New perspectives for investigating muscular perfusion response after dietary supplement intake: an exploratory, randomized, double-blind, placebo-controlled crossover trial in healthy young athletes using contrast-enhanced ultrasound (CEUS).

Background: Various dietary supplements have been reported to enhance muscular perfusion in athletes practicing resistance training, especially through modulation of nitric oxide signaling. Objectives: The aim of this study was therefore to investigate selected 'NO-boosting' supplements in a real-life setting i) to generate novel hypotheses and perfusion estimates for power calculation in view of a definitive trial and ii) to assess the feasibility of the study design with particular focus on the use of contrast-enhanced ultrasound (CEUS) for perfusion quantification. Methods: Thirty young male athletes (24 ± 4 years) regularly practicing resistance training were enrolled in this three-arm, placebo(PL)-controlled crossover trial with ingestion of two commercially available supplements: an amino acid combination (AA) (containing 3 g of L-arginine-hydrochloride and 8 g of L-citrulline-malate) and 300 mg of a specific green tea extract (GTE). After intake, CEUS examinations of the dominant biceps brachii muscle were performed under resting conditions and following standardized resistance exercising. Quantitative parameters of biceps perfusion (peak enhancement, PE; wash-in perfusion index, WiPI) and caliber were derived from corresponding CEUS video files. Additionally, subjective muscle pump was determined after exercise. Results: For PE, WiPI, and biceps caliber, the standard deviation (SD) of the within-subject differences between PL, AA, and GTE was determined, thereby allowing future sample size calculations. No significant differences between PL, AA, and GTE were observed for biceps perfusion, caliber, or muscle pump. When comparing resting with post-exercise measurements, the increase in biceps perfusion significantly correlated with the caliber increase (PE: r = 0.266, p = 0.0113; WiPI: r = 0.269, p = 0.0105). Similarly, the biceps perfusion correlated with muscle pump in the post-exercise conditions (PE: r = 0.354, p = 0.0006; WiPI: r = 0.350, p = 0.0007). A high participant adherence was achieved, and the acquisition of good quality CEUS video files was feasible. No adverse events occurred. Conclusion: Based on our novel examination protocol, CEUS seems to be feasible following higher-load resistance exercising and may be used as a new method for high-resolution perfusion quantification to investigate the effects of pre-exercise dietary supplementation on muscle perfusion and related muscle size dynamics.

Contrast-enhanced ultrasound for determining muscular perfusion after oral intake of L-citrulline, L-arginine, and galloylated epicatechines: A study protocol.

INTRODUCTION: The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters," which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation.The aim of this study was to investigate 3 of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS). METHODS: This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6 and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30-male athletes between 18 and 40 years and will be compared with a placebo. On each of the 3 appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the 3 supplements once after a wash-out period of at least 1 week. Perfusion will be quantified via VueBox quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters. DISCUSSION: The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019.