Heart Rate and Its Variability Are Associated With Resting Metabolic Rate and Substrate Oxidation in Young Women but Not in Men.

BACKGROUND: This study aims to examine the relationship between resting vagal-related heart rate variability (HRV) parameters and heart rate (HR) with resting metabolic rate (RMR) and respiratory exchange ratio (RER) in young adults. METHODS: A total of 74 young adults (22 ± 2 years old, 51 women) were included in this cross-sectional study. HRV was assessed using a HR monitor, whereas RMR and RER were determined by indirect calorimetry. RESULTS: Linear regression analyses showed a positive association between HR and RER in women (standardized ß = 0.384, p = 0.008), while negative associations were observed between vagal-related HRV parameters and RER in women (ß ranged from -0.262 to -0.254, all p ≤ 0.042). No significant association was found between the abovementioned physiological parameters in men. CONCLUSION: Here, we show that HR is positively associated with RER in young women but not in men, while vagal-related HRV parameters are inversely related to RMR, therefore suggesting a potential sexual dimorphism between cardiac rhythm and its relationship with markers of cardiometabolic health status. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02365129.

No effect of circulating leptin on energy metabolism in normal weight or overweight/obese lactating mothers: The case-control Breastmilk and the Link to Overweight/Obesity and Maternal diet (BLOOM) study.

BACKGROUND & AIMS: Pregnancy and lactation are associated with metabolic changes, including alterations in energy metabolism, which are closely linked to body mass and composition due to hormonal status. Therefore, the objective of this study was to investigate the energy metabolism in exclusively or predominantly breastfeeding mothers with normal weight (NW) and overweight/obesity (OW/OB) and evaluate its associations with fasting serum leptin. METHODS: This cross-sectional BLOOM study was conducted among 39 mothers (n = 19 NW, n = 20 OW/OB) in 15.5 ± 1.2 weeks of lactation. The leptin was analyzed in a blood sample using an enzyme-linked immunosorbent assay, body composition was analyzed by dual-energy X-ray absorptiometry, and resting metabolic rate (RMR) was measured by indirect calorimetry method. RESULTS: The average RMR for all groups was 1747.5 ± 281.9 kcal/d, with a statistically significant difference between groups (1932.7 ± 222.6 vs. 1550.5 ± 190.6, p < 0.001, respectively in the OW/OB and NW group). The OW/OB mothers had higher oxygen uptake (VO2) and exhaled carbon dioxide (VCO2), but not respiratory quotient (RQ), carbohydrate (CHO%) and lipid oxidation (FAT%). When analyzing correlations stratified by BMI category, we found that serum leptin was correlated with CHO% negatively, and with FAT% positively in the NW but not in OW/OB mothers. Additionally, serum leptin was a significant predictor of RMR, VCO2, VO2, CHO%, and RMR/kg of total body weight. However, after adjusting for confounders, the observed associations were no longer statistically significant (RMR: ß = 0.113, 95% CI -0.354-0.319; VO2: ß = 0.141, 95% CI -0.462-0.744; VCO2: ß = 0.238, 95% CI -0.411-0.888; CHO%: ß = -0.146, 95% CI -0.151-0.444; RMR/kg of total body weight: ß = -0.294, 95% CI -0.831-0.244). CONCLUSIONS: Our results did not support the hypothesis that leptin plays a role in regulating energy homeostasis during lactation.

The Energetic Saver Profile From Sit-to-Stand Does Not Persist During Very Low-Intensity Physical Activity in Healthy Men and Women.

BACKGROUND: It is essential to better characterize the energetic profile of individuals during very low-intensity physical activity. The objectives of the present study were to determine whether the saver profile from sit-to-stand persists during light physical activity and characterize patterns in substrate utilization from sit-to-stand and during very low-intensity physical activity in healthy men and women. METHODS: Sixty-two healthy adults (38 women) performed an experimental sequence that corresponded to 15-minute sitting (SIT1), followed by 15-minute standing (STAND), 15-minute sitting again (SIT2), and finally 15 minutes of light cycling. Continuous indirect calorimetry was allowed to calculate energy expenditure (EE) and respiratory quotient through the entire sequence. Savers and nonsavers (<5% and ≥ 5% increase in EE from sitting to standing, respectively) were determined. RESULTS: There was an interaction effect in EE between savers and nonsavers through the whole sequence (P = .008). Only nonsavers (71%) exhibited a significant increase in EE from SIT1 to STAND (P < .001). Nonsavers and savers significantly increased EE during 15 minutes of light cycling relative to sitting or standing (P < .001), without any difference between groups. The percentage of change in respiratory quotient from SIT1 to STAND was significantly different between the 2 groups, with increased values in savers and decreased values in nonsavers (P = .03). Significantly lower values in respiratory quotient and EE were found during 15 minutes of light cycling in women compared with men (P < .001). CONCLUSIONS: It is essential to determine individuals' energetic phenotype to determine those who may benefit more from strategies such as standing or light physical activity. The sexual dimorphism in terms of substrate use during such exercise should be considered.

Influence of the CYP1A2 c.-163 A > C polymorphism in the effect of caffeine on fat oxidation during exercise: a pilot randomized, double-blind, crossover, placebo-controlled trial.

PURPOSE: The aim of this study was to determine the influence of the CYP1A2 c.-163 A > C (rs762551) polymorphism on the effect of oral caffeine intake on fat oxidation during exercise. METHODS: Using a pilot randomized, double-blind, crossover, placebo-controlled trial, 32 young and healthy individuals (women = 14, men = 18) performed an incremental test on a cycle ergometer with 3-min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Participants performed this test after the ingestion of (a) placebo; (b) 3 mg/kg of caffeine; (c) 6 mg/kg of caffeine. Fat oxidation rate during exercise was measured by indirect calorimetry. The influence of the CYP1A2 c.-163 A > C polymorphism in the effect of caffeine on fat oxidation rates during exercise was established with a three-way ANOVA (substance × genotype × intensity). RESULTS: Eight participants were genotyped as AA, 18 participants were CA heterozygotes, and 6 participants were CC. There was a main effect of substance (F = 3.348, p = 0.050) on fat oxidation rates during exercise with no genotype effect (F = 0.158, p = 0.959). The post hoc analysis revealed that, in comparison to the placebo, 3 and 6 mg/kg of caffeine increased fat oxidation at 40-50% VO2max in AA (all p < 0.050) and 50-60% VO2max in CA and CC participants (all p < 0.050). CONCLUSION: Oral intake of 3 and 6 mg/kg of caffeine increased fat oxidation rate during aerobic exercise in individuals with AA, CA and CC genotypes. This suggests that the effect of caffeine to enhance fat oxidation during exercise is not influenced by the CYP1A2 c.-163 A > C polymorphism. TRIAL REGISTRATION: The study was registered on clinicaltrials.gov with ID: NCT05975489.

Durability and Underlying Physiological Factors: How Do They Change Throughout a Cycling Season in Semiprofessional Cyclists?

PURPOSE: To investigate how cycling time-trial (TT) performance changes over a cycling season, both in a "fresh" state and in a "fatigued" state (durability). Additionally, the aim was to explore whether these changes are related to changes in underlying physiological factors such as gross efficiency, energy expenditure (EE), and substrate oxidation (fat oxidation [FatOx] and carbohydrate oxidation [CarbOx]). METHODS: Sixteen male semiprofessional cyclists visited the laboratory on 3 occasions during a cycling season (PRE, START, and IN) and underwent a performance test in both fresh and fatigued states (after 38.1 [4.9] kJ/kg), containing a submaximal warm-up for the measurement of gross efficiency, EE, FatOx, and CarbOx and a maximal TT of 1 (TT1min) and 10 minutes (TT10min). Results were compared across states (fresh vs fatigued) and periods (PRE, START, and IN). RESULTS: The average power output (PO) in TT1min decreased (P < .05) from fresh to fatigued state across all observed periods, whereas there was no change in the PO in TT10min. Over the course of the season, the PO in TT1min in the fatigued state improved more compared with the PO in TT1min in the fresh state. Furthermore, while EE did not significantly change, there was an increase in FatOx and a decrease in CarbOx toward the fatigued state. These changes diminished during the cycling season (IN), indicating a greater contribution of CarbOx in the fatigued state. CONCLUSIONS: TT1min performance is more sensitive to fatigue compared with TT10min. Also, during a cycling season, durability improves more when compared with fresh maximal POs, which is also observed in the changes in substrate oxidation.

Exogenous erythropoietin increases hematological status, fat oxidation, and aerobic performance in males following prolonged strenuous training.

This study investigated the effects of EPO on hemoglobin (Hgb) and hematocrit (Hct), time trial (TT) performance, substrate oxidation, and skeletal muscle phenotype throughout 28 days of strenuous exercise. Eight males completed this longitudinal controlled exercise and feeding study using EPO (50 IU/kg body mass) 3×/week for 28 days. Hgb, Hct, and TT performance were assessed PRE and on Days 7, 14, 21, and 27 of EPO. Rested/fasted muscle obtained PRE and POST EPO were analyzed for gene expression, protein signaling, fiber type, and capillarization. Substrate oxidation and glucose turnover were assessed during 90-min of treadmill load carriage (LC; 30% body mass; 55 ± 5% V̇O2peak) exercise using indirect calorimetry, and 6-6-[2H2]-glucose PRE and POST. Hgb and Hct increased, and TT performance improved on Days 21 and 27 compared to PRE (p < 0.05). Energy expenditure, fat oxidation, and metabolic clearance rate during LC increased (p < 0.05) from PRE to POST. Myofiber type, protein markers of mitochondrial biogenesis, and capillarization were unchanged PRE to POST. Transcriptional regulation of mitochondrial activity and fat metabolism increased from PRE to POST (p < 0.05). These data indicate EPO administration during 28 days of strenuous exercise can enhance aerobic performance through improved oxygen carrying capacity, whole-body and skeletal muscle fat metabolism.

Effects of CurraNZ, a New Zealand Blackcurrant Extract during 1 Hour of Treadmill Running in Female and Male Marathon des Sables Athletes in Hot Conditions: Two Case Studies.

Four weeks before competition in the 2023 Marathon des Sables, a 6-stage, ~250 km running event in the Sahara Desert, we examined the effects of a 7-day intake of New Zealand blackcurrant extract (210 mg anthocyanins per day) on 1 h treadmill running-induced physiological and metabolic responses in the heat (~34 °C, relative humidity: ~30%) in non-acclimatized amateur female and male athletes (age: 23, 38 yrs, BMI: 24.2, 28.4 kg·m-2, body fat%: 29.2, 18.8%, V˙O2max: 50.1, 52.1 mL·kg-1·min-1). During the 1 h run at 50%V˙O2max (speed female: 7.3, male: 7.5 km·h-1), indirect calorimetry was used, and heart rate was recorded at 15 min intervals with core temperature monitoring (0.05 Hz). The 1 h runs took place 3 h after a light breakfast and 2 h after intake of the final dose of New Zealand blackcurrant extract with water allowed ad libitum during the run. The New Zealand blackcurrant extract had no effects on the female athlete. The respiratory exchange ratio (RER) of the female athlete in the non-supplement control condition was 0.77 ± 0.01, indicating an existing ~77% contribution of fat oxidation to the energy requirements. In the male athlete, during 1 h of running, fat oxidation was higher by 21% (p < 0.01), carbohydrate oxidation was 31% lower (p = 0.05), RER was 0.03 units lower (p = 0.04), and core temperature was 0.4 °C lower (p < 0.01) with no differences for heart rate, minute ventilation, oxygen uptake, and carbon dioxide production for the New Zealand blackcurrant condition compared to the non-supplement control condition. Seven-day intake of New Zealand blackcurrant extract (210 mg anthocyanins per day) provided beneficial physiological and metabolic responses during exertional heat stress by 1 h of indoor (~34 °C) treadmill running in a male Marathon des Sables athlete 4 weeks before competition. Future work is required to address whether New Zealand blackcurrant provides a nutritional ergogenic effect for Marathon des Sables athletes during long-duration running in the heat combined with personalized nutrition.

Investigating Ligand Sphere Perturbations on MnIII-Alkylperoxo Complexes.

Manganese catalysts that activate hydrogen peroxide carry out several different hydrocarbon oxidation reactions with high stereoselectivity. The commonly proposed mechanism for these reactions involves a key manganese(III)-hydroperoxo intermediate, which decays via O-O bond heterolysis to generate a Mn(V)-oxo species that institutes substrate oxidation. Due to the scarcity of characterized MnIII-hydroperoxo complexes, MnIII-alkylperoxo complexes are employed to understand factors that affect the mechanism of the O-O cleavage. Herein, we report a series of novel complexes, including two room-temperature-stable MnIII-alkylperoxo species, supported by a new amide-containing pentadentate ligand (6Medpaq5NO2). We use a combination of spectroscopic methods and density functional theory computations to probe the effects of the electronic changes in the ligand sphere trans to the hydroxo and alkylperoxo units to thermal stability and reactivity. The structural characterizations for both MnII(OTf)(6Medpaq5NO2) and [MnIII(OH)(6Medpaq5NO2)](OTf) were obtained via single-crystal X-ray crystallography. A perturbation to the ligand sphere allowed for a marked increase in reactivity towards an organic substrate, a modest change in the distribution of the O-O cleavage products from homolytic and heterolytic pathways, and little change in thermal stability.

Pioglitazone does not enhance exogenous glucose oxidation or metabolic clearance rate during aerobic exercise in men under acute high-altitude exposure.

Insulin insensitivity decreases exogenous glucose oxidation and metabolic clearance rate (MCR) during aerobic exercise in unacclimatized lowlanders at high altitude (HA). Whether use of an oral insulin sensitizer before acute HA exposure enhances exogenous glucose oxidation is unclear. This study investigated the impact of pioglitazone (PIO) on exogenous glucose oxidation and glucose turnover compared with placebo (PLA) during aerobic exercise at HA. With the use of a randomized crossover design, native lowlanders (n = 7 males, means ± SD, age: 23 ± 6 yr, body mass: 84 ± 11 kg) consumed 145 g (1.8 g/min) of glucose while performing 80 min of steady-state (1.43 ± 0.16 V̇o2 L/min) treadmill exercise at HA (460 mmHg; [Formula: see text] 96.6 mmHg) following short-term (5 days) use of PIO (15 mg oral dose per day) or PLA (microcrystalline cellulose pill). Substrate oxidation and glucose turnover were determined using indirect calorimetry and stable isotopes ([13C]glucose and 6,6-[2H2]glucose). Exogenous glucose oxidation was not different between PIO (0.31 ± 0.03 g/min) and PLA (0.32 ± 0.09 g/min). Total carbohydrate oxidation (PIO: 1.65 ± 0.22 g/min, PLA: 1.68 ± 0.32 g/min) or fat oxidation (PIO: 0.10 ± 0.0.08 g/min, PLA: 0.09 ± 0.07 g/min) was not different between treatments. There was no treatment effect on glucose rate of appearance (PIO: 2.46 ± 0.27, PLA: 2.43 ± 0.27 mg/kg/min), disappearance (PIO: 2.19 ± 0.17, PLA: 2.20 ± 0.22 mg/kg/min), or MCR (PIO: 1.63 ± 0.37, PLA: 1.73 ± 0.40 mL/kg/min). Results from this study indicate that PIO is not an effective intervention to enhance exogenous glucose oxidation or MCR during acute HA exposure. Lack of effect with PIO suggests that the etiology of glucose metabolism dysregulation during acute HA exposure may not result from insulin resistance in peripheral tissues.NEW & NOTEWORTHY Short-term (5 days) use of the oral insulin sensitizer pioglitazone does not alter circulating glucose or insulin responses to enhance exogenous glucose oxidation during steady-state aerobic exercise in young healthy men under simulated acute (8 h) high-altitude (460 mmHg) conditions. These results indicate that dysregulations in glucose metabolism in native lowlanders sojourning at high altitude may not be due to insulin resistance at peripheral tissue.

Postprandial energy metabolism is modulated in response to a low-intensity walking exercise in fasted healthy individuals.

Postprandial metabolism is a relevant indicator of overall metabolic health, which can be influenced by a single bout of exercise before food consumption. The present study examined the effects of an acute, fasted, low-intensity exercise on postprandial metabolism and appetite sensations. We hypothesized that exercise would induce an increase in postprandial fat oxidation, associated with better satiety responses. Twenty-two healthy adults (16 females) attended the laboratory twice separated by a minimum of 3 days to perform 2 conditions: (1) a control condition and (2) an exercise condition (EX) with a 30-minute low-intensity walking exercise performed before the breakfast (500-kcal fixed meal). Subjective appetite sensations were assessed before and up to 60 minutes after the meal in regular intervals. Energy expenditure and substrate oxidation were measured until 2 hours after the meal. Energy expenditure and carbohydrate oxidation were higher in the EX condition (condition effect: P < .01). There was no effect of exercise on appetite sensations and overall fat oxidation, but a higher increase in relative and absolute fat oxidation was observed from 15- to 45-minutes postmeal in EX compared with control (time × condition interaction effect: P < .05). In the EX condition only, postprandial satiety was associated positively with postprandial fat oxidation and negatively with carbohydrate oxidation. To conclude, a fasted low-intensity exercise induced an enhancement of postprandial metabolic flexibility through the modulation of fat oxidation. Substrate oxidation appeared to be related to satiety only after exercise, suggesting a specific regulation of appetite induced by exercise.

Influence of the time of day in the effect of caffeine on maximal fat oxidation during exercise in women: a randomized, crossover, double-blind, and placebo-controlled study.

PURPOSE: Caffeine is a stimulant with well-recognized performance and metabolic benefits, however, there is a lack of studies investigating the time-of-day influence in the properties of caffeine to enhance fat oxidation in women. Thus, the aim of the present study was to evaluate the influence of the time of the day on the effect of caffeine on the maximal rate of fat oxidation during aerobic exercise in trained women. METHODS: Fourteen female athletes (25.5 ± 7.1 years) took part in a randomized, crossover, double-blind study. All participants undertook four different experimental trials combining the ingestion of 3 mg/kg caffeine and a placebo either in the morning (8.00-10.00 h) and in the evening (17.00-19.00 h) realizing an incremental test on a cycle ergometer with 3 min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Substrate oxidation rates were measured by indirect calorimetry. In each trial, the maximum rate of fat oxidation (MFO) and the intensity that elicited MFO (Fatmax) were measured. RESULTS: In comparison to placebo, MFO was significantly higher with caffeine both in the morning (0.24 ± 0.13 vs 0.30 ± 0.14 g/min; p < 0.001; ES = 0.79) and in the evening (0.21 ± 0.08 vs 0.28 ± 0.10 g/min; p = 0.002; ES = 0.72). No time-of-day effect on the capacity of caffeine to increase MFO was found (all p = 0.336) CONCLUSION: The intake of 3 mg/kg of caffeine increased the use of fat as a fuel during exercise independently of the time-of-day in trained women. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov with the following ID: NCT05880186 by 15 May 2023.

Human HDL subclasses modulate energy metabolism in skeletal muscle cells.

In addition to its antiatherogenic role, HDL reportedly modulates energy metabolism at the whole-body level. HDL functionality is associated with its structure and composition, and functional activities can differ between HDL subclasses. Therefore, we studied if HDL2 and HDL3, the two major HDL subclasses, are able to modulate energy metabolism of skeletal muscle cells. Differentiated mouse and primary human skeletal muscle myotubes were used to investigate the influences of human HDL2 and HDL3 on glucose and fatty uptake and oxidation. HDL-induced changes in lipid distribution and mRNA expression of genes related to energy substrate metabolism, mitochondrial function, and HDL receptors were studied with human myotubes. Additionally, we examined the effects of apoA-I and discoidal, reconstituted HDL particles on substrate metabolism. In mouse myotubes, HDL subclasses strongly enhanced glycolysis upon high and low glucose concentrations. HDL3 caused a minor increase in ATP-linked respiration upon glucose conditioning but HDL2 improved complex I-mediated mitochondrial respiration upon fatty acid treatment. In human myotubes, glucose metabolism was attenuated but fatty acid uptake and oxidation were markedly increased by both HDL subclasses, which also increased mRNA expression of genes related to fatty acid metabolism and HDL receptors. Finally, both HDL subclasses induced incorporation of oleic acid into different lipid classes. These results, demonstrating that HDL subclasses enhance fatty acid oxidation in human myotubes but improve anaerobic metabolism in mouse myotubes, support the role of HDL as a circulating modulator of energy metabolism. Exact mechanisms and components of HDL causing the change, require further investigation.

The Effect of Exercise Intensity on Carbohydrate Sparing Postexercise: Implications for Postexercise Hypoglycemia.

The purpose of this study was to determine the effect of exercise intensity on the proportion and rate of carbohydrate oxidation and glucoregulatory hormone responses during recovery from exercise. Six physically active participants completed 1 hr of low-intensity (LI; 50% lactate threshold) or moderate-intensity (MI; 100% lactate threshold) exercise on separate days following a randomized counterbalanced design. During exercise and for 6 hr of recovery, samples of expired air were collected to determine oxygen consumption, respiratory exchange ratio, energy expenditure, and substrate oxidation rates. Blood samples were also collected to measure glucoregulatory hormones (catecholamines, GH) and metabolites (glucose, free fatty acids, lactate, pH, and bicarbonate). During exercise, respiratory exchange ratio, energy expenditure, and the proportion and rate of carbohydrate (CHO) oxidation were higher during MI compared with LI. However, during recovery from MI, respiratory exchange ratio and the proportion and rate of CHO oxidation were lower than preexercise levels and corresponding LI. During exercise and early recovery, catecholamines and growth hormone were higher in MI than LI, and there was a trend for higher levels of free fatty acids in the early recovery from MI compared with LI. In summary, CHO oxidation during exercise increases with exercise intensity but there is a preference for CHO sparing (and fat oxidation) during recovery from MI exercise compared with LI exercise. This exercise intensity-dependent shift in substrate oxidation during recovery is explained, in part, by the pattern of change of key glucoregulatory hormones including catecholamines and growth hormone and plasma fatty acid concentrations.

Effects of an antioxidants cocktail on glucose metabolism at rest, during exercise, and during a glucose load in healthy young subjects

Background: Reactive oxygen species (ROS) regulate glucose metabolism (GM) in skeletal muscle by improving the translocation of GLUT4. Antioxidant supplementation could block this physiological effect, altering glucose signaling during exercise. However, there is limited evidence in humans on whether antioxidant intake affects GM. Therefore, we aimed to determine the effect of an antioxidant cocktail (AOC) on GM at rest and during metabolic challenges. Methods: Ten healthy male subjects received AOC supplementation (1000 mg of Vitamin C, 600 IU of Vitamin E, and 600 mg of α-lipoic acid) or placebo (2.000 mg of talc) before two trials conducted 7 days apart. Trial 1: AOC 120 and 90 minutes before an endurance exercise (EEX) bout at 60 % of maximal oxygen uptake (VO2max); Trial 2: AOC 120 and 90 minutes before an oral glucose tolerance test (OGTT; 75 g glucose). Measurements of gas exchange and capillary blood samples were collected every 15 minutes during both trials. Results: AOC supplementation increased resting glucose levels (p<0.05). During Trial 1 (EEX), the AOC increased carbohydrate oxidation (CHOox) (p= 0.03), without effect in glucose blood levels. During Trial 2 (OGTT), the AOC supplementation had no significant effect on GM parameters. Conclusion: Acute supplementation with AOC increased resting glucose levels and CHOox during EEX in healthy subjects, with no effect on GM during the OGTT.

Antecedentes: Las especies reactivas de oxígeno (ROS) regulan el metabolismo de la glucosa (GM) en el músculo esquelético al mejorar la translocación de GLUT4. La suplementación con antioxidantes podría bloquear este efecto fisiológico, alterando la señalización de la glucosa durante el ejercicio. Sin embargo, existe evidencia limitada en humanos sobre si la ingesta de antioxidantes afecta el GM. Por lo tanto, nuestro objetivo fue determinar el efecto de un cóctel de antioxidantes (AOC) en el GM en reposo y durante desafíos metabólicos. Métodos: Sujetos sanos (sexo masculino; n= 10) recibieron suplementos de AOC (1.000 mg de vitamina C, 600 UI de vitamina E y 600 mg de ácido α-lipoico) o placebo (2.000 mg de talco) previo a dos pruebas realizadas con 7 días de diferencia. Prueba 1: AOC 120 y 90 minutos antes de una serie de ejercicio de resistencia (EEX) al 60% del consumo máximo de oxígeno (VO2max); prueba 2: AOC 120 y 90 minutos antes de una prueba de tolerancia oral a la glucosa (OGTT; 75 g de glucosa). Se obtuvieron datos de intercambio de gaseoso y muestras de sangre capilar cada 15 minutos durante ambas pruebas. Resultados: la suplementación con AOC aumentó los niveles de glucosa en reposo (p<0,05). Durante la prueba 1 (EEX), el AOC aumentó la oxidación de carbohidratos (CHOox) (p= 0,03), sin efecto en los niveles de glucosa en sangre. Durante la prueba 2 (OGTT), la suplementación con AOC no tuvo un efecto significativo en los parámetros de GM. Conclusión: Una suplementación aguda con AOC aumentó los niveles de glucosa en reposo y la CHOox durante EEX en sujetos sanos, sin efecto sobre el GM durante la OGTT.

The impact of prolonged fasting on 24h energy metabolism and its 24h rhythmicity in healthy, lean males: A randomized cross-over trial.

OBJECTIVE: Human energy expenditure and substrate oxidation are under circadian control and food intake is a time cue for the human biological clock, leading to 24h feeding-fasting cycles in energy and substrate metabolism. In recent years, (intermittent) fasting protocols have also become popular to improve metabolic health. Here, we aimed to investigate the impact of food intake on the 24h patterns of energy metabolism as well as to provide data on the timeline of changes in energy metabolism that occur upon an extended period of fasting. RESEARCH DESIGN AND METHODS: In a randomized, cross-over design, twelve healthy males underwent a 60h fast which was compared to a 60h fed condition. In the fed condition meals were provided at energy balance throughout the study. Conditions were separated by a two week period of habitual diet. Volunteers resided in a respiration chamber for the entire 60h to measure energy expenditure and substrate oxidation hour by hour. Volunteers performed a standardized activity protocol while in the chamber. Blood samples were drawn after 12, 36 and 60h. RESULTS: Immediately following the breakfast meal (in the fed condition), fat oxidation became higher in the fasted condition compared to the fed condition and remained elevated throughout the study period. The initial rapid increase in fat oxidation corresponded with a decline in the hepatokine activin A (r = -0.86, p = 0.001). The contribution of fat oxidation to total energy expenditure gradually increased with extended abstinence from food, peaking after 51h of fasting at 160 mg/min. Carbohydrate oxidation stabilized at a low level during the second day of fasting and averaged around 60 mg/min with only modest elevations in response to physical activity. Although 24h energy expenditure was significantly lower with prolonged fasting (11.0 ± 0.4 vs 9.8 ± 0.2 and 10.9 ± 0.3 vs 10.3 ± 0.3 MJ in fed vs fasting, day 2 and 3 respectively, p < 0.01), the 24h fluctuations in energy expenditure were comparable between the fasted and fed condition. The fluctuations in substrate oxidation were, however, significantly (p < 0.001 for both carbohydrate and fat oxidation) altered in the fasted state, favouring fat oxidation. CONCLUSIONS: Energy expenditure displays a day-night rhythm, which is independent of food intake. In contrast, the day-night rhythm of both carbohydrate and fat oxidation is mainly driven by food intake. Upon extended fasting, the absolute rate of fat oxidation rapidly increases and keeps increasing during a 60h fast, whereas carbohydrate oxidation becomes progressively diminished. TRIAL REGISTRATION: www.trialregister.nl NTR 2042.

Substrate oxidation during exercise in childhood acute lymphoblastic leukemia survivors.

Children with acute lymphoblastic leukemia (ALL) are at high risk of developing long-term cardiometabolic complications during their survivorship. Maximal fat oxidation (MFO) is a marker during exercise of cardiometabolic health, and is associated with metabolic risk factors. Our aim was to characterize the carbohydrate and fat oxidation during exercise in childhood ALL survivors. Indirect calorimetry was measured in 250 childhood ALL survivors to quantify substrate oxidation rates during a cardiopulmonary exercise test. A best-fit third-order polynomial curve was computed for fat oxidation rate (mg/min) against exercise intensity (%V̇O2peak) and was used to determine the MFO and the peak fat oxidation (Fatmax). The crossover point was also identified. Differences between prognostic risk groups were assessed (ie, standard risk [SR], high risk with and without cardio-protective agent dexrazoxane [HR + DEX and HR]). MFO, Fatmax and crossover point were not different between the groups (p = .078; p = .765; p = .726). Fatmax and crossover point were achieved at low exercise intensities. A higher MFO was achieved by men in the SR group (287.8 ± 111.2 mg/min) compared to those in HR + DEX (239.8 ± 97.0 mg/min) and HR groups (229.3 ± 98.9 mg/min) (p = .04). Childhood ALL survivors have low fat oxidation during exercise and oxidize carbohydrates at low exercise intensities, independently of the cumulative doses of doxorubicin they received. These findings alert clinicians on the long-term impact of cancer treatments on childhood ALL survivors' substrate oxidation.

Effect of 3 and 6 mg/kg of caffeine on fat oxidation during exercise in healthy active females.

The aim of this study was to investigate the effect of 3 and 6 mg of caffeine per kg of body mass (mg/kg) on whole-body substrate oxidation during an incremental cycling exercise test in healthy active women. Using a double-blind placebo-controlled counterbalanced experimental design, 14 subjects performed three identical exercise trials after the ingestion of 3 or 6 mg/kg of caffeine or placebo. The exercise trials consisted of an incremental test on a cycle ergometer with 3-min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Substrate oxidation rates were measured by indirect calorimetry. During exercise, there was a significant effect of substance (F = 5.221; p = 0.016) on fat oxidation rate. In comparison to the placebo, 3 mg/kg of caffeine increased fat oxidation rates at 30 to 60% of VO2max (all p < 0.050) and 6 mg/kg at 30 to 50% of VO2max (all p < 0.050). There was also a significant effect of substance (F = 5.221; p = 0.016) on carbohydrate oxidation rate (F = 9.632; p < 0.001). In comparison to placebo, both caffeine doses decreased carbohydrate oxidation rates at 40 to 60% VO2max (all p < 0.050). The maximal rate of fat oxidation with placebo was 0.24 ± 0.03 g/min, which increased with 3 mg/kg to 0.29 ± 0.04 g/min (p = 0.032) and to 0.29 ± 0.03 with 6 mg/kg of caffeine (p = 0.042). Acute intake of caffeine improves the utilization of fat as a fuel during submaximal aerobic exercise in healthy active women with an effect of similar magnitude after the intake of 3 and 6 mg of caffeine per kg of body mass. Thus, the use of 3 mg/kg of caffeine would be more recommended than 6 mg/kg for women seeking increased fat utilization during submaximal exercise.

Effects of phenylcapsaicin on aerobic capacity and physiological parameters in active young males: a randomized, triple-blinded, placebo-controlled, crossover trial.

Objective: Phenylcapsaicin (PC) is a new capsaicin analog which has exhibited a higher bioavailability. This sudy assessed the effects of a low dose (LD) of 0.625 mg and a high dose (HD) of 2.5 mg of PC on aerobic capacity, substrate oxidation, energy metabolism and exercise physiological variables in young males. Materials and methods: Seventeen active males (age = 24.7 ± 6.0 years) enrolled to this randomized, triple-blinded, placebo-controlled, crossover trial. Participants attended the laboratory on 4 sessions separated by 72-96 h. A submaximal exercise test [to determine maximal fat oxidation (MFO) and the intensity at MFO (FATmax)] followed by a maximal incremental test (to determine VO2max) were performed in a preliminary session. The subsequent sessions only differed in the supplement ingested [LD, HD or placebo (PLA)] and consisted of a steady-state test (60 min at FATmax) followed by a maximal incremental test. Energy metabolism, substrate oxidation, heart rate, general (gRPE) and quadriceps (RPEquad) rate of perceived exertion, skin temperature and thermal perception were tested. Results: Clavicle thermal perception was lower in HD compared to PLA and LD (p = 0.04) across time. HD reduced maximum heart rate in comparison to PLA and LD (p = 0.03). LD reported higher general RPE (RPEg) values during the steady-state test compared to PLA and HD across time (p = 0.02). HD and LD elicited higher peak of fat oxidation during the steady-state test compared with PLA (p = 0.05). Intra-test analyses revealed significant differences for fat oxidation (FATox) in favor of HD and LD compared to PLA (p = 0.002 and 0.002, respectively), and for carbohydrate oxidation (CHOox) (p = 0.05) and respiratory exchange ratio (RER) (p = 0.03) for PLA. In the incremental test, only general RPE at 60% of the maximal intensity (W) differed favoring HD (p ≤ 0.05). Conclusion: Therefore, PC may contribute to increase aerobic capacity through the improvement of fat oxidation, maximum heart rate and perceptual responses during exercise.

Astaxanthin Reduces Heart Rate and Carbohydrate Oxidation Rates During Exercise in Overweight Individuals.

Astaxanthin (AX) is an antioxidant which may spare endogenous carbohydrates and improve fat oxidation rates, thus improving metabolic flexibility. To date, no studies have attempted to examine the impact of AX in an overweight cohort, whom often suffer from metabolic inflexibility. Nineteen subjects (mean ± SD: age: 27.5 ± 6.3 years; height: 169.7 ± 9.0 cm; body mass: 96.4 ± 17.9 kg; BF%: 37.9 ± 7.0%; BMI: 33.4 ± 5.6 kg/m2; VO2peak: 25.9 ± 6.7 ml·kg-1·min-1) were recruited and supplemented with either 12 mg of AX or placebo (PLA) for 4 weeks. Subjects completed a graded exercise test on a cycling ergometer to examine changes in substrate oxidation rates. A total of 5 stages, each lasting 5 min and resistance increased 15 W each stage, were completed to examine changes in levels of glucose and lactate, fat and carbohydrate (CHO) oxidation rates, heart rate, and rating of perceived exertion (RPE). Although there were no changes found in rates of fat oxidation, blood lactate or glucose, or RPE (all p > 0.05), a significant decrease was observed in CHO oxidation from pre to post supplementation in the AX group only. Further, the AX group demonstrated a 7% decrease in heart rate across the graded exercise test. These findings suggest that 4 weeks of AX supplementation may offer some cardiometabolic benefits to overweight individuals, and be a favorable supplement for these individuals beginning an exercise program.

Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease.

Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild-type male mice. Peak oxygen uptake ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ ), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate-associated workload were determined by indirect calorimetry during an incremental cycle-ergometer test. Despite having a much lower V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ (24.7 ± 4 vs. 42.5 ± 11.4 mL kg-1  min-1 , respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min-1 , P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ , P < 0.0001) and MFO rate-associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg-1 , P = 0.020) than controls. No between-group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near-maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease. KEY POINTS: Physically active McArdle patients show an exceptional fat oxidation capacity. Maximal fat oxidation rate occurs near-maximal exercise capacity in these patients. McArdle patients' exercise tolerance might rely on maximal fat oxidation rate capacity. Hyperpnoea might cloud substrate oxidation measurements in some patients. An animal model revealed overall no higher molecular markers of lipid transport/metabolism.