Rats were fed ag rape seed extract (GSE) containing ( þ )-catechin,( 2 )-epicatechin and dimers, trimers, tetramers and polymeric procyanidins. Liver, kidney, brain and gastrointestinal (GI) tract together with plasma, urine and faeces were collected over a24h period and their flavan-3-ol content was analysed by HPLC with tandem mass spectrometry and diode array detection. Small amounts of the GSE flavan-3-ols moved out of the stomach and into the duodenum/jejunum, and to ag reater extent the ileum 1h after ingestion, and into the caecum after 2h with relatively small amounts being detected in the colon after 3h.T he GI tract contained the parent GSE flavan-3-ols and procyanidins with only trace amounts of metabolites and there were no indications that proanthocyanidins were depolymerised in the GI tract releasing monomeric flavan-3-ols.Plasma contained exclusively catechin glucuronidesand methylated glucuronide metabolites which were also detected in the liver and kidneys. These metabolites were also present in urine together with sulphated metabolites and low amounts of the procyanidin dimers B 1 ,B 2 ,B 3 and B 4 as well as the trimer C 2 and an unknown GSE trimer. The amounts of ( þ )-catechin and ( 2 )-epicatechin metabolitesexcreted in urine relative to the quantity of the monomers ingested were 27 and 36 %, respectively, after 24 h. This is similar to the levels of urinary excretion reported to occur by other investigators after feeding ( 2 )-epicatechin to rats and provides further, albeit indirect, evidence that the procyanidinoligomers in the GSE were not depolymerised to monomers to any extent after ingestion. No convincing analytical data were obtained for the presence of flavan-3-ol metabolites in the brain.

Functional foods contain biologically active ingredients associated with physiological health benefits for preventing and managing chronic diseases, such as type 2 diabetes mellitus (T2DM). A regular consumption of functional foods may be associated with enhanced anti-oxidant, anti-inflammatory, insulin sensitivity, and anti-cholesterol functions, which are considered integral to prevent and manage T2DM. Components of the Mediterranean diet (MD)—such as fruits, vegetables, oily fish, olive oil, and tree nuts—serve as a model for functional foods based on their natural contents of nutraceuticals, including polyphenols, terpenoids, flavonoids, alkaloids, sterols, pigments, and unsaturated fatty acids. Polyphenols within MD and polyphenol-rich herbs—such as coffee, green tea, black tea, and yerba maté—have shown clinically-meaningful benefits on metabolic and microvascular activities, cholesterol and fasting glucose lowering, and anti-inflammation and anti-oxidation in high-risk and T2DM patients. However, combining exercise with functional food consumption can trigger and augment several metabolic and cardiovascular protective benefits, but it is under-investigated in people with T2DM and bariatric surgery patients. Detecting functional food benefits can now rely on an “omics” biological profiling of individuals’ molecular, genetics, transcriptomics, proteomics, and metabolomics, but is under-investigated in multi-component interventions. A personalized approach for preventing and managing T2DM should consider biological and behavioral models, and embed nutrition education as part of lifestyle diabetes prevention studies. Functional foods may provide additional benefits in such an approach.

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.

Pomegranate juice (PJ; also known as pomegreat pure juice) provides a rich and varied source of polyphenolic compounds that may offer cardioprotective, anti-atherogenic and antihypertensive effects. The aim of this study was to investigate the effect of PJ consumption on glucocorticoids levels, blood pressure (BP) and insulin resistance in volunteers at high CVD risk. Subjects (twelve males and sixteen females) participated in a randomised, placebo-controlled cross-over study (BMI: 26·77 (sd 3·36) kg/m2; mean age: 50·4 (sd 6·1) years). Volunteers were assessed at baseline, and at weeks 2 and 4 for anthropometry, BP and pulse wave velocity. Cortisol and cortisone levels in urine and saliva were determined by specific ELISA methods, and the cortisol/cortisone ratio was calculated. Fasting blood samples were obtained to assess plasma lipids, glucose, insulin and insulin resistance (homeostasis model assessment of insulin resistance). Volunteers consumed 500 ml of PJ or 500 ml of a placebo drink containing a similar amount of energy. Cortisol urinary output was reduced but not significant. However, cortisol/cortisone ratios in urine (P = 0·009) and saliva (P = 0·024) were significantly decreased. Systolic BP decreased from 136·4 (sd 6·3) to 128·9 (sd 5·1) mmHg (P = 0·034), and diastolic BP from 80·3 (sd 4·29) to 75·5 (sd 5·17) mmHg (P = 0·031) after 4 weeks of fruit juice consumption. Pulse wave velocity decreased from 7·5 (sd 0·86) to 7·44 (sd 0·94) m/s (P = 0·035). There was also a significant reduction in fasting plasma insulin from 9·36 (sd 5·8) to 7·53 (sd 4·12) mIU/l (P = 0·025) and of homeostasis model assessment of insulin resistance (from 2·216 (sd 1·43) to 1·82 (sd 1·12), P = 0·028). No significant changes were seen in the placebo arm of the study. These results suggest that PJ consumption can alleviate key cardiovascular risk factors in overweight and obese subjects that might be due to a reduction in both systolic and diastolic BP, possibly through the inhibition of 11β-hydroxysteroid dehydrogenase type 1 enzyme activity as evidenced by the reduction in the cortisol/cortisone ratio. The reduction in insulin resistance might have therapeutic benefits for patients with non-insulin-dependent diabetes, obesity and the metabolic syndrome.

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 (þ )-catechin and (2 )-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.

The association between excess cortisol and various parameters of metabolic syndrome including hypertension, insulin resistance and dyslipidaemia is increasingly recognised. The present single-blind randomised placebo-controlled cross-over study compared the effect of polyphenol-rich dark chocolate (DC) on biomarkers of glucose metabolism, lipid profile, and blood pressure (BP) in females with BMI $ 25 kg m À2 (n ¼ 21) and females with BMI < 25 kg m À2 (n ¼ 21). Volunteers consumed 20 g of DC containing 500 mg polyphenols or a placebo DC with negligible polyphenol-content daily for 4 weeks, separated by a 2-week washout period. Systolic BP and diastolic BP decreased after 4 weeks of polyphenol-rich DC. Placebo raised fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and salivary cortisol, an effect that was significantly different from polyphenol-rich DC which had a negligible effect on fasting insulin, HOMA-IR and salivary cortisol. Females with BMI $ 25 kg m À2 responded less favourably to placebo than lean females and consequently had higher fasting insulin and HOMA-IR, in addition to a lower quantitative sensitivity check index (QUICKI) after ingestion of placebo compared to polyphenol-rich DC. No significant changes in lipid profile were observed. This study provides evidence for the metabolic benefits of consuming polyphenol-rich dark chocolate while demonstrating the possibility of adverse effects occurring with polyphenol-poor chocolate placebo. Methods DesignThe study used a single-blind randomised placebo-controlled cross-over design where each subject acted as their own control. Following a 1-week run-in phase, eligible subjects were randomly assigned to receive 20 g DC containing 500 mg polyphenols or

Lifestyle is the primary prevention of diabetes, especially type-2 diabetes (T2D). Nutritional intake of olive oil (OO), the key Mediterranean diet component has been associated with the prevention and management of many chronic diseases including T2D. Several OO bioactive compounds such as monounsaturated fatty acids, and key biophenols including hydroxytyrosol and oleuropein, have been associated with preventing inflammation and cytokine-induced oxidative damage, glucose lowering, reducing carbohydrate absorption, and increasing insulin sensitivity and related gene expression. However, research into the interaction of OO nutraceuticals with lifestyle components, especially physical activity, is lacking. Promising postprandial effects have been reported when OO or other similar monounsaturated fatty acids were the main dietary fat compared with other diets. Animal studies have shown a potential anabolic effect of oleuropein. Such effects could be further potentiated via exercise, especially strength training, which is an essential exercise prescription for individuals with T2D. There is also an evidence from in vitro, animal, and limited human studies for a dual preventative role of OO biophenols in diabetes and cancer, especially that they share similar risk factors. Putative antioxidative and anti-inflammatory mechanisms and associated gene expressions resulting from OO biophenols have produced paradoxical results, making suggested inferences from dual prevention T2D and cancer outcomes difficult. Well-designed human interventions and clinical trials are needed to decipher such a potential dual anticancer and antidiabetic effects of OO nutraceuticals. Exercise combined with OO consumption, individually or as part of a healthy diet is likely to induce reciprocal action for T2D prevention outcomes.

Lipoic acid (LA) is a naturally occurring fatty acid that exhibits anti-oxidant and antiinflammatory properties and is being pursued as a therapeutic for many diseases including multiple sclerosis, diabetic polyneuropathy and Alzheimer's disease. We previously reported on the novel finding that racemic LA (50:50 mixture of R and S LA) stimulates cAMP production, activates prostanoid EP2 and EP4 receptors and adenylyl cyclases (AC), and suppresses activation and cytotoxicity in NK cells. In this study we present evidence that furthers our understanding of the mechanisms of action of LA. Using various LA derivatives, dihydrolipoic acid (DHLA), S,Sdimethyl lipoic acid (DMLA) and lipoamide (LPM), we discovered that only LA is capable of stimulating cAMP production in NK cells. Furthermore, there is no difference in cAMP production after stimulation with either R-LA, S-LA or racemic LA. Competition and synergistic studies indicate that LA may also activate AC independent of the EP2 and EP4 receptors. Pretreatment of PBMCc with KH7 (a specific peptide inhibitor of soluble AC) and the calcium inhibitor (Bapta) prior to LA treatment resulted in reduced cAMP levels, suggesting that soluble AC and calcium signaling mediate LA stimulation of cAMP production. In addition, pharmacological inhibitor studies demonstrate that LA also activates other G-protein coupled receptors, including histamine and adenosine, but not the beta adrenergic receptors. These novel findings provide information to better understand the mechanisms of action of LA, which can help facilitate the use of LA as a therapeutic for various diseases.