Polyphenols From Grape and Blueberry Improve Episodic Memory in Healthy Elderly with Lower Level of Memory Performance: A Bicentric Double-Blind, Randomized, Placebo-Controlled Clinical Study.

Polyphenols are promising nutritional bioactives exhibiting beneficial effect on age-related cognitive decline. This study evaluated the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on memory of healthy elderly subjects (60-70 years-old). A bicentric, randomized, double-blind, placebo-controlled trial was conducted with 215 volunteers receiving 600 mg/day of PEGB (containing 258 mg flavonoids) or a placebo for 6 months. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Secondary outcomes included verbal episodic and recognition memory (VRM) and working memory (SSP). There was no significant effect of PEGB on the PAL on the whole cohort. Yet, PEGB supplementation improved VRM-free recall. Stratifying the cohort in quartiles based on PAL at baseline revealed a subgroup with advanced cognitive decline (decliners) who responded positively to the PEGB. In this group, PEGB consumption was also associated with a better VRM-delayed recognition. In addition to a lower polyphenol consumption, the urine metabolomic profile of decliners revealed that they excreted more metabolites. Urinary concentrations of specific flavan-3-ols metabolites were associated, at the end of the intervention, with the memory improvements. Our study demonstrates that PEGB improves age-related episodic memory decline in individuals with the highest cognitive impairments.

Supplementation with Resveratrol and Curcumin Does Not Affect the Inflammatory Response to a High-Fat Meal in Older Adults with Abdominal Obesity: A Randomized, Placebo-Controlled Crossover Trial.

Background: High-fat meals induce postprandial inflammation. Resveratrol is a polyphenol known to prevent comorbidities associated with cardiovascular disease and exerts an anti-inflammatory action. There is also an increasing body of evidence supporting the role of curcumin, a polyphenol from the curcuminoid family, as a modulator of proinflammatory processes. Objective: The objectives of this study were to investigate the following: 1) the bioavailability of resveratrol consumed in combination with curcumin after consumption of a high-fat meal; and 2) the acute combined effects of this combination on the postprandial inflammatory response of subjects with abdominal obesity. Methods: In a double blind, crossover, randomized, placebo-controlled study, 11 men and 11 postmenopausal women [mean ± SD age: 62 ± 5 y; mean ± SD body mass index (in kg/m2): 29 ± 3] underwent a 6-h oral fat tolerance test on 2 occasions separated by 1-2 wk: once after consumption of a dietary supplement (200 mg resveratrol and 100 mg curcumin, Res/Cur) and once after consumption of a placebo (cellulose). Plasma concentrations of total resveratrol and its major metabolites as well as inflammatory markers, adhesion molecules, and whole blood NFκB1 and PPARA gene expression were measured during both fat tolerance tests. Results: Kinetics of resveratrol and identified metabolites revealed rapid absorption patterns but also relatively limited bioavailability based on free resveratrol concentrations. Supplementation with Res/Cur did not modify postprandial variations in circulating inflammatory markers (C-reactive protein, IL-6, IL-8, monocyte chemoattractant protein-1) and adhesion molecules [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1] compared to placebo (PTreatment×Time > 0.05). However, Res/Cur significantly decreased the cumulative postprandial response of sVCAM-1, compared to placebo (incremental area under the curve -4643%, P = 0.01). Postprandial variations of whole-blood PPARA and NFKB1 gene expression were not different between Res/Cur and placebo treatments. Conclusions: Acute supplementation with Res/Cur has no impact on the postprandial inflammation response to a high-fat meal in abdominally obese older adults. Further studies are warranted to examine how resveratrol and curcumin may alter the vascular response to a high-fat meal. This trial was registered at clinicaltrials.gov as NCT01964846.

Retinal response to light in young nonaffected offspring at high genetic risk of neuropsychiatric brain disorders.

BACKGROUND: In neuropsychiatric brain disorders, such as schizophrenia (SZ) and bipolar disorder (BD), the biased effect of chronic drug therapy and the toxic effect of illness once installed constitute obstacles to the identification of valid biomarkers. Such biomarkers could lie at the level of retinal function where anomalies have already been reported in adults suffering from neuropsychiatric disorders. Here, we report a specific electroretinographic (ERG) anomaly in young nonaffected and nonmedicated offspring at high genetic risk (HR) of these disorders. METHODS: Electroretinography was performed in 29 HR offspring having one parent affected by DSM-IV SZ or BD (mean age: 20.8 years, SD 4.4) and 29 healthy control subjects (mean age: 20.6 years, SD 4.2). The HRs' parents descended from multigenerational families affected by SZ or BD. RESULTS: Rod ERG (b-wave amplitude at V(max)) in HRs was significantly lower than control subjects (p < .0001; effect size of -1.47), whereas the cone ERG V(max) showed no difference (p = .27). No effects of gender, age, and seasons of testing were observed. The anomaly in retinal response (rod V(max) b-wave amplitude) was observed independently of parents' diagnosis (SZ; p = .007, effect size of -1.09; BD: p < .0001, effect size of -1.88) and was present in both the younger and older HRs (effect size of -1.6 and -1.8, respectively). CONCLUSIONS: A rod retinal response anomaly before the age of the disease incidence may represent an early and specific biomarker of risk with meaning for further genetic and prevention research.

Intravascular kinetics of C-reactive protein and their relationships with features of the metabolic syndrome.

OBJECTIVE: The objective of the study was to describe, for the first time, the intravascular kinetics of C-reactive protein (CRP), using stable isotopes, and its relationship with features of the metabolic syndrome. METHODS: Sixteen men and 16 women [aged 49 +/- 9 years, body mass index (BMI) 28.7 +/- 4.5 kg/m(2)] underwent a 12-h primed-constant infusion of 5,5,5-(2)H(3)-l-leucine. CRP was purified from the plasma fraction rho greater than 1.25 g/ml by affinity chromatography, and isotopic enrichment over time was determined by gas chromatography/mass spectrometry. RESULTS: The CRP fractional catabolic rate was 60% higher in men than women (0.49 +/- 1.83 vs. 0.30 +/- 1.80 pool/d, P = 0.03), but this difference was no longer significant in a multivariate model that included several features associated with the metabolic syndrome. The CRP production rate (PR) and pool size were not statistically different between sexes. Plasma CRP concentrations were more strongly correlated with the PR (r = 0.80, P < 0.0001) than with the fractional catabolic rate of CRP (r = 0.39, P < 0.05). The PR of CRP was positively correlated with waist girth (r = 0.53, P < 0.01), plasma low-density lipoprotein apolipoprotein B-100 (r = 0.42, P = 0.07), triglyceride (r = 0.41, P = 0.06), and IL-6 concentrations (r = 0.61, P = 0.0008) and inversely correlated with high-density lipoprotein-cholesterol (r = -0.47, P = 0.03) and adiponectin (r = -0.63, P < 0.0005) after adjustment for sex. Blood pressure and low-density lipoprotein-cholesterol showed no association with CRP kinetics. CONCLUSION: The PR of CRP appeared as the main determinant of CRP concentrations and showed significant associations with features of the metabolic syndrome as well as with adipose tissue-derived cytokines such as IL-6 and adiponectin.

Endothelial lipase is associated with inflammation in humans.

The aim of this study was to investigate the extent to which inflammation is linked with plasma endothelial lipase (EL) concentrations among healthy sedentary men. Plasma C-reactive protein (CRP) concentrations were measured with a highly sensitive commercial immunoassay, plasma interleukin-6 (IL-6) concentrations were measured using a commercial ELISA, and plasma secretory phospholipase A(2) type IIA (sPLA(2)-IIA) concentrations were measured using a commercial assay in a sample of 74 moderately obese men (mean body mass index, 29.8 +/- 5.2 kg/m(2)). Plasma EL concentrations were positively correlated with various indices of obesity, fasting plasma insulin, and plasma CRP, IL-6, and sPLA(2)-IIA concentrations. Multiple regression analyses revealed that plasma CRP concentrations explained 14.5% (P = 0.0008) of the variance in EL concentrations. When entered into the model, LPL activity accounted for 16.1% (P < 0.0001) and plasma CRP concentrations accounted for 20.9% (P < 0.0001) of the variance in EL concentrations. The combined impact of visceral adipose tissue (VAT) and of an inflammation score on EL concentrations was investigated. Among subjects with high or low VAT, those having a high inflammation score based on plasma CRP, IL-6, and sPLA(2)-IIA concentrations had increased plasma EL concentrations (P = 0.0005). In conclusion, our data reveal a strong association between proinflammatory cytokines and plasma EL concentrations among healthy people with low or high VAT levels.