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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 1, Donato Rivas 1, Gregory J Grosicki 1 2, Yassine Ezzyat 1, Lisa Ceglia 3, Lori Lyn Price 4 5, Cemal Orhan 6, Kazim Sahin 6, Kelli Fowler 7, Tyler White 7, Shane Durkee 7, Katja Kritsch 8, Aouatef Bellamine 7
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PMID: 34836240 PMCID: PMC8625796 DOI: 10.3390/nu13113985
Free PMC article
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.

Keywords: carnitine; creatine; muscle; protein synthesis.

Conflict of interest statement
Fielding reports grants from the NIH National Institute on Aging and the USDA during the conduct of the study; grants, personal fees, and other from Axcella Health; other from Inside Tracker; grants, and personal fees from Biophytis; grants and personal fees from Astellas; personal fees from Cytokinetics; personal fees from Amazentisl grants and personal fees from Nestle’l; and personal fees from Glaxo Smith Kline outside the submitted work. Authors Fowler, White, Durkee, Katja, and Bellamine are employees of Lonza. The funder was involved in the design of this study, interpretation, and writing of the manuscript.