Lack of a relationship between vitamin D status and resting metabolic rate in Iranian adults.

OBJECTIVES: Studies suggest a positive relationship between 25-hydroxy vitamin D (25(OH)D)) and resting metabolic rate (RMR). We aimed to determine whether this relationship was also true of populations with very low vitamin D status. METHODS: Fat mass (FM) and fat free mass (FFM) were determined from multifrequency bioimpedance analysis (InBody 720, Korea). RMR was based on indirect calorimetry (Cortex Metalyser 3B, Germany). Fasting blood measurements of 25(OH)D concentration, glucose and triglycerides were measured. Data were analyzed separately on men and women by tertile of vitamin D status and multiple linear regression analysis. RESULTS: Two hundred and sixty-three subjects (115 males; 148 females) with a mean age of 37 years and mean %body fat of 30.5% were studied. In women but not men, age, body weight, waist circumference, FM, and FFM increased significantly across tertiles of 25(OH)D. However, there was no difference in unadjusted or adjusted RMR across tertiles of 25OHD in both women and men. Stepwise forward regression analysis showed that age and FFM in men, age and FM in women but not by 25(OH)D, were determinants of RMR. In addition, RMR adjusted for age, sex, FM, FFM and triglyceride-glucose index did not relate to 25(OH)D when linear (r = 0, P = .98), quadratic (r = 0.008, P = .34), or cubic (r = 0.010, P = .43) relationships were tested. CONCLUSIONS: Residual variation in RMR did not relate to vitamin D status in a group of Iranian adults with very low vitamin D status. Future studies could examine whether such a relationship holds true, after the normalization of vitamin D status.

Serum Vitamin D status is associated with increased blastocyst development rate in women undergoing IVF.

RESEARCH QUESTION: To determine the relationship between vitamin D (VitD) status and embryological, clinical pregnancy and live birth outcomes in women undergoing IVF. DESIGN: Cross-sectional, observational study conducted at a university-affiliated private IVF clinic. A total of 287 women underwent 287 IVF cycles and received a fresh embryo transfer. Patients had their serum 25-hydroxyvitamin D2/D3 (VitD) determined on the day of oocyte retrieval, which was analysed in relation to blastocyst development rate, clinical pregnancy and live birth outcomes. RESULTS: In stepwise, multivariable logistic regression models, increases in blastocyst development rate, number and quality, along with embryo cryopreservation and utilization rates were associated with women with a sufficient VitD status (≥20 ng/ml). For a single increase in the number of blastocysts generated per cycle or embryos cryopreserved per cycle, the likelihood for the patient to be VitD sufficient was increased by 32% (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.10-1.58, P = 0.002 and OR 1.33, 95% CI 1.10-1.60, P = 0.004, respectively). Clinical pregnancy (40.7% versus 30.8%, P = 0.086) and live birth rates (32.9% versus 25.8%, P = 0.195) in the sufficient VitD group versus the insufficient group were not significantly different and VitD sufficiency was not significantly associated with these outcomes. CONCLUSION: A strong relationship was observed between blastocyst development and VitD sufficiency. However, there was no association between VitD and clinical pregnancy or live birth outcomes. Further larger studies are needed to investigate whether the observed effect on blastocyst development may have downstream implications on subsequent clinical pregnancy or live birth rates, and on a potential mechanism where sufficient VitD concentrations are linked to improved IVF outcomes.

Molecular actions of vitamin D in reproductive cell biology

Vitamin D (VitD) is an important secosteroid and has attracted attention in several areas of research due to common VitD deficiency in the population, and its potential to regulate molecular pathways related to chronic and inflammatory diseases. VitD metabolites and the VitD receptor (VDR) influence many tissues including those of the reproductive system. VDR expression has been demonstrated in various cell types of the male reproductive tract, including spermatozoa and germ cells, and in female reproductive tissues including the ovaries, placenta and endometrium. However, the molecular role of VitD signalling and metabolism in reproductive function have not been fully established. Consequently, the aim of this work is to review current metabolic and molecular aspects of the VitD­VDR axis in reproductive medicine and to propose the direction of future research. Specifically, the influence of VitD on sperm motility, calcium handling, capacitation, acrosin reaction and lipid metabolism is examined. In addition, we will also discuss the effect of VitD on sex hormone secretion and receptor expression in primary granulosa cells, along with the impact on cytokine production in trophoblast cells. The review concludes with a discussion of the recent developments in VitD­VDR signalling specifically related to altered cellular bioenergetics, which is an emerging concept in the field of reproductive medicine.

Dietary fat and physiological determinants of plasma chylomicron remnant homoeostasis in normolipidaemic subjects: insight into atherogenic risk.

TAG depleted remnants of postprandial chylomicrons are a risk factor for atherosclerosis. Recent studies have demonstrated that in the fasted state, the majority of chylomicrons are small enough for transcytosis to arterial subendothelial space and accelerate atherogenesis. However, the size distribution of chylomicrons in the absorptive state is unclear. This study explored in normolipidaemic subjects the postprandial distribution of the chylomicron marker, apoB-48, in a TAG-rich lipoprotein plasma fraction (Svedberg flotation rate (Sf>400), in partially hydrolysed remnants (Sf 20-400) and in a TAG-deplete fraction (Sf<20), following ingestion of isoenergetic meals with either palm oil (PO), rice bran or coconut oil. Results from this study show that the majority of fasting chylomicrons are within the potentially pro-atherogenic Sf<20 fraction (70-75 %). Following the ingestion of test meals, chylomicronaemia was also principally distributed within the Sf<20 fraction. However, approximately 40 % of subjects demonstrated exaggerated postprandial lipaemia specifically in response to the SFA-rich PO meal, with a transient shift to more buoyant chylomicron fractions. The latter demonstrates that heterogeneity in the magnitude and duration of hyper-remnantaemia is dependent on both the nature of the meal fatty acids ingested and possible metabolic determinants that influence chylomicron metabolism. The study findings reiterate that fasting plasma TAG is a poor indicator of atherogenic chylomicron remnant homoeostasis and emphasises the merits of considering specifically, chylomicron remnant abundance and kinetics in the context of atherogenic risk. Few studies address the latter, despite the majority of life being spent in the postprandial and absorptive state.

The associations of vitamin D status and dietary calcium with the metabolic syndrome: an analysis of the Victorian Health Monitor survey.

OBJECTIVE: To examine the associations between serum 25-hydroxyvitamin D (25(OH)D), dietary Ca intake and presence of the metabolic syndrome (MetS). DESIGN: A stratified cluster sample of a population aged 18-75 years from the Victorian Health Monitor survey. SETTING: Non-institutionalized adults living in private dwellings in Victoria, Australia. SUBJECTS: Adults (n 3404) with complete data and without type 1 or type 2 diabetes. RESULTS: Adjusted for sociodemographic factors, physical characteristics and dietary covariates including Ca intake, every 10 nmol/l increase in serum 25(OH)D was significantly associated with decreased odds of MetS (adjusted odds ratio (AOR)=0·85, 95 % CI 0·80, 0·89; P<0·001). Relative to the low 25(OH)D tertile (median 33 nmol/l), there was a progressive decrease in odds of MetS that reached significance with the high 25(OH)D tertile (median 77 nmol/l; AOR=0·35, 95 % CI 0·26, 0·48; P<0·001). Every 500 mg/d increase in Ca intake adjusted for 25(OH)D did not reduce odds of MetS (AOR=0·81, 95 % CI 0·66, 1·06; P=0·141) but approached significance if unadjusted for 25(OH)D in the final model (AOR=0·81, 95 % CI 0·64, 1·02; P=0·073). No significant effect was obtained for tertiles of Ca intake. However, Ca and vitamin D tertile combinations suggested a beneficial effect of high Ca (median 1233 mg/d) only at low and medium 25(OH)D. The high 25(OH)D tertile was associated with significantly decreased odds of MetS regardless of Ca intake. CONCLUSIONS: A high vitamin D status significantly reduced the odds of MetS. A high Ca intake may have a similar favourable outcome but only at lower circulating concentrations of 25(OH)D.

The potential role of irisin in the thermoregulatory responses to mild cold exposure in adults.

OBJECTIVES: To determine the acute effect of a mild cold exposure on thermoregulatory thermogenesis and the role of circulating irisin in the process. METHODS: We studied 22 adults (9 males, 13 females) aged 57.7 ± 10.07 years and body mass index 27.8 ± 4.52 kg/m(2) . Participants experienced a 90-min exposure to 20°C and 25°C in a randomized cross-over design. Resting metabolic rate (RMR), forearm to finger-tip gradient (FFG), blood pressure (BP), in-the-ear temperature (IET), and fasting bloods were measured on each occasion. RESULTS: There were significant increases in FFG [mean ± SD: +3.8 ± 3.0°C, P < 0.001], systolic blood pressure (SBP) [+8 ± 13 mm Hg, P = 0.015], and diastolic blood pressure (DBP) [+4 ± 6 mm Hg, P = 0.005] and decreases in IET [-0.24 ± 0.29°C, P = 0.001]. Overall, RMR [+190 ± 570 kJ/d, P = 0.135], irisin, glucose or insulin did not differ between temperatures. There were no significant between-gender differences, but males significantly increased SBP (+12 ± 16, P = 0.02) and DBP (+6 ± 7, P = 0.02) with decreases in heart rate (-4 ± 3, P = 0.002), while females did not. Moreover men had approximately 50% higher thermogenic response while women had approximately 25% greater vasoconstrictor response. Adjusted for age, gender, insulin sensitivity, and body composition, fold changes in irisin were inversely related to respiratory quotient (r= -0.54, P = 0.048), while IET was related to FFG (r= -0.55, P = 0.043). CONCLUSIONS: Mild cold exposure increased vasoconstriction with a drop in IET and these were related. Greater irisin was related to a greater fasting fat oxidation in the absence of shivering. A potential gender bias in thermoregulation was noted. Am. J. Hum. Biol. 28:699-704, 2016. © 2016 Wiley Periodicals, Inc.

Plasma triglyceride and high density lipoprotein cholesterol are poor surrogate markers of pro-atherogenic chylomicron remnant homeostasis in subjects with the metabolic syndrome.

BACKGROUND: Subjects with metabolic syndrome (MetS) exhibit impaired lipoprotein metabolism and have an increased risk of cardiovascular disease. Although the risk is attributed primarily to the risk associated with individual components, it is also likely affected by other associated metabolic defects. Remnants of postprandial lipoproteins show potent atherogenicity in cell and animal models of insulin resistance and in pre-diabetic subjects with postprandial dyslipidemia. However, few studies have considered regulation of chylomicron remnant homeostasis in MetS per se. This study measured the plasma concentration in Caucasian men and women of small dense chylomicrons following fasting and explored associations with metabolic and anthropometric measures. METHODS: A total of 215 Australian Caucasian participants (median age 62 years) were investigated. Of them, 40 participants were classified as having MetS. Apolipoprotein (apo) B-48, an exclusive marker of chylomicrons, metabolic markers and anthropometric measures were determined following an overnight fast. RESULTS: The fasting apo B-48 concentration was 40 % higher in subjects with MetS than those without MetS. In all subjects, triglyceride (r = 0.445, P < 0.0005), non-HDL cholesterol (r = 0.28, P < 0.0005) and HDL cholesterol concentration (r = -0.272, P < 0.0005) were weakly associated with apo B-48 concentration. In subjects with MetS, the association of apo B-48 with triglyceride and non-HDL cholesterol was enhanced, but neither were robust markers of elevated apo B-48 in MetS (r = 0.618 and r = 0.595 respectively). There was no association between apo B-48 and HDL cholesterol in subjects with MetS. CONCLUSION: This study demonstrates a substantial accumulation of pro-atherogenic remnants in subjects with MetS. We have shown that in a Caucasian cohort, the fasting plasma concentration of triglyceride or HDL/non-HDL cholesterol serves as poor surrogate markers of atherogenic chylomicron remnants. These findings suggest that subjects with MetS exhibit a chronic defect in chylomicron metabolism that is likely to contribute to their increased CV risk.

The potential regulatory role of vitamin D in the bioenergetics of inflammation.

PURPOSE OF REVIEW: The extraskeletal health benefits of vitamin D still need scientific endorsement. Obesity and related chronic diseases are pathogenically linked by inflammation, which carries a considerable energetic cost. Recent techniques for the determination of the bioenergetic demand of inflammation, offer an avenue to cement the regulatory role of vitamin D in this process. RECENT FINDINGS: Nuclear vitamin D receptors may be translocated into mitochondria of certain cell types, opening up a pathway for direct action on cellular bioenergetics. Classical M1 (inflammatory)/M2(anti-inflammatory) phenotypes can vary with the clinical context. M2 macrophages do not always depend on oxidative metabolism/fatty acid oxidation. Newer methodologies offer real-time bioenergetic measurements that can be used as an index of metabolic health. SUMMARY: Vitamin D may prove to be a therapeutic agent for inflammation of chronic disease and understanding its role in cellular bioenergetics may offer a diagnostic/prognostic indicator of its action.

The impact of cryopreservation on human peripheral blood leucocyte bioenergetics.

Circulating immune cells are considered a source for biomarkers in health and disease, since they are exposed to nutritional, metabolic and immunological stimuli in the vasculature. Cryopreservation of leucocytes is routinely used for long-term storage and determination of phenotypic/functional changes at a later date. Exploring the role of bioenergetics and mitochondrial (dys)function in leucocytes is often examined by using freshly isolated cells. The aim of the pilot study described herein was to assess leucocyte bioenergetics in cryopreserved cells. Leucocytes were isolated from whole blood, counted and frozen in liquid nitrogen (LN2) for a period of 3 months. Cells were thawed at regular intervals and bioenergetic analysis performed using the Seahorse XFe96 flux analyser. Cryogenic storage reduced cell viability by 20%, but cell bioenergetic responses were largely intact for up to 1 month storage in LN2. However, after 1 month storage, mitochondrial function was impaired as reflected by decreasing basal respiration, ATP production, maximum (MAX) respiration, reserve capacity and coupling efficiency. Conversely, glycolytic activity was increased after 1 month, most notably the enhanced glycolytic response to 25 mM glucose without any change in glycolytic capacity. Finally, calculation of bioenergetic health index (BHI) demonstrated that this potential diagnostic parameter was sensitive to cryopreservation. The present study has demonstrated for the first time that cryopreservation of primary immune cells modified their metabolism in a time-dependent fashion, indicated by attenuated aerobic respiration and enhanced glycolytic activity. Taken together, we recommend caution in the interpretation of bioenergetic responses or BHI in cryopreserved samples.

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.

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.

Food consumption of Sri Lankan adults: an appraisal of serving characteristics.

OBJECTIVE: The main aim of the present study was to identify food consumption in Sri Lankan adults based on serving characteristics. DESIGN: Cross-sectional study. Fruits, vegetables, starch, meat, pulses, dairy products and added sugars in the diet were assessed with portion sizes estimated using standard methods. SETTING: Twelve randomly selected clusters from the Sri Lanka Diabetes and Cardiovascular Study. SUBJECTS: Six hundred non-institutionalized adults. RESULTS: The daily intake of fruit (0·43), vegetable (1·73) and dairy (0·39) portions were well below national recommendations. Only 3·5 % of adults consumed the recommended 5 portions of fruits and vegetables/d; over a third of the population consumed no dairy products and fewer than 1 % of adults consumed 2 portions/d. In contrast, Sri Lankan adults consumed over 14 portions of starch and 3·5 portions of added sugars daily. Almost 70 % of those studied exceeded the upper limit of the recommendations for starch intake. The total daily number of meat and pulse portions was 2·78. CONCLUSIONS: Dietary guidelines emphasize the importance of a balanced and varied diet; however, a substantial proportion of the Sri Lankan population studied failed to achieve such a recommendation. Nutrition-related diseases in the country may be closely correlated with unhealthy eating habits.

High dietary diversity is associated with obesity in Sri Lankan adults: an evaluation of three dietary scores.

BACKGROUND: Dietary diversity is recognized as a key element of a high quality diet. However, diets that offer a greater variety of energy-dense foods could increase food intake and body weight. The aim of this study was to explore association of diet diversity with obesity in Sri Lankan adults. METHODS: Six hundred adults aged > 18 years were randomly selected by using multi-stage stratified sample. Dietary intake assessment was undertaken by a 24 hour dietary recall. Three dietary scores, Dietary Diversity Score (DDS), Dietary Diversity Score with Portions (DDSP) and Food Variety Score (FVS) were calculated. Body mass index (BMI) ≥ 25 kg.m⁻² is defined as obese and Asian waist circumference cut-offs were used diagnosed abdominal obesity. RESULTS: Mean of DDS for men and women were 6.23 and 6.50 (p=0.06), while DDSP was 3.26 and 3.17 respectively (p=0.24). FVS values were significantly different between men and women 9.55 and 10.24 (p=0.002). Dietary diversity among Sri Lankan adults was significantly associated with gender, residency, ethnicity, education level but not with diabetes status. As dietary scores increased, the percentage consumption was increased in most of food groups except starches. Obese and abdominal obese adults had the highest DDS compared to non obese groups (p<0.05). With increased dietary diversity the level of BMI, waist circumference and energy consumption was significantly increased in this population. CONCLUSION: Our data suggests that dietary diversity is positively associated with several socio-demographic characteristics and obesity among Sri Lankan adults. Although high dietary diversity is widely recommended, public health messages should emphasize to improve dietary diversity in selective food items.

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.

Development of a food frequency questionnaire for Sri Lankan adults.

BACKGROUND: Food Frequency Questionnaires (FFQs) are commonly used in epidemiologic studies to assess long-term nutritional exposure. Because of wide variations in dietary habits in different countries, a FFQ must be developed to suit the specific population. Sri Lanka is undergoing nutritional transition and diet-related chronic diseases are emerging as an important health problem. Currently, no FFQ has been developed for Sri Lankan adults. In this study, we developed a FFQ to assess the regular dietary intake of Sri Lankan adults. METHODS: A nationally representative sample of 600 adults was selected by a multi-stage random cluster sampling technique and dietary intake was assessed by random 24-h dietary recall. Nutrient analysis of the FFQ required the selection of foods, development of recipes and application of these to cooked foods to develop a nutrient database. We constructed a comprehensive food list with the units of measurement. A stepwise regression method was used to identify foods contributing to a cumulative 90% of variance to total energy and macronutrients. In addition, a series of photographs were included. RESULTS: We obtained dietary data from 482 participants and 312 different food items were recorded. Nutritionists grouped similar food items which resulted in a total of 178 items. After performing step-wise multiple regression, 93 foods explained 90% of the variance for total energy intake, carbohydrates, protein, total fat and dietary fibre. Finally, 90 food items and 12 photographs were selected. CONCLUSION: We developed a FFQ and the related nutrient composition database for Sri Lankan adults. Culturally specific dietary tools are central to capturing the role of diet in risk for chronic disease in Sri Lanka. The next step will involve the verification of FFQ reproducibility and validity.

Prevalence and trends of the diabetes epidemic in South Asia: a systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus has reached epidemic proportions worldwide. South Asians are known to have an increased predisposition for diabetes which has become an important health concern in the region. We discuss the prevalence of pre-diabetes and diabetes in South Asia and explore the differential risk factors reported. METHODS: Prevalence data were obtained by searching the Medline® database with; 'prediabetes' and 'diabetes mellitus' (MeSH major topic) and 'Epidemology/EP' (MeSH subheading). Search limits were articles in English, between 01/01/1980-31/12/2011, on human adults (≥19 years). The conjunction of the above results was narrowed down with country names. RESULTS: The most recent reported prevalence of pre-diabetes:diabetes in regional countries were; Bangladesh-4.7%:8.5% (2004-2005;Rural), India-4.6%:12.5% (2007;Rural); Maldives-3.0%:3.7% (2004;National), Nepal-19.5%:9.5% (2007;Urban), Pakistan-3.0%:7.2% (2002;Rural), Sri Lanka-11.5%:10.3% (2005-2006;National). Urban populations demonstrated a higher prevalence of diabetes. An increasing trend in prevalence of diabetes was observed in urban/rural India and rural Sri Lanka. The diabetes epidemicity index decreased with the increasing prevalence of diabetes in respective countries. A high epidemicity index was seen in Sri Lanka (2005/2006-52.8%), while for other countries, the epidemicity index was comparatively low (rural India 2007-26.9%; urban India 2002/2005-31.3%, and urban Bangladesh-33.1%). Family history, urban residency, age, higher BMI, sedentary lifestyle, hypertension and waist-hip ratio were associated with an increased risks of diabetes. CONCLUSION: A significant epidemic of diabetes is present in the South Asian region with a rapid increase in prevalence over the last two decades. Hence there is a need for urgent preventive and curative strategies.

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.

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.

Cross sectional determinants of VO2 max in free living Iranians: Potential role of metabolic syndrome components and vitamin D status.

BACKGROUND AND AIMS: The purpose of the study was to evaluate the determinants of cardiorespiratory fitness (CRF) in Iranian adults and the potential contribution of vitamin D status. METHODS: In this cross-sectional study 264 cases (116 men and 147 women aged 18-70 years old were participated. Maximal oxygen consumption (VO2 max) was measured by the Bruce protocol utilizing treadmill exercise testing. Anthropometric data, body composition and fasting blood glucose and lipid concentrations were measured. Serum levels of 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were assessed using enzyme-linked immunosorbent assay. Stepwise linear regression analysis was applied to determine significant predictors of VO2 peak. We tested non-linear (quadratic and cubic terms) versus linear association of adjusted (for determinants) VO2 max and vitamin D levels. RESULTS: Multiple regression results showed that fat free mass, HDL-C and physical activity, waist circumference, age and sex were determinants of VO2 peak. All of these explained the 65.3% of VO2 peak. There was a non-linear cubic association (R2 = 0.03, p = 0.046) between serum 25(OH)D and adjusted VO2 peak in which 25(OH)D in people with a high 25(OH)D levels (>60 nmol/L), had better fitness and those with serum 25(OH) less than 20 nmol/L. We found no linear and non-linear associations between serum 1,25(OH)2 D and adjusted VO2 max. CONCLUSIONS: Our results showed that waist circumference and HDL-C, as components of metabolic syndrome, contribute ∼2% to the variance in VO2 max. Moreover, high concentrations of 25(OH)D but not 1,25(OH)2 D may make additional contributions to CRF.

The Association between Exposure to Residential Indoor Volatile Organic Compounds and Measures of Central Arterial Stiffness in Healthy Middle-Aged Men and Women.

It is well reported that individuals spend up to 90% of their daily time indoors, with between 60% to 90% of this time being spent in the home. Using a cross-sectional study design in a population of 111 healthy adults (mean age: 52.3 ± 9.9 years; 65% women), we investigated the association between exposure to total volatile organic compounds (VOCs) in indoor residential environments and measures of central arterial stiffness, known to be related to cardiovascular risk. Indoor VOC concentrations were measured along with ambulatory measures of pulse pressure (cPP), augmentation index (cAIx) and cAIx normalized for heart rate (cAIx75), over a continuous 24-h period. Pulse wave velocity (cfPWV) was determined during clinical assessment. Multiple regression analysis was performed to examine the relationship between measures of arterial stiffness and VOCs after adjusting for covariates. Higher 24-h, daytime and night-time cAIx was associated with an interquartile range increase in VOCs. Similar effects were shown with cAIx75. No significant effects were observed between exposure to VOCs and cPP or cfPWV. After stratifying for sex and age (≤50 years; >50 years), effect estimates were observed to be greater and significant for 24-h and daytime cAIx in men, when compared to women. No significant effect differences were seen between age groups with any measure of arterial stiffness. In this study, we demonstrated that residential indoor VOCs exposure was adversely associated with some measures of central arterial stiffness, and effects were different between men and women. Although mechanistic pathways remain unclear, these findings provide a possible link between domestic VOCs exposure and unfavourable impacts on individual-level cardiovascular disease risk.