible for the multivariate discrimination between the chocolates were of dietary origin. Interestingly, small but significant level changes were also observed for a subset of endogenous metabolites. H-1 NMR revealed that flavan-3-ol-enriched dark chocolate and standard dark chocolate reduced urinary levels of creatinine, lactate, some amino acids, and related degradation products and increased the levels of pyruvate and 4-hydroxyphenylacetate, a phenolic compound of bacterial origin. This study demonstrates that an acute chocolate intervention can significantly affect human metabolism.

Purpose Low fruit and vegetable consumption is linked with an increased risk of death from vascular disease and cancer. The benefit of eating fruits and vegetables is attributed in part to antioxidants, vitamins and phytochemicals. Whether increasing intake impacts on markers of disease remains to be established. This study investigates whether increasing daily intake of fruits, vegetables and juices from low (approx. 3 portions), to high intakes (approx. 8 portions) impacts on nutritional and clinical biomarkers. Barriers to achieving the recommended fruit and vegetable intakes are also investigated. Method In a randomised clinical trial, the participants [19 men and 26 women (39–58 years)] with low reported fruit, juice and vegetable intake ( Results Intake increased significantly in the intervention group compared to controls, achieving 8.4 portions/day after 12 weeks. Plasma vitamin C (35%), folate (15%) and certain carotenoids [α-carotene (50%) and β-carotene (70%) and lutein/zeaxanthin (70%)] were significantly increased (P Conclusion While increasing fruit, juice and vegetable consumption increases circulating level of beneficial nutrients in healthy subjects, a 12-week intervention was not associated with effects on antioxidant status or lymphocyte DNA damage. Trial registration This trial was registered at Controlled-Trials.com; registration ISRCTN71368072.

Polyphenols are widely regarded to have a wide range of health-promoting qualities, including beneficial effects on cardiovascular disease. Historically, the benefits have been linked to their well-recognized powerful antioxidant activity. However, the concept that the beneficial effects are attributable to direct antioxidant activity in vivo does not pay sufficient heed to the fact that polyphenols degrade rapidly, are poorly absorbed and rapidly metabolized, resulting in very low bioavailability. This review explores alternative mechanisms by which polyphenols, or their metabolites, exert biological activity via mechanisms that can be activated by physiologically relevant concentrations. Evidence is presented to support the action of phenolic derivatives on receptors and signalling pathways to induce adaptive responses that drive changes in endogenous antioxidant, antiplatelet, vasodilatory and anti-inflammatory effects. The implications are that in vitro antioxidant measures as predictors of polyphenol protective activity in vivo hold little relevance and that closer attention needs to be paid to bioavailable metabolites to understand the mode of action of these diet-derived components. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc

The oxidative and physical stability of the reformulated mayonnaise with processed beetroot was investigated and compared with a control (mayonnaise without beetroot) and a commercially available product. Processing of beetroot had an impact on the structural integrity of the antioxidants present. Microwaving (960 W for 7 min) was advantageous for preserving the betalain and polyphenol content of beetroot compared to roasting (180 °C for 90 min) and boiling (100 °C for 30 min). The oxidative stability of mayonnaise samples was determined by Rancimat and the thiobarbituric (TBA) assay. The addition of microwaved beetroot significantly enhanced the oxidative stability of mayonnaise at the end of a storage period of 4 weeks (4 °C). Although no significant differences ( P > 0.05) were detected between the mayonnaise samples containing beetroot and the commercial control, the latter was less susceptible to oxidation during storage. The turbiscan stability index (TSI) revealed that the commercial mayonnaise was less prone to destabilization phenomena. All the textural parameters increased with the incorporation of beetroot. The sensory evaluation revealed that, with the exception of graininess and uniformity, most of the sensory attributes are preserved if not improved with the addition of beetroot.

Summary The aim of this study was to compare the efficiency of three different food-grade emulsifiers to form and stabilise an orange oil-in-water emulsion. The emulsifier type and concentration had a profound effect on the initial particle size of the oil droplets with Tween 80 being the most effective in reducing the particle size (1% w/w, 1.88 ± 0.01 μm) followed by sodium caseinate (10% w/w, 2.14 ± 0.03 μm) and gum arabic (10% w/w, 4.10 ± 0.24 μm). The long-term stability of the concentrated beverages was monitored using Turbiscan analysis. The Turbiscan stability indices after 4 weeks of storage followed the order: Tween 80 (1.70 ± 0.08)

In a large cohort of older women, we investigated the relationships that different forms of vitamin E may have with bone turnover markers and bone mineral density (BMD). We found a suggestive positive association between serum alpha-tocopherol and BMD at the femoral neck, but no other clinically relevant observations. Vitamin E has anti-oxidant and anti-inflammatory properties hypothesized to benefit bone, but limited studies exist regarding its homologues. We examined circulating and dietary α- and γ-tocopherols with bone turnover markers (BTMs) and bone mineral density (BMD), and the role of inflammation in this relationship. We performed two cross-sectional analyses from two visits (V2, 1997–1999, n = 3883; V3, 2007–2011, n = 2130) of the Aberdeen Prospective Osteoporosis Screening Study. Dietary and supplement intakes by food frequency questionnaire were assessed at both visits. V2 BTMs (urinary free pyridinoline and deoxypyridinoline, serum N-terminal propeptide of type 1 collagen) and V3 serum α- and γ-tocopherols, inflammatory markers (interleukin-6 [IL-6], serum amyloid A [SAA], high-sensitivity C-reactive protein [hs-CRP], E-selectin) and dual X-ray absorptiometry BMD at the femoral neck and lumbar spine were collected. Food sources of tocopherol homologues and diet-serum correlations were determined. The relationships between dietary tocopherols and BTMs (V2), and dietary and serum tocopherols with BMD (V3) were examined by multivariable regression (adjusting for age, cholesterol, inflammatory markers, carotenoids, body mass index, physical activity level, alcohol intake, smoking status and national deprivation category). Serum γ-tocopherol was associated with increasing concentrations of hs-CRP, SAA and E-selectin (P-trend all

Many oils from plants are important components of our food chain and maintaining their oxidative stability (OS) is economically and nutritionally important. OS is dependent in part on antioxidant capacity (AC) arising from the electron donating ability of endogenous compounds in the oils. Attention has focused on the contribution to AC of phenolic compounds in oils as many have bioactivities in vitro. However, the relevance of such phenolics to healthy nutrition remains unclear. In contrast, many plant-derived oils also contain tocopherol homologs, which as vitamin E are dietary-essential, lipid-soluble antioxidants. We have determined the AC of twelve “off the shelf” edible oils by assessing their ability to quench galvinoxyl, a stable free radical species. The stochiometric reactivity of vitamin E with galvinoxyl indicates that the combined dα-tocopherol and dγ-tocopherol homologs contribute between 20% (olive) and 85% (soya) to AC depending on type of oil. Tocopherols are important contributors to the AC of several vegetable oils. Breeding and photo mixotrophic programmes to enhance content in edible oil crops of this important vitamin may have a positive impact not only on oil stability during storage but also in contributing to provision of optimum dietary intakes for health.

Oxidation is a significant problem in processed foods affecting their physico-chemical, shelf life and health properties. Natural antioxidants could be viable alternatives to synthetic variants for safely improving antioxidation properties of processed foods. The aim of this study was to assess the singular and combined effects of beetroot and chocolate on the oxidative stability of a high fat and protein processed food (sponge cake) during storage and gastrointestinal digestion. Cakes were prepared and assessed for antioxidant potential, polyphenols, and oxidative stability, and macronutrient oxidation during simulated gastro-intestinal digestion. Beetroot significantly improved the antioxidant and polyphenol profiles of sponge cake which further improved with chocolate addition. Beetroot also significantly increased the oxidative stability and shelf-life of sponge cake, and these effects were enhanced when combined with chocolate. Chocolate significantly reduced lipid oxidation during the gastric phase of digestion. However, both chocolate and beetroot did not curtail lipid oxidation in the intestinal phase, nor protein oxidation at any of the phases. Promisingly, beetroot and chocolate addition did not affect textural parameters and delayed staling by up to 2 days. Overall, the benefits of beetroot and chocolate addition were manifested more in the food system than during its digestion. Beetroot improves the oxidative stability and shelf life of processed foods, and its effects could be enhanced through combining with other natural products.

20 Páginas; 3 Tablas; 3 Figuras, Purpose This study explored the in vitro antioxidant and anti-platelet activities of hydroxytyrosol, hydroxytyrosol acetate, 3,4-dihydroxyphenylglycol and two phenolic olive extracts. These compounds and extracts were obtained from a new industrial process to hydrothermally treat the alperujo (160 °C/60 min), a by-product of olive oil extraction. Methods The extracts and the purified compounds were obtained chromatographically using both ionic and adsorbent resins. The antioxidant activity was determined by measuring inhibition of human platelet aggregation and inhibition of lipid peroxidation in liver microsomes of vitamin E-deficient rats. Results The positive effect of the extracts on the inhibition of platelet aggregation is showed, being higher in the case of hydroxytyrosol acetate up to 38 %, and for the first time, its synergist effect with hydroxytyrosol has been proved, obtaining more than double of inhibition. The phenolic extracts and the isolated phenols showed good results for inhibiting the lipid oxidation, up to 62 and 25 %, respectively. A synergistic effect occurred when the hydroxytyrosol acetate and the 3,4-dihydroxyphenylglycol were supplemented by hydroxytyrosol. Conclusion These results suggest the extract and these compounds obtained from a novel industrial process could be natural alternatives for the prevention of diseases related to cardiovascular disorder or oxidative damage., The authors wish to express their gratitude to the Ministerio de Economía y Competitividad of Spain and co-funded by European Social Fund (ESF) (Project AGL2013-48291-R) for providing financial support. Dr. Rodríguez-Gutiérrez (RYC-2012-10456 contract) wishes to thank to the “Ramón y Cajal” Program from the Spanish Ministry of Economy and Competitiveness, and Ms Rubio-Senent (JAE-Pre104) to the Spanish National Research Council and co-funded by European Social Fund (CSIC-ESF) for providing financial support.

Summary In a large cohort of older women, a mechanism-driven statistical technique for assessing dietary patterns that considers a potential nutrient pathway found two dietary patterns associated with lumbar spine and femoral neck bone mineral density. A “healthy” dietary pattern was observed to be beneficial for bone mineral density. Introduction Dietary patterns represent a broader, more realistic representation of how foods are consumed, compared to individual food or nutrient analyses. Partial least-squares (PLS) is a data-reduction technique for identifying dietary patterns that maximizes correlation between foods and nutrients hypothesized to be on the path to disease, is more hypothesis-driven than previous methods, and has not been applied to the study of dietary patterns in relation to bone health. Methods Women from the Aberdeen Prospective Osteoporosis Screening Study (2007–2011, n = 2129, age = 66 years (2.2)) provided dietary intake using a food frequency questionnaire; 37 food groups were created. We applied PLS to the 37 food groups and 9 chosen response variables (calcium, potassium, vitamin C, vitamin D, protein, alcohol, magnesium, phosphorus, zinc) to identify dietary patterns associated with bone mineral density (BMD) cross-sectionally. Multivariable regression was used to assess the relationship between the retained dietary patterns and BMD at the lumbar spine and femoral neck, adjusting for age, body mass index, physical activity level, smoking, and national deprivation category. Results Five dietary patterns were identified, explaining 25% of the variation in food groups and 77% in the response variables. Two dietary patterns were positively associated with lumbar spine (per unit increase in factor 2: 0.012 g/cm2 [95% CI: 0.006, 0.01]; factor 4: 0.007 g/cm2 [95% CI: 0.00001, 0.01]) and femoral neck (factor 2: 0.006 g/cm2 [95% CI: 0.002, 0.01]; factor 4: 0.008 g/cm2 [95% CI: 0.003, 0.01)]) BMD. Dietary pattern 2 was characterized by high intakes of milk, vegetables, fruit and vegetable juices, and wine, and low intakes of processed meats, cheese, biscuits, cakes, puddings, confectionary, sweetened fizzy drinks and spirits while dietary pattern 4 was characterized by high intakes of fruits, red and white meats, and wine, and low intakes of vegetables and sweet spreads. Conclusion Our findings using a robust statistical technique provided important support to initiatives focusing on what constitutes a healthy diet and its implications. Electronic supplementary material The online version of this article (doi:10.1007/s11657-017-0355-y) contains supplementary material, which is available to authorized users.

Despite limited bioavailability and rapid degradation, dietary anthocyanins are antioxidants with cardiovascular benefits. This study tested the hypothesis that the antioxidant protection conferred by the anthocyanin, delphinidin, is mediated by modulation of endogenous antioxidant defences, driven by its degradation product, gallic acid. Delphinidin was found to degrade rapidly (t1/2 ~ 30 min), generating gallic acid as a major degradation product. Both delphinidin and gallic acid generated oxygen-centred radicals at high (100 μM) concentrationsin vitro. In a cultured human umbilical vein endothelial cell model of oxidative stress, the antioxidant protective effects of both delphinidin and gallic acid displayed a hormesic profile; 100 μM concentrations of both were cytotoxic, but relatively low concentrations (100 nM–1 μM) protected the cells and were associated with increased intracellular glutathione. We conclude that delphinidin is intrinsically unstable and unlikely to confer any direct antioxidant activityin vivoyet it offered antioxidant protection to cells at low concentrations. This paradox might be explained by the ability of the degradation product, gallic acid, to confer benefit. The findings are important in understanding the mode of protection conferred by anthocyanins and reinforce the necessity to conductin vitroexperiments at biologically relevant concentrations.

Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997–2000 (n3237, mean age 54·8 (sd2·2) years). Participants (n2130, mean age 66·0 (sd2·2) years) returned during 2007–11 for follow-up. Diet was assessed by FFQ (n1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past ‘prudent’ dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of the dietary pattern;P= 0·002 andP= 0·001, respectively; ANCOVA). Contemporary dietary patterns were also associated with inflammatory biomarkers. The concentrations of hs-CRP and IL-6 decreased across the quintiles of the ‘prudent’ dietary pattern (P= 0·030 andP= 0·006, respectively). hs-CRP concentration increased across the quintiles of a ‘meat-dominated’ dietary pattern (P= 0·001). Inflammatory biomarker concentrations decreased markedly across the quintiles of carotenoid component score (PP= 0·016 for E-selectin; ANCOVA). Prudent dietary pattern and carotenoid component scores were negatively associated with serum hs-CRP concentration (unstandardised β for prudent component: − 0·053, 95 % CI − 0·102, − 0·003; carotenoid component: − 0·183, 95 % CI − 0·233, − 0·134) independent of study covariates. A prudent dietary pattern (which reflects a diet high in the intakes of fish, yogurt, pulses, rice, pasta and wine, in addition to fruit and vegetable consumption) and a serum carotenoid profile characteristic of a fruit and vegetable-rich diet are associated with lower concentrations of intermediary markers that are indicative of CVD risk reduction.

Scope Cell defenses regulating homeostatic control of postprandial stress are influenced by interindividual variation, food composition and health status. This study investigates effects of food composition on individual postprandial responses and associations with health. Methods and results Volunteers (n = 16) consumed four food formulations (50% unsaturated/saturated fat, with/without beetroot extract 10 g/100 g) on separate occasions. GeXP assay measured whole blood postprandial gene expression profiles of 28 cell defense markers at baseline and postprandial time points 1, 2, 4, 6, 24 h. Plasma markers of metabolic lipids, hormones, inflammatory cytokines, oxidative stress, and DNA damage/repair were also assessed. SIRT 1, UCP2, HO1, GSS, PTGS2, TP53, CDKN2A, PPIA, SOCS3, and APE1 expression profiles revealed distinct stratified subgroups associated with plasma HDLs, TNF-α and postprandial responses of SOCS3, and PPIA. Leptin, IL6, and DNA strand breaks revealed differing responses to fat type consumed. Conclusion This study demonstrates postprandial immune, inflammatory, redox, metabolic, and DNA repair responses that are largely independent of fat type consumed (unsaturated/saturated) or addition of beetroot extract, in apparently healthy individuals. However, postprandial responses can be characterized by regulation of gene expression associated with markers linked to health status and are subject to interindividual variation that can influence postprandial responses.

Lipid and protein oxidation decreases the shelf-life of foods and may result in formation of end-products potentially detrimental for health. Consumer pressure to decrease the use of synthetic phenolic antioxidants has encouraged identification of alternative compounds or extracts from natural sources. We have assessed whether inclusion of dried vegetable powders improves the oxidative stability of turkey meat patties. Such powders are not only potentially-rich sources of phenolic antioxidants, but also may impart additional health benefits, as inadequate vegetable consumption is a risk factor for heart disease and several cancers. In an accelerated oxidation system, six of eleven vegetable powders significantly (p < 0.05) improved oxidative stability of patties by 20%–30% (spinach < yellow pea < onion < red pepper < green pea < tomato). Improved lipid oxidative stability was strongly correlated with the decreased formation of protein carbonyls (r = 0.747, p < 0.01). However, improved lipid stability could not be ascribed to phenolic acids nor recognized antioxidants, such as α- and γ-tocopherol, despite their significant (p < 0.01) contribution to the total antioxidant capacity of the patties. Use of chemically complex vegetable powders offers an alternative to individual antioxidants for increasing shelf-life of animal-based food products and may also provide additional health benefits associated with increased vegetable intake.

Background The perimenopausal and postmenopausal periods are times of pronounced physiological change in body mass index (BMI), physical activity and energy intake. Understanding these changes in middle age could contribute to formation of potential public health targets. Method A longitudinal cohort of 5119 perimenopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) recruited between 1990 and 1994, with follow-up visits at 1997–1999 and 2009–2011. At each visit, participants were weighed, measured and completed socioeconomic and demographic questionnaires. Participants at the first visit were asked to recall body weights at 20, 30 and 40 years of age. We assessed trends in BMI, physical activity and energy intake across and within visits. Results Over 2 decades, obesity prevalence doubled from 14% to 28% of the participants, with 69% of participants being categorised as overweight or obese. Greater than 70% of participants gained >5% of their baseline BMI with weight gain occurring across all weight categories. Energy intake and physical activity levels (PALs) did not change during the 2 decades after menopause (p trend=0.06 and 0.11, respectively), but, within the second visit, energy intake increased concomitantly with a decrease in physical activity across increasing quartiles of BMI (p trend Conclusions Overweight and obesity increased by over 50% over the course of 20 years. Weight gain occurred across the adult life course regardless of starting weight. The marked increase in dietary intake and decrease in PALs in middle age suggest a potential critical period for intervention to curb excess weight gain.

Background: Cardiovascular disease (CVD) is a major cause of mortality in the United Kingdom. Epidemiologic studies suggest that consumption of tomato-based foods may lower CVD risk. Such potential benefits have been ascribed in part to high concentrations of lycopene in the tomatoes. However, these findings have not yet been validated by comprehensive intervention trials. Objective: The aim of this study was to conduct a single-blind, randomized controlled intervention trial with healthy middle-aged volunteers to assess whether the consumption of tomato-based foods affects recognized biomarkers of CVD risk. Design: After a 4-wk run-in period with a low-tomato diet, 225 volunteers (94 men and 131 women) aged 40‐65 y were randomly assigned into 1 of 3 dietary intervention groups and asked to consume a control diet (low in tomato-based foods), a high-tomato-based diet, or a control diet supplemented with lycopene capsules (10 mg/d) for 12 wk. Blood samples were collected at baseline, at 6 wk, and after the intervention and were analyzed for carotenoid and lipid profiles and inflammatory markers. Blood pressure, weight, and arterial stiffness were also measured. Dietary intake was also determined during the intervention. Results: None of the systemic markers (inflammatory markers, markers of insulin resistance and sensitivity) changed significantly after the dietary intervention. Moreover, lipid concentrations and arterial stiffness were also unaffected by the interventions. Conclusion: These data indicate that a relatively high daily consumption of tomato-based products (equivalent to 32‐50 mg lycopene/d) or lycopene supplements (10 mg/d) is ineffective at reducing conventional CVD risk markers in moderately overweight, healthy, middle-aged individuals. This trial was registered at isrctn.org as ISRCTN34203810. Am J Clin Nutr 2012;95:1013‐22.

Flavonoids are polyphenolic compounds with potential antioxidant activity via multiple reduction capacities. Oxidation of cellular lipids has been implicated in many diseases. Consequently, this study has assessed the ability of several dietary flavonoid aglycones to suppress lipid peroxidation of hepatic microsomes derived from rats deficient in the major lipid soluble antioxidant, dα-tocopherol. Antioxidant effectiveness was galangin > quercetin > kaempferol > fisetin > myricetin > morin > catechin > apigenin. However, none of the flavonoids were as effective as dα-tocopherol, particularly at the lowest concentrations used. In addition, there appears to be an important distinction between thein vitroantioxidant effectiveness of flavonoids and their ability to suppress indices of oxidationin vivo. Compared with dα-tocopherol, repletion of vitamin E deficient rats with quercetin, kaempferol, or myricetin did not significantly affect indices of lipid peroxidation and tissue damage. Direct antioxidant effect of flavonoidsin vivowas not apparent probably due to low bioavailability although indirect redox effects through stimulation of the antioxidant response element cannot be excluded.

Scope: Bioactive polyphenols from fruits, vegetables, and beverages have anti-platelet effects and may thus affect the development of cardiovascular disease. We screened the effects of 26 low molecular weight phenolic compounds on two in vitro measures of human platelet function. Methods and results: After platelets had been incubated with one of 26 low molecular weight phenolic compounds in vitro, collagen-induced human platelet aggregation and in vitro TRAP-induced P-selectin expression (as marker of platelet activation) were assessed. Incubation of platelet-rich plasma from healthy volunteers with 100 μmol/L hippuric acid, pyrogallol, catechol, or resorcinol significantly inhibited collagen-induced platelet aggregation (all p

Purpose: Platelets play a key role in haemostasis and wound healing, contributing to formation of vascular plugs. They are also involved in formation of atherosclerosic plaques. Some traditional diets, like the Mediterranean diet, are associated with a lower risk of cardiovascular disease. Components in these diets may have anti-platelet functions contributing to their health benefits. Methods: We studied the effects of alperujo extract, an olive oil production waste product containing the majority of polyphenols found in olive fruits, through measurement of effects on platelet aggregation and activation in isolated human platelets, and through identification of changes in the platelet proteome. Results: Alperujo extract (40 mg/L) significantly decreased in vitro ADP- (p = 0.002) and TRAP- (p = 0.02) induced platelet activation as measured by the flow cytometry using the antibody for p-selectin (CD62p), but it did not affect the conformation of the fibrinogen receptor as measured by flow cytometry using the antibodies for anti-fibrinogen, CD42a and CD42b. Alperujo extract (100 mg/L) inhibited both collagen- and TRAP-induced platelet aggregation by 5% (p < 0.05), and a combination of hydroxytyrosol and 3,4-dihydroxyphenylglycol were, at least partly, responsible for this effect. Proteomic analysis identified nine proteins that were differentially regulated by the alperujo extract upon ADP-induced platelet aggregation. These proteins represent important mechanisms that may underlie the anti-platelet effects of this extract: regulation of platelet structure and aggregation, coagulation and apoptosis, and signalling by integrin αIIb/β3. Conclusions: Alperujo extract may protect against platelet activation, platelet adhesion and possibly have anti-inflammatory properties. © 2010 Springer-Verlag.

Cardiovascular disease is a chronic disease influenced by many factors, with activated blood platelets being one of them. Platelets play a central role in the formation of plaques within blood vessels, contributing to early inflammatory events. Consumption of diets rich in plant-based products protects against the development of cardiovascular disease. Polyphenols, which are secondary plant metabolites found in a wide range of foodstuffs and beverages, may be partially responsible for these effects. Their protective properties include inhibitory effects on platelet function in vitro and in vivo. However, the bioavailability of many polyphenols is poor and it is unclear whether sufficient quantities can be obtained by dietary means to exert protective effects. Consequently, this review summarizes 25 well-controlled human intervention studies examining the effect of polyphenol-rich diets on platelet function. These studies report a huge variety of research methods, study designs, and study subjects, resulting in controversial assertions. One consistent finding is that cocoa-related products, however, have platelet-inhibiting effects when consumed in moderate amounts. To assess whether other classes of dietary polyphenols, or their metabolites, also beneficially affect platelet function requires more well-controlled intervention studies as well as the adoption of more uniform methods to assess platelet aggregation and activation.

Despite fruit, vegetables and many processed products counting towards achieving the recommended five-a-day strategy, it is inevitable that produce choice will affect the benefits delivered. Fruits locally produced and commonly consumed in Scotland were compared for their phenolic acid content and form. The phenolic acid composition was highly variable, but the locally produced fruits were significantly ( p – 4.89 g/kg compared to 0.06 – 0.22 g/kg). The majority of the phenolic acids were conjugated to other plant components, suggesting that any health benefits derived from these compounds are likely to be after they are released/metabolised by the colonic microbiota. Although the potential protective effects of the individual compounds will not be ascertained until the exact role of these compounds in disease prevention has been clarified, it is clear that the total amount of phenolic acids in the diet will vary enormously depending on the types of fruits consumed.

Trials in free-living populations involving increased consumption of fruit and vegetables are difficult to monitor. We evaluated biomarkers for assessing fruit and vegetable intake and compliance in a 2-year trial. Postmenopausal women were randomised to 300 g additional fruit and vegetables per d (n 66), placebo (n 70) or potassium citrate (n 140). They completed dietary checklists (3-monthly) and food diaries or FFQ (yearly). We measured whole-blood folate, plasma vitamin C and homocysteine (yearly), serum vitamin E and carotenoids (at 12 months) and urinary vitamin K metabolites (yearly). Plasma vitamin C was associated with fruit and vegetable intake at baseline (r +0·31; P r +0·43; P P = 0·07) but was not significantly associated with fruit and vegetable intake; vitamin E, β-carotene and β-cryptoxanthin were higher compared with the non-fruit and vegetable group (P 500 g/d, whereas whole-blood folate, β-carotene and β-cryptoxanthin continued to increase. Concentrations of vitamin C, folate and β-cryptoxanthin were lower and the 7C-aglycone metabolite of vitamin K higher, in smokers compared with non-smokers. Suitable markers for monitoring fruit and vegetable compliance include β-carotene and β-cryptoxanthin. Plasma vitamin C and whole-blood folate may be suitable for monitoring intakes in populations but for monitoring compliance the former may be restricted to low intakes of fruit and vegetables and the latter to vegetable intake.

Evidence from a wide range of sources suggests that individuals taking aspirin and related non-steroidal anti-inflammatory drugs have reduced risk of large bowel cancer. Work in animals supports cancer reduction with aspirin, but no long-term randomised clinical trials exist in human beings, and randomisation would be ethically unacceptable because vascular protection would have to be denied to a proportion of the participants. However, opportunistic trials of aspirin, designed to test vascular protection, provide some evidence of a reduction in cancer, but only after at least 10 years. We summarise evidence for the potential benefit of aspirin and natural salicylates in cancer prevention. Possible mechanisms of action and directions for further work are discussed, and implications for clinical practice are considered.

Scottish strawberries were found to be a rich source of phenolic acids, namely benzoic (1287.95 +/- 279.98 mg/kg) and cinnamic (1159.40 +/- 233.96 mg/kg) acids, both free and attached to other plant components. Studies suggest a chemopreventive role for such compounds in several major clinical conditions, but the anticipated benefits are likely to be affected by their bio-availability and metabolic fate. In this pilot study, strawberries (750 g) was consumed by four healthy human volunteers (32 +/- 6 years). Only the benzoic acids were detected in the plasma. Of these, the major free (gentisic, protocatechuic and p-hydroxybenzoic acid) and conjugated (syringic acid) benzoic acids were 26-27% recovered in the urine within 5 h. Cinnamic acids were completely undetected in plasma and only trace amounts were found in the urine. Since, the cinnamic acids escaped absorption early in the gastrointestinal tract, their release and/or metabolism is dependent on the host colonic microbiota. Results indicate that there is a high degree of selective absorption of strawberry phenolic acids into the systemic circulation. If selective absorption of phenolic acids is observed with consumption of other plant-based foods, this is likely to have implications for the bioactive role of these compounds in chronic disease prevention.

Life-history theory assumes that animal life histories are a consequence of trade-offs between current activities and future reproductive performance or survival, because resource supply is limited. Empirical evidence for such trade-offs in the wild are common, yet investigations of the underlying mechanisms are rare. Life-history trade-offs may have both physiological and ecological mediated costs. One hypothesized physiological mechanism is that elevated energy metabolism may increase reactive oxygen species production, leading to somatic damage and thus compromising future survival. We investigated the impact of experimentally elevated energy expenditure on oxidative damage, protection and lifespan in short-tailed field voles (Microtus agrestis) maintained in captivity to remove any confounding ecological factor effects. Energy expenditure was elevated via lifelong cold exposure (7±2°C), relative to siblings in the warm (22±2°C). No treatment effect on cumulative mortality risk was observed, with negligible effects on oxidative stress and antioxidant protection. These data suggest that in captive animals physiologically mediated costs on life history do not result from increased energy expenditure and consequent elevations in oxidative stress and reduced survival.

The effects of dietary antioxidant supplementation on oxidative stress and life span are confused. We maintained C57BL/6 mice at 7 +/- 2 degrees C and supplemented their diet with alpha-tocopherol from 4 months of age. Supplementation significantly increased (p = 0.042) median life span by 15% (785 days, n = 44) relative to unsupplemented controls (682 days, n = 43) and also increased maximum life span (oldest 10%, p = 0.028). No sex or sex by treatment interaction effects were observed on life span, with treatment having no effect on resting or daily metabolic rate. Lymphocyte and hepatocyte oxidative DNA damage and hepatic lipid peroxidation were unaffected by supplementation, but hepatic oxidative DNA damage increased with age. Using a cDNA macroarray, genes associated with xenobiotic metabolism were significantly upregulated in the livers of female mice at 6 months of age (2 months supplementation). At 22 months of age (18 months supplementation) this response had largely abated, but various genes linked to the p21 signaling pathway were upregulated at this time. We suggest that alpha-tocopherol may initially be metabolized as a xenobiotic, potentially explaining why previous studies observe a life span extension generally when lifelong supplementation is initiated early in life. The absence of any significant effect on oxidative damage suggests that the life span extension observed was not mediated via any antioxidant properties of alpha-tocopherol. We propose that the life span extension observed following alpha-tocopherol supplementation may be mediated via upregulation of cytochrome p450 genes after 2 months of supplementation and/or upregulation of p21 signaling genes after 18 months of supplementation. However, these signaling pathways now require further investigation to establish their exact role in life span extension following alpha-tocopherol supplementation.

Obesity has recently become a focus of research to elucidate diet and lifestyle factors as important risk factors for colon cancer. Altered levels of insulin, leptin, and adiponectin have been identified as potential candidates increasing colon cancer risk within the prevailing obesogenic environment. There has been considerable research to characterize signaling via these hormones in the brain, liver, and adipose tissue; however, very little is known of their emerging role in peripheral signaling, particularly in epithelial tissues. This study profiles insulin, leptin, and adipokine receptors in the rat colon, revealing novel microanatomical location of these receptors and thereby supporting a potential role in regulating colonic tissue. Potential involvement of insulin, leptin, and adiponectin receptors in increased risk of colon cancer was investigated using Sprague-Dawley rats, either resistant or susceptible to diet-induced obesity. Regulation of insulin, leptin, and adiponectin receptors as a consequence of differing levels of adiposity was assessed regionally in the colon in response to treatment with the chemical carcinogen 1,2-dimethylhydrazine (DMH). However, significantly increased fat mass, increased levels of plasma insulin, leptin, and triglycerides, previously associated with an increased risk of colon cancer, were not associated with promotion of precancerous lesions in the experimental rats or deregulation of insulin, leptin, or adiponectin receptors. These findings do not support a direct link between the deregulation of insulin and adipokine levels observed in obese rats and an increased risk of colon carcinogenesis.

Epidemiological studies assessing the health benefits of drinking black tea are equivocal. Such disparity may reflect an inability of semiquantitative assessment to consider how infusion time and addition of milk affect the bioavailability of potentially beneficial antioxidant polyphenols. Six brands of tea demonstrated similar increases in antioxidant capacity and total phenolic and catechin contents with increasing infusion time. These results were unaffected by the addition of milk. Consumption of black tea (400 mL) was associated with significant increases in plasma antioxidant capacity (10%) and concentrations of total phenols (20%), catechins (32%), and the flavonols quercetin (39%) and kaempferol (45%) (all p < 0.01) within 80 min. This was unaffected by adding milk. Infusion time may therefore be a more important determinant in the absorption of polyphenols from black tea. Observational studies assessing the health benefits of tea consumption require recording of brewing methods as well as frequency of consumption.

The polyacetylene falcarinol, isolated from carrots, has been shown to be protective against chemically induced colon cancer development in rats, but the mechanisms are not fully understood. In this study CaCo-2 cells were exposed to falcarinol (0.5-100 microM) and the effects on proliferation, DNA damage, and apoptosis investigated. Low-dose falcarinol exposure (0.5-10 microM) decreased expression of the apoptosis indicator caspase-3 concomitantly with decreased basal DNA strand breakage. Cell proliferation was increased (1-10 microM), whereas cellular attachment was unaffected by10 microM falcarinol. At concentrations above 20 microM falcarinol, proliferation of CaCo-2 cells decreased and the number of cells expressing active caspase-3 increased simultaneously with increased cell detachment. Furthermore, DNA single-strand breakage was significantly increased at concentrations above 10 microM falcarinol. Thus, the effects of falcarinol on CaCo-2 cells appear to be biphasic, inducing pro-proliferative and apoptotic characteristics at low and high concentrations of falcarinol, respectively.

Oxidative stress is a key feature of the atherothrombotic process involved in the etiology of heart attacks, ischemic strokes, and peripheral arterial disease. It stands to reason that antioxidants represent a credible therapeutic option to prevent disease progression and thereby improve outcome, but despite positive findings from in vitro studies, clinical trials have failed to consistently show benefit. The aim of this review is to re-appraise the concept of antioxidants in the prevention and management of cardiovascular disease. In particular, the review will explore the reasons behind failed antioxidant strategies with vitamin supplements and will evaluate how flavonoids might improve cardiovascular function despite bioavailability that is not sufficiently high to directly influence antioxidant capacity. As well as reaching conclusions relating to those antioxidant strategies that might hold merit, the major myths, limitations, and pitfalls associated with this research field are explored.

The dietary phenolic compound, salicylic acid, decreases oxidative stress and pro-inflammatory and potentially neo-plastic prostaglandins with a concomitant increase in glutathione peroxidase activity. Salicylic acid, a dietary plant-based phenolic compound and also the main metabolite of aspirin, may contribute to the colon protective effects of plant-based diets. Oxidative stress is a characteristic of pre-cancerous and cancerous colon and inflammatory bowel diseases (IBD) that increase colon cancer risk. The mechanism(s) whereby salicylic acid modulates potentially pro-cancerous activity associated with oxidative stress is further investigated here using a proteomic approach. A rat model of oxidative stress was supplemented with salicylic acid (1 mg/kg diet, mean plasma levels 310+/-32 micromol/l). Soluble colon protein extracts were subjected to 2D PAGE. Salicylic acid modulated proteins, identified using MALDI-TOF and LC/MS/MS, are involved in protein folding, transport, redox, energy metabolism and cytoskeletal regulation. A partial least squares (PLS) analysis approach was used to assist biological interpretation of the altered protein profiles via their associations between previously published biochemical measurements of oxidative stress, prostaglandin levels and increased glutathione peroxidase activity. Early detection of altered homeostasis in colon may assist in identifying pre-pathological features preceding colon tumorigenesis and contribute to an understanding of epidemiological evidence supporting a protective effect of plant-based diets.

Glutathione peroxidases (Gpx) are important moderators of oxidative stress that is implicated in the pathogenesis of numerous diseases including colon cancer. Previous studies report limited examinations of cytosolic glutathione peroxidase location of expression in colon tissue. This study reports evidence of both common sites of Gpx1 and Gpx2 expression in rat colon and sites that are exclusive to each isoform. Semi-quantitative PCR performed previously demonstrated RNA expression of Gpx1 and Gpx2 in proximal, transverse and distal colon. Mapping the distribution throughout the entire colon has revealed specific, novel sites of glutathione peroxidase expression in colon lymphatic tissue. In situ hybridisation and immunohistochemistry confirmed micro-anatomical location of Gpx1 within lymphatic tissue and the lamina propria, sub-mucosa, muscularis and serosa, but not the lumenal epithelium. In situ hybridisation and immunohistochemistry were consistent with reports of microanatomical location of Gpx2 in the lumenal epithelium. Novel sites of Gpx2 expression were also observed in lymphatic tissue. Immunolocalisation in the vicinity of aberrant crypt foci was also examined to further investigate the link between glutathione peroxidases and colon cancer. This did not reveal significant abnormalities, nor did measurement of cytosolic glutathione peroxidase activity or gene expression in colon tissue from rats treated with the colontropic chemical, 1,2-dimethylhydrazine. These results support the potential for Gpx1 and Gpx2 redundancy in lymphatic tissue, but not in epithelial cells of the colon crypt or in the lamina propria, sub-mucosa, muscularis or serosa.

Oxidative stress is a characteristic of cancerous colon tissue and inflammatory bowel diseases that increase colon cancer risk. Epidemiological evidence supports a protective effect of plant-derived compounds. Aspirin is also protective against colon cancer. The mechanism of action is unclear although salicylic acid, the main metabolite of aspirin, has been shown to decrease the synthesis of pro-inflammatory and potentially neo-plastic prostaglandins. Salicylic acid is found in significant quantities in a plant-based diet. However, in plants salicylic acid is also reported to modulate the expression of numerous enzymes with antioxidant activity. The aim of this study was to assess whether salicylic acid can modulate pro-cancerous biological pathways in the colon. Oxidative stress, prostaglandins and cytosolic glutathione peroxidase (cyGPX) were analysed in proximal, transverse and distal colon from a rat model of diet-induced oxidative stress. Elevated plasma pyruvate kinase activity (1293+/-206 U/ml) and increased indices of lipid peroxidation in colon (proximal 6.4+/-0.84 nM MDA/mg protein; transverse 6.9+/-0.97 nM MDA/mg protein; distal 5.2+/-0.62 nM MDA/mg protein) from rats fed a Vitamin E deficient diet were significantly decreased on supplementation with salicylic acid (plasma pyruvate 546+/-43 U/ml; salicylic acid proximal 3.6+/-0.39 nM MDA/mg protein; transverse 4.5+/-0.61 nM MDA/mg protein; distal 4.4+/-0.27 nM MDA/mg protein). Reductions in oxidative stress and prostaglandin production on supplementation with salicylic acid were associated with an elevation in glutathione peroxidase activity (Vitamin E deficient proximal 0.056+/-0.013 U/mg protein; transverse 0.073+/-0.008 U/mg protein; distal 0.088+/-0.010 U/mg protein; Vitamin E deficient with salicylic acid proximal 0.17+/-0.01 U/mg protein; transverse 0.23+/-0.016 U/mg protein; distal 0.16+/-0.020 U/mg protein). Gpx1 and Gpx2 gene transcripts were not elevated in association with increased activity of the soluble glutathione peroxidase activity. Glutathione peroxidases are key antioxidant enzymes, catalysing the decomposition of potentially toxic lipid peroxides. Gpx activity and regulation of Gpx gene transcription has been shown previously to be complex with activity not necessarily mirrored by a corresponding elevation in gene transcription. By supplementing the diet of Vitamin E deficient rats with salicylic acid (1 g/kg diet), this study assessed effects of salicylic acid on cytosolic glutathione peroxidase activity in the colon. The ability of salicylic acid to modulate antioxidant enzymes in colon tissue may be an important mechanism in inhibiting colon cancer development.

Quercetin-4'-glucoside is a major flavonol in onions, and this study investigated the absorption and fate of radiolabeled quercetin-4'-glucoside in rats. Rats ingested [2-(14)C]quercetin-4'-glucoside and the distribution of radioactivity throughout the body was determined after 0.5, 1, 2, and 5 h. The gastrointestinal tract, liver, kidney, and plasma were extracted, and radiolabeled components were identified and quantified using high-performance liquid chromatography with on-line radioactivity detection and tandem mass spectrometry. Two hours after dosing, all the [2-(14)C]quercetin-4'-glucoside had been metabolized. More than 85% of the ingested radioactivity was present in the gastrointestinal tract at all time points with approximately 6% being absorbed and present in blood and internal organs, primarily the liver and kidneys. More than 95% of the absorbed radioactivity was in the form of >20 different methylated glucuronated and/or sulfated quercetin conjugates. Five hours after ingestion, the main radiolabeled metabolites were quercetin diglucuronides in the gut, liver, and kidneys and glucuronyl sulfates of methylated quercetin in plasma. The main site of quercetin metabolism seemed to be the gastrointestinal tract. Quercetin metabolites may have a major influence on the gut mucosal epithelium and on colonic disease.

The aim of this study was to assess whether regular consumption of cranberry juice results in elevations in urinary salicylate concentrations in persons not taking salicylate drugs. Two groups of healthy female subjects (11/group) matched for age, weight, and height consumed 250 mL of either cranberry juice or a placebo solution three times a day (i.e., 750 mL/day) for 2 weeks. At weekly intervals, salicylic acid and salicyluric acid (the major urinary metabolite of salicylic acid) concentrations were determined in urine by HPLC with electrochemical detection. Concentrations of salicylic acid in plasma were also determined. Consumption of cranberry juice was associated with a marked increase (p0.001) of salicyluric and salicylic acids in urine within 1 week of the intervention. After 2 weeks, there was also a small but significant (p0.05) increase in salicylic acid in plasma. The regular consumption of cranberry juice results in the increased absorption of salicylic acid, an anti-inflammatory compound that may benefit health.

The effects of moderate red wine consumption on the antioxidant status and indices of lipid peroxidation and oxidative stress associated with CHD were investigated. A randomised, controlled study was performed with twenty free-living healthy volunteers. Subjects in the red wine group consumed 375 ml red wine daily for 2 weeks. We measured the total concentration of phenolics and analysed the individual phenolics in the wine and plasma by HPLC with tandem MS. The antioxidant capacity of plasma was measured with electron spin resonance spectroscopy while homocysteine and fasting plasma lipids were also determined. The production of conjugated dienes and thiobarbituric acid-reactive substances (TBARS) were measured in Cu-oxidised LDL. Plasma total phenolic concentrations increased significantly after 2 weeks of daily red wine consumption (P≤0·001) and trace levels of metabolites, mainly glucuronides and methyl glucuronides of (+)-catechin and (−)-epicatechin, were detected in the plasma of the red wine group. These flavan-3-ol metabolites were not detected in plasma from the control group. The maximum concentrations of conjugated dienes and TBARS in Cu-oxidised LDL were reduced (P≤0·05) and HDL cholesterol concentrations increased (P≤0·05) following red wine consumption. The findings from the present study provide some evidence for potential protective effects of moderate consumption of red wine in healthy volunteers.

Fruit and vegetable consumption is inversely related to the incidence of heart disease and several cancers. However, many people in countries in Northern latitudes do not eat the recommended “5-a-day” of fruit and vegetables. For such populations, a potentially important source of fruit may be locally grown soft fruits (eg. raspberries, blackberries, blueberries, blackcurrants). Such berries contain micronutrients such as vitamin C and folic acid which are essential for health. However, berries may have additional health benefits as they are also rich in phytochemicals such as anthocyanins which are glycosidic-linked flavonoids responsible for their red, violet, purple and blue colours. In vitro studies indicate that anthocyanins and other polyphenols in berries have a range of potential anti-cancer and heart disease properties including antioxidant, anti-inflammatory, and cell regulatory effects. Such experimental data has lead to numerous health claims on the internet implying that “berries are edible superstars that may protect against heart disease, cancers and ageing”. However, the bioavailabilty of polyphenols such as anthocyanins would appear to be limited, thus compromising their nutritional relevance. Consequently the aim of the article is to assess the current scientific evidence for claims that berries may have additional health benefits to those normally associated with consuming fruit and vegetables.

Fruit and vegetable consumption protects against cancer. This is attributed in part to antioxidants such as vitamin E combating oxidative DNA damage. Anthocyanins are found in significant concentrations in the human diet. However, it remains to be established whether they are bioactive in vivo.To investigate the consequence both of vitamin E deficiency on oxidative damage to DNA and lipids and the cytoprotective effect of nutritionally relevant levels of cyanidin-3-glycoside both in vivo in rats and in vitro in human colonocytes.Male Rowett Hooded Lister rats were fed a diet containing less than 0.5 mg/kg vitamin E or a vitamin E supplemented control diet containing 100 mg d alpha-tocopherol acetate/kg. Half of the controls and vitamin E-deficient rats received cyanidin-3-glycoside (100 mg/kg). After 12 weeks endogenous DNA stability in rat lymphocytes (strand breaks and oxidised bases) and response to oxidative stress ex vivo (H2O2; 200 microM) was measured by single cell gel electrophoresis (SCGE). Tissue levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-Oxo-dG) were measured by HPLC with EC detection. D alpha-tocopherol and lipid peroxidation products (thiobarbituric acid reactive substances; TBARS) were measured by HPLC. Rat plasma pyruvate kinase and the production of reactive oxygen by phagocytes were detected spectrophotometrically and by flow cytometry respectively. Immortalised human colon epithelial cells (HCEC) were preincubated in vitro with the anthocyanins cyanidin and cyanidin-3-glycoside and the flavonol quercetin (all 50 microM) before exposure to H2O2 (200 microM). DNA damage was measured by SCGE as above.Plasma and liver d alpha-tocopherol declined progressively over 12 weeks in rats made vitamin E deficient. Lipid peroxidation was increased significantly in plasma, liver and red cells. Reactive oxygen levels in phagocytes and plasma pyruvate kinase were increased. Vitamin E deficiency did not affect DNA stability in rat lymphocytes, liver or colon. Cyanidin-3-glycoside did not alter lipid peroxidation or DNA damage in rats. However, it was chemoprotective against DNA damage in human colonocytes.DNA strand breakage was decreased 38.8 +/- 2.2% after pretreatment with anthocyanin.While it is accepted that vitamin E alters lipid oxidation in vivo, its role in maintaining DNA stability remains unclear. Moreover, whereas cyanidin-3-glycoside protects against oxidative DNA damage in vitro, at nutritionally relevant concentrations it is ineffective against oxidative stress in vivo.

The flavonol myricetin, reacts with oxygen-centred galvinoxyl radicals 28 times faster than d-α-tocopherol (vitamin E), the main lipid-soluble antioxidant in biological membranes. Moreover, each myricetin molecule reduces twice as many such radicals as vitamin E. However, myricetin fails to protect vitamin E-deficient microsomes from lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances (TBARS). Novel and potentially therapeutic antioxidants have been prepared that combine the radical-scavenging ability of a myricetin-like head group with a lipophilic chain similar to that of vitamin E. C 6 –C 12 alkyl chains are attached to the A-ring of either a 3,3 ′ ,4 ′ ,5 ′ -tetrahydroxyflavone or a 3,2 ′ ,4 ′ ,5 ′ -tetrahydroxyflavone head group to give lipophilic flavonoids ( C log P =4 to 10) that markedly inhibit iron-ADP catalysed oxidation of microsomal preparations. Orientation of the head group as well as total lipophilicity are important determinants of antioxidant efficacy. MM2 models indicate that our best straight chain 7-alkylflavonoids embed to the same depth in the membrane as vitamin E. The flavonoid head groups are prepared by aldol condensation followed by Algar–Flynn–Oyamada (AFO) oxidation or by Baker–Venkataraman rearrangement. The alkyl tails are introduced by Suzuki or Negishi palladium-catalysed cross-coupling or by cross-metathesis catalysed by first generation Grubbs catalyst, which tolerate phenolic hydroxyl and ketone groups.

Epidemiological evidence suggests that diets rich in fruit and vegetables decrease the risk of premature mortality from major clinical conditions, including cancer and heart disease. However, it is not yet clear which components or combination of components in fruit and vegetables are protective and what is their mechanism of action. Such scientific uncertainty does not seem to inhibit the marketing of a huge range of plant-based concoctions, promoted as ‘magic bullets’ for optimum health. For example, the purported health-giving properties of plant polyphenols represent a case in which enthusiastic marketing claims may far exceed the current scientific evidence. Even when good experimental evidence exists, results need to be interpreted with caution in relation to human health benefits, as polyphenols may have limited bioavailability and may also be extensively metabolised. In addition, some polyphenols can be toxic and mutagenic in some cell culture systems. Until more is known about the activity and metabolic fate of polyphenols in the body, it would be better for the consumer to increase fruit and vegetable intake, and also to be wary of claims that these compounds are a panacea for good health.

Analysis of extracts of Glen Ample raspberries (Rubus idaeus L.) by gradient, reverse phase HPLC with diode array and tandem mass spectrometry identified eleven anthocyanins, including cyanidin-3-sophoroside, cyanidin-3-(2(G)-glucosylrutinoside), cyanidin-3-glucoside, cyanidin-3-rutinoside, pelargonidin-3-sophoroside, pelargonidin-3-(2(G)-glucosylrutinoside), and pelargonidin-3-glucoside. Significant quantities of an ellagitannin, sanguiin H-6, with an M(r) of 1870 were detected along with lower levels of a second ellagitannin, lambertianin C, which has an M(r) of 2804. Other phenolic compounds that were detected included trace levels of ellagic acid and its sugar conjugates along with one kaempferol- and four quercetin-based flavonol conjugates. Fractionation by preparative HPLC revealed that sanguiin H-6 was a major contributor to the antioxidant capacity of raspberries together with vitamin C and the anthocyanins. Vasodilation activity was restricted to fractions containing lambertianin C and sanguiin H-6.

Phytophenols present in cereals are metabolised to compounds that could be partly responsible for the reduced risk of chronic diseases and all-cause mortality associated with fibre-rich diets. The bioavailability, form and in vivo concentrations of these metabolites require to be established.Eight healthy volunteers consumed a test meal containing a recommended dose (40 g) and high dose (120 g) of ready-to-eat wheat bran cereal and the systemic and colonic metabolites determined quantitatively by LC-MS.Analysis of the systemic metabolomes demonstrated that a wide range of phytophenols were absorbed/excreted (43 metabolites) within 5 h of consumption. These included 16 of the 21 major parent compounds identified in the intervention product and several of these were also found to be significantly increased in the colon. Not all of the metabolites were increased with the higher dose, suggesting some limitation in absorption due to intrinsic factors and/or the food matrix. Many compounds identified (e.g. ferulic acid and major metabolites) exhibit anti-inflammatory activity and impact on redox pathways. The combination of postprandial absorption and delivery to the colon, as well as hepatic recycling of the metabolites at these concentrations, is likely to be beneficial to both systemic and gut health.

Twenty-three commercial essential oils were tested for their anti-rancidity effect and potential implications to prolong the induction time of corn oil and extend the shelf life of cooked turkey patties. Moreover, the potential health benefit was investigated through DPPH, ABTS, β-carotene bleaching, FRAP, and α-amylase inhibitory assays. Essential oils' composition was investigated by GC-MS. Cumin, thyme, clove, and cinnamon oils improved oxidative stability and increased the induction time of the corn oil 1.5–3 fold. Clove and cinnamon oils were particularly effective in delaying lipid oxidation of cooked turkey patties (time of induction 11.04 and 9.43 h) compared with the plain burger (5.04 h). Both oils are also characterized by a potent radical scavenging activity in ABTS test (IC50 values of 1.43 and 2.05 μg/ml for cinnamon and clove, respectively). In the α-amylase inhibitory assay, cumin and grape fruits were the most potent with IC50 values of 21.88 and 23.95 μg/ml, respectively.