Application of Bayesian analysis to the doubly labelled water method for total energy expenditure in humans.

RATIONALE: The doubly labelled water (DLW) method is the reference method for the estimation of free-living total energy expenditure (TEE). In this method, where both 2 H and 18 O are employed, different approaches have been adopted to deal with the non-conformity observed regarding the distribution space for the labels being non-coincident with total body water. However, the method adopted can have a significant effect on the estimated TEE. METHODS: We proposed a Bayesian reasoning approach to modify an assumed prior distribution for the space ratio using experimental data to derive the TEE. A Bayesian hierarchical approach was also investigated. The dataset was obtained from 59 adults (37 women) who underwent a DLW experiment during which the 2 H and 18 O enrichments were measured using isotope ratio mass spectrometry (IRMS). RESULTS: TEE was estimated at 9925 (9106-11236) [median and interquartile range], 9646 (9167-10540), and 9,638 (9220-10340) kJ·day-1 for women and at 13961 (12851-15347), 13353 (12651-15088) and 13211 (12653-14238) kJ·day-1 for men, using normalized non-Bayesian, independent Bayesian and hierarchical Bayesian approaches, respectively. A comparison of hierarchical Bayesian with normalized non-Bayesian methods indicated a marked difference in behaviour between genders. The median difference was -287 kJ·day-1 for women, and -750 kJ·day-1 for men. In men there is an appreciable compression of the TEE distribution obtained from the hierarchical model compared with the normalized non-Bayesian methods (range of TEE 11234-15431 kJ·day-1 vs 10786-18221 kJ·day-1 ). An analogous, yet smaller, compression is seen in women (7081-12287 kJ·day-1 vs 6989-13775 kJ·day-1 ). CONCLUSIONS: The Bayesian analysis is an appealing method to estimate TEE during DLW experiments. The principal advantages over those obtained using the classical least-squares method is the generation of potentially more useful estimates of TEE, and improved handling of outliers and missing data scenarios, particularly if a hierarchical model is used

Descriptive epidemiology of energy expenditure in the UK: findings from the National Diet and Nutrition Survey 2008-15.

BACKGROUND: Little is known about population levels of energy expenditure, as national surveillance systems typically employ only crude measures. The National Diet and Nutrition Survey (NDNS) in the UK measured energy expenditure in a 10% subsample by gold-standard doubly labelled water (DLW). METHODS: DLW-subsample participants from the NDNS (383 males, 387 females) aged 4-91 years were recruited between 2008 and 2015 (rolling programme). Height and weight were measured and body-fat percentage estimated by deuterium dilution. RESULTS: Absolute total energy expenditure (TEE) increased steadily throughout childhood, ranging from 6.2 and 7.2 MJ/day in 4- to 7-year-olds to 9.7 and 11.7 MJ/day for 14- to 16-year-old girls and boys, respectively. TEE peaked in 17- to 27-year-old women (10.7 MJ/day) and 28- to 43-year-old men (14.4 MJ/day), before decreasing gradually in old age. Physical-activity energy expenditure (PAEE) declined steadily with age from childhood (87 kJ/day/kg in 4- to 7-year-olds) through to old age (38 kJ/day/kg in 71- to 91-year-olds). No differences were observed by time, region and macronutrient composition. Body-fat percentage was strongly inversely associated with PAEE throughout life, irrespective of expressing PAEE relative to body mass or fat-free mass. Compared with females with 40% recorded 29 kJ/day/kg body mass and 18 kJ/day/kg fat-free mass less PAEE in analyses adjusted for age, geographical region and time of assessment. Similarly, compared with males with 35% recorded 26 kJ/day/kg body mass and 10 kJ/day/kg fat-free mass less PAEE. CONCLUSIONS: This first nationally representative study reports levels of human-energy expenditure as measured by gold-standard methodology; values may serve as a reference for other population studies. Age, sex and body composition are the main determinants of energy expenditure. Key Messages This is the first nationally representative study of human energy expenditure, covering the UK in the period 2008-2015. Total energy expenditure (MJ/day) increases steadily with age throughout childhood and adolescence, peaks in the 3rd decade of life in women and 4th decade of life in men, before decreasing gradually in old age. Physical activity energy expenditure (kJ/day/kg or kJ/day/kg fat-free mass) declines steadily with age from childhood to old age, more steeply so in males. Body-fat percentage is strongly inversely associated with physical activity energy expenditure. We found little evidence that energy expenditure varied by geographical region, over time, or by dietary macronutrient composition.The authors were supported by the UK Medical Research Council (unit programme numbers. MC_UU_12015/1, MC_UU_12015/3, U105960371) and the NIHR Biomedical Research Centre in Cambridge (IS-BRC-1215-20014). TL was funded by the Cambridge Trust

Physical activity, sedentary behaviors, and estimated insulin sensitivity and secretion in pregnant and non-pregnant women

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Overweight and obesity during pregnancy raise the risk of gestational diabetes and birth complications. Lifestyle factors like physical activity may decrease these risks through beneficial effects on glucose homeostasis. Here we examined physical activity patterns and their relationships with measures of glucose homeostasis in late pregnancy compared to non-pregnant women. Methods Normal weight and overweight women without diabetes (N = 108; aged 25-35 years) were studied; 35 were pregnant (in gestational weeks 28-32) and 73 were non-pregnant. Insulin sensitivity and β-cell response were estimated from an oral glucose tolerance test. Physical activity was measured during 10-days of free-living using a combined heart rate sensor and accelerometer. Total (TEE), resting (REE), and physical activity (PAEE) energy expenditure were measured using doubly-labeled water and expired gas indirect calorimetry. Results Total activity was associated with reduced first-phase insulin response in both pregnant (Regression r2 = 0.11; Spearman r = -0.47; p = 0.007) and non-pregnant women (Regression r2 = 0.11 Spearman; r = -0.36; p = 0.002). Relative to non-pregnant women, pregnant women were estimated to have secreted 67% more insulin and had 10% lower fasting glucose than non-pregnant women. Pregnant women spent 13% more time sedentary, 71% less time in moderate-to-vigorous intensity activity, had 44% lower objectively measured total activity, and 12% lower PAEE than non-pregnant women. Correlations did not differ significantly for any comparison between physical activity subcomponents and measures of insulin sensitivity or secretion. Conclusions Our findings suggest that physical activity conveys similar benefits on glucose homeostasis in pregnant and non-pregnant women, despite differences in subcomponents of physical activity.Published versio

Assessment of Volume Depletion in Children with Malaria

BACKGROUND: The degree of volume depletion in severe malaria is currently unknown, although knowledge of fluid compartment volumes can guide therapy. To assist management of severely ill children, and to test the hypothesis that volume changes in fluid compartments reflect disease severity, we measured body compartment volumes in Gabonese children with malaria. METHODS AND FINDINGS: Total body water volume (TBW) and extracellular water volume (ECW) were estimated in children with severe or moderate malaria and in convalescence by tracer dilution with heavy water and bromide, respectively. Intracellular water volume (ICW) was derived from these parameters. Bioelectrical impedance analysis estimates of TBW and ECW were calibrated against dilution methods, and bioelectrical impedance analysis measurements were taken daily until discharge. Sixteen children had severe and 19 moderate malaria. Severe childhood malaria was associated with depletion of TBW (mean [SD] of 37 [33] ml/kg, or 6.7% [6.0%]) relative to measurement at discharge. This is defined as mild dehydration in other conditions. ECW measurements were normal on admission in children with severe malaria and did not rise in the first few days of admission. Volumes in different compartments (TBW, ECW, and ICW) were not related to hyperlactataemia or other clinical and laboratory markers of disease severity. Moderate malaria was not associated with a depletion of TBW. CONCLUSIONS: Significant hypovolaemia does not exacerbate complications of severe or moderate malaria. As rapid rehydration of children with malaria may have risks, we suggest that fluid replacement regimens should aim to correct fluid losses over 12–24 h

Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults

25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18–23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life

Effects of dietary supplementation with the green tea polyphenol epigallocatechin3-gallate on insulin resistance and associated metabolic risk factors: randomized controlled

Animal evidence indicates that green tea may modulate insulin sensitivity, with epigallocatechin-3-gallate (EGCG) proposed as a likely healthpromoting component. The purpose of this study was to investigate the effect of dietary supplementation with EGCG on insulin resistance and associated metabolic risk factors in man. Overweight or obese male subjects, aged 40-65 years, were randomly assigned to take 400 mg capsules of EGCG (n 46) or the placebo lactose (n 42), twice daily for 8 weeks. Oral glucose tolerance testing and measurement of metabolic risk factors (BMI, waist circumference, percentage body fat, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG) was conducted pre-and post-intervention. Mood was evaluated weekly using the University of Wales Institute of Science and Technology mood adjective checklist. EGCG treatment had no effect on insulin sensitivity, insulin secretion or glucose tolerance but did reduce diastolic blood pressure (mean change: placebo 20·058 (SE 0·75) mmHg; EGCG 2 2·68 (SE 0·72) mmHg; P¼0·014). No significant change in the other metabolic risk factors was observed. The EGCG group also reported feeling in a more positive mood than the placebo group across the intervention period (mean score for hedonic tone: EGCG, 29·11 (SE 0·44); placebo, 27·84 (SE 0·46); P¼0·048). In conclusion, regular intake of EGCG had no effect on insulin resistance but did result in a modest reduction in diastolic blood pressure. This antihypertensive effect may contribute to some of the cardiovascular benefits associated with habitual green tea consumption. EGCG treatment also had a positive effect on mood. Further studies are needed to confirm the findings and investigate their mechanistic basis

A pilot study of a non-invasive oral nitrate stable isotopic method suggests that arginine and citrulline supplementation increases whole-body NO production in Tanzanian children with sickle cell disease.

BACKGROUND: Low bioavailability of nitric oxide (NO) is implicated in the pathophysiology of sickle cell disease (SCD). We designed a nested pilot study to be conducted within a clinical trial testing the effects of a daily ready-to-use supplementary food (RUSF) fortified with arginine (Arg) and citrulline (Citr) vs. non-fortified RUSF in children with SCD. The pilot study evaluated 1) the feasibility of a non-invasive stable isotope method to measure whole-body NO production and 2) whether Arg+Citr supplementation was associated with increased whole-body NO production. SUBJECTS: Twenty-nine children (70% male, 9-11years, weight 16.3-31.3 kg) with SCD. METHODS: Sixteen children received RUSF+Arg/Citr (Arg, 0.2  g/kg/day; Citr, 0.1  g/kg/day) in combination with daily chloroquine (50 mg) and thirteen received the base RUSF in combination with weekly chloroquine (150 mg). Plasma amino acids were assessed using ion-exchange elution (Biochrom-30, Biochrom, UK) and whole-body NO production was measured using a non-invasive stable isotopic method. RESULTS: The RUSF+Arg/Citr intervention increased plasma arginine (P = .02) and ornithine (P = .003) and decreased the ratio of asymmetric dimethylarginine to arginine (P = .01), compared to the base RUSF. A significant increase in whole-body NO production was observed in the RUSF-Arg/Citr group compared to baseline (weight-adjusted systemic NO synthesis 3.38 ± 2.29 μmol/kg/hr vs 2.35 ± 1.13 μmol/kg/hr, P = .04). No significant changes were detected in the base RUSF group (weight-adjusted systemic NO synthesis 2.64 ± 1.14 μmol/kg/hr vs 2.53 ± 1.12 μmol/kg/hr, P = .80). CONCLUSIONS: The non-invasive stable isotopic method was acceptable and the results provided supporting evidence that Arg/Citr supplementation may increase systemic NO synthesis in children with SCD

The effect of food preparation on the bioavailability of carotenoids from carrots using intrinsic labelling

A strategy to reduce the incidence of vitamin A deficiency is to improve precursor bioavailability from meals. Since vitamin A precursors are fat-soluble, we noted that carotenoids are more easily absorbed from food if prepared in such a way that the food matrix containing provitamin A (β-carotene) is sufficiently fat rich. To quantify this effect, we have developed a stable isotope methodology. By regular watering with 2H-labelled water, we were able to produce several kg of intrinsically labelled carrots, with carotenoids labelled to 0·63 % excess 2H. These were divided into 100 g portions and fed to a small group of healthy subjects both raw and stir-fried. To normalise for inter-individual variation in absorption and subsequent metabolism, small quantities of extrinsically 13C-labelled β-carotene and 2H-labelled retinol acetate were also incorporated into the meal. After ingestion of the carrots, blood lipids were monitored for a period of 3 d in order to determine the kinetics of β-carotene and retinol. From kinetic data, it was estimated that the bioavailability of carrot-derived β-carotene compared with pure β-carotene was about 11 % for raw carrots, but 75 % when the carrots were stir-fried. Conversely, there was a slight reduction in the bioconversion to retinol from β-carotene when the latter was derived from the stir-fried meal compared with that from raw carrots. When these two factors are combined, the yield of retinol from the carotene in carrots was found to be enhanced by a factor of 6·5 by stir-frying