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B-vitamins and body composition: integrating observational and experimental evidence from the B-PROOF study.
Oliai Araghi, S, Braun, KVE, van der Velde, N, van Dijk, SC, van Schoor, NM, Zillikens, MC, de Groot, LCPGM, Uitterlinden, AG, Stricker, BH, Voortman, T, et al
European journal of nutrition. 2020;(3):1253-1262
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PURPOSE Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals. METHODS A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (n = 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA). RESULTS Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m2 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per μgmol/L) was associated with a 1.108 kg/m2 lower FMI (95% CI - 1.899; - 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention. CONCLUSIONS Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.
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Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics.
Valsesia, A, Chakrabarti, A, Hager, J, Langin, D, Saris, WHM, Astrup, A, Blaak, EE, Viguerie, N, Masoodi, M
Scientific reports. 2020;(1):9236
Abstract
Weight loss aims to improve glycemic control in obese but strong variability is observed. Using a multi-omics approach, we investigated differences between 174 responders and 201 non-responders, that had lost >8% body weight following a low-caloric diet (LCD, 800 kcal/d for 8 weeks). The two groups were comparable at baseline for body composition, glycemic control, adipose tissue transcriptomics and plasma ketone bodies. But they differed significantly in their response to LCD, including improvements in visceral fat, overall insulin resistance (IR) and tissue-specific IR. Transcriptomics analyses found down-regulation in key lipogenic genes (e.g. SCD, ELOVL5) in responders relative to non-responders; metabolomics showed increase in ketone bodies; while proteomics revealed differences in lipoproteins. Findings were consistent between genders; with women displaying smaller improvements owing to a better baseline metabolic condition. Integrative analyses identified a plasma omics model that was able to predict non-responders with strong performance (on a testing dataset, the Receiving Operating Curve Area Under the Curve (ROC AUC) was 75% with 95% Confidence Intervals (CI) [67%, 83%]). This model was based on baseline parameters without the need for intrusive measurements and outperformed clinical models (p = 0.00075, with a +14% difference on the ROC AUCs). Our approach document differences between responders and non-responders, with strong contributions from liver and adipose tissues. Differences may be due to de novo lipogenesis, keto-metabolism and lipoprotein metabolism. These findings are useful for clinical practice to better characterize non-responders both prior and during weight loss.
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Deep Learning-Based Quantification of Epicardial Adipose Tissue Volume and Attenuation Predicts Major Adverse Cardiovascular Events in Asymptomatic Subjects.
Eisenberg, E, McElhinney, PA, Commandeur, F, Chen, X, Cadet, S, Goeller, M, Razipour, A, Gransar, H, Cantu, S, Miller, RJH, et al
Circulation. Cardiovascular imaging. 2020;(2):e009829
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BACKGROUND Epicardial adipose tissue (EAT) volume (cm3) and attenuation (Hounsfield units) may predict major adverse cardiovascular events (MACE). We aimed to evaluate the prognostic value of fully automated deep learning-based EAT volume and attenuation measurements quantified from noncontrast cardiac computed tomography. METHODS Our study included 2068 asymptomatic subjects (56±9 years, 59% male) from the EISNER trial (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) with long-term follow-up after coronary artery calcium measurement. EAT volume and mean attenuation were quantified using automated deep learning software from noncontrast cardiac computed tomography. MACE was defined as myocardial infarction, late (>180 days) revascularization, and cardiac death. EAT measures were compared to coronary artery calcium score and atherosclerotic cardiovascular disease risk score for MACE prediction. RESULTS At 14±3 years, 223 subjects suffered MACE. Increased EAT volume and decreased EAT attenuation were both independently associated with MACE. Atherosclerotic cardiovascular disease risk score, coronary artery calcium, and EAT volume were associated with increased risk of MACE (hazard ratio [95%CI]: 1.03 [1.01-1.04]; 1.25 [1.19-1.30]; and 1.35 [1.07-1.68], P<0.01 for all) and EAT attenuation was inversely associated with MACE (hazard ratio, 0.83 [95% CI, 0.72-0.96]; P=0.01), with corresponding Harrell C statistic of 0.76. MACE risk progressively increased with EAT volume ≥113 cm3 and coronary artery calcium ≥100 AU and was highest in subjects with both (P<0.02 for all). In 1317 subjects, EAT volume was correlated with inflammatory biomarkers C-reactive protein, myeloperoxidase, and adiponectin reduction; EAT attenuation was inversely related to these biomarkers. CONCLUSIONS Fully automated EAT volume and attenuation quantification by deep learning from noncontrast cardiac computed tomography can provide prognostic value for the asymptomatic patient, without additional imaging or physician interaction.
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Percent Fat Mass Increases with Recovery, But Does Not Vary According to Dietary Therapy in Young Malian Children Treated for Moderate Acute Malnutrition.
McDonald, CM, Ackatia-Armah, RS, Doumbia, S, Kupka, R, Duggan, CP, Brown, KH
The Journal of nutrition. 2019;(6):1089-1096
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BACKGROUND Moderate acute malnutrition (MAM) affects 34.1 million children globally. Treatment effectiveness is generally determined by the amount and rate of weight gain. Body composition (BC) assessment provides more detailed information on nutritional stores and the type of tissue accrual than traditional weight measurements alone. OBJECTIVE The aim of this study was to compare the change in percentage fat mass (%FM) and other BC parameters among young Malian children with MAM according to receipt of 1 of 4 dietary supplements, and recovery status at the end of the 12-wk intervention period. METHODS BC was assessed using the deuterium oxide dilution method in a subgroup of 286 children aged 6-35 mo who participated in a 12-wk community-based, cluster-randomized effectiveness trial of 4 dietary supplements for the treatment of MAM: 1) lipid-based, ready-to-use supplementary food (RUSF); 2) special corn-soy blend "plus plus" (CSB++); 3) locally processed, fortified flour (MI); or 4) locally milled flours plus oil, sugar, and micronutrient powder (LMF). Multivariate linear regression modeling was used to evaluate change in BC parameters by treatment group and recovery status. RESULTS Mean ± SD %FM at baseline was 28.6% ± 5.32%. Change in %FM did not vary between groups. Children who received RUSF vs. MI gained more (mean; 95% CI) weight (1.43; 1.13, 1.74 kg compared with 0.84; 0.66, 1.03 kg; P = 0.02), FM (0.70; 0.45, 0.96 kg compared with 0.20; 0.05, 0.36 kg; P = 0.01), and weight-for-length z score (1.23; 0.79, 1.54 compared with 0.49; 0.34, 0.71; P = 0.03). Children who recovered from MAM exhibited greater increases in all BC parameters, including %FM, than children who did not recover. CONCLUSIONS In this study population, children had higher than expected %FM at baseline. There were no differences in %FM change between groups. International BC reference data are needed to assess the utility of BC assessment in community-based management of acute malnutrition programs. This trial was registered at clinicaltrials.gov as NCT01015950.
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Metabolic rate and substrate utilisation resilience in men undertaking polar expeditionary travel.
Hattersley, J, Wilson, AJ, Thake, CD, Facer-Childs, J, Stoten, O, Imray, C
PloS one. 2019;(8):e0221176
Abstract
The energy expenditure and substrate utilisation were measured in 5 men pre- and post- a 67 day, 1750km unassisted Antarctic traverse from the Hercules Inlet to the Ross Sea Ice via the South pole pulling sledges weighing 120kg whilst experiencing temperatures as low as -57°C. A 36-hours protocol in a whole body calorimeter was employed to measure periods of rest, sleep and three periods of standardised stepping exercises at 80, 100 and 120 steps min-1; participants were fed isocalorically. Unlike previous expeditions where large weight loss was reported, only a modest loss of body weight (7%, P = 0.03) was found; fat tissue was reduced by 53% (P = 0.03) together with a small, but not statistically significant, increase in lean tissue weight (P = 0.18). This loss occurred despite a high-energy intake (6500 kcal/day) designed to match energy expenditure. An energy balance analysis suggested the loss in body weight could be due to the energy requirements of thermoregulation. Differences in energy expenditure [4.9 (0.1) vs 4.5 (0.1) kcal/min. P = 0.03], carbohydrate utilisation [450 (180) vs 569 (195) g/day; P = 0.03] and lipid utilisation [450 (61) vs 388 (127) g/day, P = 0.03] at low levels of exertion were different from pre-expedition values. Only carbohydrate utilisation remained statistically significant when normalised to body weight. The differences in energy expenditure and substrate utilisation between the pre- and post-expedition for other physiological states (sleeping, resting, higher levels of exercise, etc) were small and not statistically significant. Whilst inter-subject variability was large, there was a tendency for increased carbohydrate utilisation, post-expedition, when fasted that decreased upon feeding.
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Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease: A double-blind, randomized, placebo-controlled study.
Oscarsson, J, Önnerhag, K, Risérus, U, Sundén, M, Johansson, L, Jansson, PA, Moris, L, Nilsson, PM, Eriksson, JW, Lind, L
Journal of clinical lipidology. 2018;(6):1390-1403.e4
Abstract
BACKGROUND Treatment with omega-3 fatty acids and fenofibrates reduces serum triglyceride levels, but few studies have compared the effect of these agents on liver fat. OBJECTIVE The aim of the EFFECT I trial (NCT02354976) was to determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate on liver fat in overweight or obese individuals with non-alcoholic fatty liver disease and hypertriglyceridemia. METHODS Seventy-eight patients were randomized to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver proton density fat fraction (PDFF) and volume, pancreas volume, and adipose tissue volumes were assessed by magnetic resonance imaging. RESULTS Changes in liver PDFF at 12 weeks were not significantly different across treatment groups (relative changes from baseline: placebo, +4%; OM-3CA, -2%; and fenofibrate, +17%). The common PNPLA3 genetic polymorphism (I148M) did not significantly influence the effects of OM-3CA or fenofibrate on liver PDFF. Fenofibrate treatment significantly increased liver and pancreas volumes vs placebo treatment, and the changes in liver and pancreas volumes were positively correlated (rho 0.45, P = .02). Total liver fat volume increased significantly in patients using fenofibrate vs OM-3CA (+23% vs -3%, P = .04). Compared with OM-3CA, fenofibrate increased total liver fat and liver volume. Serum triglycerides decreased with OM-3CA (-26%, P = .02) and fenofibrate (-38%, P < .001) vs placebo. In contrast to OM-3CA, fenofibrate reduced plasma docosahexaenoic acid levels and increased plasma acetylcarnitine and butyrylcarnitine levels, estimated delta-9 desaturase activity and the concentration of urine F2-isoprostanes. CONCLUSIONS OM-3CA and fenofibrate reduced serum triglycerides but did not reduce liver fat. Fenofibrate increased total liver volume and total liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human hepatic lipid metabolism.
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Epicardial and paracardial adipose tissue volume and attenuation - Association with high-risk coronary plaque on computed tomographic angiography in the ROMICAT II trial.
Lu, MT, Park, J, Ghemigian, K, Mayrhofer, T, Puchner, SB, Liu, T, Fleg, JL, Udelson, JE, Truong, QA, Ferencik, M, et al
Atherosclerosis. 2016;:47-54
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BACKGROUND AND AIMS To determine whether epicardial (EAT) and paracardial adipose tissue (PAT) volume and attenuation are associated with high-risk coronary plaque features. METHODS In subjects with suspected acute coronary syndrome (ACS) enrolled in the ROMICAT II trial, EAT and PAT volumes indexed to body surface area (BSA) and attenuation were measured on non-contrast coronary artery calcium score (CACS) CT. High-risk plaque features (napkin-ring sign, positive remodeling, low density plaque, spotty calcium) and stenosis were assessed on coronary CT angiography (CTA). The association of EAT and PAT volume and attenuation with high-risk plaque and whether this was independent of clinical risk assessment, CACS and significant coronary artery disease (CAD) was determined. RESULTS Of 467 (mean 54 ± 8 yrs, 53% male) with CACS and CTA, 167 (36%) had high-risk plaque features. Those with high-risk plaque had significantly higher indexed EAT (median 59 (Q1-Q3:45-75) cc/m(2) vs. 49 (35-65) cc/m(2), p < 0.001) and PAT volume (median:51 (36-73) cc/m(2) vs. 33 (22-52) cc/m(2), p < 0.001). Higher indexed EAT volume was associated with high-risk plaque [univariate OR 1.02 (95%-CI:1.01-1.03) per cc/m(2) of EAT, p < 0.001], which remained significant [univariate OR 1.04 (95%-CI:1.00-1.08) per cc/m(2) of EAT, p = 0.040] after adjustment for risk factors, CACS, and stenosis ≥50%. Higher indexed PAT volume was associated with high-risk plaque in univariate analysis [OR 1.02 (1.01-1.03) per cc/m(2) of PAT, p < 0.001], though this was not significant in multivariate analysis. At a threshold of >62.3 cc/m(2), EAT volume was associated with high-risk plaque [univariate OR 2.50 (95%-CI:1.69-3.72), p < 0.001)], which remained significant [OR 1.83 (95%-CI:1.10-3.05), p = 0.020] after adjustment. Subjects with high-risk plaque had lower mean attenuation EAT (-88.1 vs. -86.9 HU, p = 0.008) and PAT (-106 vs. -103 HU, p < 0.001), though this was not significant in multivariable analysis. CONCLUSIONS Greater volumes of EAT are associated with high-risk plaque independent of risk factors, CACS and obstructive CAD. This observation supports possible local influence of EAT on development of high-risk coronary plaque.
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Comparison of epicardial adipose tissue volume and coronary artery disease severity in asymptomatic adults with versus without diabetes mellitus.
Groves, EM, Erande, AS, Le, C, Salcedo, J, Hoang, KC, Kumar, S, Mohar, DS, Saremi, F, Im, J, Agrawal, Y, et al
The American journal of cardiology. 2014;(5):686-91
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Epicardial adipose tissue (EAT) has been shown to have important effects on the development of coronary artery disease (CAD) through local paracrine influences on the vascular bed. We compared a cohort of asymptomatic patients with type II diabetes mellitus (DM) without known CAD to an age- and gender-matched group of asymptomatic patients without DM from the CTRAD (Cardiac CT's Role in Asymptomatic Patients with DM-II) study in which patients underwent a cardiac computed tomography angiogram, for early detection of CAD. Mean EAT volumes of 118.6 ± 43.0 and 70.0 ± 44.0 cm(3) were found in the DM and non-DM groups, respectively. When stratified by the presence and severity of CAD, it was found that in the DM (p = 0.003) and non-DM groups (p <0.001), there was a statistically significant increase in EAT volume as the patients were found to have increasingly severe CAD. After adjusting for age, race, gender, DM, hypertension, insulin use, body mass index, and coronary artery calcium (CAC) score, the presence of >120 cm(3) of EAT was found to be highly correlated with the presence of significant CAD (adjusted odds ratio 4.47, 95% confidence interval 1.35 to 14.82). We found that not only is EAT volume an independent predictor of CAD but that an increasing volume of EAT predicted increasing severity of CAD even after adjustment for CAC score.
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Defining body fatness in adolescents: a proposal of the AFAD-A classification.
Bibiloni, Mdel M, Pons, A, Tur, JA
PloS one. 2013;(2):e55849
Abstract
AIMS: Body mass index (BMI) shows several limitations as indicator of fatness. Using the International Obesity Task Force (IOTF) reference and the World Health Organization (WHO) standard 2007 on the same dataset yielded widely different rates. At higher levels, BMI and the BMI cut-offs may be help in informing a clinical judgement, but at levels near the norm additional criteria may be needed. This study compares the prevalence of overweight and obesity using IOTF and WHO-2007 references and interprets body composition by comparing measures of BMI and body fatness (fat mass index, FMI; and waist-to-height ratio, WHtR) among an adolescent population. METHODS AND RESULTS A random sample (n = 1231) of adolescent population (12-17 years old) was interviewed. Weight, height, waist circumference, triceps and subscapular skinfolds were used to calculate BMI, FMI, and WHtR. The prevalence of overweight and obesity were 12.3% and 15.4% (WHO standards) and 18.6% and 6.1% (IOTF definition). Despite that IOTF cut-offs misclassified less often than WHO standards, BMI categories were combined with FMI and WHtR resulting in the Adiposity & Fat Distribution for adolescents (AFAD-A) classification, which identified the following groups normal-weight normal-fat (73.2%), normal-weight overfat (2.1%), overweight normal-fat (6.7%), overweight overfat (11.9%) and obesity (6.1%), and also classified overweight at risk and obese adolescents into type-I (9.5% and 1.3%, respectively) and type-II (2.3% and 4.9%, respectively) depending if they had or not abdominal fatness. CONCLUSIONS There are differences between IOTF and WHO-2007 international references and there is a misclassification when adiposity is considered. The BMI limitations, especially for overweight identification, could be reduced by adding an estimate of both adiposity (FMI) and fat distribution (WHtR). The AFAD-A classification could be useful in clinical and population health to identify overfat adolescent and those who have greater risk of developing weight-related cardiovascular diseases according to the BMI category.
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Effect of titrated parenteral nutrition on body composition after allogeneic hematopoietic stem cell transplantation in children: a double-blind, randomized, multicenter trial.
Sharma, TS, Bechard, LJ, Feldman, HA, Venick, R, Gura, K, Gordon, CM, Sonis, A, Guinan, EC, Duggan, C
The American journal of clinical nutrition. 2012;(2):342-51
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BACKGROUND Children undergoing hematopoietic stem cell transplantation (HSCT) often require parenteral nutrition (PN) to optimize caloric intake. Standard approaches to nutritional supplementation provide 130-150% of estimated energy expenditure, but resting energy expenditure (REE) may be lower than expected after HSCT. Provision of PN exceeding energy needs may lead to overfeeding and associated complications. OBJECTIVE We conducted a blinded, randomized, controlled, multicenter trial in children undergoing HSCT to determine the effect on body composition of 2 different approaches of nutrition support: standard amounts of energy from PN (130-150% of REE) compared with PN titrated to match measured REE. DESIGN Twenty-six children undergoing HSCT were randomly assigned to standard or titrated PN. Energy intake was monitored until day 30 after HSCT. Body-composition and anthropometric measures were obtained through day 100. The primary outcome variable was percentage body fat (%BF) measured by dual energy X-ray absorptiometry. RESULTS The estimated change in %BF from baseline to day 30 was 1.2 ± 0.5% in the standard group and 0.1 ± 0.5% in the experimental group, but the overall time course of %BF did not differ significantly by treatment (P = 0.39 for time × treatment interaction). A profound loss of lean body mass (LBM) occurred in both groups during the intervention period and persisted through day 100. CONCLUSIONS Parenteral energy intake titrated to energy expenditure does not result in a lower accumulation of BF than does standard energy intake. Neither titrated nor standard PN regimens during HSCT preserve LBM. Alternative approaches to preserve LBM are needed. This trial is registered at clinicaltrials.gov as 00115258.