The impact of leucine supplementation on body composition and glucose tolerance following energy restriction: an 8-week RCT in adults at risk of the metabolic syndrome.

BACKGROUND: L-Leucine (Leu) supplementation may benefit fat-free mass (FFM) per se and glucose metabolism. OBJECTIVES: To determine whether Leu supplementation during energy restriction blunted the loss of FFM, enhanced the loss of fat mass (FM) and improved glucose tolerance. DESIGN: Thirty-seven adults, aged 20-65 years, with increased waist circumference and at least one other metabolic syndrome (MetS) component, were selected. We employed a two-arm parallel, double blind, randomized control trial (RCT) design. Participants were randomly assigned to an intervention group (leucine - 3 g/d) or placebo (lactose - 2.67 g/d), while following an individualised energy restricted diet for an 8-week period. Detailed body composition (DEXA), oral glucose tolerance test (OGTT), insulin and components of MetS were measured before and after the trial. Analysis of covariance (ANCOVA) assessed the effect of Leu on an intention-to-treat (ITT) principle. Bootstrapping method with 1000 bootstrap samples was used to derive parameter estimates, standard errors, p-values, and 95% confidence intervals for all outcomes. RESULTS: Adjusted for baseline values and other covariates, FFM (p = 0.045) and lean tissue mass (LTM) (p = 0.050) were significantly higher following Leu. These outcomes were modified by a significant treatment x sex interaction that indicated Leu had the greater effect in men. However, on adjustment for body composition changes, there was no difference in insulin sensitivity, oral glucose tolerance, or change in MetS components following Leu. CONCLUSION: Short-term leucine supplementation during energy restriction resulted in a greater preservation of FFM and LTM particularly in men, but did not impact glucose metabolism.

Higher fasting fibroblast growth factor 21 was associated with a greater decline in postprandial blood pressure.

BACKGROUND: A fall in blood pressure (BP) following a meal is well known and is usually a transient phenomenon, due to appropriate cardiovascular adjustments. Older individuals and those with high BP experience a greater postprandial fall that can manifest as postprandial hypotension (PPH). Fibroblast growth factor 21 (FGF21) is positively associated with BP, and is known to increase after meal ingestion. We explored whether fasting FGF21 or its postprandial change would be associated with meal induced BP change, after accounting for several covariates. METHODS: Eighty-three Western Australian adults were studied. Supine resting BP was recorded and an oral glucose test was administered. Serial measurements of systolic BP (SBP) and diastolic BP (DBP) were then made in duplicate every 30 min up to 120 min. Fasting and 120 min blood samples were analysed for FGF21 and clinical chemistry. Multiple linear regression analyses of the incremental area under curve of postprandial SBP and DBP was conducted on 12 known determinants. RESULTS: The final parsimonious model based on backward regression of postprandial SBP included fasting SBP, gender, fasting insulin and fasting FGF21 (ß = -0.009 (95% confidence interval (CI): 0.017, -0.002, P = 0.015)). For postprandial DBP these included fasting DBP, gender, fasting glucose, fasting insulin and fasting FGF21 (ß = -0.005; 95% CI: 0.010, -0.001, P = 0.021). CONCLUSIONS: A higher fasting FGF21, independent of glucose and insulin, was associated with a greater postprandial decline in SBP and in DBP.

Triglycerides and systolic blood pressure negatively mediate the direct relationship of vitamin D status to resting energy expenditure: A cross sectional analysis.

BACKGROUND AND AIMS: We determined whether individual components of metabolic syndrome (MetS) mediated the direct association of vitamin D status (25OHD) on resting energy expenditure (REE). METHODS: Multiple linear regression determined predictors of REE from data on 180 men and women from two ethnic groups. We then modelled a mediation pathway through components of MetS on the direct association between 25OHD and REE. The mediation modelling used the PROCESS SPSS Macro (version 4.0) based on 5000 bootstrapped samples, with the adjustment for different sets of covariates. RESULTS: REE was significantly predicted by age, fat mass (FM), fat free mass (FFM), ethnicity, inverse ln insulin, 25OHD, triglycerides (TG), systolic blood pressure (SBP) and, to some extent, by time of REE measurements (p < 0.094). Adjustment for all these covariates, resulted in a negative indirect mediation effect of TG [ß coefficient (bootstrapped SE): 0.95 (0.519); bootstrapped 95% CI: 2.172, -0.165; p < 0.05] and a concurrent negative mediation of SBP [ß coefficient (bootstrapped SE): 0.72(0.484); bootstrapped 95% CI: 1.851, -0.011; p < 0.05]. There remained a positive direct pathway from 25OHD to REE [ß coefficient (S.E): 4.715 (2.129); p = 0.028], however the total effect of 25OHD was dampened [ß coefficient (S.E): 3.04 (2.126); p = 0.154]. CONCLUSIONS: Independent of insulin sensitivity, a negative mediation by TG and SBP dampened the overall effect of 25OHD on REE.

The Impact of the Metabolic Syndrome and Its Components on Resting Energy Expenditure.

We determined whether metabolic syndrome (MetS) and the increasing number of its components influenced the resting energy expenditure (REE). Data on adult men (n = 72, 40%) and women (n = 108, 60%) from European (n = 154, 86%) and Sub-Saharan African (n = 26, 14%) ancestry were used. Ninety-five (53%) participants had MetS (MetS+), while 85 (47%) were without MetS (MetS-). REE was determined through indirect calorimetry, body composition by DEXA, and clinical biochemistry by standard laboratory techniques. MetS+ had a significantly higher REE (mean ± se: MetS+: 5995 ± 87.3 vs. MetS-: 5760 ± 86.3 kJ/d, p = 0.025) when adjusted for age, gender, fat mass (FM), fat-free mass (FFM), ethnicity, season, 25OHD, insulin sensitivity, and time of data collection. Within each MetS status group, an increase in the number of components (C) resulted in a stepwise increase in REE. Relative to zero components, those with 1C had adjusted REE higher by +526 ± 248.1 kJ/d (p = 0.037), while 2C were higher than 1C by +298 ± 140.8 kJ/d (p = 0.037). Similarly, relative to 3C, those with 4C had REE higher by +242 ± 120.7 kJ/d (p = 0.049). The higher REE of 5C over 4C by 132 ± 174.5 kJ/d did not achieve statistical significance. MetS was associated with a significantly higher REE. This greater energetic cost varied directly with the numbers of its components but was most evident in those not diagnosed with the syndrome.

Hypothesized pathways for the association of vitamin D status and insulin sensitivity with resting energy expenditure: a cross sectional mediation analysis in Australian adults of European ancestry.

BACKGROUND: The role of vitamin D in human energy expenditure requires confirmation. We explored whether insulin sensitivity (IS)/insulin resistance (IR) mediated the association of vitamin D status (25OHD) on resting energy expenditure (REE). METHODS: REE, body composition (by DEXA) and clinical biochemistry of 155 Australian men and women were collated. A hypothesized mediation pathway through IS/IR on the direct association between 25OHD and REE was modeled, using three surrogate indices of IS/IR: McAuley's insulin sensitivity index (McA), Quantitative insulin sensitivity check index (QUICKI) and triglyceride to glucose ratio (TYG). The modeling was performed on PROCESS SPSS Macro (version 4.0) based on 5000 bootstrapped samples, with and without the adjustment for covariates. RESULTS: Unadjusted models indicated a sizeable negative mediation by all IS/IR indices but no significant direct effect of 25OHD on REE. On adjustment for covariates, a negative indirect mediation effect of McA [ß coefficient (SE) -2.1(0.821); bootstrapped 95% CI:-3.934, -0.703; p < 0.05] and a similar negative mediation of TYG [-1.935 (0.780); bootstrapped 95% CI: (-3.679, -0.622; p < 0.05] was observed. These models also showed a positive direct effect of 25OHD on REE. In contrast, QUICKI made a smaller contribution to the total effect though in the same direction as the other two measures [-0.783 (0.534); bootstrapped 95% CI: (-1.939, 0.134; P > 0.05]. CONCLUSIONS: A sizeable, partial, negative mediation of IS/IR on the direct relationship between 25OHD and REE, dampened the total effect of vitamin D on REE. Validation of the proposed causal framework would clarify vitamin D's role in human energy metabolism.

The Utility of Forearm to Fingertip Skin Temperature Gradients During Measurements of Resting Energy Expenditure.

The measurement of resting energy expenditure (REE) is important to both human physiology and nutrition. There are several pre-conditions for the proper measurement of REE, but a key criterion is that it takes place in the thermoneutral zone (TNZ). Deciding whether a person is in his or her TNZ is not an easy task, and a suggested way forward is the monitoring of forearm to fingertip skin temperature gradients (FFG). In this commentary, we highlight our recent findings that FFG varies between individuals even when measured at a temperature within TNZ. Interestingly, FFG showed a consistent direct relationship with adjusted REE, in both cross-sectional and longitudinal study designs. In addition, we provide new findings that FFG is sensitive to small ambient temperature variations within the TNZ, in comparison to visual analogue scale (VAS)-derived subjective measures of thermal comfort. While further research is needed in this area, our view is measurements of FFG should be included in REE protocols. This would inform investigators on how their participants are responding to the ambient room temperature and also allow appropriate statistical adjustments in REE for between-group comparisons.

Postprandial changes in glucose oxidation and insulin sensitivity in metabolic syndrome: Influence of fibroblast growth factor 21 and vitamin D status.

OBJECTIVE: Metabolic inflexibility due to insulin resistance has been reported in metabolic syndrome (MetS). Fibroblast growth factor 21 (FGF21) and vitamin D status may improve insulin sensitivity. The aim of this study was to investigate glucose-induced thermogenesis and oxidation in MetS, and to examine whether changes in FGF21 or prevailing vitamin D status modulated defined metabolic parameters. METHODS: Forty-eight overweight and obese older adults (14 men, 34 women; ages 51 ± 15 y) were studied. Resting metabolic rate (RMR) and respiratory quotient (RQ) were measured before and intermittently for 2 h after an oral glucose tolerance test (OGTT). The total area under the curve (TAUC) was calculated. Insulin sensitivity index (ISI) was determined as 104/(insulin × glucose) for fasting and 2 h venous blood. Fat mass (FM) and fat free mass (FFM) were measured by dual-energy x-ray absorptiometry. Participants were grouped by metabolic syndrome (MetS+ for disease presence; MetS- when no disease was present) and by median 25 hydroxyvitamin D (OHD) concentration as VD_low and VD_high. 25 OHD was also tested as a continuous variable. A parsimonious 2 × 2 analysis of variance included age, FM, FFM and MetS × sex interaction. RESULTS: Adjusted RMR was similar between groups but an interactive effect of MetS and sex was noted. Fasting RQ was significantly different between vitamin groups (VD_low: 0.835 ± 0.008 versus VD_high: 0.810 ± 0.008; P = 0.024) and fasting ISI was significantly greater in MetS- compared with MetS+ (P = 0.037). Postglucose increases in thermogenesis, RQ, and FGF21 were significant, but ISI decreased. Adjusted postprandial TAUC_RQ (VD_low: 1.71 ± 0.01; VD_high: 1.74 ± 0.001; P = 0.041) and ISI_2 h (VD_low: 35.41 ± 0.21; VD_high: 101.90 ± 0.21; P = 0.001) were significantly different. Adjusted FGF21 was similar across all comparisons before and after OGTT. CONCLUSIONS: Higher vitamin D status, but not FGF21, was associated with greater postprandial glucose oxidation and improved insulin sensitivity.

Calcium and vitamin D in the regulation of energy balance: where do we stand?

There is a pandemic of obesity and associated chronic diseases. Dietary calcium and vitamin D have many extra-skeletal roles in human health. In this review we have summarized the current understanding of their influence on human energy balance by examining the epidemiological, clinical, animal, cellular and molecular evidence. We opine that while calcium and vitamin D are functional nutrients in the battle against obesity, there is a need for prospective human trials to tilt the balance of evidence in favour of these nutrients.