The impact of cholecalciferol supplementation on the systemic inflammatory profile: a systematic review and meta-analysis of high-quality randomized controlled trials.

Causal links between vitamin D status [25(OH)D] and systemic inflammation were examined through a systematic review of randomized controlled trials (RCTs). Selected RCTs were ⩾12 weeks, conducted in adults free of acute inflammatory disease, and of high-quality (Jadad score ⩾3). Of 14 studies that met our criteria, 9 studies (15 study arms) permitted extraction of data. There was no effect on the weighted mean difference (WMD) of IL-6 (WMD (95% confidence interval)=0.1, (-0.166, 0.366) pg/ml, P=0.462) or C-reactive protein (CRP) (WMD=-0.324, (-1.007, 0.359) mg/l, P=0.352). Subgroup analyses of trials achieving ⩾80 nmol/l indicated a trend for lower CRP (WMD=-0.834, (-1.726, 0.058) mg/l, P=0.067), however heterogeneity was significant (I2=66.7%, P=0.017). Studies employing a low dose (<1000 IU/d) showed increased CRP (WMD=0.615, (0.132, 1.098), P=0.013). In contrast, ⩾1000 IU/d had a favourable effect on CRP (WMD=-0.939, (-1.805, -0.073), P=0.034) but heterogeneity was significant (I2=61.3%, P=0.017). Meta-regression indicated that older age predicted a significant decrease in IL-6 (ß=-0.02, (-0.034, -0.006) pg/ml, P=0.013) and CRP (ß=-0.06, (-0.103, -0.017), P=0.01), whereas a greater percentage of females (ß=0.027, (0.011, 0.044), P=0.004) and longer study duration independently predicted a higher WMD for CRP (ß=0.049, (0.018, 0.079), P=0.005). Available high-quality RCTs did not support a beneficial effect of cholecalciferol on systemic IL-6 and CRP. Future studies should consider the confounding effects of age, gender and study duration, while possibly targeting an achieved 25(OH)D ⩾80 nmol/l.

Forearm to fingertip skin temperature gradients in the thermoneutral zone were significantly related to resting metabolic rate: potential implications for nutrition research.

BACKGROUND: Resting metabolic rate (RMR) should be measured in the thermoneutral zone (TNZ). Forearm to fingertip skin temperature gradients (FFG) could serve as an objective measure of this pre-condition. SUBJECTS/METHODS: Eighty-six adult Australians were studied at 25 °C in a temperature-controlled chamber. Measurements of overnight fasted RMR, respiratory quotient (RQ) and FFG were complemented by clinical biochemistry. McAuley's Index of insulin sensitivity (McA_ISI) and presence of metabolic syndrome was determined. Physical activity was estimated from the short version of the International Physical Activity Questionnaire. Fat mass (FM) and fat-free mass (FFM) were obtained from dual-energy x-ray absorptiometry. Twenty-nine participants were assessed for changes in RMR (ΔRMR), RQ (ΔRQ) and FFG (ΔFFG) following a 6-month free-living period. Multiple linear regression analyses of RMR and RQ on FFG, and of ΔRMR and ΔRQ on ΔFFG were conducted after controlling for 12 known determinants of energy metabolism. RESULTS: There were wide between-subject variations in unadjusted FFG ranging from -4.25 to +7.8 °C. The final parsimonious model for cross-sectional observations of RMR included age, FM, FFM, McA_ISI and FFG (ß=63 kJ/d (95% confidence interval (CI): 14.2, 112.1, P=0.012)). However, FFG was unrelated to RQ.In the longitudinal cohort, adjusted ΔRMR significantly associated only with ΔFFG (ß=100 kJ/d (95% CI: 10.3, 189.1; P=0.030)), and adjusted ΔRQ associated with ΔFFG (-0.003 (95% CI: -0.005, 0.0002, P=0.038)), age and McA_ISI. CONCLUSIONS: Sizeable between-subject variations in FFG at 25 °C were associated with RMR and RQ. Monitoring FFG may serve as an objective assessment of the TNZ during RMR measurements.

The bioenergetics of inflammation: insights into obesity and type 2 diabetes.

Diabetes mellitus is one of the most common chronic metabolic disorders worldwide, and its incidence in Asian countries is alarmingly high. Type 2 diabetes (T2DM) is closely associated with obesity, and the staggering rise in obesity is one of the primary factors related to the increased frequency of T2DM. Low-grade chronic inflammation is also accepted as an integral metabolic adaption in obesity and T2DM, and is believed to be a major player in the onset of insulin resistance. However, the exact mechanism(s) that cause a persistent chronic low-grade infiltration of leukocytes into insulin-target tissues such as adipose, skeletal muscle and liver are not entirely known. Recent developments in the understanding of leukocyte metabolism have revealed that the inflammatory polarization of immune cells, and consequently their immunological function, are strongly connected to their metabolic profile. Therefore, it is hypothesized that dysfunctional immune cell metabolism is a central cellular mechanism that prevents the resolution of inflammation in chronic metabolic conditions such as that observed in obesity and T2DM. The purpose of this review is to explore the metabolic demands of different immune cell types, and identify the molecular switches that control immune cell metabolism and ultimately function. Understanding of these concepts may allow the development of interventions that can correct immune function and may possibly decrease chronic low-grade inflammation in humans suffering from obesity and T2DM. We also review the latest clinical techniques used to measure metabolic flux in primary leukocytes isolated from obese and T2DM patients.

Vitamin D status and insulin sensitivity are novel predictors of resting metabolic rate: a cross-sectional analysis in Australian adults.

PURPOSE: Resting metabolic rate (RMR) accounts for two-thirds of the total energy expenditure in sedentary individuals. After accounting for traditional factors, there still remains a considerable unexplained variance in RMR. There is a pandemic of obesity and metabolic syndrome (MetS) which coexists with a high prevalence of vitamin D insufficiency. The aim of this study was to evaluate the potential effects of vitamin D status, insulin sensitivity (IS) and the metabolic syndrome (MetS) on RMR in Australian adults. METHODS: RMR, respiratory quotient (RQ), McAuley's insulin sensitivity index, fat mass (FM), fat-free mass (FFM) and vitamin D status were assessed in Australian adults. The presence of MetS was evaluated by current standard criteria. Predictors of RMR were examined through multiple linear regression based on stepwise and backward regression approaches with attention to multi-collinearity. All analyses were conducted on SPSS version 21. RESULTS: One hundred and twenty-seven participants (45 men, 82 women), aged 53.4 ± 11.7 years and BMI 31.9 ± 5.2 kg/m(2), were included. Forty-one subjects were insufficient in vitamin D status (<50 nmol/L), and 75 participants had the MetS. A parsimonious regression model explained 85.8 % of RMR and was given by: RMR (kJ/d) = 1931 + 83.5 × FFM (kg) + 29.5 × FM (kg) + 5.65 × 25(OH)D (nmol/L) - 17.6 × age (years) - 57.51 × IS. CONCLUSION: Vitamin D status and IS are novel independent predictors of RMR in adults. Future studies could validate a causal role for these factors in human energy metabolism.

Vitamin D supplementation and body weight status: a systematic review and meta-analysis of randomized controlled trials.

Vitamin D is anticipated to have many extra-skeletal health benefits. We questioned whether supplementation with the vitamin influenced body weight and composition. A systematic review and meta-analysis was conducted on high-quality, randomized controlled trials (RCTs) that had supplemented vitamin D without imposing any caloric restriction. Eighteen trials reporting either body weight, body mass index (BMI), fat mass (FM), percentage fat mass (%FM) or lean body mass (LBM) met our criteria. Twelve studies provided the required data for the meta-analysis. Vitamin D supplementation did not influence the standardized mean difference (SMD) for body weight, FM, %FM or LBM. A small but non-significant decrease in BMI (SMD = -0.097, 95% confidence interval: [-0.210, 0.016], P = 0.092) was observed. Meta-regression confirmed that neither the absolute vitamin D status achieved nor its change from baseline influenced the SMD of any obesity measure. However, increasing age of the subjects predicted a shift in the SMD for FM towards the placebo treatment, whereas a greater percentage of women in these studies favoured a decrease in FM following vitamin D. Vitamin D supplementation did not decrease measures of adiposity in the absence of caloric restriction. A potential confounding by age and gender was encountered.

Factors determining the risk of the metabolic syndrome: is there a central role for adiponectin?

BACKGROUND AND OBJECTIVES: The pathogenesis of the metabolic syndrome (MetS) is not well understood. This review is based on the hypothesis that both traditional and emerging risk factors act through adiponectin. SUBJECTS AND METHODS: We conducted a search of the literature using prominent electronic databases and search terms that included in combination: adiponectin, diet, dietary patterns, exercise, metabolic rate, MetS and testosterone. Articles were restricted to studies conducted on adult humans, reported in English and within the time period 2000-2012. RESULTS AND CONCLUSIONS: Both traditional and emerging risk factors associated with the MetS show some evidence of exerting their influence through adiponectin. High-quality randomized controlled trials that alter adiponectin levels are required to further corroborate this hypothesis.