Resveratrol and ω-3 PUFAs Promote Human Macrophage Differentiation and Function.

Monocytes differentiate into M1 and M2 macrophages, which are classically activated by microbial products such as LPS or IFN-γ and interleukins (e.g., the anti-inflammatory and Th2 promoting IL-4), respectively. The contribution of nutrients or nutrient-based substances such as ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and resveratrol (Res) on the differentiation and function of M1 and M2 macrophages was evaluated. THP-1 cells and peripheral blood mononuclear cells (PBMCs) were differentiated into M1 and M2 cells and activated with LPS/IFN-γ or IL-4/IL-13. Macrophage lineage specific surface determinants (e.g., CD11b, CD11c, CD14, CD206, CD209, CD274, HLA-DR, CCR7, CCR2) were analysed by cytofluorometry. Res and ω-3 PUFAs altered CD14, CD206, CD274 and HL-DR surface expression patterns in M1 and M2 macrophages differentiated from PBMC. LPS/IFN-γ or IL-14/IL-13 activated macrophages subpopulations, which secreted cytokines and chemokines as measured by multiplex ELISA. Res and ω-3 PUFA reduced IL-1ß, IL-6, TNF-α, CXCL10/IP-10, CCL13/MCP-4 and CCL20/MIP-3α in LPS/IFN-γ activated human leukaemia THP-1 cells, which is indicative of a dampening effect on M1 macrophages. However, Res increased M1 prototypic cytokines such as IL-1ß or IL-6 in macrophages derived from PBMCs and also modified the expression of IL-12p70. Collectively, Res and ω-3 PUFAs distinctly promoted the differentiation and function of M1 and M2 macrophages. We conclude that these substances strengthen the macrophage-mediated effects on the innate and adaptive immune response.

Resveratrol, EGCG and Vitamins Modulate Activated T Lymphocytes.

Vitamins and bioactives, which are constituents of the food chain, modulate T lymphocyte proliferation and differentiation, antibody production, and prevent inflammation and autoimmunity. We investigated the effects of vitamins (vitamin A (VA), D (VD), E (VE)) and bioactives (i.e., resveratrol (Res), epigallocatechin-3-gallate (EGCG)) on the adaptive immune response, as well as their synergistic or antagonistic interactions. Freshly isolated T lymphocytes from healthy individuals were activated with anti-CD3/CD28 antibodies for 4-5 days in the presence of bioactives and were analyzed by cytofluorometry. Interleukins, cytokines, and chemokines were measured by multiple ELISA. Gene expression was measured by quantitative RT-PCR. Res and EGCG increased CD4 surface intensity. EGCG led to an increased proportion of CD8+ lymphocytes. Anti-CD3/CD28 activation induced exuberant secretion of interleukins and cytokines by T lymphocyte subsets. VD strongly enhanced Th2 cytokines (e.g., IL-5, IL-13), whereas Res and EGCG favored secretion of Th1 cytokines (e.g., IL-2, INF-γ). Res and VD mutually influenced cytokine production, but VD dominated the cytokine secretion pattern. The substances changed gene expression of interleukins and cytokines in a similar way as they did secretion. Collectively, VD strongly modulated cytokine and interleukin production and favored Th2 functions. Resveratrol and EGCG promoted the Th1 response. VA and VE had only a marginal effect, but they altered both Th1 and Th2 response. In vivo, bioactives might therefore interact with vitamins and support the outcome and extent of the adaptive immune response.

In Vitro Fermentation of Selected Prebiotics and Their Effects on the Composition and Activity of the Adult Gut Microbiota.

Recently, the concept of prebiotics has been revisited to expand beyond non-digestible oligosaccharides, and the requirements for selective stimulation were extended to include microbial groups other than, and additional to, bifidobacteria and lactobacilli. Here, the gut microbiota-modulating effects of well-known and novel prebiotics were studied. An in vitro fermentation screening platform (i-screen) was inoculated with adult fecal microbiota, exposed to different dietary fibers that had a range of concentrations (inulin, alpha-linked galacto-oligosaccharides (alpha-GOS), beta-linked GOS, xylo-oligosaccharides (XOS) from corn cobs and high-fiber sugar cane, and beta-glucan from oats), and compared to a positive fructo-oligosaccharide (FOS) control and a negative control (no fiber addition). All dietary fibers displayed prebiotic activity, with beta-glucan showing more distinct effects on the microbial composition and metabolism compared to the other fibers. Beta-glucan induced the growth of Prevotella and Roseburia with a concomitant increase in propionate production. Inulin and both forms of GOS and XOS had a strong bifidogenic effect on the microbial composition. A dose-response effect was observed for butyrate when exposed to beta-glucan and inulin. The findings of this study support the potential for alpha-GOS, XOS, and oat beta-glucan to serve as novel prebiotics, due to their association with the positive shifts in microbiome composition and short-chain fatty acid production that point to potential health benefits.

The effects of fermentation products of prebiotic fibres on gut barrier and immune functions in vitro.

The beneficial effects of prebiotic fibres on human health have been related to their capacities to alter the gut microbiota and modify the growth of beneficial microorganisms. It is long appreciated that bacterial metabolites affect the host's physiology. The inner lining of the intestinal tract is the first level of interaction between the host and bacteria and their metabolites. Therefore, we set out to test the effects of five common dietary fibres (oat ß-glucan 28%; oat ß-glucan 94%; dried chicory root containing inulin 75%; xylo-oligosaccharide; inulin 90%) and maltodextrin, after fermentation by human gut microbiota in vitro, on measures of gut barrier integrity using a Caco-2/HT29-MTX co-culture as well as mucus production and immune parameters using HT29-MTX and HT29 cell models, respectively. Our data show that all fibres, fermentation products increased the tightness of the gut barrier with oat ß-glucan 28% having the largest effect. Fermentation supernatants were tested also in models of the compromised gut barrier (leaky gut). After the addition of ethanol as basolateral stressor, only fermentation supernatant of oat ß-glucan 28%, oat ß-glucan 94% and maltodextrin improved the gut barrier integrity, while oat ß-glucan 28% and dried chicory root containing inulin 75% significantly improved the gut barrier integrity after addition of rhamnolipids as apical stressor. Using the Luminex Technology, we demonstrated an important role of oat ß-glucan fermentation products in modulating cytokine and chemokine productions. Furthermore, treating the goblet cells with effluent from xylo-oligosaccharide fermentation significantly increased mucus production. In summary, our data emphasize the potential positive effects of fermentation supernatant of dietary fibres on gut-related physiological outcomes and show that prebiotic fibres may have promising potential to induce specific gut health benefits.

Correction: The effects of fermentation products of prebiotic fibres on gut barrier and immune functions in vitro.

[This corrects the article DOI: 10.7717/peerj.5288.].

Cardiovascular and Antiobesity Effects of Resveratrol Mediated through the Gut Microbiota.

Encouraging scientific research into the health effects of dietary bioactive resveratrol has been confounded by its rapid first-pass metabolism, which leads to low in vivo bioavailability. Preliminary studies have shown that resveratrol can modulate gut microbiota composition, undergo biotransformation to active metabolites via the intestinal microbiota, or affect gut barrier function. In rodents, resveratrol can modify the relative Bacteroidetes:Firmicutes ratio and reverse the gut microbial dysbiosis caused by a high-fat diet. By upregulating the expression of genes involved in maintaining tight junctions between intestinal cells, resveratrol contributes to gut barrier integrity. The composition of the gut microbiome and rapid metabolism of resveratrol determines the production of resveratrol metabolites, which are found at greater concentrations in humans after ingestion than their parent molecule and can have similar biological effects. Resveratrol may affect cardiovascular risk factors such as elevated blood cholesterol or trimethylamine N-oxide concentrations. Modulating the composition of the gut microbiota by resveratrol may affect central energy metabolism and modify concentrations of satiety hormones to produce antiobesity effects. Encouraging research from animal models could be tested in humans.

Resveratrol distinctively modulates the inflammatory profiles of immune and endothelial cells.

BACKGROUND: The phenolic substance resveratrol (RES) is a plant metabolite known to modulate numerous physiological functions and to exert beneficial effects as a cancer-chemopreventing agent and on neurological, hepatic, and cardiovascular systems. Since the compound affects the lifespan of yeast and flies it might be an anti-aging substance. Mechanistically, RES is involved in down regulating the inflammatory response. The pleiotropic effects of RES in cells of the immune and endothelial system were examined in this study. RESULTS: Murine macrophages (RAW264.7 cells), human monocytic/leukemia cells (THP-1), PBLs and HUVECs were incubated with RES and activated with inflammatory stimuli such as LPS or TNF-α. Inflammatory mediators and adhesion molecules were measured by multiplex analysis and gene expression was quantified by RT-PCR. In PBLs, which were activated with LPS, RES blunted the production of TNF-α, CCL2/MCP-1, CCL5/RANTES, CXCL8/IL-8, whereas it increased the production of IL-1ß, IL-6, CCL4/MIP-1ß and CXCL10/IP-10. Thus, in the blood compartment chemokines attracting mainly monocytes were up-regulated by RES, while those attracting T lymphocytes or neutrophils were diminished. At conditions of endothelial dysfunction (ED), RES reduced the expression of cytokines, chemokines, ICAM and GM-CSF in TNF-α activated HUVECs, whereas eNOS expression was corrected to pre-ED homeostasis. In macrophages nitric oxide, PGE2, cytokines (TNF-α, IL-1ß, IL-6) and chemokines (CCL2/MCP-1, CCL4/MIP-1ß, CCL5/RANTES, CXCL10/IP-10) were reduced by the phenolic substance. CONCLUSIONS: RES had cell-specific and context-dependent effects, in particular on the expression of IL-1ß, IL-6, CCL4/MIP-1ß and CXCL10/IP-10. It enhanced cellular features that mirror increased alertness to disturbed immune homeostasis in the vascular-endothelial compartment (e.g. increased production of IL-1ß or IL-6), whereas it blunted inflammatory mediators in macrophages and consequently chronic inflammation. We infer from the present in vitro study, that RES has unique properties in the regulation of inflammatory and immune responses, which are controlled in a complex hierarchical and temporal order.

Fruitflow®: the first European Food Safety Authority-approved natural cardio-protective functional ingredient.

Hyperactive platelets, in addition to their roles in thrombosis, are also important mediators of atherogenesis. Antiplatelet drugs are not suitable for use where risk of a cardiovascular event is relatively low. It is therefore important to find alternative safe antiplatelet inhibitors for the vulnerable population who has hyperactive platelets in order to reduce the risk of cardiovascular disease. Potent antiplatelet factors were identified in water-soluble tomato extract (Fruitflow®), which significantly inhibited platelet aggregation. Human volunteer studies demonstrated the potency and bioavailability of active compounds in Fruitflow®. Fruitflow® became the first product in Europe to obtain an approved, proprietary health claim under Article 13(5) of the European Health Claims Regulation 1924/2006 on nutrition and health claims made on foods. Fruitflow® is now commercially available in different countries worldwide. In addition to its reduction in platelet reactivity, Fruitflow® contains anti-angiotensin-converting enzyme and anti-inflammatory factors, making it an effective and natural cardio-protective functional food.

Effect of Consuming Oat Bran Mixed in Water before a Meal on Glycemic Responses in Healthy Humans-A Pilot Study.

BACKGROUND: Viscous dietary fibers including oat ß-glucan are one of the most effective classes of functional food ingredients for reducing postprandial blood glucose. The mechanism of action is thought to be via an increase in viscosity of the stomach contents that delays gastric emptying and reduces mixing of food with digestive enzymes, which, in turn, retards glucose absorption. Previous studies suggest that taking viscous fibers separate from a meal may not be effective in reducing postprandial glycemia. METHODS: We aimed to re-assess the effect of consuming a preload of a commercially available oat-bran (4.5, 13.6 or 27.3 g) containing 22% of high molecular weight oat ß-glucan (O22 (OatWell(®)22)) mixed in water before a test-meal of white bread on glycemic responses in 10 healthy humans. RESULTS: We found a significant effect of dose on blood glucose area under the curve (AUC) (p = 0.006) with AUC after 27.3 g of O22 being significantly lower than white bread only. Linear regression analysis showed that each gram of oat ß-glucan reduced glucose AUC by 4.35% ± 1.20% (r = 0.507, p = 0.0008, n = 40) and peak rise by 6.57% ± 1.49% (r = 0.582, p < 0.0001). CONCLUSION: These data suggest the use of oat bran as nutritional preload strategy in the management of postprandial glycemia.

Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus.

BACKGROUND: Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus (T2DM). We conducted a randomized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM. We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness (CVR) to hypercapnia. We now report the effects of resveratrol on neurovascular coupling capacity (CVR to cognitive stimuli), cognitive performance and correlations with plasma resveratrol concentrations. METHODS: Thirty-six T2DM adults aged 40-80 years were randomized to consume single doses of resveratrol (0, 75, 150 and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity (BFV) during a cognitive test battery. The battery consisted of dual-tasking (finger tapping with both Trail Making task and Serial Subtraction 3 task) and a computerized multi-tasking test that required attending to four tasks simultaneously. CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV. RESULTS: Compared to placebo, 75 mg resveratrol significantly improved neurovascular coupling capacity, which correlated with plasma total resveratrol levels. Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol. CONCLUSION: a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM. Evaluation of benefits of chronic resveratrol supplementation is now warranted.

Carnosol and Related Substances Modulate Chemokine and Cytokine Production in Macrophages and Chondrocytes.

Phenolic diterpenes present in Rosmarinus officinalis and Salvia officinalis have anti-inflammatory and chemoprotective effects. We investigated the in vitro effects of carnosol (CL), carnosic acid (CA), carnosic acid-12-methylether (CAME), 20-deoxocarnosol and abieta-8,11,13-triene-11,12,20-triol (ABTT) in murine macrophages (RAW264.7 cells) and human chondrocytes. The substances concentration-dependently reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-stimulated macrophages (i.e., acute inflammation). They significantly blunted gene expression levels of iNOS, cytokines/interleukins (IL-1α, IL-6) and chemokines including CCL5/RANTES, CXCL10/IP-10. The substances modulated the expression of catabolic and anabolic genes in chondrosarcoma cell line SW1353 and in primary human chondrocytes that were stimulated by IL-1ß (i.e., chronic inflammation In SW1353, catabolic genes like MMP-13 and ADAMTS-4 that contribute to cartilage erosion were down-regulated, while expression of anabolic genes including Col2A1 and aggrecan were shifted towards pre-pathophysiological homeostasis. CL had the strongest overall effect on inflammatory mediators, as well as on macrophage and chondrocyte gene expression. Conversely, CAME mainly affected catabolic gene expression, whereas ABTT had a more selectively altered interleukin and chemokine gene exprssion. CL inhibited the IL-1ß induced nuclear translocation of NF-κBp65, suggesting that it primarily regulated via the NF-κB signalling pathway. Collectively, CL had the strongest effects on inflammatory mediators and chondrocyte gene expression. The data show that the phenolic diterpenes altered activity pattern of genes that regulate acute and chronic inflammatory processes. Since the substances affected catabolic and anabolic gene expression in cartilage cells in vitro, they may beneficially act on the aetiology of osteoarthritis.

Tomato Aqueous Extract Modulates the Inflammatory Profile of Immune Cells and Endothelial Cells.

Nutrients transiently or chronically modulate functional and biochemical characteristics of cells and tissues both in vivo and in vitro. The influence of tomato aqueous extract (TAE) on the in vitro inflammatory response of activated human peripheral blood leukocytes (PBLs) and macrophages was investigated. Its effect on endothelial dysfunction (ED) was analyzed in human umbilical vein endothelial cells (HUVECs). Murine macrophages (RAW264.7 cells), PBLs and HUVECs were incubated with TAE. They were activated with LPS or TNF-α in order to induce inflammatory processes and ED, respectively. Inflammatory mediators and adhesion molecules were measured by immune assay-based multiplex analysis. Gene expression was quantified by RT-PCR. TAE altered the production of interleukins (IL-1ß, IL-6, IL-10, IL-12) and chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CXCL8/IL-8, CXCL10/IP-10) in PBLs. TAE reduced ED-associated expression of adhesion molecules (ICAM-1, VCAM-1) in endothelial cell. In macrophages, the production of nitric oxide, PGE2, cytokines and ILs (TNF-α, IL-1ß, IL-6, IL-12), which reflects chronic inflammatory processes, was reduced. Adenosine was identified as the main bioactive of TAE. Thus, TAE had cell-specific and context-dependent effects. We infer from these in vitro data, that during acute inflammation TAE enhances cellular alertness and therefore the sensing of disturbed immune homeostasis in the vascular-endothelial compartment. Conversely, it blunts inflammatory mediators in macrophages during chronic inflammation. A novel concept of immune regulation by this extract is proposed.

Nutritional Solutions to Reduce Risks of Negative Health Impacts of Air Pollution.

Air pollution worldwide has been associated with cardiovascular and respiratory morbidity and mortality, particularly in urban settings with elevated concentrations of primary pollutants. Air pollution is a very complex mixture of primary and secondary gases and particles, and its potential to cause harm can depend on multiple factors-including physical and chemical characteristics of pollutants, which varies with fine-scale location (e.g., by proximity to local emission sources)-as well as local meteorology, topography, and population susceptibility. It has been hypothesized that the intake of anti-oxidant and anti-inflammatory nutrients may ameliorate various respiratory and cardiovascular effects of air pollution through reductions in oxidative stress and inflammation. To date, several studies have suggested that some harmful effects of air pollution may be modified by intake of essential micronutrients (such as B vitamins, and vitamins C, D, and E) and long-chain polyunsaturated fatty acids. Here, we review the existing literature related to the potential for nutrition to modify the health impacts of air pollution, and offer a framework for examining these interactions.

Vitamin E function and requirements in relation to PUFA.

Vitamin E (α-tocopherol) is recognised as a key essential lipophilic antioxidant in humans protecting lipoproteins, PUFA, cellular and intra-cellular membranes from damage. The aim of this review was to evaluate the relevant published data about vitamin E requirements in relation to dietary PUFA intake. Evidence in animals and humans indicates a minimal basal requirement of 4-5 mg/d of RRR-α-tocopherol when the diet is very low in PUFA. The vitamin E requirement will increase with an increase in PUFA consumption and with the degree of unsaturation of the PUFA in the diet. The vitamin E requirement related to dietary linoleic acid, which is globally the major dietary PUFA in humans, was calculated to be 0·4-0·6 mg of RRR-α-tocopherol/g of linoleic acid. Animal studies show that for fatty acids with a higher degree of unsaturation, the vitamin E requirement increases almost linearly with the degree of unsaturation of the PUFA in the relative ratios of 0·3, 2, 3, 4, 5 and 6 for mono-, di-, tri-, tetra-, penta- and hexaenoic fatty acids, respectively. Assuming a typical intake of dietary PUFA, a vitamin E requirement ranging from 12 to 20 mg of RRR-α-tocopherol/d can be calculated. A number of guidelines recommend to increase PUFA intake as they have well-established health benefits. It will be prudent to assure an adequate vitamin E intake to match the increased PUFA intake, especially as vitamin E intake is already below recommendations in many populations worldwide.

Ascorbic acid modulates cell migration in differentiated HL-60 cells and peripheral blood leukocytes.

SCOPE: The impact of L-ascorbic acid (L-AA) on the chemokinesis (CK) and chemotaxis (CT) of HL-60 cells and polymorphonuclear cells (PMN) was investigated. METHODS AND RESULTS: HL-60 cells were differentiated with DMSO, retinoic acid (RA), vitamin D, or L-AA. Chemokinesis and chemotaxis of differentiated HL-cells were assayed. Vitamin D3-treated HL-60 cells (dHL-60vitD3 cells) and RA-treated cells (dHL-60RA cells) acquired monocyte/macrophage-like and neutrophil-like phenotypes, respectively. DMSO induced the differentiation of an intermediate phenotype (dHL-60DMSO cells), whereas L-AA downregulated neutrophil markers (dHL-60L-AA cells). dHL-60DMSO cells had increased CK and potent CT in gradients of IL-8 and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). dHL-60RA cells and dHL-60L-AA cells migrated less toward IL-8 and fMLP; dHL-60vitD3 cells preferably responded to fMLP. L-AA enhanced CK of dHL-60DMSO cells and was a weak chemo-attractant. In human leukocytes, IL-8 and fMLP triggered receptor-mediated chemotaxis. CXCR2 and fMLPR were downregulated by IL-8 and fMLP, respectively. L-AA stimulated chemotaxis although significantly less than IL-8 and fMLP. IL-8 targeted chemotaxis was enhanced both in HL-60 cells and leukocytes when cells were incubated with L-AA. CONCLUSION: L-AA modulated chemokinesis and had significant chemo-attractant properties, which were independent on fMLP or IL-8 receptors. The results suggest that L-AA improves leukocyte function in innate immune responses.

Resveratrol, from experimental data to nutritional evidence: the emergence of a new food ingredient.

The polyphenol resveratrol is found notably in grapes and in a variety of medicinal plants. Recently, resveratrol has been suggested to have cardioprotective effects and to improve metabolic health by mimicking the effects of calorie restriction. Numerous animal and in vitro studies suggest that resveratrol could improve cardiovascular and metabolic health in humans. In view of this compelling preclinical evidence, several human studies investigating the effects of resveratrol on vascular and metabolic health have been initiated. Collectively, the animal, human epidemiological, and first human intervention studies support a role of resveratrol in vascular and metabolic health. This has led to the introduction of the first supplement and food products containing resveratrol and its emergence as a promising new health ingredient. Thus, supplementation with resveratrol may be included in nutritional and lifestyle programs aiming to reduce the risk of vascular and obesity-related problems.

Dietary fish oil preserves cardiac function in the hypertrophied rat heart.

Regular fish or fish oil intake is associated with a low incidence of heart failure clinically, and fish oil-induced reduction in cardiac remodelling seen in hypertrophy models may contribute. We investigated whether improved cardiac energy efficiency in non-hypertrophied hearts translates into attenuation of cardiac dysfunction in hypertrophied hearts. Male Wistar rats (n 33) at 8 weeks of age were sham-operated or subjected to abdominal aortic stenosis to produce pressure-overload cardiac hypertrophy. Starting 3 weeks post-operatively to follow initiation of hypertrophy, rats were fed a diet containing 10 % olive oil (control) or 5 % fish oil (ROPUFA® 30 (17 % EPA, 10 % DHA))+5 % olive oil (FO diet). At 15 weeks post-operatively, ventricular haemodynamics and oxygen consumption were evaluated in the blood-perfused, isolated working heart. Resting and maximally stimulated cardiac output and external work were >60 % depressed in hypertrophied control hearts but this was prevented by FO feeding, without attenuating hypertrophy. Cardiac energy efficiency was lower in hypertrophy, but greater in FO hearts for any given cardiac mass. Coronary blood flow, restricted in hypertrophied control hearts, increased with increasing work in hypertrophied FO hearts, revealing a significant coronary vasodilator reserve. Pronounced cardiac dysfunction in hypertrophied hearts across low and high workloads, indicative of heart failure, was attenuated by FO feeding in association with membrane incorporation of n-3 PUFA, principally DHA. Dietary fish oil may offer a new approach to balancing the high oxygen demand and haemodynamic requirements of the failing hypertrophied heart independently of attenuating hypertrophy.

Docosahexaenoic acid, but not eicosapentaenoic acid, lowers ambulatory blood pressure and shortens interval QT in spontaneously hypertensive rats in vivo.

This study was designed to evaluate the effects of individual dietary long-chain n-3 polyunsaturated fatty acids (LCPUFA) on hypertension and cardiac consecutive disorders in spontaneously hypertensive rats (SHR) as compared to Wistar-Kyoto rats (WKY). Rats were fed for 2 months an eicosapentaenoic (EPA)- or docosahexaenoic acid (DHA)-rich diet (240 mg/day) or an n-3 PUFA-free diet. Male SHR (n=6), implanted with cardiovascular telemetry devices, were housed in individual cages for continuous measurements of cardiovascular parameters (blood pressure (BP) and heart rate (HR)) during either activity or rest periods, ECG were recorded during the quiet period. The n-6 PUFA upstream of arachidonic acid was affected in SHR tissues. The cardiac phospholipid fatty acid profile was significantly affected by dietary DHA supply, and EPA in a very lower extent, since DHA only was incorporated in the membranes instead of n-6 PUFAs. Endothelium n-6 PUFA content increased in all SHR groups. Compared to WKY, linoleic acid content decreased in both studied tissues. Cardiac noradrenalin decreased while the adrenal catecholamine stores decreased in SHR as compared to WKY. Both n-3 PUFA supply induced a decrease of adrenal catecholamine stores. Nevertheless after 6 weeks, DHA but not EPA induced a lowering-blood pressure effect and shortened the QT interval in SHR, most probably through its tissue enrichment and a specific effect on adrenergic function. Dietary DHA supply retards blood pressure development and has cardioprotective effect. These findings, showing the cardioprotective effects of DHA in living animals, were obtained in SHR, but may relate to essential hypertension in humans.

Antioxidant activity of olive polyphenols in humans: a review.

In vitro and animal studies show that polyphenols from olives have potent antioxidant activities; 50 % of the phenolic compounds contained in olives and virgin olive oil are hydroxytyrosol and derivatives thereof. Hydroxytyrosol is the major olive polyphenol consumed and well absorbed in humans. It is considered to have the highest antioxidant potency compared to the other olive polyphenols. Review of the human intervention studies showed that olive polyphenols decreased the levels of oxidized-LDL in plasma and positively affected several biomarkers of oxidative damage. The antioxidant effects of olive polyphenols on low-density lipoprotein (LDL) oxidation are observed after a dietary intake of about 10 mg per day. The overall evidence from in vitro assays, and animal and human studies support the antioxidant effect of olive polyphenols. However, further larger human studies are needed to clarify the effect of olive polyphenols on markers of oxidative stress, particularly DNA damage and plasma isoprostane levels.

A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.

Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg(-1) day(-1)), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.