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.

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.

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.

Exercise training improves sleep quality: A randomized controlled trial.

BACKGROUND: Exercise holds promise as a non-pharmacological intervention for the improvement of sleep quality. Therefore, this study investigates the effects of different training modalities on sleep quality parameters. MATERIAL & METHODS: A total of 69 (52.7% women) middle-aged sedentary adults were randomized to (a) control group, (b) physical activity recommendation from the World Health Organization, (c) high-intensity interval training (HIIT) and (d) high-intensity interval training group adding whole-body electromyostimulation training (HIITEMS). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) scale and accelerometers. RESULTS: All intervention groups showed a lower PSQI global score (all P < .022). HIIT-EMS group improved all accelerometer parameters, with higher total sleep time and sleep efficiency, and lower wake after sleep onset (all P < .016). No differences were found between groups in any sleep quality parameter. CONCLUSION: In conclusion, exercise training induced an improvement in subjective sleep quality in sedentary middleaged adults. Moreover, HIIT-EMS training showed an improvement in objective sleep quality parameters (total sleep time, sleep efficiency and wake after sleep onset) after 12 weeks of exercise intervention. The changes observed in the HIIT-EMS group were not statistically different to the other exercise modalities.

Predictors of Sexual Desire and Sexual Function in Sedentary Middle-Aged Adults: The Role of Lean Mass Index and S-Klotho Plasma Levels. The FIT-AGEING Study.

BACKGROUND: Unhealthy lifestyle and aging negatively impact sexuality; consequently, the prevalence of sexual problems increases sharply in middle-aged adults, but the determinants of low sexual desire and sexual dysfunction are not fully elucidated. AIMS: To investigate the association of cardiometabolic profile, free testosterone plasma levels, body composition, physical fitness, and S-Klotho plasma levels with sexual desire and sexual function in middle-aged sedentary adults. METHODS: Seventy-four (39 women) sedentary middle-aged adults (45-65 years old) were recruited for the present cross-sectional study. OUTCOMES: The blood samples were collected in the morning (12 h of fasting) to determine cardiometabolic biomarkers and free testosterone and S-Klotho plasma levels. The cardiometabolic risk score was calculated based on the International Diabetes Federation's clinical criteria, quantitative insulin sensitivity check index, and homeostatic model assessment of insulin resistance index. A dual-energy X-ray absorptiometry scanner was used to determine the lean mass index (LMI) and the fat mass index. Maximal oxygen uptake was determined by a maximum treadmill test using indirect calorimetry. Muscular strength was measured with knee extensor isokinetic dynamometry (60° s-1). Sexual desire was assessed with the Sexual Desire Inventory 2. Sexual function was assessed with the Massachusetts General Hospital-Sexual Functioning Questionnaire. RESULTS: After age adjustment, free testosterone plasma levels were associated with solitary sexual desire in women (R2 = 0.193, ß = 0.342, P = .044). The LMI was associated with solitary sexual desire in men (R2 = 0.258, ß = 0.445, P = .024) and sexual function in women (R2 = 0.470, ß = -0.607, P < .001). S-Klotho plasma levels were associated with solitary sexual desire and sexual function in men (R2 = 0.412, ß = 0.817, P = .001; R2 = 0.193, ß = -0.659, P = .021, respectively) and with dyadic sexual desire and sexual function in women (R2 = 0.270, ß = 0.508, P = .020; R2 = 0.467, ß = -0.676, P < .001, respectively). CLINICAL IMPLICATIONS: S-Klotho plasma levels may represent a potential new biomarker for sexual desire and sexual function. Lean body mass development may benefit sexual desire and sexual function. STRENGTHS AND LIMITATIONS: Strengths include the analysis of novel and diverse biomarkers of health for sexual desire and sexual function. Limitations include the cross-sectional design and a relatively small sample size; thus, results should be interpreted cautiously and in the study population context. CONCLUSION: S-Klotho plasma levels were strongly associated with dyadic sexual desire, solitary sexual desire, and sexual function in sedentary middle-aged adults. The LMI was also positively associated with solitary sexual desire and sexual function in men and women, respectively. Dote-Montero M, De-la-O A, Castillo MJ, et al. Predictors of Sexual Desire and Sexual Function in Sedentary Middle-Aged Adults: The Role of Lean Mass Index and S-Klotho Plasma Levels. The FIT-AGEING Study. J Sex Med 2020;17:665-677.

Dietary Patterns and Their Relationship With the Perceptions of Healthy Eating in European Adolescents: The HELENA Study.

Objective: The aim of this study was to identify dietary patterns (DPs) in European adolescents and to examine the association between perceptions of healthy eating and the obtained DPs.Method: A multinational cross-sectional study was carried out in adolescents aged 12.5 to 17.5 years and 2,027 (44.9% males) were considered for analysis. A self-reported questionnaire with information on food choices and preferences, including perceptions of healthy eating, and two 24-hour dietary recalls were used. Principal component analysis was used to obtain sex-specific DPs, and linear analyses of covariance were used to compare DPs according to perceptions of healthy eating.Results: Three and four DPs for boys and girls were obtained. In boys and girls, there were significant associations between some perceptions about healthy food and the Breakfast-DP (p < 0.05). In boys, Breakfast-DP and Healthy Beverage-DP were associated with the perception of the own diet as healthy (p < 0.05). Healthy Beverage-DP was associated with those disliking fruits and vegetables (p < 0.05). Girls considering the own diet as healthy were associated with Mediterranean-DP, Breakfast-DP, and Unhealthy Beverage and Meat-DP (p < 0.05). The perception of snacking as a necessary part of a healthy diet was associated with Breakfast-DP in both genders (p < 0.05).Conclusions: In European adolescents, perceptions of healthy eating were mainly associated with a DP characterized by foods consumed at breakfast. Future studies should further explore these findings in order to implement health promotion programs to improve healthy eating habits in adolescents.

Dietary differences between metabolically healthy overweight-obese and metabolically unhealthy overweight-obese adults.

The aim of the study is to determine the differences in dietary parameters (energy and nutrient intake, adherence to the Mediterranean diet and consumption of food groups) in metabolically healthy overweight-obese (MHOO) v. metabolically unhealthy overweight-obese (MUOO) middle-aged adults. A total of fifty-one middle-aged adults were classified as MHOO or MUOO. BMI and blood pressure were evaluated following the recommendations. HDL, TAG and blood glycaemia were measured in blood samples. Blood pressure was also assessed. Dietary factors were assessed through three 24-h recalls, a validated FFQ and the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. All variables were evaluated between September and October 2016 and 2017. Our results showed that MHOO individuals registered a higher fish consumption (P = 0·035) and higher compliance (lower consumption) in the commercial sweets and confectionery item of the PREDIMED questionnaire (P = 0·036). No differences were noted in other dietary factors including energy and nutrient intake, consumption of other food groups and in the PREDIMED total score. A near-significant trend toward significance was observed in nuts consumption, wine and fish items of the PREDIMED questionnaire. In conclusion, higher fish consumption and a higher compliance in the commercial sweets and confectionery item of the PREDIMED questionnaire were observed in MHOO middle-aged adults.

Effects of different exercise training programs on body composition: A randomized control trial.

We aimed to investigate the effects of different exercise training programs on body composition parameters in sedentary middle-aged adults. A total of 89 middle-aged adults (53.5 ± 4.9 years old; ~53% women) participated in the FIT-AGEING study. A 12-week randomized controlled trial was performed with a parallel group design. The participants were randomly assigned to (a) a concurrent training based on physical activity recommendation from the World Health Organization group (PAR group), (b) a high-intensity interval training group (HIIT group), and (c) a high-intensity interval training group adding whole-body electromyostimulation group (WB-EMS group). A significant decrease of fat body mass, fat body mass index, and visceral adipose tissue was observed in all training modalities compared to the control group (all P ≤ 0.001). There was a significant increase in lean body mass in the HIIT group as well as in the WB-EMS group compared to the control group and the PAR group (all P ≤ 0.044), whereas an increment of lean body mass index was only observed in the WB-EMS group compared to the control group and the PAR group (all P ≤ 0.042). A significant increase of bone mineral content was observed in the WB-EMS group compared to the control group (P = 0.015), while no changes were found in the PAR group and in the HIIT group compared to the control group (all P ≥ 0.2). Our findings suggest that PAR, HIIT, and WB-EMS can be used as a strategy to improve body composition parameters, obtaining slightly better results with the application of WB-EMS.

Assessment of maximal fat oxidation during exercise: A systematic review.

Maximal fat oxidation during exercise (MFO) and the exercise intensity eliciting MFO (Fatmax ) are considered biological markers of metabolic health and performance. A wide range of studies have been performed to increase our knowledge about their regulation by exercise and/or nutritional intervention. However, numerous data collection and analysis approaches have been applied, which may have affected the MFO and Fatmax estimation. We aimed to systematically review the available studies describing and/or comparing different data collection and analysis approach factors that could affect MFO and Fatmax estimation in healthy individuals and patients. Two independent researchers performed the search. We included all original studies in which MFO and/or Fatmax were estimated by indirect calorimetry through an incremental graded exercise protocol published from 2002 to 2019. This systematic review provides key information about the factors that could affect MFO and Fatmax estimation: ergometer type, metabolic cart used, warm-up duration and intensity, stage duration and intensities imposed in the graded exercise protocol, time interval selected for data analysis, stoichiometric equation selected to estimate fat oxidation, data analysis approach, time of the day when the test was performed, fasting time/previous meal before the test, and testing days for MFO/Fatmax and maximal oxygen uptake assessment. We suggest that researchers measuring MFO and Fatmax should take into account these key methodological issues that can considerably affect the accuracy, validity, and reliability of the measurement. Likewise, when comparing different studies, it is important to check whether the above-mentioned key methodological issues are similar in such studies to avoid ambiguous and unacceptable comparisons.

Associations between a Mediterranean diet pattern and inflammatory biomarkers in European adolescents.

AIM: To test whether the Mediterranean diet score and each food-subgroup is associated with inflammatory biomarkers in European adolescents. METHODS: In 464 adolescents (13-17 years) of the European HELENA study, data were available on body composition, inflammation markers, and food intake determined by two computerized 24-h recalls. The Mediterranean diet score and its food-subgroups (Vegetables, Fruits and Nuts, Pulses, Cereal and Roots, Monounsaturated/Saturated fat ratio, Dairy, Fish, Meat and Alcohol) were evaluated. A set of inflammation-related biomarkers was measured: IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, TGFß-1, TNF-α, sVCAM-1, sICAM1, sE-selectin, white blood cells, lymphocytes, CD3, CRP, GGT, ALT, and homocysteine. Multivariate and multiple linear regression analyses were adjusted for age, sex, country, socioeconomic status, paternal and maternal education, adiposity, and smoking habits. RESULTS: The Mediterranean diet score was positively associated with CRP, and negatively with sVCAM-1. The subgroups showed the following positive/negative associations: Vegetables with IL-10(+), CRP(+), CD3(+), ALT(+), lymphocytes(+), sE-selectin(-); Fruits and Nuts with IL-4(-), TNF-alpha; Pulses with IL-5(+), IL-6(+), IL-2(-); Cereals and Roots with IL-6(-), IL-10(-); Monounsaturated/Saturated-fat ratio with IL-6(+), TGFß-1(+), sVCAM-1(+boys, -girls), homocysteine(-); Dairy with IL-1(+), IL-5(+), IL-6(+), IL-10(+), TGFß-1(+), homocysteine(-); Fish with homocysteine(-); Meat with IL-2(+), IL-10(+); Alcohol with CRP(+), lymphocytes(-). Sex differences were found. CONCLUSION: Some specific food-inflammation associations were found, suggesting that diet is to a certain extent already related to inflammation in adolescents and can be used in disease prevention. Also some counterintuitive results were found, which might be due to grouping very different foods into a single group, besides considering that the human body may respond differently depending on the interaction between diet, lifestyle, genetics, biochemical individuality, age and sex.

Association between Sleep Quality and Body Composition in Sedentary Middle-Aged Adults.

Background: Ageing is associated with sleep pattern changes and body composition changes, which are related to several diseases. Purpose: This study aimed to analyse the association between sleep quality and an extensive set of body composition parameters (waist-hip ratio, body mass index, bone mineral content, bone mineral density, lean mass, lean mass index, fat mass, fat mass percentage, fat mass index, visceral adipose tissue) and sleep quality in sedentary middle-aged adults. We also aimed to evaluate whether the possible associations accord between subjective and objective measurements of sleep quality. Methods: 74 (39 women) middle-aged sedentary adults (40⁻65 years old) participated in the present study. The sleep quality was assessed using the Pittsburgh sleep quality index (PSQI) scale and accelerometers. A PSQI global score more than 5 indicates poor sleep quality. Weight, height, waist and hip circumferences were measured, and body mass index and waist-hip ratio were also calculated. Body composition was assessed with a dual-energy X-ray absorptiometry scanner. Results: The PSQI global score was negatively associated with bone mineral content, bone mineral density, lean mass, lean mass index and positively associated with fat mass percentage. No association was found between accelerometer parameters and body composition variables. Conclusion: We showed that a subjective poor sleep quality was negatively associated with bone mineral content (BMC), bone mineral density (BMD), lean mass and lean mass index (LMI) whereas was positively associated with fat mass percentage in middle-aged adults. We also observed that these associations did not accord with objective sleep quality measurements.

Dietary sources and sociodemographic and lifestyle factors affecting vitamin D and calcium intakes in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study.

OBJECTIVE: To investigate dietary sources of Ca and vitamin D (VitD) intakes, and the associated sociodemographic and lifestyle factors, among European adolescents. DESIGN: Linear regression mixed models were used to examine sex-specific associations of Ca and VitD intakes with parental education, family affluence (FAS), physical activity and television (TV) watching while controlling for age, Tanner stage, energy intake and diet quality. SETTING: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA)Cross-Sectional Study. SUBJECTS: Adolescents aged 12·5-17·5 years (n 1804). RESULTS: Milk and cheese were the main sources of Ca (23 and 19 % contribution to overall Ca intake, respectively). Fish products were the main VitD source (30 % contribution to overall VitD intake). Ca intake was positively associated with maternal education (ß=56·41; 95 % CI 1·98, 110·82) and negatively associated with TV viewing in boys (ß=-0·43; 95 % CI -0·79, -0·07); however, the significance of these associations disappeared when adjusting for diet quality. In girls, Ca intake was positively associated with mother's (ß=73·08; 95 % CI 34·41, 111·74) and father's education (ß=43·29; 95 % CI 5·44, 81·14) and FAS (ß=37·45; 95 % CI 2·25, 72·65). This association between Ca intake and mother's education remained significant after further adjustment for diet quality (ß=41·66; 95 % CI 0·94, 82·38). Girls with high-educated mothers had higher Ca intake. CONCLUSIONS: Low-educated families with poor diet quality may be targeted when strategizing health promotion programmes to enhance dietary Ca.

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.

Investigating the Alcohol Effects on the Response to Strenuous Exercise Training: Protocol for a Multidisciplinary Intervention Study in Young Healthy Adults-The BEER-HIIT Study.

High-intensity interval training (HIIT) is a time-efficient strategy to improve fitness and performance. Whereas the multiple and negative effects of high intake of alcohol have been widely studied, the effect of moderate alcohol doses after exercise is not clear, and it is currently under debate. For that, a total of 80 young healthy adults are studied and allocated into 5 groups, each including 16 participants. Four groups follow a HIIT program, while the fifth group is a control non-training group. The training groups will be randomized according to the characteristics of the ingested beverage (alcohol beer, beer 0.0%, sparkling water, or ethanol). The effects of HIIT on several aspects of physical performance and mental health in young healthy adults are evaluated, also the concomitant effect of daily and moderate alcohol consumption. The novelty of this study lies in the continuous measurement of the psychological parameters associated with carrying out a highly demanding training program in conjunction with alcohol consumption in moderate quantities, reflecting real-life conditions.

Time-restricted eating and supervised exercise for improving hepatic steatosis and cardiometabolic health in adults with obesity: protocol for the TEMPUS randomised controlled trial.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease is a major public health problem considering its high prevalence and its strong association with extrahepatic diseases. Implementing strategies based on an intermittent fasting approach and supervised exercise may mitigate the risks. This study aims to investigate the effects of a 12-week time-restricted eating (TRE) intervention combined with a supervised exercise intervention, compared with TRE or supervised exercise alone and with a usual-care control group, on hepatic fat (primary outcome) and cardiometabolic health (secondary outcomes) in adults with obesity. METHODS AND ANALYSIS: An anticipated 184 adults with obesity (50% women) will be recruited from Granada (south of Spain) for this parallel-group, randomised controlled trial (TEMPUS). Participants will be randomly designated to usual care, TRE alone, supervised exercise alone or TRE combined with supervised exercise, using a parallel design with a 1:1:1:1 allocation ratio. The TRE and TRE combined with supervised exercise groups will select an 8-hour eating window before the intervention and will maintain it over the intervention. The exercise alone and TRE combined with exercise groups will perform 24 sessions (2 sessions per week+walking intervention) of supervised exercise combining resistance and aerobic high-intensity interval training. All participants will receive nutritional counselling throughout the intervention. The primary outcome is change from baseline to 12 weeks in hepatic fat; secondary outcomes include measures of cardiometabolic health. ETHICS AND DISSEMINATION: This study was approved by Granada Provincial Research Ethics Committee (CEI Granada-0365-N-23). All participants will be asked to provide written informed consent. The findings will be disseminated in scientific journals and at international scientific conferences. TRIAL REGISTRATION NUMBER: NCT05897073.

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 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.

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.