Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents.

Roger A Fielding,Yassine Ezzyat,Shane Durkee,Kelli Fowler,Tyler White,Donato Rivas,Kazim Sahin,Cemal Orhan,Gregory J Grosicki,Lori Lyn Price,Aouatef Bellamine,Katja Kritsch,Lisa Ceglia

doi:10.3390/nu13113985

Abstract

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis.

Highlights

Both exercise and age influence skeletal muscle protein turnover
We first assessed the effect of 2 combinations of CARN/Cr at 0.05 mM/0.05 mM or 0.1 mM/0.1 mM on muscle protein synthesis in human primary myoblasts
We found that both combinations led to a significant increase in protein synthesis (Figure 1)

Summary

Introduction

Both exercise and age influence skeletal muscle protein turnover. Biochemical processes such as hypoxia of the muscle, tissue degradation, free radical formation, and sarcolemma disruption may occur and can be prevented by nutritional supplements [2]. The decrease in skeletal muscle size and loss of function leads to clinically relevant complaints, including progressive strength loss, fatigue, and lack of mobility [3]. The prevention of muscle dysfunction with established treatment protocols is primarily symptom-oriented and includes physical therapy and exercise, but no approved pharmacologic interventions are currently available [4,5]. Considering the lack of therapies for age-related muscle atrophy, the idea that nutritional supplements might have beneficial effects on muscle growth is of renewed interest [6]

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