The short-term effect of dark chocolate flavanols on cognition in older adults: A randomized controlled trial (FlaSeCo).

BACKGROUND: Cocoa flavanols in the diet have had positive effects on cognition, blood lipid levels, and glucose metabolism. METHODS: Cognitively healthy older adults aged 65-75 years were recruited for an eight-week randomized, double-blind controlled trial to investigate the effectiveness of cocoa flavanols on cognitive functions. At baseline, nutrient and polyphenol intakes from diet were assessed with three-day food diaries. The intervention group received 50 g dark chocolate containing 410 mg of flavanols per day, and the control group 50 g dark chocolate containing 86 mg of flavanols per day, for eight weeks. Cognition was assessed with Verbal Fluency (VF) and the Trail Making Test (TMT) A and B as the main outcome measures. Changes in blood lipids and glucose were also measured. RESULTS: The older adults participating numbered 100 (63% women), mean 69 y (range 65 to 74). They were highly educated with a mean 14.9 years of education (SD 3.6). No differences in changes in cognition were seen between groups. The mean change (± SEs) in the time to complete the TMT A and B in the intervention group was -4.6 s (-7.1 to -2.1) and -16.1 s (-29.1 to -3.1), and in the controls -4.4 s (-7.0 to -1.9) and -12.5 s (-22.8 to -2.1)(TMT A p = 0.93; TMT B p = 0.66). No difference was apparent in the changes in blood lipids, glucose levels, or body weight between the groups. CONCLUSIONS: The healthy older adults showed no effect from the eight-week intake of dark chocolate flavanols on cognition.

Significance of the extracellular domain and the carbohydrates of the human neutrophil N-formyl peptide chemotactic receptor for the signal transduction by the receptor.

The N-formyl peptide chemotactic receptor of human neutrophils possesses a 2-kDa papain-removable extracellular domain that contains two N-linked oligosaccharide side chains and is not required for the high-affinity ligand binding. In the present study, the significance of the extracellular domain and the carbohydrates for signal transduction was elucidated by measuring the N-formyl hexapeptide-induced intracellular free calcium ([Ca2+]i) and the change in myeloperoxidase secretion in the control and papain-treated human neutrophils. [Ca2+]i was monitored both in cell suspension and individual cells with intracellularly trapped Fura 2 acetoxymethyl ester, using spectrofluorometric analysis and fluorescence ratio image analysis, respectively. The exposure of the cells in suspension to N-formyl hexapeptide resulted in an immediate, dose-dependent burst of elevated [Ca2+]i, which was virtually identical in both control and papain-treated cells with respect to the extent and kinetics. The maximum burst was 1.6-fold and was obtained at 10(-6) M hexapeptide. The individual control and papain-treated cells responded to 10(-6) M hexapeptide in a similar manner with several successive transients of [Ca2+]i, the maximum level being 3.0-3.5 microM. In both groups the [Ca2+]i transient began initially in the cell periphery, expanding rapidly throughout the cells. Concomitantly, the cells became polarized, and their chemokinesis increased. The secretion of myeloperoxidase was monitored as a physiological end response to N-formyl chemotactic peptides. The exposure of the control and papain-treated cells in suspension to hexapeptide resulted in a dose-dependent secretion of myeloperoxidase. The maximum secretion after exposure to 10(-8)-10(-6) M hexapeptide was equal in control and papain-treated neutrophils. These results indicate that the functional properties of the membrane-inserted N-formyl peptide chemotactic receptor are inherent to the receptor's transmembrane and intracellular domains, as far as binding of the ligand and subsequent receptor activation are concerned.