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

Authors: FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RIVAS, DONATO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GROSICKI, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; EZZYAT, YASSINE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CEGLIA, LISA - Tufts Medical Center; PRICE, LORI LYN - Tufts Medical Center; ORHAN, CEMAL - Firat University; SAHIN, KAZIM - Firat University; FOWLER, KELLI - Lonza Corporation; WHITE, TYLER - Lonza Corporation; DURKEE, SHANE - Lonza Corporation; KRITSCH, KATJA - Lonza Corporation; BELLAMINE, AOUATEF - Lonza Corporation

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/5/2021
Publication Date: 11/9/2021
Citation: Fielding, R.A., Rivas, D.A., Grosicki, G.J., Ezzyat, Y., Ceglia, L., Price, L., Orhan, C., Sahin, K., Fowler, K., White, T., Durkee, S., Kritsch, K., Bellamine, A. 2021. 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. Nutrients. 13(11):3985. https://doi.org/10.3390/nu13113985.
DOI: https://doi.org/10.3390/nu13113985

Interpretive Summary: L-carnitine tartrate and creatine monohydrate are dietary ingredients that have been reported to have effects on muscle function at relatively high doses. We conducted studies using a "cell culture" model with skeletal muscle cells. Using this laboratory based approach, we found that low doses of L-carnitine tartrate and creatine monohydrate did not affect muscle cell growth when treated with either ingredient alone. However, when combined, L-carnitine tartrate and creatine monohydrate did increase muscle cell growth. We then confirmed in an animal model and in humans that the low dose of L-carnitine tartrate and creatine monohydrate caused significant increases in the serum concentration of creatine. These results provide preliminary evidence that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to increased muscle growth.

Technical 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 muM and creatine monohydrate at 0.5 muM 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 muM L-carnitine tartrate 5 muM 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.