RESUMEN
Although the mechanisms underpinning short-term muscle disuse atrophy and associated insulin resistance remain to be elucidated, perturbed lipid metabolism might be involved. Our aim was to determine the impact of acipimox administration [i.e., pharmacologically lowering circulating nonesterified fatty acid (NEFA) availability] on muscle amino acid metabolism and insulin sensitivity during short-term disuse. Eighteen healthy individuals (age: 22 ± 1 years; body mass index: 24.0 ± 0.6 kg·m-2) underwent 2 days forearm immobilization with placebo (PLA; n = 9) or acipimox (ACI; 250 mg Olbetam; n = 9) ingestion four times daily. Before and after immobilization, whole body glucose disposal rate (GDR), forearm glucose uptake (FGU; i.e., muscle insulin sensitivity), and amino acid kinetics were measured under fasting and hyperinsulinemic-hyperaminoacidemic-euglycemic clamp conditions using forearm balance and l-[ring-2H5]-phenylalanine infusions. Immobilization did not affect GDR but decreased insulin-stimulated FGU in both groups, more so in ACI (from 53 ± 8 to 12 ± 5 µmol·min-1) than PLA (from 52 ± 8 to 38 ± 13 µmol·min-1; P < 0.05). In ACI only, and in contrast to our hypothesis, fasting arterialized NEFA concentrations were elevated to 1.3 ± 0.1 mmol·L-1 postimmobilization (P < 0.05), and fasting forearm NEFA balance increased approximately fourfold (P = 0.10). Forearm phenylalanine net balance decreased following immobilization (P < 0.10), driven by an increased rate of appearance [from 32 ± 5 (fasting) and 21 ± 4 (clamp) preimmobilization to 53 ± 8 and 31 ± 4 postimmobilization; P < 0.05] while the rate of disappearance was unaffected by disuse or acipimox. Disuse-induced insulin resistance is accompanied by early signs of negative net muscle amino acid balance, which is driven by accelerated muscle amino acid efflux. Acutely elevated NEFA availability worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance.NEW & NOTEWORTHY We demonstrate that 2 days of forearm cast immobilization in healthy young volunteers leads to the rapid development of insulin resistance, which is accompanied by accelerated muscle amino acid efflux in the absence of impaired muscle amino acid uptake. Acutely elevated fasting nonesterified fatty acid (NEFA) availability as a result of acipimox supplementation worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance.
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Resistencia a la Insulina , Pirazinas , Humanos , Adulto Joven , Aminoácidos/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Antebrazo , Glucosa/metabolismo , Hipolipemiantes/metabolismo , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Insulina/metabolismo , Músculos/metabolismo , Fenilalanina/metabolismo , Poliésteres/metabolismo , VoluntariosRESUMEN
Accepting a continued rise in the prevalence of vegan-type diets in the general population is also likely to occur in athletic populations, it is of importance to assess the potential impact on athletic performance, adaptation, and recovery. Nutritional consideration for the athlete requires optimization of energy, macronutrient, and micronutrient intakes, and potentially the judicious selection of dietary supplements, all specified to meet the individual athlete's training and performance goals. The purpose of this review is to assess whether adopting a vegan diet is likely to impinge on such optimal nutrition and, where so, consider evidence based yet practical and pragmatic nutritional recommendations. Current evidence does not support that a vegan-type diet will enhance performance, adaptation, or recovery in athletes, but equally suggests that an athlete can follow a (more) vegan diet without detriment. A clear caveat, however, is that vegan diets consumed spontaneously may induce suboptimal intakes of key nutrients, most notably quantity and/or quality of dietary protein and specific micronutrients (eg, iron, calcium, vitamin B12, and vitamin D). As such, optimal vegan sports nutrition requires (more) careful consideration, evaluation, and planning. Individual/seasonal goals, training modalities, athlete type, and sensory/cultural/ethical preferences, among other factors, should all be considered when planning and adopting a vegan diet.
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Dieta Vegana , Veganos , Humanos , Suplementos Dietéticos , Atletas , Estado Nutricional , DietaRESUMEN
Increasing skeletal muscle carnitine content can manipulate fuel metabolism and improve exercise performance. Intravenous insulin infusion during hypercarnitinemia increases plasma carnitine clearance and Na+ -dependent muscle carnitine accretion, likely via stimulating Na+ /K+ ATPase pump activity. We hypothesized that the ingestion of high-dose caffeine, also known to stimulate Na+ /K+ ATPase activity, would stimulate plasma carnitine clearance during hypercarnitinemia in humans. In a randomized placebo-controlled study, six healthy young adults (aged 24 ± 5 years, height 175 ± 8 cm, and weight 70 ± 13 kg) underwent three 5-h laboratory visits involving the primed continuous intravenous infusion of l-carnitine (CARN and CARN + CAFF) or saline (CAFF) in parallel with ingestion of caffeine (CARN + CAFF and CAFF) or placebo (CARN) at 0, 2, 3, and 4 h. Regular blood samples were collected to determine concentrations of blood Na+ and K+ , and plasma carnitine and caffeine, concentrations. Caffeine ingestion (i.e., CAFF and CARN + CAFF conditions) and l-carnitine infusion (i.e., CARN and CARN + CAFF) elevated steady-state plasma caffeine (to ~7 µg·mL-1 ) and carnitine (to ~400 µmol·L-1 ) concentrations, respectively, throughout the 5 h infusions. Plasma carnitine concentration was ~15% lower in CARN + CAFF compared with CARN during the final 90 min of the infusion (at 210 min, 356 ± 96 vs. 412 ± 94 µmol·L-1 ; p = 0.0080: at 240 min, 350 ± 91 vs. 406 ± 102 µmol·L-1 ; p = 0.0079: and at 300 min, 357 ± 91 vs. 413 ± 110 µmol·L-1 ; p = 0.0073, respectively). Blood Na+ concentrations were greater in CAFF and CARN + CAFF compared with CARN. Ingestion of high-dose caffeine stimulates plasma carnitine clearance during hypercarnitinemia, likely via increased Na+ /K+ ATPase activity. Carnitine co-ingestion with caffeine may represent a novel muscle carnitine loading strategy in humans, and therefore manipulate skeletal muscle fuel metabolism and improve exercise performance.
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Cafeína , Carnitina , Adulto Joven , Humanos , Músculo Esquelético/metabolismo , Ejercicio Físico/fisiología , Sodio/metabolismo , Ingestión de AlimentosRESUMEN
NEW FINDINGS: What is the central question of this study? Does acute ketone monoester supplementation enhance the recovery of muscle force and modulate circulating cytokine concentrations after muscle-damaging eccentric exercise? What is the main finding and its importance? Ketone monoester supplementation increased plasma ß-hydroxybutyrate concentrations but did not attenuate the reduction in muscle force or the increase in plasma inflammatory cytokine concentrations that occurred after eccentric exercise. Notably we report novel data demonstrating a reduction in plasma TRAIL concentrations after eccentric exercise, highlighting TRAIL signalling as a possibly novel regulator of muscle recovery. ABSTRACT: Muscle-damaging eccentric exercise is associated with inflammation and impaired muscle force. ß-Hydroxybutyrate (ß-OHB) reduces muscle protein breakdown during inflammation but whether oral ketone monoester supplementation accelerates recovery of muscle force after eccentric exercise is unknown. Sixteen healthy males and females consumed thrice daily ketone monoester (27 g per dose; n = 8; six females; KES) or isocaloric maltodextrin placebo (n = 8; four females; PLA) drinks (randomized, double-blind, parallel group design) for 3 days beginning immediately after 300 unilateral eccentric quadriceps contractions during complete eucaloric dietary control (1.2 ± 0.1 g/kg BM/day standardized protein). Bilateral muscle force measurements and venous blood sampling were performed before and 3, 6, 24, 48 and 72 h after eccentric exercise. Plasma ß-OHB concentrations were greater in KES compared with PLA at 3 h (0.56 ± 0.13 vs. 0.22 ± 0.04 mM, respectively; P = 0.080) and 6 h (0.65 ± 0.41 vs. 0.23 ± 0.02 mM, respectively; P = 0.031) post-eccentric exercise. Relative to the control leg, isokinetic work (by 20 ± 21% in PLA and 21 ± 19% in KES; P = 0.008) and isometric torque (by 23 ± 13% in PLA and 20 ± 18% in KES; P < 0.001) decreased from baseline at 3 h in the eccentrically exercised leg, and remained below baseline at 48 and 72 h, with no significant group differences. Of eight measured plasma cytokines, interleukin-6 (P = 0.008) and monocyte chemoattractant protein-1 (P = 0.024) concentrations increased after 6 h, whereas tumour necrosis factor-related apoptosis-inducing ligand concentrations decreased after 3 h (P = 0.022) and 6 h (P = 0.011) post-exercise with no significant group differences. Oral ketone monoester supplementation elevates plasma ß-OHB concentrations but does not prevent the decline in muscle force or alter plasma inflammatory cytokine profiles induced by eccentric exercise.
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Citocinas , Cetonas , Masculino , Femenino , Humanos , Ácido 3-Hidroxibutírico , Suplementos Dietéticos , Músculo Cuádriceps/fisiología , Inflamación , Poliésteres , Músculo Esquelético/fisiologíaRESUMEN
BACKGROUND: Obesity and insulin resistance are associated with an impaired sensitivity to anabolic stimuli such as dietary protein (anabolic resistance). Omega-3 polyunsaturated fatty acids (n-3 PUFA) may be protective against the deleterious effects of saturated fatty acids (SFA) on insulin resistance. However, the contribution of excess fat consumption to anabolic and insulin resistance and the interaction between SFA and n-3 PUFA is not well studied. AIM: The primary aim of this study was to investigate the effects of an oral fat pre-load, with or without the partial substitution of SFA with fish oil (FO)-derived n-3 PUFA, on indices of insulin and anabolic sensitivity in response to subsequent dietary protein and carbohydrate (dextrose) co-ingestion. METHODS: Eight middle-aged males with overweight or obesity (52.8 ± 2.0 yr, BMI 31.8 ± 1.4 kg·m-2) ingested either an SFA, or isoenergetic SFA and FO emulsion (FO), or water/control (Con), 4 h prior to a bolus of milk protein and dextrose. RESULTS: Lipid ingestion (in particular FO) impaired the early postprandial uptake of branched chain amino acids (BCAA) into the skeletal muscle in response to protein and dextrose, and attenuated the peak glycaemic response, but was not accompanied by differences in whole body (Matsuda Index: Con: 4.66 ± 0.89, SFA: 5.10 ± 0.94 and FO: 4.07 ± 0.59) or peripheral (forearm glucose netAUC: Con: 521.7 ± 101.7; SFA: 470.2 ± 125.5 and FO: 495.3 ± 101.6 µmol·min-1·100 g lean mass·min [t = 240-420 min]) insulin sensitivity between visits. Postprandial whole body fat oxidation was affected by visit (P = 0.024) with elevated rates in SFA and FO, relative to Con (1.85 ± 0.55; 2.19 ± 0.21 and 0.65 ± 0.35 kJ·h-1·kg-1 lean body mass, respectively), however muscle uptake of free fatty acids (FFA) was unaffected. CONCLUSION: Oral lipid preloads, consisting of SFA and FO, impair the early postprandial BCAA uptake into skeletal muscle, which occurs independent of changes in insulin sensitivity. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov Identifier NCT03146286.
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Ácidos Grasos Omega-3 , Resistencia a la Insulina , Glucemia/metabolismo , Estudios Cruzados , Grasas de la Dieta/farmacología , Proteínas en la Dieta , Ingestión de Alimentos , Ácidos Grasos , Aceites de Pescado/farmacología , Humanos , Masculino , Obesidad/metabolismo , Sobrepeso , Periodo PosprandialRESUMEN
Intramyocellular lipid (IMCL) utilization is impaired in older individuals, and IMCL accumulation is associated with insulin resistance. We hypothesized that increasing muscle total carnitine content in older men would increase fat oxidation and IMCL utilization during exercise, and improve insulin sensitivity. Fourteen healthy older men (69 ± 1 year, BMI 26.5 ± 0.8 kg/m2 ) performed 1 h of cycling at 50% VO2 max and, on a separate occasion, underwent a 60 mU/m2 /min euglycaemic hyperinsulinaemic clamp before and after 25 weeks of daily ingestion of a 220 ml insulinogenic beverage (44.4 g carbohydrate, 13.8 g protein) containing 4.5 g placebo (n = 7) or L-carnitine L-tartrate (n = 7). During supplementation, participants performed twice-weekly cycling for 1 h at 50% VO2 max. Placebo ingestion had no effect on muscle carnitine content or total fat oxidation during exercise at 50% VO2 max. L-carnitine supplementation resulted in a 20% increase in muscle total carnitine content (20.1 ± 1.2 to 23.9 ± 1.7 mmol/kg/dm; p < 0.01) and a 20% increase in total fat oxidation (181.1 ± 15.0 to 220.4 ± 19.6 J/kg lbm/min; p < 0.01), predominantly due to increased IMCL utilization. These changes were associated with increased expression of genes involved in fat metabolism (ACAT1, DGKD & PLIN2; p < 0.05). There was no change in resting insulin-stimulated whole-body or skeletal muscle glucose disposal after supplementation. This is the first study to demonstrate that a carnitine-mediated increase in fat oxidation is achievable in older individuals. This warrants further investigation given reduced lipid turnover is associated with poor metabolic health in older adults.
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Carnitina/metabolismo , Ejercicio Físico , Grasas/metabolismo , Músculo Esquelético/metabolismo , Anciano , Humanos , Masculino , Oxidación-ReducciónRESUMEN
Circulating uric acid concentrations have been linked to various metabolic diseases. Consumption of large boluses of nucleotides increases serum uric acid concentrations. We investigated the effect of a nucleotide-rich mixed meal on postprandial circulating uric acid, glucose, and insulin responses. Ten healthy adults participated in a randomised, controlled, double-blind, crossover trial in which they consumed a mixed-meal containing either nucleotide-depleted mycoprotein (L-NU) or high-nucleotide mycoprotein (H-NU) on two separate visits. Blood samples were collected in the postabsorptive state and throughout a 24 h postprandial period, and were used to determine circulating uric acid, glucose, and insulin concentrations. Mixed meal ingestion had divergent effects on serum uric acid concentrations across conditions (time x condition interaction; P < 0.001), with L-NU decreasing transiently (from 45 to 240 min postprandially) by ~7% (from 279 ± 16 to 257 ± 14 µmol·L-1) and H-NU resulting in a ~12% increase (from 284 ± 13 to 319 ± 12 µmol·L-1 after 210 min), remaining elevated for 12 h and returning to baseline concentrations after 24 h. There were no differences between conditions in blood glucose or serum insulin responses, nor in indices of insulin sensitivity. The ingestion of a nucleotide-rich mixed-meal increases serum uric acid concentrations for ~12 h, but does not influence postprandial blood glucose or serum insulin concentrations.
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Glucemia/metabolismo , Dieta , Proteínas en la Dieta/administración & dosificación , Suplementos Dietéticos , Ingestión de Alimentos/fisiología , Voluntarios Sanos , Insulina/sangre , Nucleótidos/administración & dosificación , Nucleótidos/farmacología , Periodo Posprandial , Ácido Úrico/sangre , Adulto , Estudios Cruzados , Proteínas en la Dieta/química , Proteínas en la Dieta/farmacología , Método Doble Ciego , Femenino , Humanos , Masculino , Factores de Tiempo , Adulto JovenRESUMEN
Increasing skeletal muscle carnitine availability alters muscle metabolism during steady-state exercise in healthy humans. We investigated whether elevating muscle carnitine, and thereby the acetyl-group buffering capacity, altered the metabolic and physiological adaptations to 24 weeks of high-intensity interval training (HIIT) at 100% maximal exercise capacity (Wattmax ). Twenty-one healthy male volunteers (age 23±2 years; BMI 24.2±1.1 kg/m2 ) performed 2 × 3 minute bouts of cycling exercise at 100% Wattmax , separated by 5 minutes of rest. Fourteen volunteers repeated this protocol following 24 weeks of HIIT and twice-daily consumption of 80 g carbohydrate (CON) or 3 g l-carnitine+carbohydrate (CARN). Before HIIT, muscle phosphocreatine (PCr) degradation (P<.0001), glycogenolysis (P<.0005), PDC activation (P<.05), and acetylcarnitine (P<.005) were 2.3-, 2.1-, 1.5-, and 1.5-fold greater, respectively, in exercise bout two compared to bout 1, while lactate accumulation tended (P<.07) to be 1.5-fold greater. Following HIIT, muscle free carnitine was 30% greater in CARN vs CON at rest and remained 40% elevated prior to the start of bout 2 (P<.05). Following bout 2, free carnitine content, PCr degradation, glycogenolysis, lactate accumulation, and PDC activation were all similar between CON and CARN, albeit markedly lower than before HIIT. VO2max , Wattmax , and work output were similarly increased in CON and CARN, by 9, 15, and 23% (P<.001). In summary, increased reliance on non-mitochondrial ATP resynthesis during a second bout of intense exercise is accompanied by increased carnitine acetylation. Augmenting muscle carnitine during 24 weeks of HIIT did not alter this, nor did it enhance muscle metabolic adaptations or performance gains beyond those with HIIT alone.
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Adaptación Fisiológica , Carnitina/administración & dosificación , Entrenamiento de Intervalos de Alta Intensidad , Músculo Esquelético/metabolismo , Acetilación , Adenosina Trifosfato/metabolismo , Adulto , Carnitina/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Suplementos Dietéticos , Método Doble Ciego , Humanos , Ácido Láctico , Masculino , Adulto JovenRESUMEN
The ability to maintain skeletal muscle mass appears to be impaired in insulin-resistant conditions, such as type 2 diabetes, that are characterized by muscle lipid accumulation. The current study investigated the effect of acutely increasing lipid availability on muscle protein synthesis. Seven healthy young male volunteers underwent a 7-h intravenous infusion of l-[ring-(2)H5]phenylalanine on two randomized occasions combined with 0.9% saline or 10% Intralipid at 100 mL/h. After a 4-h "basal" period, a 21-g bolus of amino acids was administered and a 3-h hyperinsulinemic-euglycemic clamp was commenced ("fed" period). Muscle biopsy specimens were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion reduced fed whole-body glucose disposal by 20%. Furthermore, whereas the mixed muscle fractional synthetic rate increased from the basal to the fed period during saline infusion by 2.2-fold, no change occurred during lipid infusion, despite similar circulating insulin and leucine concentrations. This "anabolic resistance" to insulin and amino acids with lipid infusion was associated with a complete suppression of muscle 4E-BP1 phosphorylation. We propose that increased muscle lipid availability may contribute to anabolic resistance in insulin-resistant conditions by impairing translation initiation.
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Aminoácidos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Resistencia a la Insulina/fisiología , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Fosfolípidos/farmacología , Aceite de Soja/farmacología , Emulsiones/farmacología , Glucosa/metabolismo , Humanos , Masculino , Proteínas Musculares/genética , Transducción de Señal , Adulto JovenRESUMEN
Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic-hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater following n6PUFA compared with Control and n3PUFA, suggesting that mitochondrial lipid overload was responsible for the lower insulin action observed. Despite these favourable metabolic effects of n3PUFA, accumulation of total muscle acylcarnitine was not attenuated when compared with n6PUFA. These findings demonstrate that n3PUFA exert beneficial effects on insulin-stimulated skeletal muscle glucose storage and oxidation independently of total acylcarnitine accumulation, which does not always reflect mitochondrial lipid overload.
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Carnitina/análogos & derivados , Ácidos Grasos Omega-3/farmacología , Resistencia a la Insulina/fisiología , Lípidos/farmacología , Adulto , Carnitina/metabolismo , Aceites de Pescado , Glucógeno/metabolismo , Humanos , Insulina/farmacología , Masculino , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , TriglicéridosRESUMEN
Reduced skeletal muscle free coenzyme A (CoASH) availability may decrease the contribution of fat oxidation to ATP production during high-intensity, submaximal exercise or, alternatively, limit pyruvate dehydrogenase complex (PDC) flux and thereby carbohydrate oxidation. Here we attempted to increase the muscle CoASH pool in humans, via pantothenic acid and cysteine feeding, in order to elucidate the role of CoASH availability on muscle fuel metabolism during exercise. On three occasions, eight healthy male volunteers (age 22.9 ± 1.4 yr, body mass index 24.2 ± 1.5 kg/m(2)) cycled at 75% maximal oxygen uptake (Vo(2max)) to exhaustion, followed by a 15-min work output performance test. Muscle biopsies were obtained at rest, and after 60 min and 91.3 ± 3.1 min of exercise (time to exhaustion on baseline visit) on each occasion. Two weeks following the first visit (baseline), 1 wk of oral supplementation with either 3 g/day of a placebo control (glucose polymer; CON) or 1.5 g/day each of d-pantothenic acid and l-cysteine (CP) was carried out prior to the second and third visits in a randomized, counterbalanced, double-blind manner, leaving a 3-wk gap in total between each visit. Resting muscle CoASH content was not altered by supplementation in any visit. Following 60 min of exercise, muscle CoASH content was reduced by 13% from rest in all three visits (P < 0.05), and similar changes in the respiratory exchange ratio, glycogenolysis (â¼235 mmol/kg dry muscle), PCr degradation (â¼57 mmol/kg dry muscle), and lactate (â¼25 mmol/kg dry muscle) and acetylcarnitine (â¼12 mmol(.)kg/dry muscle) accumulation was observed during exercise when comparing visits. Furthermore, no difference in work output was observed when comparing CON and CP. Acute feeding with pantothenic acid and cysteine does not alter muscle CoASH content and consequently does not impact on muscle fuel metabolism or performance during exercise in humans.
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Coenzima A/metabolismo , Cisteína/administración & dosificación , Tolerancia al Ejercicio/efectos de los fármacos , Músculo Esquelético/enzimología , Ácido Pantoténico/administración & dosificación , Biomarcadores/análisis , Biomarcadores/metabolismo , Biopsia , Prueba de Esfuerzo , Tolerancia al Ejercicio/fisiología , Glucógeno/análisis , Glucógeno/metabolismo , Humanos , Masculino , Músculo Esquelético/química , Músculo Esquelético/efectos de los fármacos , Consumo de Oxígeno , Adulto JovenRESUMEN
We have previously shown that insulin increases muscle total carnitine (TC) content during acute i.v. l-carnitine infusion. Here we determined the effects of chronic l-carnitine and carbohydrate (CHO; to elevate serum insulin) ingestion on muscle TC content and exercise metabolism and performance in humans. On three visits, each separated by 12 weeks, 14 healthy male volunteers (age 25.9 ± 2.1 years, BMI 23.0 ± 0.8 kg m−2) performed an exercise test comprising 30 min cycling at 50% , 30 min at 80% , then a 30 min work output performance trial. Muscle biopsies were obtained at rest and after exercise at 50% and 80% on each occasion. Following visit one, volunteers ingested either 80 g of CHO (Control) or 2 g of l-carnitine-l-tartrate and 80 g of CHO (Carnitine) twice daily for 24 weeks in a randomised, double blind manner. All significant effects reported occurred after 24 weeks. Muscle TC increased from basal by 21% in Carnitine (P < 0.05), and was unchanged in Control. At 50% , the Carnitine group utilised 55% less muscle glycogen compared to Control (P < 0.05) and 31% less pyruvate dehydrogenase complex (PDC) activation compared to before supplementation (P < 0.05). Conversely, at 80% , muscle PDC activation was 38% higher (P < 0.05), acetylcarnitine content showed a trend to be 16% greater (P < 0.10), muscle lactate content was 44% lower (P < 0.05) and the muscle PCr/ATP ratio was better maintained (P < 0.05) in Carnitine compared to Control. The Carnitine group increased work output 11% from baseline in the performance trial, while Control showed no change. This is the first demonstration that human muscle TC can be increased by dietary means and results in muscle glycogen sparing during low intensity exercise (consistent with an increase in lipid utilisation) and a better matching of glycolytic, PDC and mitochondrial flux during high intensity exercise, thereby reducing muscle anaerobic ATP production. Furthermore, these changes were associated with an improvement in exercise performance.
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Carnitina/administración & dosificación , Carnitina/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Metabolismo Energético/fisiología , Ejercicio Físico/fisiología , Músculo Esquelético/metabolismo , Administración Oral , Adulto , Método Doble Ciego , Prueba de Esfuerzo/métodos , Humanos , Masculino , Consumo de Oxígeno/fisiología , Deportes/fisiología , Factores de Tiempo , Adulto JovenRESUMEN
Maintaining hyperinsulinemia (approximately 150 mU/l) during steady-state hypercarnitinemia (approximately 550 micromol/l) increases skeletal muscle total carnitine (TC) content by approximately 15% within 5 h. The present study aimed to investigate whether an increase in whole body carnitine retention can be achieved through L-carnitine feeding in conjunction with a dietary-induced elevation in circulating insulin. On two randomized visits (study A), eight men ingested 3 g/day L-carnitine followed by 4 x 500-ml solutions, each containing flavored water (Con) or 94 g simple sugars (glucose syrup; CHO). In addition, 14 men ingested 3 g/day L-carnitine followed by 2 x 500 ml of either Con or CHO for 2 wk (study B). Carbohydrate ingestion in study A resulted in a fourfold greater serum insulin area under the curve when compared with Con (P < 0.001) and in a lower plasma TC concentration throughout the CHO visit (P < 0.05). Twenty-four-hour urinary TC excretion in the CHO visit was lower than in the Con visit in study A (155.0 +/- 10.7 vs. 212.1 +/- 17.2 mg; P < 0.05). In study B, daily urinary TC excretion increased after 3 days (65.9 +/- 18.0 to 281.0 +/- 35.0 mg; P < 0.001) and remained elevated throughout the Con trial. During the CHO trial, daily urinary TC excretion increased from a similar basal value of 53.8 +/- 9.2 to 166.8 +/- 17.3 mg after 3 days (P < 0.01), which was less than during the Con trial (P < 0.01), and it remained lower over the course of the study (P < 0.001). The difference in plasma TC concentration in study A and 24-h urinary TC excretion in both studies suggests that insulin augmented the retention of carnitine in the CHO trials.