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We previously reported that a combined myo-inositol, probiotics, and enriched micronutrient supplement (intervention) taken preconception and in pregnancy reduced postpartum blood loss (PBL) and major postpartum hemorrhage compared with a standard micronutrient supplement (control), as secondary outcomes of the NiPPeR trial. This study aimed to identify the intervention components that may contribute to this effect. Associations of plasma concentrations of myoinositol and vitamins B2, B6, B12, and D at preconception (before and after supplementation), early (~7-weeks), and late pregnancy (~28-weeks) with PBL were assessed by multiple linear regression, adjusting for site, ethnicity, preconception BMI, parity, and previous cesarean section. Amongst 583 women, a higher concentration of myo-inositol in early pregnancy was associated with a PBL reduction [βadj −1.26 (95%CI −2.23, −0.29) mL per µmol/L myo-inositol increase, p = 0.011]. Applying this co-efficient to the increase in mean 7-week-myo-inositol concentration of 23.4 µmol/L with the intervention equated to a PBL reduction of 29.5 mL (~8.4% of mean PBL of 350 mL among controls), accounting for 84.3% of the previously reported intervention effect of 35 mL. None of the examined vitamins were associated with PBL. Therefore, myo-inositol may be a key intervention component mediating the PBL reduction. Further work is required to determine the mechanisms involved [ABSTRACT FROM AUTHOR]

Aim: Myo‐inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at‐risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo‐inositol‐containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. Methods: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo‐inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. Results: Higher 7‐week myo‐inositol, but not 28‐week myo‐inositol, associated with higher 1 h PG [βadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge μmol/L, p =.022] and 2 h PG [0.08 (0.03, 0.12), p =.001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7‐week myo‐inositol increase of 23.4 μmol/L with myo‐inositol supplementation. Higher 7‐week myo‐inositol associated with a lower 28‐week Stumvoll index (first phase), an approximation of insulin secretion [−0.08 (−0.15, −0.01), p =.020] but not with 28‐week Matsuda insulin sensitivity index. However, the clinical significance of a 7‐week myo‐inositol‐related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C‐peptide levels. In‐silico modelling found higher 28‐week myo‐inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7‐week myo‐inositol effects. Conclusion: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo‐inositol may slightly exacerbate later pregnancy post‐challenge glycaemia, indicating that the optimal timing for starting prenatal myo‐inositol supplementation needs further investigation. [ABSTRACT FROM AUTHOR]

Isotope labeled tracers are commonly used to quantify the turnover rates of various metabolic intermediates and yield information regarding physiological regulation. Studies often only consider either one nutritional state (fasted or fed) and/or one question (e.g., measure of lipid or protein turnover). In this article, we consider a novel application combining the global approach of metabonomics with widespread stable isotope labeling as a way of being able to map metabolism in open mammalian systems, an approach we call 'isotopomics'. A total of 45 15-week-old male Zucker rats were administrated different amounts (from 0.5 to 8 mmol/kg) of sodium [1,2-[sup.13][C.sub.2]] acetate. Plasma samples taken at 1, 4, and 24 h were analyzed with [sup.13]C nuclear magnetic resonance (NMR) and gas chromatography/mass spectrometry (GC/MS) to measure [sup.13]C isotopic enrichment of 39 plasma metubolites across a wide range of compound classes (amino acids, short-chain fatty acids, lactate, glucose, and free fatty acids). Isotopic enrichment from 0.1-7.1 mole percent excess (MPE) for the highest dose could be reliably measured in 16 metabolites, and the kinetics of their [sup.13]C isotopic enrichment are reported. Clustering metabolites based on [sup.13]C kinetic curves enabled highlighting of time dependent patterns of 13C distribution through the key metabolic pathways. These kinetic and quantitative data were reported into a biochemical map. This type of isotopomic approach for mapping dynamic metabolism in an open system has great potential for advancing our mechanistic knowledge of how different interventions and diseases can impact the metabolic response of animals and humans. 10.1021/ac902086g

The high requirement of the gut for threonine has often been ascribed to the synthesis of mucins, secreted threonine-rich glycoproteins protecting the intestinal epithelium from injury. This requirement could be even greater during intestinal inflammation, when mucin synthesis is enhanced. In this study, we used an animal model to investigate the effects of an acute ileitis on threonine splanchnic fluxes. Eight adult multi-catheterized minipigs were fed with an enteral solution. Four of them were subjected to experimental ileitis involving direct administration of trinitrobenzene sulfonic acid (TNBS) into the ileum (TNBS-treated group) and the other 4 were not treated (control group). Threonine fluxes across the portal-drained viscera (PDV) were quantified with the use of simultaneous i.g. L-[[sup.15]N]threonine and i.v. L-[U-[sup.13]C]threonine infusions. Ileal mucosa was sampled for mucin fractional synthesis rate measurement, which was greater in the TNBS-treated group (114 [+ or -] 15%/d) than in the control group (61 [+ or -] 8%/d) (P = 0.021). The first-pass extraction of dietary threonine by the PDV and liver did not differ between groups and accounted for ~27 and 10% of the intragastric delivery, respectively. PDV uptake of arterial threonine increased from 25 [+ or -] 14 [micro]mol x [kg.sup.-1] x [h.sup.-1] in the control group to 171 [+ or -] 35 [micro]mol x [kg.sup.-1] x [h.sup.-1] in the TNBS-treated group (P < 0.001). In conclusion, ileitis increased intestinal mucin synthesis and PDV utilization of threonine from arterial but not luminal supply. This leads to the mobilization of endogenous proteins to meet the increased threonine demand associated with acute intestinal inflammation.

The utility of liquid chromatography coupled to the isotope ratio mass spectrometry technique (LC-IRMS) has already been established through a variety of successful applications. However, the analytical constraint related to the use of aqueous mobile phases limits the LC separation mechanism. We report here a new strategy for high-precision [sup.13]C isotopic analyses based on temperature-programmed LC-IRMS using aqueous mobile phases. Under these conditions, the isotopic precision and accuracy were studied. On one hand, experiments were carried out with phenolic acids using isothermal LC conditions at high temperature (170 [degrees]C); on the other hand, several experiments were performed by ramping the temperature, as conventionally used in a gas chromatography-based method with hydrosoluble fatty acids and pulses of C[O.sub.2] reference gas. In isothermal conditions at 170 [degrees]C, despite the increase of the C[O.sub.2] background, p-coumaric acid and its glucuronide conjugate gave reliable isotopic ratios compared to flow injection analysis-isotopic ratio mass spectrometry (FIA-IRMS) analyses (isotopic precision and accuracy are lower than 0.3 [per thousand]). On the opposite, for its sulfate conjugate, the isotopic accuracy is affected by its coelution with p-coumaric acid. Not surprisingly, this study also demonstrates that at high temperature (170 [degrees]C), a compound eluting with long residence time (i.e., ferulic acid) is degraded, affecting thus the [[delta].sup.13]C (drift of 3 [per thousand]) and the peak area (compared to FIA-IRMS analysis at room temperature). Quantitation is also reported in isothermal conditions for p-coumaric acid in the range of 10-400 ng/mL and with benzoic acid as an internal standard. For temperature gradient LC-IRMS, in the area of the LC gradient (set up at 20 [degrees]C/ min), the drift of the background observed produces a nonlinearity of SD ([[delta].sup.13]C) ~0.01 [per thousand]/mV. To circumvent this drift, which impacts severely the precision and accuracy, an alternative approach, i.e., eluting the compound on the plateau of temperature studied was reported here. Other experiments with temperature-programmed LC-IRMS experiments are also reported with the presence of methanol in the injected solution to mimic residual solvent originating from the sample preparation or to slightly increase the solubility of the targeted compound for high-precision measurement.

We hypothesized that the dietary threonine demand for the anabolic response may be increased more than that of other essential amino acids during sepsis. Using a flooding dose of either L-[1-[sup.13]C]valine or L-[U- [sup.13]C]threonine, we measured valine and threonine utilization for syntheses of plasma proteins (minus albumin), and wall, mucosal, and mucin proteins of the small intestine in infected (INF; d 2 and d 6 of postinfection) and control pair-fed (PF) rats. At d 2, the protein absolute synthesis rate (ASR) of INF rats was 21% (mucins) to 41% (intestinal wall) greater than that of PF when measured using valine as tracer, and 45% (mucosa) to 113% (mucins) greater than that of PF when measured with threonine as tracer. Plasma protein ASR was higher in INF than in PF rats, reaching 5- to 6-fold the value of PF. The utilization of both amino acid tracers for the protein synthesis was significantly increased by the infection in all compartments studied. The daily increased absolute threonine utilization for protein synthesis in gut wall plus plasma proteins was 446 [micro]mol/d compared with 365 [micro]mol/d for valine, and it represented 2.6 times the dietary threonine intake of rats at d 2. Most changes in protein ASR and threonine utilization observed at d 6 of postinfection were limited. In conclusion, sepsis increased the utilization of threonine for the anabolic splanchnic response. Because this threonine requirement is likely covered by muscle protein mobilization, increasing the threonine dietary supply would be an effective early nutritional management for patients with sepsis.

During the anabolic response associated with inflammation, mucin synthesis and colonic protection may be compromised by the limited availability of specific amino acids. We therefore determined the effect of dietary amino acid supplementation on the microbiota, mucin status, and mucosal damage in dextran sulfate sodium (DSS)-treated rats. From 8 d before to 28 d after colitis induction, male Sprague-Dawley rats (10 mo old, n = 8/group) were fed a control diet supplemented or not with 2 different doses of an amino acid cocktail containing L-threonine, L-serine, L-proline, and L-cysteine. All diets were isonitrogenous (adjusted with L-alanine). The higher dose of amino acids increased the number of Muc2-containing goblet cells in the surface epithelium of the ulcerated area, stimulated mucin production in the colon, and restored the mucin amino acid composition and mucosal content to healthy, control values. The colonic mucin synthesis rate was specifically stimulated by 95%, whereas the protein turnover was unchanged. All bacterial populations, markedly altered by the DSS treatment, were promoted. In conclusion, in inflammatory situations, an increase in threonine, serine, proline, and cysteine dietary supply can promote mucin synthesis, reequilibrate the gut microbiota, and thus favor colonic protection and mucosal healing. KEY WORDS: * mucin * amino acids * protein synthesis * intestine * rats

Mycobacterium aurum can degrade nitrogen heterocyclic compounds, as illustrated by the degradation of piperidine. Heterocyclic compounds are common industrial organic pollutants.

Background There are limited data from randomized control trials to support or refute the contention that whole-grains can enhance protein metabolism in humans. Objectives To examine: 1) the clinical effects of a whole-grain diet on whole-body protein turnover; 2) the cellular effects of whole-grains on protein synthesis in skeletal muscle cells; and 3) the population effects of whole-grain intake on age-related muscle loss. Methods Adults with overweight/obesity (n = 14; age = 40 ± 7 y; BMI = 33 ± 5 kg/m2) were recruited into a crossover, randomized controlled trial (NCT01411540) in which isocaloric, macronutrient-matched whole-grain and refined-grain diets were fully provisioned for two 8-wk periods. Diets differed only in the presence of whole-grains (50 g/1000 kcal). Whole-body protein kinetics were assessed at baseline and after each diet in the fasted-state (13C-leucine) and integrated over 24 h (15N-glycine). In vitro studies using C2C12 cells assessed global protein synthesis by surface sensing of translation and anabolic signaling by Western blot. Complementary epidemiological assessments using the NHANES database assessed the effect of whole-grain intake on muscle function assessed by gait speed in older adults (n = 2783). Results Integrated 24-h net protein balance was 3-fold higher on a whole-grain diet compared with a refined-grain diet (P = 0.04). A whole-grain wheat extract increased submaximal rates of global protein synthesis (27%, P < 0.05) in vitro. In a large sample of older adults, whole-grain intake was associated with greater muscle function (OR = 0.92; 95% CI: 0.86, 0.98). Conclusions Consuming 50 g/1000 kcal whole-grains per day promotes greater protein turnover and enhances net protein balance in adults. Whole-grains impact skeletal muscle at the cellular level, and are associated with greater muscle function in older adults. Collectively, these data point to a new mechanism whereby whole-grain consumption favorably enhances protein turnover and improves health outcomes. This clinical trial is registered on clinicaltrials.gov (identifier: NCT01411540). [ABSTRACT FROM AUTHOR]

Abstract Background The pattern of protein intake following exercise may impact whole-body protein turnover and net protein retention. We determined the effects of different protein feeding strategies on protein metabolism in resistance-trained young men. Methods Participants were randomly assigned to ingest either 80g of whey protein as 8x10g every 1.5h (PULSE; n=8), 4x20g every 3h (intermediate, INT; n=7), or 2x40g every 6h (BOLUS; n=8) after an acute bout of bilateral knee extension exercise (4x10 repetitions at 80% maximal strength). Whole-body protein turnover (Q), synthesis (S), breakdown (B), and net balance (NB) were measured throughout 12h of recovery by a bolus ingestion of [15N]glycine with urinary [15N]ammonia enrichment as the collected end-product. Results PULSE Q rates were greater than BOLUS (~19%, P Conclusion We conclude that the pattern of ingested protein, and not only the total daily amount, can impact whole-body protein metabolism. Individuals aiming to maximize NB would likely benefit from repeated ingestion of moderate amounts of protein (~20g) at regular intervals (~3h) throughout the day.

Introduction: Counteracting impaired brain glucose metabolism with ketones may improve cognition in mild cognitive impairment (MCI). Methods: Cognition, plasma ketone response, and metabolic profile were assessed before and 6 months after supplementation with a ketogenic drink containing medium chain triglyceride (ketogenic medium chain triglyceride [kMCT]; 15 g twice/day; n = 39) or placebo (n = 44). Results: Free and cued recall (Trial 1; P =.047), verbal fluency (categories; P =.024), Boston Naming Test (total correct answers; P =.033), and the Trail‐Making Test (total errors; P =.017) improved significantly in the kMCT group compared to placebo (analysis of covariance; pre‐intervention score, sex, age, education, and apolipoprotein E4 as covariates). Some cognitive outcomes also correlated positively with plasma ketones. Plasma metabolic profile and ketone response were unchanged. Conclusions: This kMCT drink improved cognitive outcomes in MCI, at least in part by increasing blood ketone level. These data support further assessment of MCI progression to Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated a direct link between increased exogenous CHO oxidation (CHOexog) and enhanced performance. The limiting factor for CHOexog appears to be at the level of intestinal transporters, with sodium/glucose cotransporter 1 (SGLT1) and glucose transporter Type 5 (GLUT5) responsible for glucose and fructose transport, respectively. Studies in animal models have shown that SGLT1 and intestinal glucose uptake are up-regulated by high carbohydrate diets or noncaloric sweeteners. The aim of this study was to determine the effect of preexercise ingestion of noncaloric sweeteners on CHOexog during exercise in athletes. In a randomized, crossover, double-blind fashion twenty-three healthy male cyclists (age = 29 ± 7yrs, mass = 73.6 ± 7.4kg, VO2peak = 68.3 ± 9.3 ml/kg/min) consumed 8 x 50ml doses of either placebo (CON) or 1mM sucralose (SUCRA) every 15 min starting 120 min before the onset of exercise. This was followed by 2h of cycling at 48.5 ± 8.6% of VO2peak with continual ingestion of a maltodextrin drink (1.2g/min; 828ml/ hr). Average CHOexog during the first hour of exercise did not differ between SUCRA and CON conditions (0.226 } 0.081 g/min vs. 0.212 ± 0.076 g/min, Δ =0.015 g/min, 95%CI -0.008 g/min, 0.038 g/min, p = .178). Blood glucose, plasma insulin and lactate, CHO and fat substrate utilization, heart rate, ratings of perceived exertion, and gastrointestinal symptoms did not differ between conditions. Our data suggest that consumption of noncaloric sweeteners in the immediate period before exercise does not lead to a significant increase in CHOexog during exercise. [ABSTRACT FROM AUTHOR]