Urea-13C

Docosahexaenoic acid (DHA, 22:6n-3) accretion in brain phospholipids is critical for maintaining the structural fluidity that permits proper assembly of protein complexes for signaling. Furthermore, membrane DHA can be released by phospholipase A₂ and act as a substrate for the synthesis of bioactive metabolites that regulate synaptogenesis, neurogenesis, inflammation, and oxidative stress. Thus, brain DHA is consumed through multiple pathways including mitochondrial β-oxidation, autoxidation to neuroprostanes, as well as enzymatic synthesis of bioactive metabolites including oxylipins, synaptamide, fatty-acid amides, and epoxides. By using models developed by Rapoport and colleagues, brain DHA loss has been estimated to be 0.07-0.26 μmol DHA/g brain/d. Since β-oxidation of DHA in the brain is relatively low, a large portion of brain DHA loss may be attributed to the synthesis of autoxidative and bioactive metabolites. In recent years, we have developed a novel application of compound specific isotope analysis to trace DHA metabolism. By the use of natural abundance in ¹³C-DHA in the food supply, we are able to trace brain phospholipid DHA loss in free-living mice with estimates ranging from 0.11 to 0.38 μmol DHA/g brain/d, in reasonable agreement with previous methods. This novel fatty acid metabolic tracing methodology should improve our understanding of the factors that regulate brain DHA metabolism.

Previous research has shown the efficacy of mulberry extracts for lowering post-prandial glucose (PPG) responses. The postulated mechanism is slowing of glucose absorption, but effects on glucose disposal or endogenous production are also possible. This research assessed the effect of a specified mulberry fruit extract (MFE) on these three glucose flux parameters.

The study used a double-blind, randomized, controlled, full cross-over design. In 3 counter-balanced treatments, 12 healthy adult male subjects, mean (SD) age 24.9 (2.50) years and body mass index 22.5 (1.57) kg/m², consumed porridge prepared from ¹³C-labelled wheat, with or without addition of 0.75 g MFE, or a solution of ¹³C-glucose in water. A co-administered ²H-glucose venous infusion allowed for assessment of glucose disposal. Glucose flux parameters, cumulative absorption (time to 50% absorption, T_50%abs), and PPG positive incremental area under the curve from 0 to 120 min (+iAUC_0-120) were determined from total and isotopically labelled glucose in plasma. As this exploratory study was not powered for formal inferential statistical tests, results are reported as the mean percent difference (or minutes for T_50%abs) between treatments with 95% CI.

MFE increased mean T_50%abs by 10.2 min, (95% CI 3.9-16.5 min), and reduced mean 2 h post-meal rate of glucose appearance by 8.4% (95% CI -14.9 to -1.4%) and PPG + iAUC_0-120 by 11% (95% CI -26.3 to -7.3%), with no significant changes in glucose disposal or endogenous production.

The PPG-lowering effect of MFE is primarily mediated by a reduced rate of glucose uptake.