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

• Published in: Nutrients 2021-11, Vol.13 (11), p.3985
• Main Authors: Fielding, Roger A, Rivas, Donato, Grosicki, Gregory J, Ezzyat, Yassine, Ceglia, Lisa, Price, Lori Lyn, Orhan, Cemal, Sahin, Kazim, Fowler, Kelli, White, Tyler, Durkee, Shane, Kritsch, Katja, Bellamine, Aouatef
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; Adolescent; Adult; Age; AKT protein; Animals; Bioavailability; Biological Availability; Carnitine; Carnitine - pharmacology; Cells, Cultured; Chromatography; Clinical trials; Creatine; Creatine - pharmacokinetics; Creatine - pharmacology; Dehydrogenases; Dietary supplements; Energy; Exercise; Female; Human subjects; Humans; Kinases; Laboratory animals; Lipids; Lipids - chemistry; Male; Metabolism; muscle; Muscle Proteins - biosynthesis; Muscles; Musculoskeletal system; Myoblasts; Myoblasts - drug effects; Myoblasts - metabolism; Particulates; Phosphorylation; Phosphorylation - drug effects; Physical fitness; Protein biosynthesis; Protein Biosynthesis - drug effects; Protein synthesis; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Ribosomal Protein S6 - metabolism; Rodents; Signal Transduction - drug effects; Stability analysis; Young Adult
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13113985

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.