Exercise-induced changes in plasma S-Klotho levels are associated with the obtained enhancements of heart rate variability in sedentary middle-aged adults: the FIT-AGEING study.

The shed form of the Klotho protein (S-Klotho) is considered a biomarker of longevity, but it is still unknown whether the levels are related to heart rate (HR) and heart rate variability (HRV); both of them greatly influenced by the ageing process, physical fitness, exercise, and health status. This study aimed (i) to investigate the association between S-Klotho plasma levels with HR and HRV parameters and (ii) to examine the association of exercise-induced changes in S-Klotho and those obtained in HR and HRV parameters after a 12-week exercise intervention in sedentary middle-aged adults. Sixty-six sedentary middle-aged adults participated in this study (50% women; 45-65 years old). Participants were randomized into 4 groups: (a) a control group (no exercise), (b) a physical activity recommendation from the World Health Organization group, (c) a high-intensity interval training group, and (d) a high-intensity interval training group adding whole-body electromyostimulation. S-Klotho plasma levels, HR, and HRV parameters (SDNN, RMSSD, high frequency, stress score, and sympathetic/parasympathetic ratio) were measured. At baseline, S-Klotho plasma levels were not related to HR and HRV parameters. After the intervention, exercise-induced changes in S-Klotho plasma levels were positively associated with changes in SDNN (ß=0.261; R2=0.102; p=0.014) and negatively related to changes in stress score and sympathetic/parasympathetic ratio (all ß=-0.257; R2 ranges between 0.092 and 0.131; all p<0.020). Our study suggests that higher S-Klotho plasma levels are related to increased vagal influence and reduced sympathetic tone in the autonomic nervous system in sedentary middle-aged adults after different training programs. ClinicalTrials.gov identifier: CT03334357.

Physical exercise improves memory in sedentary middle-aged adults: Are these exercise-induced benefits associated with S-Klotho and 1,25-dihydroxivitamin D? The FIT-AGEING randomized controlled trial.

We aimed to investigate the effect of three types of exercise interventions on memory (i.e., immediate memory (IM), long-term memory (LTM), and recognition). We also investigated whether exercise-induced changes in circulating S-Klotho and 1,25-dihydroxivitamin D (1,25(OH)2 D) levels were related to those observed in memory in healthy middle-aged sedentary adults. A 12-week randomized controlled trial was performed with a parallel-group design. Seventy-four participants (45-65 years old: 53% women) were randomly assigned to (1) no exercise (control) group, (2) concurrent training based on the international physical activity recommendations (PAR) group, (3) high-intensity interval training (HIIT) group, or (4) HIIT plus whole-body electromyostimulation (HIIT-EMS) group. Memory outcomes were assessed using the Wechsler Memory Scale-third edition. S-Klotho plasma levels were determined according to a solid-phase sandwich enzyme-linked immunosorbent assay kit while 1,25(OH)2 D plasma levels were measured using a DiaSorin-Liaison immunochemiluminometric analyzer. IM-Verbal Paired Associates (IM-VPA) and IM-Logical Memory (IM-LM) were improved in both the HIIT and HIIT-EMS groups compared with the control group (all p ≤ 0.045). Exercise-induced changes in S-Klotho plasma levels were positively associated with those observed in IM, LTM, and recognition (all p ≤ 0.007), whereas exercise-induced changes in 1,25(OH)2 D plasma levels were directly related to changes in IM and LTM (all p ≤ 0.048). In conclusion, a 12-week HIIT intervention with or without WB-EMS seems to be the most effective exercise program to improve IM. The significant and positive associations between exercise-induced changes in S-Klotho and 1,25(OH)2 D levels with those observed in memory outcomes suggest that these factors may be potentially related to exercise-induced improvements of memory in middle-aged adults.

Intra-Assessment Resting Metabolic Rate Variability Is Associated with Cardiometabolic Risk Factors in Middle-Aged Adults.

The intra-assessment resting metabolic rate variability is related to cardiometabolic health, as suggested by previous literature. We studied whether that variability (expressed as coefficient of variation [CV; %]) for oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), and resting energy expenditure (REE) is similar between men and women, and if is similarly associated with cardiometabolic risk factors. Gas exchange in 72 middle-aged adults was measured by indirect calorimetry. Anthropometrics and body composition, cardiorespiratory fitness, circulating cardiometabolic risk factors, and heart rhythm parameters were also determined. Men and women presented similar intra-assessment resting metabolic rate variability (all p > 0.05). Notably, in men, CV for RER was positively associated with BMI and adiposity (both standardized ß = 0.35, Ps ≤ 0.048), while CVs for VO2, VCO2, and REE were negatively associated (standardized ß ranged from -0.37 to -0.46, all p ≤ 0.036) with cardiometabolic risk factors. In women, CVs for VCO2 and REE were negatively associated with adiposity (both standardized ß = -0.36, Ps ≤ 0.041) and cardiometabolic risk Z-score (standardized ß = -0.40 and -0.38, respectively, Ps ≤ 0.05). In conclusion, intra-assessment resting metabolic rate variability could be considered an indicator of cardiometabolic health in middle-aged adults.

Fit-Fat Index is better associated with heart rate variability compared to fitness and fatness alone as indicators of cardiometabolic human health.

OBJECTIVES: Cardiorespiratory fitness and fatness indicators have been related to heart rate variability (HRV) parameters. The Fit-Fat Index (FFI) is a single index combining cardiorespiratory fitness and fatness indicators. To the best of our knowledge, no studies have previously analyzed whether FFI are related to cardiac autonomic nervous system activity assessed through HRV parameters. This study aimed (i) to examine the association of cardiorespiratory fitness, fatness indicators, and FFI with HRV parameters; and (ii) to report what of the different fatness indicators included in FFI is better associated with HRV parameters in sedentary adults. METHODS: One hundred and fifty healthy adults (74 women; 76 men), aged between 18 and 65 years old, participated in this cross-sectional study. We measured cardiorespiratory fitness (maximal oxygen consumption) and fatness indicators (waist-to-height ratio [WHR], fat mass percentage [FM%] and visceral adipose tissue [VAT]). Three FFIs were calculated as the quotient between cardiorespiratory fitness and one out of three possible fatness indicators: Fit-Fat Index calculated waist-to-height ratio (FFIWHR ), Fit-Fat Index calculated with FM% (FFIFM% ), and Fit-Fat Index calculated with VAT (FFIVAT ). HRV parameters were measured in resting conditions using a Polar RS800CX. RESULTS: FFIWTHR , FFIFM% and FFIVAT were related to different HRV parameters (ß ranges between -0.507 and 0.529; R2 ranges between 0.096 and 0.275; all p < .001) and the association was stronger with HRV parameters than the isolated fitness or fatness indicators (ß ranges between -0.483 and 0.518; R2 ranges between 0.071 and 0.263; all p < .001). FFIVAT was the index more consistently associated with HRV parameters (ß ranges between -0.507 and 0.529; R2 ranges between 0.235 and 0.275; all p < .001). CONCLUSION: Our study suggests that compound FFIs are better predictors of HRV parameters than either cardiorespiratory fitness or fatness indicators alone. The FFIVAT was the best index in terms of its association to HRV.

Relative validity of the Planetary Health Diet Index by comparison with usual nutrient intakes, plasma food consumption biomarkers, and adherence to the Mediterranean diet among European adolescents: the HELENA study.

PURPOSE: The EAT-Lancet Commission proposed an evidence-based global reference diet to improve human health within planetary boundaries. Recently, the Planetary Health Diet Index (PHDI) was developed based on the EAT-Lancet recommendations and validated among Brazilian adults. However, the relative validity of the PHDI in adolescents has yet to be assessed. Thus, we aimed to evaluate the relative validity of the PHDI in European adolescents. METHODS: We used cross-sectional data from 1804 adolescents (12.5-17.5 years) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. The PHDI (0-150 points) was calculated based on dietary intake data from two non-consecutive 24-h dietary recalls. Associations between the PHDI and usual nutrient intakes, plasma food consumption biomarkers, and adherence to the Mediterranean diet were evaluated using multivariable-adjusted mixed-effects linear regression models. RESULTS: Higher PHDI score was associated with greater intakes of nutrients predominantly from plant-source foods, such as vegetable protein, vitamin E, and folate and with lower intake of nutrients predominately from animal-source foods, such as total and saturated fat, cholesterol, and animal protein. Furthermore, a higher PHDI score was also positively associated with plasma ß-carotene, vitamin C, vitamin D, folate, and ferritin concentrations, while negatively associated with trans-fatty acids concentration. Moreover, higher PHDI was related to a greater adherence to the Mediterranean dietary pattern. CONCLUSIONS: The PHDI showed good relative validity among adolescents in the HELENA study. Hence, future research should assess adherence to the PHDI and long-term health outcomes.

New indices in predicting cardiometabolic risk and its relation to endothelial dysfunction in adolescents: The HELENA study.

BACKGROUND AND AIMS: Blood pressure (BP) changes and insulin resistance (IR) are important cardiometabolic risk (CMR) factors; their early identification can contribute to the reduction of cardiovascular events in adulthood. This necessitates the search for more accessible and easily applied indicators for their prediction. Therefore, this study aimed to evaluate the predictive power of the indices, TyG, TG/HDL-c, height-corrected lipid accumulation product (HLAP), and visceral adiposity index (VAI), in identifying the CMR obtained by high BP and IR and to verify their relationship with biomarkers of endothelial dysfunction (ED) in European adolescents. METHODS AND RESULTS: The anthropometric data and blood biomarkers of 744 adolescents (343 boys and 401 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS), with a mean age of 14.67 (SD 1.15) years, were assessed. The adolescents were then classified according to the presence or absence of high BP and IR. The cut-off points of the indices evaluated for the identification of CMR were determined. The relationship between CMR diagnosed using these indices and ED biomarkers was tested. The HLAP and TG/HDL-c were fair predictors of CMR obtained by IR in male adolescents. These indices showed association with hsCRP in sVCAM-1 in boys, but it lost significance after adjusting for age and body mass index. CONCLUSION: TG/HDL-c and HLAP indices showed a fair performance in predicting CMR, obtained by IR, in male adolescents. ED showed no association with the CMR identified by the indices.

High omega-6/omega-3 fatty acid and oxylipin ratio in plasma is linked to an adverse cardiometabolic profile in middle-aged adults.

Omega-6 and omega-3 oxylipins may be surrogate markers of systemic inflammation, which is one of the triggers for the development of cardiometabolic disorders. In the current study, we investigated the relationship between plasma levels of omega-6 and omega-3 oxylipins with body composition and cardiometabolic risk factors in middle-aged adults. Seventy-two 72 middle-aged adults (39 women; 53.6±5.1 years old; 26.7±3.8 kg/m2) were included in this cross-sectional study. Plasma levels of omega-6 and omega-3 fatty acids and oxylipins were determined using targeted lipidomic. Body composition, dietary intake, and cardiometabolic risk factors were assessed with standard methods. The plasma levels of the omega-6 fatty acids and derived oxylipins, the hydroxyeicosatetraenoic acids (HETEs; arachidonic acid (AA)-derived oxylipins) and dihydroxy-eicosatrienoic acids (DiHETrEs; AA-derived oxylipins), were positively associated with glucose metabolism parameters (i.e., insulin levels and homeostatic model assessment of insulin resistance index (HOMA); all r≥0.21, P<.05). In contrast, plasma levels of omega-3 fatty acids and derived oxylipins, specifically hydroxyeicosapentaenoic acids (HEPEs; eicosapentaenoic acid-derived oxylipins), as well as series-3 prostaglandins, were negatively associated with plasma glucose metabolism parameters (i.e., insulin levels, HOMA; all r≤0.20, P<.05). The plasma levels of omega-6 fatty acids and derived oxylipins, HETEs and DiHETrEs were also positively correlated with liver function parameters (i.e., glutamic pyruvic transaminase, gamma-glutamyl transferase (GGT), and fatty liver index; all r≥0.22 and P<.05). In addition, individuals with higher omega-6/omega-3 fatty acid and oxylipin ratio showed higher levels of HOMA, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and GGT (on average +36%), as well as lower levels of high-density lipoprotein cholesterol (-13%) (all P<.05). In conclusion, the omega-6/omega-3 fatty acid and oxylipin ratio, as well as specific omega-6 and omega-3 oxylipins plasma levels, reflect an adverse cardiometabolic profile in terms of higher insulin resistance and impaired liver function in middle-aged adults.

Clinical and physical characteristics of thinness in adolescents: the HELENA study.

PURPOSE: Thinness in adolescence has not been studied as extensively as overweight or obesity. The aim of this study was to assess the prevalence, characteristics, and health impacts of thinness in a European adolescent population. METHODS: This study included 2711 adolescents (1479 girls, 1232 boys). Blood pressure, physical fitness, sedentary behaviors, physical activity (PA), and dietary intake were assessed. A medical questionnaire was used to report any associated diseases. A blood sample was collected in a subgroup of the population. Thinness and normal weight were identified using the IOTF scale. Thin adolescents were compared with adolescents of normal weight. RESULTS: Two hundred and fourteen adolescents (7.9%) were classified as being thin; the prevalence rates were 8.6% in girls and 7.1% in boys. Systolic blood pressure was significantly lower in adolescents with thinness. The age at the first menstrual cycle was significantly later in thin female adolescents than in those with normal weight. Upper-body muscular strength measured in performance tests and time spent in light PA were significantly lower in thin adolescents. The Diet Quality Index was not significantly lower in thin adolescents, but the percentage of adolescents who skipped breakfast was higher in adolescents with a normal weight (27.7% vs 17.1%). Serum creatinine level and HOMA-insulin resistance were lower and vitamin B12 level was higher in thin adolescents. CONCLUSIONS: Thinness affects a notable proportion of European adolescents with no physical adverse health consequences.

Sleep and Anabolic/Catabolic Hormonal Profile in Sedentary Middle-Aged Adults: The FIT-AGEING Study.

Sleep quality plays an important role in the modulation of several aging markers. This influence could be explained by aging-induced hormonal changes. Indeed, poor sleep quality has been associated with the development of several endocrine-related health complications. This study examined the relationship of both subjective and objective sleep quantity and quality, with basal levels of selected plasma anabolic and catabolic hormones in sedentary middle-aged adults. A total of 74 volunteers (52.7% women; aged 53.7 ± 5.1) were recruited for this study. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI; higher scores indicate worse sleep quality), and objective sleep quality parameters (total sleep time [TST], wake after sleep onset [WASO], and sleep efficiency [SE]) were measured using a wrist-worn accelerometer. Basal levels of plasma dehydroepiandrosterone sulphate (DHEAS), total testosterone, sex hormone binding globulin (SHBG), somatotropin, and cortisol levels, were determined. Free testosterone was calculated from the total testosterone and SHBG levels. No associations of global PSQI score, TST, WASO, and SE with DHEAS, free testosterone, and somatotropin plasma levels were found, neither in men nor in women (all p ≥ 0.05). Global PSQI score was inversely related to cortisol plasma levels in women (p = 0.043). WASO was positively associated with cortisol plasma levels, while SE was negatively associated with cortisol plasma levels in women (all p ≤ 0.027). Sleep quality is not related to levels of plasma anabolic hormones, but to levels of catabolic hormones, in sedentary middle-aged adults. Therefore, these results suggest that potential changes in aging biomarkers associated with sleep disturbances, could be mediated by age-related changes in the catabolic endocrine system.

Developing a risk assessment tool for identifying individuals at high risk for developing insulin resistance in European adolescents: the HELENA-IR score.

OBJECTIVES: To develop and validate an easy-to-use screening tool for identifying adolescents at high-risk for insulin resistance (IR). METHODS: Α total of 1,053 adolescents (554 females), aged 12.5 to 17.5 years with complete data on glucose and insulin levels were included. Body mass index (BMI), fat mass index (FMI) and the homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. VO2max was predicted using 20 m multi-stage fitness test. The population was randomly separated into two cohorts for the development (n=702) and validation (n=351) of the index, respectively. Factors associated with high HOMA-IR were identified by Spearman correlation in the development cohort; multiple logistic regression was performed for all identified independent factors to develop a score index. Finally, receiver operating characteristic (ROC) analysis was performed in the validation cohort and was used to define the cut-off values that could identify adolescents above the 75th and the 95th percentile for HOMA-IR. RESULTS: BMI and VO2max significantly identified high HOMA-IR in males; and FMI, TV watching and VO2max in females. The HELENA-IR index scores range from 0 to 29 for males and 0 to 43 for females. The Area Under the Curve, sensitivity and specificity for identifying males above the 75th and 95th of HOMA-IR percentiles were 0.635 (95%CI: 0.542-0.725), 0.513 and 0.735, and 0.714 (95%CI: 0.499-0.728), 0.625 and 0.905, respectively. For females, the corresponding values were 0.632 (95%CI: 0.538-0.725), 0.568 and 0.652, and 0.708 (95%CI: 0.559-0.725), 0.667 and 0.617, respectively. Simple algorithms were created using the index cut-off scores. CONCLUSIONS: Paediatricians or physical education teachers can use easy-to-obtain and non-invasive measures to apply the HELENA-IR score and identify adolescents at high risk for IR, who should be referred for further tests.

Different exercise training modalities similarly improve heart rate variability in sedentary middle-aged adults: the FIT-AGEING randomized controlled trial.

PURPOSE: This study aimed to investigate the influence of different exercise training modalities on heart rate variability (HRV) in sedentary middle-aged adults; and to study whether changes in health-related outcomes (i.e., body composition and cardiometabolic risk) are associated with those hypothetical HRV changes in sedentary middle-aged adults. METHODS: A total of 66 middle-aged adults (53.6 ± 4.4 years old; 50% women) were enrolled in the FIT-AGEING study. We conducted a 12-week randomized controlled trial. The participants were randomly assigned to 4 groups: (a) a control group (no exercise); (b) a physical activity recommendation from the World Health Organization group (PAR); (c) a high-intensity interval training group (HIIT); and (d) a high-intensity interval training group adding whole-body electromyostimulation (HIIT + EMS). RESULTS: All exercise training modalities induced changes in HRV parameters (all P ≤ 0.001) without statistical differences between them (all P > 0.05). We found associations between changes in body composition and cardiometabolic risk and exercise-related changes in HRV. CONCLUSION: Our results suggest that different exercise interventions (i.e., PAR, HIIT and HIIT + EMS) induced an enhancement of HRV in sedentary middle-aged adults. Our findings support the notion that exercise-related changes in HRV are associated with changes in body composition and cardiometabolic risk after the intervention program CLINICAL TRIAL REGISTRY: NCT03334357 (ClinicalTrials.gov). November 7, 2017 retrospectively registered.

References Values of Soluble α-Klotho Serum Levels Using an Enzyme-Linked Immunosorbent Assay in Healthy Adults Aged 18-85 Years.

α-Klotho protein is a powerful predictor of the aging process and lifespan. Although lowered circulating soluble α-Klotho levels have been observed in aged non-healthy individuals, no specific reference values across a wide range of ages and sex using an enzyme-linked immunosorbent assay (ELISA) are available for larger cohorts of healthy individuals. The present analytical cross-sectional study was aimed to establish the reference values of soluble α-Klotho serum levels in healthy adults by age and sex groups. A total of 346 (59% women) healthy individuals aged from 18 to 85 years were recruited. Subjects were divided by sex and age as: (i) young (18−34.9 years), (ii) middle-aged (35−54.9 years), and (iii) senior (55−85 years) individuals. The soluble α-Klotho levels were measured in serum using ELISA. Senior adults were the age-group that presented the lowest soluble α-Klotho serum levels (p < 0.01), with age showing a negative association with soluble α-Klotho serum levels (p < 0.001). No differences between sexes were observed. Therefore, soluble α-Klotho levels were especially decreased­regardless of sex­in our cohort of healthy individuals because of the physiological decline derived from the aging process. We recommend routine assessments of soluble α-Klotho levels using ELISA as a simple and cheap detectable marker of aging that improves quality of life in the elderly.

Effect of Different Exercise Training Modalities on Fasting Levels of Oxylipins and Endocannabinoids in Middle-Aged Sedentary Adults: A Randomized Controlled Trial.

This study aimed to investigate the effects of different exercise training programs on fasting plasma levels of oxylipins, endocannabinoids (eCBs), and eCBs-like molecules in middle-aged sedentary adults. A 12-week randomized controlled trial was conducted using a parallel group design. Sixty-five middle-aged adults (40-65 years old) were randomly assigned to: (a) no exercise (control group), (b) concurrent training based on international physical activity recommendations (PAR group), (c) high-intensity interval training (HIIT group), and (d) HIIT together with whole-body electromyostimulation (HIIT + EMS group). Plasma levels of oxylipins, eCBs, and eCBs-like molecules were determined in plasma samples before and after the intervention using targeted lipidomics. Body composition was assessed through dual-energy X-ray absorptiometry, and dietary intake through a food frequency questionnaire and three nonconsecutive 24-hr recalls. The physical activity recommendations, HIIT, and HIIT-EMS groups showed decreased plasma levels of omega-6 and omega-3-derived oxylipins, and eCBs and eCBs-like molecules after 12 weeks (all Δ ≤ -0.12; all p < .05). Importantly, after Bonferroni post hoc corrections, the differences in plasma levels of omega-6 and omega-3 oxylipins were not statistically significant compared with the control group (all p > .05). However, after post hoc corrections, plasma levels of anandamide and oleoylethanolamide were increased in the physical activity recommendations group compared with the control group (anandamide: Δ = 0.05 vs. -0.09; oleoylethanolamide: Δ = -0.12 vs. 0.013, all p ≤ .049). In conclusion, this study reports that a 12-week exercise training intervention, independent of the modality applied, does not modify fasting plasma levels of omega-6 and omega-3 oxylipins, eCBs, and eCBs-like molecules in middle-aged sedentary adults.

Interplay of physical activity and genetic variants of the endothelial lipase on cardiovascular disease risk factors.

BACKGROUND: The aim of this study was to investigate the association of endothelial lipase gene (LIPG) polymorphisms with cardiovascular disease (CVD) risk factors in adolescents and their interaction with physical activity. METHODS: Six polymorphisms of LIPG were genotyped in 1057 European adolescents (12-18 years old) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study. CVD risk factors related to lipid profile, blood pressure, adiposity and glucose regulation were recorded. Physical activity was objectively measured by accelerometry. RESULTS: The major C allele of rs2000813, the minor T allele of rs2276269 and the minor G allele of rs9951026 were associated with lower levels of several CVD risk factors related to lipid profile. We also found a significant association of the TTACA LIPG haplotype (rs2000812, rs2000813, rs8093249, rs2276269 and rs9951026) with higher concentrations of low-density cholesterol and apolipoprotein B. Finally, the interaction between physical activity and the polymorphisms rs2000813, rs2276269 and rs9951026 had a significant influence on several CVD risk factors. CONCLUSIONS: LIPG polymorphisms were significantly associated with CVD risk factors in European adolescents. Interestingly, alleles of these polymorphisms were associated with a better cardiovascular profile in physically active adolescents only. High physical activity may reduce the development of CVD, modulating its genetic risk. IMPACT: Using gene-phenotype and gene × environment analyses, we detected associations between the endothelial lipase gene and cardiovascular risk factors, along with interactions with physical activity. This study shows that physical activity may modulate the influence of LIPG gene on cardiovascular risk in adolescents. These results bring insights into the mechanisms by which physical activity positively influences CVD in adolescents.

Effect of Exercise Training on 1,25(OH)2D Levels: The FIT-AGEING Randomized Controlled Trial.

BACKGROUND: Vitamin D deficiency is currently endemic worldwide and is considered as an important factor in the development of several chronic conditions. Physical exercise has been postulated as an auspicious strategy to counteract age-related disorders preventing premature mortality. However, the effects of chronic exercise training on 1,25-dihydroxyvitamin D [1,25(OH)2D] is unclear. This 12-week randomized controlled trial aimed to investigate the effects of different training modalities on 1,25(OH)2D in healthy sedentary adults. HYPOTHESIS: Exercise training will increase 1,25(OH)2D in the study cohort. STUDY DESIGN: Randomized controlled clinical trial. LEVEL OF EVIDENCE: Level 1. METHODS: A total of 89 healthy sedentary adults (53% women; 53.5 ± 4.9 years old) were enrolled in the FIT-AGEING study. The participants were randomized to (1) a control group (no exercise), (2) physical activity recommendation from the World Health Organization (PAR group), (3) high-intensity interval training (HIIT group), and (4) HIIT adding whole-body electromyostimulation training (HIIT + EMS). 1,25(OH)2D plasma levels were measured using a DiaSorin Liaison immunochemiluminometric analyzer. RESULTS: Compared with the control group, 1,25(OH)2D increased in PAR (Δ = 10.99 ± 3.44 pg/mL; P = 0.01), HIIT (Δ = 11.63 ± 3.51 pg/mL; P = 0.009), and HIIT + EMS groups (Δ = 14.01 ± 3.59 pg/mL; P = 0.001) without statistical differences between them (all Ps > 0.1). CONCLUSION: In summary, the results show that a 12-week exercise intervention produced an increment of 1,25(OH)2D independently of age, sex, and exercise modality in healthy sedentary adults. CLINICAL RELEVANCE: The implementation of physical exercise could be considered a strategy not only aiming to reverse the seasonal decrease of 1,25(OH)2D in winter explained by low sunlight exposure but also for obtaining subsequent increases of this hormone even in these a priori adverse conditions.

1,25-dihydroxyvitamin D and cardiometabolic risk in healthy sedentary adults: The FIT-AGEING study.

BACKGROUND: A growing body of scientific works investigating the physio-pathological mechanisms behind cardiovascular disease has suggested that vitamin D deficiency could play a key role on its development. However, it remains unclear whether its active form (1,25-dihydroxyvitamin D [1,25(OH)2D] is associated with cardiometabolic risk factors in healthy individuals. The aim of the present study was to investigate the relationships of 1,25(OH)2D plasma levels with cardiometabolic risk factors in a sample of healthy sedentary adults. METHODS: A total of 73 adults (~53% women; 54 ± 5 years old) were included in the current cross-sectional study. A sex-specific cardiometabolic risk score (MetScore) was calculated for each subject based on clinical parameters (i.e., waist circumference, systolic and diastolic blood pressure, plasma glucose, high-density lipoprotein cholesterol, and triglycerides) according to the International Diabetes Federation's clinical criteria. Plasma levels of 1,25(OH)2D were measured using a DiaSorin Liaison® immunochemiluminometric analyzer. RESULTS: No significant association was detected between 1,25(OH)2D and MetScore (ß = 0.037, R2 = 0.001, p = 0.77), independently of age, sex and fat body mass index. A significant inverse association were observed between 1,25(OH)2D and waist circumference (ß = -0,303, R2 = 0.092, p = 0.01). These results were consistent after controlling by potential confounders. CONCLUSION: In summary, the present results suggest that 1,25(OH)2D plasma levels are not associated with either cardiometabolic risk factors or insulin resistance in healthy sedentary adults. However, an inverse association of 1,25(OH)2D plasma levels with central adiposity was observed in our study sample.

Relationship of sedentary time, physical activity and fitness with 1,25-dihydroxyvitamin D in middle-aged sedentary adults: The FIT-AGEING study.

PURPOSE: Potential interactions between sedentary behaviour, physical activity (PA), and physical fitness with 25-hydroxyvitamin D (25(OH)D) status have been previously suggested. However, data are scarce concerning the association between these predictors of general health and the main active metabolite of vitamin D, the 1,25-dihidroxyvitamin D (1,25(OH)2D). This study aimed to analyse the relationship of sedentary time, PA levels, and physical fitness (i.e., maximal oxygen uptake (VO2max) and muscular strength) with 1,25(OH)2D in middle-aged sedentary adults. METHODS: A total of 73 (39 women) middle-aged sedentary adults (53.7 ± 5.1 years old) participated in this cross-sectional study. Sedentary time and PA intensity levels were objectively measured with triaxial accelerometers for 7 consecutive days. VO2max was determined by a maximum treadmill test. Lower and upper limb muscular strength was assessed by an isokinetic strength test and by a handgrip strength test, respectively. 1,25(OH)2D plasma levels were measured using a DiaSorin Liaison® immunochemiluminometric assay. RESULTS: No significant relationships were found between objectively measured sedentary time, PA levels or physical fitness (i.e., VO2max, extension and flexion peak torque, and hand grip strength) and 1,25(OH)2D (all P > 0.05). All results persisted after controlling for age, sex, fat mass or energy, vitamin D, calcium, and phosphorus intake. CONCLUSIONS: In summary, our results show that vitamin D status is not affected by physical activity habits and sedentary behaviour in middle-aged sedentary adults.

The effects of three types of exercise training on steroid hormones in physically inactive middle-aged adults: a randomized controlled trial.

PURPOSE: Physical inactivity and ageing are associated with imbalances in anabolic/catabolic steroid hormones, jeopardizing health. We investigated the effects of three types of training on plasma steroid hormone levels in physically inactive, middle-aged adults. METHODS: A 12-week randomized controlled trial was performed with a parallel-group design. A total of 67 (36 women) middle-aged adults (45-65 years old) were randomly assigned to (1) no exercise (control), (2) concurrent training based on the international physical activity recommendations (PAR), (3) high-intensity interval training (HIIT), or (4) HIIT plus whole-body electromyostimulation (HIIT + EMS). The training volume in the PAR group was 150 min/week at 60-65% of the heart rate reserve for aerobic training and ~ 60 min/week at 40-50% of the one-repetition maximum for resistance training. The training volume in the HIIT and HIIT + EMS groups was 40-65 min/week at > 95% of the maximum oxygen uptake in long interval sessions, and > 120% of the maximum oxygen uptake in short interval sessions. RESULTS: Compared to the control group, dehydroepiandrosterone sulfate increased in the PAR, HIIT, and HIIT + EMS groups (~ 14%, ~ 14%, and ~ 20%, respectively; all P < 0.01). Cortisol decreased in the PAR, HIIT, and HIIT + EMS groups (~ - 17%, ~ - 10%, and ~ - 23%, respectively; all P ≤ 0.05). Testosterone increased in the HIIT and HIIT + EMS groups (~ 28%, and ~ 16%, respectively; all P ≤ 0.01). Free testosterone increased in the HIIT and HIIT + EMS groups (~ 30% and ~ 18% respectively; all P ≤ 0.01). No significant increase in sex hormone-binding globulin was observed (P = 0.869). CONCLUSION: Our findings suggest that HIIT, with or without whole-body EMS, can significantly enhance steroid hormones status in previously physically inactive middle-aged adults. The PAR program led to slight improvements than the HIIT and HIIT + EMS groups despite the application of a higher training volume. CLINICAL TRIAL REGISTRY: NCT03334357 (ClinicalTrials.gov). November 7, 2017 retrospectively registered.

1,25-Dihydroxyvitamin D and S-Klotho Plasma Levels: The Relationship Between Two Renal Antiaging Biomarkers Mediated by Bone Mineral Density in Middle-Aged Sedentary Adults.

The main active metabolite of vitamin D, the 1,25-dihydroxyvitamin D (1,25(OH)2D), and the shed form of the α-Klotho gene (S-Klotho) play an important role in aging-related physiological processes and are currently considered powerful antiaging renal biomarkers. We aimed to investigate the relationship between 1,25(OH)2D and S-Klotho plasma levels in middle-aged sedentary healthy adults. We also aimed to study the mediation role of body composition, physical activity levels, dietary parameters, and blood markers in the association between 1,25(OH)2D and S-Klotho plasma levels. A total of 73 middle-aged sedentary adults (53.4% women; 53.7 ± 5.1 years old) were enrolled in this cross-sectional study. The 1,25(OH)2D plasma levels were measured using a DiaSorin Liaison® immunochemiluminometric analyzer. S-Klotho plasma levels were measured using a solid-phase sandwich enzyme-linked immunosorbent assay. Body composition analysis was performed using dual-energy X-ray absorptiometry scanner. A tendency toward a negative association was observed between 1,25(OH)2D and S-Klotho plasma levels (ß = -0.222, R2 = 0.049, p = 0.059). The association was attenuated after controlling for age and sex and become significant after controlling for fat mass index. In addition, the association between 1,25(OH)2D and S-Klotho levels was indirectly influenced by bone mineral density (BMD), with a percentage of mediation of 31.40%. Our study shows that 1,25(OH)2D is negatively associated with S-Klotho plasma levels in middle-aged sedentary adults, which is partially mediated by BMD. Clinicaltrial.gov: ID: NCT03334357.

Role of physical activity and fitness on sleep in sedentary middle-aged adults: the FIT-AGEING study.

The association of physical activity and fitness with sleep still remains unclear since there is a lack of studies in this field of research using objective measurements of these variables. This study aimed to investigate the association of objectively-measured sedentariness, physical activity levels, and physical fitness with sleep quantity and quality in sedentary middle-aged adults. A total of 74 volunteers (52.7% women; aged 53.7 ± 5.1) were recruited for the present study. Cardiorespiratory fitness was measured through a maximal treadmill test, and muscular strength by extension and flexion peak torque, and by the hand grip test. Physical activity and objective sleep parameters were determined through accelerometry, and subjective sleep by the Pittsburgh Sleep Quality Index (PSQI). Reduced levels of sedentariness, greater VO2max, and greater muscular strength were positively related to improved objective sleep quantity and quality (all P ≤ 0.05). Furthermore, higher levels of overall physical activity, VO2max, and muscular strength were related to better subjective sleep quantity and quality (all P ≤ 0.05). Reduced sedentariness and increased physical activity and fitness may be a potential prevention and/or treatment pathway to reduce sleep disturbances and, in general, to improve patients physical and psychological health for a successful aging process.