Load carriage physiology in normoxia and hypoxia.

PURPOSE: To determine the effects of load carriage in normoxia and normobaric hypoxia on ventilatory responses, hemodynamics, tissue oxygenation, and metabolism. METHODS: Healthy males (n = 12) completed 3 randomly ordered baseline graded exercise tests in the following conditions: (1) unloaded normoxic (U: FIO2 = 20.93%), (2) loaded (~ 30 kg) normoxic (LN), and (3) loaded hypoxic simulating ~ 3650 m (LH: FIO2 = ~ 13%). Thereafter, experimental exercise trials were completed in quasi-randomized order (i.e., U completed first) consisting of 3 × 10 min of walking (separated by 5 min seated rest) with stages matched with the U condition (in ascending order) for relative intensity, absolute oxygen consumption ([VO2]; 1.7 L min-1), and walking speed (1.45 ± 0.15 m s-1). RESULTS: Load carriage increased perceived exertion and reduced VO2max (LN: - 7%; LH: - 32%; p < 0.05). At matched VO2, stroke volume and tidal volume were reduced and maintained with LN and LH vs. U, respectively (p < 0.05). Increases in cardiac output and minute ventilation at matched VO2 (with LH) and speed (with LN and LH), were primarily accomplished via increases in heart rate and breathing frequency (p < 0.05). Cerebral oxygenated hemoglobin (O2HHb) was increased at all intensities with LN, but deoxygenated hemoglobin and total hemoglobin were increased with LH (p < 0.05). Muscle oxygen kinetics and substrate utilization were similar between LN and U, but LH increased CHO dependence and reduced muscle O2HHb at matched speed (p < 0.05). CONCLUSION: Load carriage reduces cardiorespiratory efficiency and increases physiological strain, particularly in hypoxic environments. Potential load carriage-induced alterations in cerebral blood flow may increase the risk for altitude illnesses and requires further study.

Substrate utilization and durability during prolonged intermittent exercise in elite road cyclists.

PURPOSE: This study investigated the effects of prolonged intermittent cycling exercise on peak power output (PPO) and 6-min time-trial (6 min-TT) performance in elite and professional road cyclists. Moreover, the study aimed to determine whether changes in performance in the fatigued state could be predicted from substrate utilization during exercise and laboratory measures obtained in a fresh state. METHODS: Twelve cyclists (age: 23 years [21;25]; body mass: 71.5 kg [66.7;76.8]; height: 181 cm [178;185]; V ˙ O2peak: 73.6 ml kg-1 min-1 [71.2;76.0]) completed a graded submaximal cycling test to determine lactate threshold (LT1), gross efficiency (GE), and maximal fat oxidation (MFO) as well as power output during a maximal 6 min-TT (MPO6 min) in a fresh condition. On a separate day, the cyclists completed a 4-h intermittent cycling protocol with a high CHO intake (100 g h-1). Substrate utilization and PPO was measured hourly during the protocol, which was followed by another 6 min-TT. RESULTS: MPO6 min and PPO was reduced by 10% [4;15] and 6% [0;6], respectively, after the cycling protocol. These reductions were accompanied by reductions in the anaerobic energy contribution and V ˙ O2peak, whereas the average V ˙ O2 during the 6 min-TT was unchanged. Correlation analyses showed no strong associations between reductions in MPO6 min and PPO and laboratory measures (i.e., LT1, GE, MFO, V ˙ O2peak) obtained in the fresh condition. Additionally, fat oxidation rates during the cycling protocol were not related to changes in neither PPO nor MPO6 min. CONCLUSION: PPO and MPO6 min were reduced following prolonged intermittent cycling, but the magnitude of these reductions could not be predicted from laboratory measures obtained in the fresh condition.

Recovery from FOLFOX chemotherapy-induced systemic and skeletal muscle metabolic dysfunction in mice.

FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy is used to treat colorectal cancer and can acutely induce metabolic dysfunction. However, the lasting effects on systemic and skeletal muscle metabolism after treatment cessation are poorly understood. Therefore, we investigated the acute and lasting effects of FOLFOX chemotherapy on systemic and skeletal muscle metabolism in mice. Direct effects of FOLFOX in cultured myotubes were also investigated. Male C57BL/6J mice completed four cycles (acute) of FOLFOX or PBS. Subsets were allowed to recover for 4 wk or 10 wk. Comprehensive Laboratory Animal Monitoring System (CLAMS) metabolic measurements were performed for 5 days before study endpoint. C2C12 myotubes were treated with FOLFOX for 24 hr. Acute FOLFOX attenuated body mass and body fat accretion independent of food intake or cage activity. Acute FOLFOX decreased blood glucose, oxygen consumption (V̇o2), carbon dioxide production (V̇co2), energy expenditure, and carbohydrate (CHO) oxidation. Deficits in V̇o2 and energy expenditure remained at 10 wk. CHO oxidation remained disrupted at 4 wk but returned to control levels after 10 wk. Acute FOLFOX reduced muscle COXIV enzyme activity, AMPK(T172), ULK1(S555), and LC3BII protein expression. Muscle LC3BII/I ratio was associated with altered CHO oxidation (r = 0.75, P = 0.03). In vitro, FOLFOX suppressed myotube AMPK(T172), ULK1(S555), and autophagy flux. Recovery for 4 wk normalized skeletal muscle AMPK and ULK1 phosphorylation. Our results provide evidence that FOLFOX disrupts systemic metabolism, which is not readily recoverable after treatment cessation. FOLFOX effects on skeletal muscle metabolic signaling did recover. Further investigations are warranted to prevent and treat FOLFOX-induced metabolic toxicities that negatively impact survival and life quality of patients with cancer.NEW & NOTEWORTHY The present study demonstrates that FOLFOX chemotherapy induces long-lasting deficits in systemic metabolism. Interestingly, FOLFOX modestly suppressed skeletal muscle AMPK and autophagy signaling in vivo and in vitro. The FOLFOX-induced suppression of muscle metabolic signaling recovered after treatment cessation, independent of systemic metabolic dysfunction. Future research should investigate if activating AMPK during treatment can prevent long-term toxicities to improve health and quality of life of patients with cancer and survivors.

Influence of lactation stage on heat production and macronutrient oxidation in dairy cows during a 24-hour fasting period.

Understanding nutrient utilization and partitioning is essential for advancing the efficiency of dairy cattle. Our objective was to determine if dairy cows exposed to a 24-h fasting period differ in heat production (HP) and macronutrient oxidation at different stages of lactation. Twelve primiparous, lactating German Holstein dairy cows were used in a longitudinal study design spanning from 2013 to 2014. Dairy cows were housed in respiration chambers during 3 stages of the lactation cycle: early (mean ± SD; 28.8 ± 6.42 d), mid- (89.4 ± 4.52 d), and late (293 ± 7.76 d) lactation. Individual CO2, O2, and CH4 gas exchanges were measured every 6 min for two 24-h periods, an ad libitum period and fasting period (RES). Blood was sampled at the start and end of the RES period. Gas measurements were used to calculate HP, net carbohydrate oxidation (COX), and net fat oxidation (FOX). Measurements were corrected with metabolic BW (kg of BW0.75; cBW). The RES period for each stage of lactation was further subdivided into the start (RESstart) and end (RESend) by averaging the first and last 2 h of the RES period. The net change was calculated as RESend - RESstart. All energy variables differed among lactation stage within the RES period except for HP/cBW. As expected, COX, COX/cBW, COX/HP, HP, and HP/cBW, were greater at the RESstart compared with RESend, whereas FOX, FOX/cBW, and FOX/HP were greater at the RESend except for FOX and FOX/cBW during mid lactation, which was only a tendency for a difference. The net change for COX, COX/cBW, HP, HP/cBW, and FOX/cBW did not differ among stages of lactation. Despite detecting a tendency for a difference among stage of lactation for FOX, pairwise analysis revealed no differences. Plasma triglyceride, urea, and nonesterified fatty acid concentrations were greater at RESend than RESstart. The net change for plasma glucose, urea, ß-hydroxybutyrate, and nonesterified fatty acid concentrations were greater in early than late lactation. Our results demonstrate that despite differences in absolute measurements of energy variables and plasma metabolites, the change in whole-body macronutrient oxidation and HP as cows' transition from a fed-like state to a starvation-like state during a 24-h fasting period is consistent throughout lactation.

High fat diet improves metabolic flexibility during progressive exercise to exhaustion (VO2max testing) and during 5 km running time trials.

Recently we reported similar performances in both progressive tests to exhaustion (VO2max) and 5km running time trials (5KTT) after consuming low-carbohydrate, high-fat (LCHF) or high-carbohydrate, low-fat (HCLF) diets. Accordingly, we tested the null hypothesis that the metabolic responses during both tests would be similar across diets. In a randomized, counterbalanced, cross-over design, seven male athletes (VO2max: 61.9 ± 6.1 mL/kg/min; age: 35.6 ± 8.4 years; height: 178.7 ± 4.1 cm; mass: 68.6 ± 1.6 kg; body fat: 5.0 ± 1.3%) completed six weeks of LCHF (6/69/25% energy carbohydrate/fat/protein) and HCLF (57/28/15% energy carbohydrate/fat/protein) diets, separated by a two-week washout. Substrate utilization and energy expenditure were measured during VO2max tests and 5KTTs. The LCHF diet markedly increased fat oxidation and reduced carbohydrate oxidation, with no associated impairment in either the VO2max tests or the 5KTTs. Following the LCHF diet, athletes generated 50% or more of their energy requirements from fat at exercise intensities up to 90% VO2max and reached the crossover point for substrate utilization at ~85% VO2max. In contrast, following the HCLF diet, carbohydrate provided more than 50% of the total energy consumption at all exercise intensities. During the 5KTT, ~56% of energy was derived from fat following the LCHF diet whereas more than 93% of the energy came from carbohydrate following the HCLF diet. This study provides evidence of greater metabolic flexibility following LCHF eating and challenges the popular doctrines of "carbohydrate dependence" for high intensity exercise and the role dietary macronutrients play in human performance.

Increased exogenous but unaltered endogenous carbohydrate oxidation with combined fructose-maltodextrin ingested at 120 g h-1 versus 90 g h-1 at different ratios.

PURPOSE: This study aimed to investigate whether carbohydrate ingestion during 3 h long endurance exercise in highly trained cyclists at a rate of 120 g h-1 in 0.8:1 ratio between fructose and glucose-based carbohydrates would result in higher exogenous and lower endogenous carbohydrate oxidation rates as compared to ingestion of 90 g h-1 in 1:2 ratio, which is the currently recommended approach for exercise of this duration. METHODS: Eleven male participants (V̇O2peak 62.6 ± 7 mL kg-1 min-1, gas exchange threshold (GET) 270 ± 17 W and Respiratory compensation point 328 ± 32 W) completed the study involving 4 experimental visits consisting of 3 h cycling commencing after an overnight fast at an intensity equivalent to 95% GET. During the trials they received carbohydrates at an average rate of 120 or 90 g h-1 in 0.8:1 or 1:2 fructose-maltodextrin ratio, respectively. Carbohydrates were naturally high or low in 13C stable isotopes enabling subsequent calculations of exogenous and endogenous carbohydrate oxidation rates. RESULTS: Exogenous carbohydrate oxidation rates were higher in the 120 g h-1 condition (120-180 min: 1.51 ± 0.22 g min-1) as compared to the 90 g h-1 condition (1.29 ± 0.16 g min-1; p = 0.026). Endogenous carbohydrate oxidation rates did not differ between conditions (2.15 ± 0.30 and 2.20 ± 0.33 g min-1 for 120 and 90 g h-1 conditions, respectively; p = 0.786). CONCLUSIONS: The results suggest that carbohydrate ingestion at 120 g h-1 in 0.8:1 fructose-maltodextrin ratio as compared with 90 g h-1 in 1:2 ratio offers higher exogenous carbohydrate oxidation rates but no additional sparing of endogenous carbohydrates. Further studies should investigate potential performance effects of such carbohydrate ingestion strategies.

Effects of 2 liquid feeding rates over the first 3 months of life on whole-body energy metabolism and energy use efficiency of dairy calves up to 5 months.

Intensified milk replacer (MR) feeding in calves has nutritional long-term effects and is suggested to increase milk production later in life. However, the underlying mechanisms are not completely understood. The aim of our study was to investigate whether MR feeding intensity has long-term effects on energy metabolism and energy use efficiency of dairy calves. Newborn female Holstein calves (n = 28) were randomly assigned to 2 liquid feeding groups offered daily either 10% of body weight (BW) colostrum followed by 10% of BW MR (10%-MR) or 12% of BW colostrum followed by 20% of BW MR (20%-MR). Calves were housed individually. Weaning was completed by the end of wk 12. Hay and calf starter were fed from d 1 until the end of wk 14 and 16, respectively. A total mixed ration was fed from wk 11 onward, and the metabolizable energy intake (MEI) was determined daily. Energy metabolism of calves was measured in respiratory chambers before weaning in wk 6 and 9, and after weaning in wk 14 and 22. The MEI/BW0.75 was higher before weaning but lower during and shortly after weaning in 20%-MR calves. During the preweaning period, the 20%-MR animals had higher average daily gain, BW, back fat thickness and muscle diameter, but lower plasma ß-hydroxybutyrate concentrations. The group difference in average daily gain ceased in wk 9, differences in back fat thickness and muscle diameter ceased after weaning, whereas difference in BW0.75 persisted until wk 23. The energy conversion ratio (BW gain/MEI) was not different before weaning, but was lower during and after weaning in 20%-MR calves. The higher MEI and BW0.75 in 20%-MR calves resulted in higher heat production (HP), as well as in higher carbohydrate oxidation (COX) and fat oxidation during the preweaning period. Gas exchange variables normalized to BW0.75 or MEI differed between groups only during preweaning. The energy balance was lower in 10%-MR calves in wk 6 and 9. The HP/BW0.75 and COX/BW0.75 were higher, whereas HP/MEI was lower in 20%-MR calves in wk 6. When normalized to BW0.75 and MEI, HP in wk 6 and 9, and COX in wk 9 was lower in 20%-MR calves. In conclusion, 20%-MR calves showed greater efficiency estimates preweaning, but this effect did not occur after weaning, suggesting that energy use efficiency does not persist until later stages in life.

Influence of Fluid Delivery Schedule and Composition on Fluid Balance, Physiologic Strain, and Substrate Use in the Heat.

INTRODUCTION: Wildfire suppression is characterized by high total energy expenditure and water turnover rates. Hydration position stands outline hourly fluid intake rates. However, dose interval remains ambiguous. We aimed to determine the effects of microdosing and bolus-dosing water and microdosing and bolus-dosing carbohydrate-electrolyte solutions on fluid balance, heat stress (physiologic strain index [PSI]), and carbohydrate oxidation during extended thermal exercise. METHODS: In a repeated-measures cross-over design, subjects completed four 120-min treadmill trials (1.3 m·s-1, 5% grade, 33°C, 30% relative humidity) wearing a US Forest Service wildland firefighter uniform and a 15-kg pack. Fluid delivery approximated losses calculated from a pre-experiment familiarization trial, providing 22 doses·h-1 or 1 dose·h-1 (46±11, 1005±245 mL·dose-1). Body weight (pre- and postexercise) and urine volume (pre-, during, and postexercise) were recorded. Heart rate, rectal temperature, skin temperature, and steady-state expired air samples were recorded throughout exercise. Statistical significance (P<0.05) was determined via repeated-measures analysis of variance. RESULTS: Total body weight loss (n=11, -0.6±0.3 kg, P>0.05) and cumulative urine output (n=11, 677±440 mL, P>0.05) were not different across trials. The micro-dosed carbohydrate-electrolyte trial sweat rate was lower than that of the bolus-dosed carbohydrate-electrolyte, bolus-dosed water, and microdosed water trials (n=11, 0.8±0.2, 0.9±0.2, 0.9±0.2, 0.9±0.2 L·h-1, respectively; P<0.05). PSI was lower at 60 than 120 min (n=12, 3.6±0.7 and 4.5±0.9, respectively; P<0.05), with no differences across trials. The carbohydrate-electrolyte trial's carbohydrate oxidation was higher than water trial's (n=12, 1.5±0.3 and 0.8±0.2 g·min-1, respectively; P<0.05), with no dosing style differences. CONCLUSIONS: Equal-volume diverse fluid delivery schedules did not affect fluid balance, PSI, or carbohydrate oxidation during extended thermal work.

Lactose and Digestible Maltodextrin in Milk Replacers Differently Affect Energy Metabolism and Substrate Oxidation: A Calorimetric Study in Piglets.

BACKGROUND: In recent years, lactose-free infant formulas have been increasingly used. Digestible maltodextrins are commonly used as a substitute for lactose in these formulas, but the effects on energy metabolism are unknown. OBJECTIVE: We aimed to evaluate the differences in energy metabolism and substrate oxidation in piglets fed milk replacers containing lactose compared with maltodextrin as the only source of carbohydrates. METHODS: Piglets (Tempo × Topigs 20) from 8 litters were fed milk replacers containing lactose or maltodextrin (28% w/w, milk powder basis) from 1 to 9 wk of age (n =  4 litters/milk replacer). At 5 wk of age, 4 females and 4 entire males (mean ± SEM bodyweight, 10 ± 0.3 kg) were selected per litter, and housed in 16 groups of 4 littermates, with 2 females and 2 males per pen (n = 8 groups/milk replacer). Between 7 and 9 wk of age, groups were housed for 72 h in climate respiration chambers, and fed their experimental milk replacer in 2 meals per day, at 08:30 and 16:30. Heat production data were calculated from the continuous measurement of gaseous exchanges and analyzed using general linear models in SAS. RESULTS: Resting metabolic rate was 6% less in maltodextrin- than in lactose-fed piglets, notably before the morning meal. The postprandial respiratory quotient was 13% greater in maltodextrin- than in lactose-fed piglets after both meals. Net rates of carbohydrate oxidation were on average 5% greater in maltodextrin- than in lactose-fed piglets, particularly after the afternoon meal, whereas net rates of fat oxidation were 9% less in maltodextrin- than in lactose-fed piglets, particularly after the morning meal. CONCLUSIONS: Compared with lactose, maltodextrin in milk replacers reduced resting metabolic rate in the fasting state, and induced a shift in postprandial substrate oxidation profiles in pigs. Further research is warranted to evaluate the consequences of these metabolic changes for body composition.

Effect of flaxseed oil on muscle protein loss and carbohydrate oxidation impairment in a pig model after lipopolysaccharide challenge.

Flaxseed oil is rich in α-linolenic acid (ALA), which is the metabolic precursor of EPA and DHA. The present study investigated the effect of flaxseed oil supplementation on lipopolysaccharide (LPS)-induced muscle atrophy and carbohydrate oxidation impairment in a piglet model. Twenty-four weaned pigs were used in a 2 × 2 factorial experiment including dietary treatment (5 % maize oil v. 5 % flaxseed oil) and LPS challenge (saline v. LPS). On day 21 of treatment, the pigs were injected intraperitoneally with 100 µg/kg body weight LPS or sterile saline. At 4 h after injection, blood, gastrocnemius muscle and longissimus dorsi muscle were collected. Flaxseed oil supplementation increased ALA, EPA, total n-3 PUFA contents, protein:DNA ratio and pyruvate dehydrogenase complex quantity in muscles (P < 0·05). In addition, flaxseed oil reduced mRNA expression of toll-like receptor (TLR) 4 and nucleotide-binding oligomerisation domain protein (NOD) 2 and their downstream signalling molecules in muscles and decreased plasma concentrations of TNF-α, IL-6 and IL-8, and mRNA expression of TNF-α, IL-1ß and IL-6 (P < 0·05). Moreover, flaxseed oil inclusion increased the ratios of phosphorylated protein kinase B (Akt) 1:total Akt1 and phosphorylated Forkhead box O (FOXO) 1:total FOXO1 and reduced mRNA expression of FOXO1, muscle RING finger (MuRF) 1 and pyruvate dehydrogenase kinase 4 in muscles (P < 0·05). These results suggest that flaxseed oil might have a positive effect on alleviating muscle protein loss and carbohydrates oxidation impairment induced by LPS challenge through regulation of the TLR4/NOD and Akt/FOXO signalling pathways.

A 3-day dietary manipulation affects muscle glycogen and results in modifications of carbohydrate and fat metabolism during exercise when hyperglycaemic.

PURPOSE: The effect of hyperglycaemia on exercise with low and elevated muscle glycogen on glucose utilization (GUR), carbohydrate and fat oxidation, hormonal and metabolite responses, as well as rating of perceived exertion (RPE) were explored. METHODS: Five healthy trained males were exercised for 90 min at 70% V̇O2max in two trials, while glucose was infused intravenously at rates to "clamp" blood glucose at 12 mM. On one occasion, participants were 'loaded' with carbohydrate (CHO-L), whilst on a separate occasion, participants were glycogen depleted (CHO-D). Prior exercise and dietary manipulations produced the 'loaded' and 'depleted' states. RESULTS: The CHO-L and CHO-D conditions resulted in muscle glycogen concentrations of 377 and 159 mmol/g dw, respectively. Hyperglycaemia elevated plasma insulin concentrations with higher levels for CHO-L than for CHO-D (P < 0.01). Conversely, CHO-D elevated plasma adrenaline and noradrenaline higher than CHO-L (P < 0.05). Plasma fat metabolites (NEFA, ß-hydroxybutyrate, and glycerol) were higher under CHO-D than CHO-L (P < 0.01). The resultant was that the rates of total carbohydrate and fat oxidation were elevated and depressed for loaded CHO-L vs CHO-D respectively (P < 0.01), although no difference was found for GUR (P > 0.05). The RPE over the exercise period was higher for CHO-D than CHO-L (P < 0.05). CONCLUSION: Hyperglycaemia during exercise, when muscle glycogen is reduced, attenuates insulin but promotes catecholamines and fat metabolites. The effect is a subsequent elevation of fat oxidation, a reduction in CHO oxidation without a concomitant increase in GUR, and an increase in RPE.

Hyperinsulinaemia and hyperglycaemia promote glucose utilization and storage during low- and high-intensity exercise.

PURPOSE: The effect of hyperglycaemia with and without additional insulin was explored at a low and high intensity of exercise (40% vs 70% VO2peak) on glucose utilization (GUR), carbohydrate oxidation, non-oxidative glucose disposal (NOGD), and muscle glycogen. METHODS: Eight healthy trained males were exercised for 120 min in four trials, twice at 40% VO2peak and twice at 70% VO2peak, while glucose was infused intravenously (40%G; 70%G) at rates to "clamp" blood glucose at 10 mM. On one occasion at each exercise intensity, insulin was also infused at 40 mU/m2/per min (i.e. 40%GI and 70%GI). The glucose and insulin infusion began 30 min prior to exercise and throughout exercise. A muscle biopsy was taken at the end of exercise for glycogen analysis. RESULTS: Hyperglycaemia significantly elevated plasma insulin concentration (p < 0.001), although no difference was observed between the exercise intensities. Insulin infusion during both mild and severe exercise resulted in increased insulin concentrations (p < 0.01) and GUR (p < 0.01) compared with glucose (40%GI by 25.2%; 70%GI by 26.2%), but failed to significantly affect carbohydrate, fat and protein oxidation. NOGD was significantly higher for GI trials at both intensities (p < 0.05) with storage occurring during both lower intensities (62.7 ± 19.6 g 40%GI; 127 ± 20.7 g 40%GI) and 70%GI (29.0 ± 20.0 g). Muscle glycogen concentrations were significantly depleted from rest (p < 0.01) after all four trials. CONCLUSION: Hyperinsulinaemia in the presence of hyperglycaemia during both low- and high-intensity exercise promotes GUR and NOGD, but does not significantly affect substrate oxidation.

Carbohydrate oxidation and glucose utilisation under hyperglycaemia in aged and young males during exercise at the same relative exercise intensity.

PURPOSE: The purpose of the present study was to investigate the age-related carbohydrate oxidation and glucose utilisation rate response during exercise at the same relative intensity under hyperglycaemia in aged and young males. METHODS: 16 endurance-trained aged (n = 8; 69.1 ± 5.2 year) and young (n = 8; 22.4 ± 2.9 year) males were studied during 40 min of cycling exercise (60% [Formula: see text]) under both hyperglycaemic and euglycaemic (control) conditions. Venous blood samples were collected at baseline, post-infusion, mid- and post-exercise. Carbohydrate and fat oxidation rates were determined at both 15 and 35 min during exercise, and glucose utilisation rates were calculated. RESULTS: The aged group displayed significantly lower rates of carbohydrate oxidation during exercise during maintained hyperglycemia (15 min = 2.3 ± 0.4 vs. 1.6 ± 0.5 g min-1; 35 min = 2.3 ± 0.5 vs. 1.5 ± 0.5 g min-1) and control (15 min = 2.2 ± 0.4 vs. 1.6 ± 0.7 g min-1; 35 min = 1.9 ± 0.7 vs. 1.3 ± 0.7 g min-1) conditions (P = 0.01). The rate of glucose utilisation during exercise was also significantly reduced (85.76 ± 23.95 vs. 56.67 ± 15.09 µM kg-1 min-1). There were no differences between age groups for anthropometric measures, fat oxidation, insulin, glucose, NEFA, glycerol and lactate (P > 0.05) although hyperglycemia resulted in elevated glucose and insulin, and attenuated fat metabolite levels. CONCLUSION: Our findings highlight that ageing results in a reduction in carbohydrate oxidation and utilisation rates during exercise at the same relative exercise intensity.

The effects of diurnal Ramadan fasting on energy expenditure and substrate oxidation in healthy men.

The study aimed to examine the effects of diurnal Ramadan fasting (RF) on substrate oxidation, energy production, blood lipids and glucose as well as body composition. Nine healthy Muslim men (fasting (FAST) group) and eight healthy non-practicing men (control (CNT) group) were assessed pre- and post-RF. FAST were additionally assessed at days 10, 20 and 30 of RF in the morning and evening. Body composition was determined by hydrodensitometry, substrate oxidation and energy production by indirect calorimetry, blood metabolic profile by biochemical analyses and energy balance by activity tracker recordings and food log analyses. A significant group×time interaction revealed that chronic RF reduced body mass and adiposity in FAST, without changing lean mass, whereas CNT subjects remained unchanged. In parallel to these findings, a significant main diurnal effect (morning v. evening) of RF on substrate oxidation (a shift towards lipid oxidation) and blood metabolic profile (a decrease in glucose and an increase in total cholesterol and TAG levels, respectively) was observed, which did not vary over the course of the Ramadan. In conclusion, although RF induces diurnal metabolic adjustments (morning v. evening), no carryover effect was observed throughout RF despite the extended daily fasting period (18·0 (sd 0·3) h) and changes in body composition.

Change in maximal fat oxidation in response to different regimes of periodized high-intensity interval training (HIIT).

PURPOSE: Increased capacity for fat oxidation (FatOx) is demonstrated in response to chronic endurance training as well as high-intensity interval training (HIIT). This study examined changes in maximal fat oxidation (MFO) in response to 20 sessions of periodized HIIT in an attempt to identify if various regimes of HIIT similarly augment capacity for FatOx. METHODS: Thirty-nine habitually active men and women (mean age and VO2max = 22.5 ± 4.4 year and 40.0 ± 5.6 mL/kg/min) completed training and 32 men and women with similar physical activity and fitness level served as non-exercising controls (CON). Training consisted of ten sessions of progressive low-volume HIIT on the cycle ergometer after which participants completed an additional ten sessions of sprint interval training (SIT), high-volume HIIT, or periodized HIIT, whose assignment was randomized. Before and throughout training, MFO, FatOx, and carbohydrate oxidation (CHOOx) were assessed during progressive cycling to exhaustion. RESULTS: Compared to CON, there was no effect of HIIT on MFO (p = 0.11). Small increases (p = 0.03) in FatOx were evident in response to HIIT leading to an additional 4.3 g of fat oxidized, although this value may not be clinically meaningful. CONCLUSIONS: Our results refute the widely reported increases in capacity for FatOx demonstrated with HIIT, which is likely due to marked day-to-day variability in determinations of MFO and exercise fat oxidation as well as the heterogeneity of our sample.

The metabolic effects of habitual leg shaking: A randomized crossover trial.

AIMS: The adverse effects of sedentary behavior on obesity and chronic diseases are well established. However, the prevalence of sedentary behavior has increased, with only a minority of individuals meeting the recommended physical activity guidelines. This study aimed to investigate whether habitual leg shaking, a behavior traditionally considered unfavorable, could serve as an effective strategy to improve energy metabolism. MATERIALS AND METHODS: A randomized crossover study was conducted, involving 15 participants (mean [SD] age, 25.4 [3.6]; mean [SD] body mass index, 22 [3]; 7 women [46.7%]). The study design involved a randomized sequence of sitting and leg shaking conditions, with each condition lasting for 20 min. Energy expenditure, respiratory rate, oxygen saturation, and other relevant variables were measured during each condition. RESULTS: Compared to sitting, leg shaking significantly increased total energy expenditure [1.088 kj/min, 95% confidence interval, 0.69-1.487 kj/min], primarily through elevated carbohydrate oxidation. The average metabolic equivalent during leg shaking exhibited a significant increase from 1.5 to 1.8. Leg shaking also raised respiratory rate, minute ventilation, and blood oxygen saturation levels, while having no obvious impact on heart rate or blood pressure. Electromyography data confirmed predominant activation of lower leg muscles and without increased muscle fatigue. Intriguingly, a significant correlation was observed between the increased energy expenditure and both the frequency of leg shaking and the muscle mass of the legs. CONCLUSIONS: Our study provides evidence that habitual leg shaking can boost overall energy expenditure by approximately 16.3%. This simple and feasible approach offers a convenient way to enhance physical activity levels.

A combination of Citrus aurantifolia fruit rind and Theobroma cacao seed extracts supplementation enhances metabolic rates in overweight subjects: a randomized, placebo-controlled, cross-over study.

Background and objective: LN19183 is a proprietary, synergistic combination of Citrus aurantifolia fruit rind and Theobroma cacao seed extracts that increased resting energy expenditure (REE) in high-fat diet (HFD)-fed obese rats. The objective of this study was to validate the thermogenic potential of LN19183 in obese Sprague Dawley (SD) rats and to assess its clinical efficacy in a proof-of-concept, randomized, placebo-controlled, cross-over human trial. Methods: In the rat study, HFD-fed obese rats were supplemented with either HFD alone or with 45, 90, or 180 mg LN19183 per kg body weight (BW) for 28 days. In the human study, 60 overweight adults (male and female, aged 20-39 years) were randomized. Subjects took LN19183 (450 mg) or a matched placebo capsule on two consecutive days in phases one and two of the study, separated by a 10-day washout period. In each phase, on day 1, REE at pre-dose, 60-, 120-, and 180-min post-dose, and on day 2, metabolic rates at pre-dose and post-dose during and 20 min after exercise were measured using indirect calorimetry. Results: In rats, LN19183 significantly increased REE, reduced BW gain and fat masses, and increased fat and carbohydrate metabolism marker proteins including beta 3 adrenergic receptor (ß3-AR), phospho-AMP-activated protein kinase (AMPK), glucagon-like peptide-1 receptor (GLP-1R) in the liver, and serum adiponectin levels. Furthermore, LN19183-supplemented human volunteers increased (P < 0.05, vs. placebo) the metabolic rates at rest and with exercise; their fat oxidation was increased (P < 0.05, vs. placebo) at rest and 20 min post-exercise. The groups' systolic and diastolic blood pressure (BP), heart rates (HR), and safety parameters were comparable. Conclusion: These observations suggest that LN19183 is a thermogenic botanical composition with no stimulatory effects on BP and HR.

Effects of post-exercise intake of exogenous lactate on energy substrate utilization at rest.

PURPOSE: This study investigated the effects of exogenous lactate intake on energy metabolism during 1 h of rest after acute exercise. METHODS: Eight-week-old ICR mice were randomly divided into four groups: SED (no treatment), EXE (exercise only), LAC (post-exercise oral lactate administration), and SAL (post-exercise saline administration) (n=8 per group). The exercise intensity was at VO2max 80% at 25 m/min and 15° slope for 50 min. After acute exercise, the LAC and SAL groups ingested lactate and saline orally, respectively, and were allowed to rest in a chamber. Energy metabolism was measured for 1 h during the resting period. RESULTS: LAC and SAL group mice ingested lactate and saline, respectively, after exercise and the blood lactate concentration was measured 1 h later through tail blood sampling. Blood lactate concentration was not significantly different between the two groups. Energy metabolism measurements under stable conditions revealed that the respiratory exchange ratio in the LAC group was significantly lower than that in the SAL group. Additionally, carbohydrate oxidation in the LAC group was significantly lower than that in the SAL group at 10-25 min. No significant difference was observed in the fat oxidation level between the two groups. CONCLUSION: We found that post-exercise lactate intake modified the respiratory exchange ratio after 1 h of rest. In addition, acute lactate ingestion inhibits carbohydrate oxidation during the post-exercise recovery period.

The impact of natural menstrual cycle and oral contraceptive pill phase on substrate oxidation during rest and acute submaximal aerobic exercise.

Previous research has identified sex differences in substrate oxidation during submaximal aerobic exercise including a lower respiratory exchange ratio (RER) in females compared with males. These differences may be related to differences in sex hormones. Our purpose was to examine the impact of the natural menstrual cycle (NAT) and second- and third-generation oral contraceptive pill (OCP2 and OCP3) cycle phases on substrate oxidation during rest and submaximal aerobic exercise. Fifty female participants (18 NAT, 17 OCP2, and 15 OCP3) performed two experimental trials that coincided with the low (i.e., nonactive pill/early follicular) and the high hormone (i.e., active pill/midluteal) phase of their cycle. RER and carbohydrate and lipid oxidation rates were determined from gas exchange measurements performed during 10 min of supine rest, 5 min of seated rest, and two 8-min bouts of submaximal cycling exercise at ∼40% and ∼65% of peak oxygen uptake (V̇o2peak). For all groups, there were no differences in RER between the low and high hormone phases during supine rest (0.73 ± 0.05 vs. 0.74 ± 0.05), seated rest (0.72 ± 0.04 vs. 0.72 ± 0.04), exercise at 40% (0.77 ± 0.04 vs. 0.78 ± 0.04), and 65% V̇o2peak (0.85 ± 0.04 vs. 0.86 ± 0.03; P > 0.19 for all). Similarly, carbohydrate and lipid oxidation rates remained largely unchanged across phases during both rest and exercise, apart from higher carbohydrate oxidation in NAT vs. OCP2 at 40% V̇o2peak (P = 0.019) and 65% V̇o2peak (P = 0.001). NAT and OCPs do not appear to largely influence substrate oxidation at rest and during acute submaximal aerobic exercise.NEW & NOTEWORTHY This study was the first to examine the influence of NAT and two generations of OCPs on substrate oxidation during rest and acute submaximal aerobic exercise. We reported no differences across cycle phases or groups on RER, and minimal impact on carbohydrate or lipid oxidation apart from an increase in carbohydrate oxidation in NAT compared with OCP2 during exercise. Based on these findings, NAT/OCP phase controls may not be necessary in studies investigating substrate oxidation.

Low and high carbohydrate isocaloric diets on performance, fat oxidation, glucose and cardiometabolic health in middle age males.

High carbohydrate, low fat (HCLF) diets have been the predominant nutrition strategy for athletic performance, but recent evidence following multi-week habituation has challenged the superiority of HCLF over low carbohydrate, high fat (LCHF) diets, along with growing interest in the potential health and disease implications of dietary choice. Highly trained competitive middle-aged athletes underwent two 31-day isocaloric diets (HCLF or LCHF) in a randomized, counterbalanced, and crossover design while controlling calories and training load. Performance, body composition, substrate oxidation, cardiometabolic, and 31-day minute-by-minute glucose (CGM) biomarkers were assessed. We demonstrated: (i) equivalent high-intensity performance (@∼85%VO2max), fasting insulin, hsCRP, and HbA1c without significant body composition changes across groups; (ii) record high peak fat oxidation rates (LCHF:1.58 ± 0.33g/min @ 86.40 ± 6.24%VO2max; 30% subjects > 1.85 g/min); (iii) higher total, LDL, and HDL cholesterol on LCHF; (iv) reduced glucose mean/median and variability on LCHF. We also found that the 31-day mean glucose on HCLF predicted 31-day glucose reductions on LCHF, and the 31-day glucose reduction on LCHF predicted LCHF peak fat oxidation rates. Interestingly, 30% of athletes had 31-day mean, median and fasting glucose > 100 mg/dL on HCLF (range: 111.68-115.19 mg/dL; consistent with pre-diabetes), also had the largest glycemic and fat oxidation response to carbohydrate restriction. These results: (i) challenge whether higher carbohydrate intake is superior for athletic performance, even during shorter-duration, higher-intensity exercise; (ii) demonstrate that lower carbohydrate intake may be a therapeutic strategy to independently improve glycemic control, particularly in those at risk for diabetes; (iii) demonstrate a unique relationship between continuous glycemic parameters and systemic metabolism.