Introduction: To increase the total carnitine (TC) content in muscles, L-carnitine (LC) should be co-ingested with carbohydrates to induce an insulin response. Leucine has an insulin secretagogue effect. Therefore, the primary aim of this study was to examine the effects of 24 weeks of LC and leucine supplementation on the skeletal muscle TC content, muscle mass, and strength in active college-aged subjects. The secondary aim was to determine the activation of the Akt/mTOR signaling pathway in skeletal muscles after supplementation. Methods: Over the 24 weeks, the participants were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC + L group; n = 7) or 4 g of leucine per day (L group; n = 7) as a placebo. Before and 24 weeks after the initiation of the study protocol, the free carnitine (FC) and TC content in plasma and muscle samples, as well as body composition and muscle strength, were measured. In addition, the phosphorylation of the Akt/mTOR pathway proteins in muscles was evaluated. Results: Plasma FC and TC content increased in LC + L group after 24 weeks of supplementation (p = 0.003 and 0.010, respectively). However, the skeletal muscle FC and TC contents were not affected by the supplementation protocol. No changes were noted in the body mass and composition; serum insulin-like growth factor-1 concentration; and phosphorylation of the signaling pathway proteins Akt, mTOR, and p70S6K. Conclusion: LC supplementation may have the potential to exert beneficial effects in muscle atrophy. Therefore, additional research is necessary to investigate the effect of various LC supplementation protocols.

1.
Brass EP. Supplemental carnitine and exercise. Am J Clin Nutr. 2000;72(2 Suppl):618S–23S.
2.
Oliveira C, Sousa M. The effects of L-carnitine supplementation in athletic performance. Sci Sports. 2019;34(2):63–72.
3.
Barnett C, Costill DL, Vukovich MD, Cole KJ, Goodpaster BH, Trappe SW, et al. Effect of L-carnitine supplementation on muscle and blood carnitine content and lactate accumulation during high-intensity sprint cycling. Int J Sport Nutr. 1994;4(3):280–8.
4.
Lee JK, Lee JS, Park H, Cha YS, Yoon CS, Kim CK. Effect of L-carnitine supplementation and aerobic training on FABPc content and beta-HAD activity in human skeletal muscle. Eur J Appl Physiol. 2007;99(2):193–9.
5.
Novakova K, Kummer O, Bouitbir J, Stoffel SD, Hoerler-Koerner U, Bodmer M, et al. Effect of L-carnitine supplementation on the body carnitine pool, skeletal muscle energy metabolism and physical performance in male vegetarians. Eur J Nutr. 2016;55(1):207–17.
6.
Stephens FB, Evans CE, Constantin-Teodosiu D, Greenhaff PL. Carbohydrate ingestion augments L-carnitine retention in humans. J Appl Physiol. 2007;102(3):1065–70.
7.
Stephens FB, Constantin-Teodosiu D, Laithwaite D, Simpson EJ, Greenhaff PL. Insulin stimulates L-carnitine accumulation in human skeletal muscle. FASEB J. 2006;20(2):377–9.
8.
Wall BT, Stephens FB, Constantin-Teodosiu D, Marimuthu K, Macdonald IA, Greenhaff PL. Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. J Physiol. 2011;589(Pt 4):963–73.
9.
Ringseis R, Keller J, Eder K. Mechanisms underlying the anti-wasting effect of L-carnitine supplementation under pathologic conditions: evidence from experimental and clinical studies. Eur J Nutr. 2013;52(5):1421–42.
10.
Sawicka AK, Renzi G, Olek RA. The bright and the dark sides of L-carnitine supplementation: a systematic review. J Int Soc Sports Nutr. 2020;17(1):49.
11.
Keller J, Couturier A, Haferkamp M, Most E, Eder K. Supplementation of carnitine leads to an activation of the IGF-1/PI3K/Akt signalling pathway and down regulates the E3 ligase MuRF1 in skeletal muscle of rats. Nutr Metab. 2013;10(1):28.
12.
Schiaffino S, Dyar KA, Ciciliot S, Blaauw B, Sandri M. Mechanisms regulating skeletal muscle growth and atrophy. FEBS J. 2013;280(17):4294–314.
13.
Evans M, Guthrie N, Pezzullo J, Sanli T, Fielding RA, Bellamine A. Efficacy of a novel formulation of L-Carnitine, creatine, and leucine on lean body mass and functional muscle strength in healthy older adults: a randomized, double-blind placebo-controlled study. Nutr Metab. 2017;14:7.
14.
Anthony JC, Anthony TG, Kimball SR, Jefferson LS. Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr. 2001;131(3):856S–60S.
15.
Plotkin DL, Delcastillo K, Van Every DW, Tipton KD, Aragon AA, Schoenfeld BJ. Isolated leucine and branched-chain amino acid supplementation for enhancing muscular strength and hypertrophy: a narrative review. Int J Sport Nutr Exerc Metab. 2021;31(3):292–301.
16.
van Loon LJC. Leucine as a pharmaconutrient in health and disease. Curr Opin Clin Nutr Metab Care. 2012;15(1):71–7.
17.
Sawicka AK, Hartmane D, Lipinska P, Wojtowicz E, Lysiak-Szydlowska W, Olek RA. l-Carnitine supplementation in older women. A pilot study on aging skeletal muscle mass and function. Nutrients. 2018;10(2):255.
18.
Symons TB, Vandervoort AA, Rice CL, Overend TJ, Marsh GD. Reliability of a single-session isokinetic and isometric strength measurement protocol in older men. J Gerontol A Biol Sci Med Sci. 2005;60(1):114–9.
19.
Devan MR, Pescatello LS, Faghri P, Anderson J. A prospective study of overuse knee injuries among female athletes with muscle imbalances and structural abnormalities. J Athl Train. 2004;39(3):263–7.
20.
Olek RA, Kujach S, Ziemann E, Ziolkowski W, Waz P, Laskowski R. Adaptive changes after 2 Weeks of 10-s sprint interval training with various recovery times. Front Physiol. 2018;9:392.
21.
Sowell J, Fuqua M, Wood T. Quantification of total and free carnitine in human plasma by hydrophilic interaction liquid chromatography tandem mass spectrometry. J Chromatogr Sci. 2011;49(6):463–8.
22.
Thalheimer W, Cook SR. How to calculate effect sizes from published research: a simplified methodology. Work-Learning Research; 2002.
23.
Costell M, O’Connor JE, Grisolia S. Age-dependent decrease of carnitine content in muscle of mice and humans. Biochem Biophys Res Commun. 1989;161(3):1135–43.
24.
D’Antona G, Nisoli E. mTOR signaling as a target of amino acid treatment of the age-related sarcopenia. Interdiscip Top Gerontol. 2010;37:115–41.
25.
Talenezhad N, Mohammadi M, Ramezani-Jolfaie N, Mozaffari-Khosravi H, Salehi-Abargouei A. Effects of l-carnitine supplementation on weight loss and body composition: a systematic review and meta-analysis of 37 randomized controlled clinical trials with dose-response analysis. Clin Nutr ESPEN. 2020;37:9–23.
26.
Borack MS, Volpi E. Efficacy and safety of leucine supplementation in the elderly. J Nutr. 2016;146(12):2625S–2629S.
27.
Aguiar AF, Grala AP, da Silva RA, Soares-Caldeira LF, Pacagnelli FL, Ribeiro AS, et al. Free leucine supplementation during an 8-week resistance training program does not increase muscle mass and strength in untrained young adult subjects. Amino Acids. 2017;49(7):1255–62.
28.
DE Andrade IT, Gualano B, Hevia-Larrain V, Neves-Junior J, Cajueiro M, Jardim F, et al. Leucine supplementation has No further effect on training-induced muscle adaptations. Med Sci Sports Exerc. 2020;52(8):1809–14.
29.
Sawicka AK, Jaworska J, Brzeska B, Sabisz A, Samborowska E, Radkiewicz M, et al. L-carnitine combined with leucine supplementation does not improve the effectiveness of progressive resistance training in healthy aged women. J Nutr Health Aging. 2022;26(10):945–53.
30.
Dzik KP, Kaczor JJ. Mechanisms of vitamin D on skeletal muscle function: oxidative stress, energy metabolism and anabolic state. Eur J Appl Physiol. 2019;119(4):825–39.
31.
Salles J, Chanet A, Giraudet C, Patrac V, Pierre P, Jourdan M, et al. 1,25 (OH)2-vitamin D3 enhances the stimulating effect of leucine and insulin on protein synthesis rate through Akt/PKB and mTOR mediated pathways in murine C2C12 skeletal myotubes. Mol Nutr Food Res. 2013;57(12):2137–46.
32.
Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. J Appl Physiol. 1996;81(1):232–7.
33.
Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;14:18.
34.
Kita K, Kato S, Amanyaman M, Okumura J, Yokota H. Dietary L-carnitine increases plasma insulin-like growth factor-I concentration in chicks fed a diet with adequate dietary protein level. Br Poult Sci. 2002;43(1):117–21.
35.
Busquets S, Serpe R, Toledo M, Betancourt A, Marmonti E, Orpi M, et al. L-Carnitine: an adequate supplement for a multi-targeted anti-wasting therapy in cancer. Clin Nutr. 2012;31(6):889–95.
36.
Keller J, Ringseis R, Priebe S, Guthke R, Kluge H, Eder K. Dietary L-carnitine alters gene expression in skeletal muscle of piglets. Mol Nutr Food Res. 2011;55(3):419–29.
37.
Jang J, Park J, Chang H, Lim K. l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats. Appl Physiol Nutr Metab. 2016;41(12):1240–7.
38.
Malaguarnera M, Cammalleri L, Gargante MP, Vacante M, Colonna V, Motta M. L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr. 2007;86(6):1738–44.
39.
Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, et al. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab. 1994;78(3):744–52.
40.
Bidlingmaier M, Friedrich N, Emeny RT, Spranger J, Wolthers OD, Roswall J, et al. Reference intervals for insulin-like growth factor-1 (igf-i) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations. J Clin Endocrinol Metab. 2014;99(5):1712–21.
You do not currently have access to this content.