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Researchers and practitioners in sports nutrition would greatly benefit from a rapid, portable, and non-invasive technique to measure muscle glycogen, both in the laboratory and field. This explains the interest in MuscleSound ® , the first commercial system to use high-frequency ultrasound technology and image analysis from patented cloud-based software to estimate muscle glycogen content from the echogenicity of the ultrasound image. This technique is based largely on muscle water content, which is presumed to act as a proxy for glycogen. Despite the promise of early validation studies, newer studies from independent groups reported discrepant results, with MuscleSound ® scores failing to correlate with the glycogen content of biopsy-derived mixed muscle samples or to show the expected changes in muscle glycogen associated with various diet and exercise strategies. The explanation of issues related to the site of assessment do not account for these discrepancies, and there are substantial problems with the premise that the ratio of glycogen to water in the muscle is constant. Although further studies investigating this technique are warranted, current evidence that MuscleSound ® technology can provide valid and actionable information around muscle glycogen stores is at best equivocal.

Introduction: Creatine (Cr) and carbohydrate loadings are dietary strategies used to enhance exercise capacity. This study examined the metabolic and performance effects of a combined CR and CHO loading regiment on time trial (TT) cycling bouts., Methods: Eighteen well-trained (~65 mL·kg·min V˙O2peak) men completed three performance trials (PT) that comprised a 120-km cycling TT interspersed with alternating 1- and 4-km sprints (six sprints each) performed every 10 km followed by an inclined ride to fatigue (~90% V˙O2peak). Subjects were pair matched into either CR-loaded (20 g·d for 5 d + 3 g·d for 9 d) or placebo (PLA) groups (n = 9) after the completion of PT1. All subjects undertook a crossover application of the carbohydrate interventions, consuming either moderate (6 g·kg body mass (BM) per day; MOD) or CHO-loaded (12 g·kg BM·d; LOAD) diets before PT2 and PT3. Muscle biopsies were taken before PT1, 18 h after PT1, and before both PT2 and PT3., Results: No significant differences in overall TT or inclined ride times were observed between intervention groups. PLA + LOAD improved power above baseline (P < 0.05) during the final 1-km sprint, whereas CR + MOD and CR + LOAD improved power (P < 0.05) during the final 4-km sprint. Greater power was achieved with MOD and LOAD compared with baseline with PLA (P < 0.05). CR increased pre-PT BM compared with PLA (+1.54% vs +0.99% from baseline). CR + LOAD facilitated greater [total CR] (P < 0.05 vs baseline) and muscle [glycogen] (P < 0.01 vs baseline and MOD) compared with PLA + LOAD. Mechanistic target of rapamycin decreased from baseline after glycogen depletion (~30%; P < 0.05)., Conclusions: Power output in the closing sprints of exhaustive TT cycling increased with CR ingestion despite a CR-mediated increase in weight. CR cosupplemented with carbohydrates may therefore be beneficial strategy for late-stage breakaway moments in endurance events.

Standardizing a dual x-ray absorptiometry (DXA) protocol is thought to provide a reliable measurement of body composition., Purpose: We investigated the effects of manipulating muscle glycogen and creatine content independently and additively on DXA estimates of lean mass., Method: Eighteen well-trained male cyclists undertook a parallel group application of creatine loading (n = 9) (20 g·d for 5 d loading; 3 g·d maintenance) or placebo (n = 9) with crossover application of glycogen loading (12 v 6 g·kg BM per day for 48 h) as part of a larger study involving a glycogen-depleting exercise protocol. Body composition, total body water, muscle glycogen and creatine content were assessed via DXA, bioelectrical impedance spectroscopy and standard biopsy techniques. Changes in the mean were assessed using the following effect-size scale: >0.2 small, >0.6, moderate, >1.2 large and compared with the threshold for the smallest worthwhile effect of the treatment., Results: Glycogen loading, both with and without creatine loading, resulted in substantial increases in estimates of lean body mass (mean ± SD; 3.0% ± 0.7% and 2.0% ± 0.9%) and leg lean mass (3.1% ± 1.8% and 2.6% ± 1.0%) respectively. A substantial decrease in leg lean mass was observed after the glycogen depleting condition (-1.4% ± 1.6%). Total body water showed substantial increases after glycogen loading (2.3% ± 2.3%), creatine loading (1.4% ± 1.9%) and the combined treatment (2.3% ± 1.1%)., Conclusions: Changes in muscle metabolites and water content alter DXA estimates of lean mass during periods in which minimal change in muscle protein mass is likely. This information needs to be considered in interpreting the results of DXA-derived estimates of body composition in athletes.

Purpose: Creatine uptake by muscle cells is increased in the presence of insulin. Accordingly, compounds with insulin-like actions may also augment creatine uptake. The aim of this study was to investigate whether Trigonella foenum-graecum (fenugreek), an insulin mimetic, increases total intracellular creatine levels in vitro., Methods: Total cellular creatine content was measured fluorometrically in L6C11 muscle myotubes treated for 1, 4, and 24 h with 0.5 mM creatine (CR), CR and 20 μg/mL fenugreek seed extract (CR + FEN), CR and 100 nM insulin (CR + INS), and CR + INS + FEN (n = 6 per treatment group). Alterations in the expression of the sodium- and chloride-dependent creatine transporter, SLC6A8, and key signaling proteins in the PI3-K/Akt pathway were determined., Results: Compared to control (CON), CR + INS + FEN increased total creatine content after 4 h (P < 0.05), whereas all conditions increased SLC6A8 protein expression above CON at this time (P < 0.05). Changes in insulin signaling were demonstrated via increases in Akt Thr308 phosphorylation, with CR + INS > CON and CR at 1 h (P < 0.05) and with CR + INS + FEN > CON, CR, and CR + INS at 4 h (P < 0.05). In contrast, no changes in PKCζ/λ or GLUT4 phosphorylation were detected., Conclusion: Fenugreek, when combined with insulin, modulates creatine content via a mechanism which is independent of the activity of SLC6A8, suggesting that an alternative mechanism is responsible for the regulation and facilitation of insulin-mediated creatine uptake in skeletal muscle cells.

Calcium levulinate (4-ketopentanoate) is used as an oral and parenteral source of calcium. We hypothesized that levulinate is converted in the liver to 4-hydroxypentanoate, a new drug of abuse, and that this conversion is accelerated by ethanol oxidation. We confirmed these hypotheses in live rats, perfused rat livers, and liver subcellular preparations. Levulinate is reduced to (R)-4-hydroxypentanoate by a cytosolic and a mitochondrial dehydrogenase, which are NADPH- and NADH-dependent, respectively. A mitochondrial dehydrogenase or racemase system also forms (S)-4-hydroxypentanoate. In livers perfused with [(13)C(5)]levulinate, there was substantial CoA trapping in levulinyl-CoA, 4-hydroxypentanoyl-CoA, and 4-phosphopentanoyl-CoA. This CoA trapping was increased by ethanol, with a 6-fold increase in the concentration of 4-phosphopentanoyl-CoA. Levulinate is catabolized by 3 parallel pathways to propionyl-CoA, acetyl-CoA, and lactate. Most intermediates of the 3 pathways were identified by mass isotopomer analysis and metabolomics. The production of 4-hydroxypentanoate from levulinate and its stimulation by ethanol is a potential public health concern.