Endocrinol Metab.  2025 Feb;40(1):93-102. 10.3803/EnM.2024.2117.

Carnitine Metabolite as a Potential Circulating Biomarker for Sarcopenia in Men

• Seo JH
• Koh JM
• Cho HJ
• Kim H
• Lee Y
• Kim SJ
• Yoon PW
• Kim W
• Bae SJ
• Kim HK
• Yoo HJ
• Lee SH

• KMID: 2565257
• DOI: http://doi.org/10.3803/EnM.2024.2117

Abstract

Background
Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia.
Methods
Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort.
Results
An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027).
Conclusion
C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Keyword

Aging; Metabolomics; Sarcopenia; Biomarkers; Carnitine

Figure

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  Fig. 1. Changes in carnitine (CN) levels during myoblast differentiation. CN levels in the cell lysates of myoblasts (MBs), myocytes (MCs), and myotubes (MTs). The error bar represents the standard deviation. P values were calculated using Mann-Whitney U test. Significant changes in the levels of each fatty acid amide in MCs and MTs compared to those in MBs are indicated by afor P<0.05 and bfor P<0.01.

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  Fig. 2. Receiver operating characteristic (ROC) curve of the carnitine (CN) score to detect sarcopenia in men in the (A) discovery cohort (n=144) and (B) validation cohort (n=68). CN score=–0.006–[0.493×log (C5-CN)SD]. SD, standard deviation; HGS, hand grip strength; AUROC, area under the receiver operating characteristic curve; CI, confidence interval.

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Reference

1. Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc. 2020; 21:300–7.

2. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019; 48:16–31.

3. Cruz-Jentoft AJ, Sayer AA. Sarcopenia. Lancet. 2019; 393:2636–46.

4. Norman K, Otten L. Financial impact of sarcopenia or low muscle mass: a short review. Clin Nutr. 2019; 38:1489–95.

5. Pugh TD, Conklin MW, Evans TD, Polewski MA, Barbian HJ, Pass R, et al. A shift in energy metabolism anticipates the onset of sarcopenia in rhesus monkeys. Aging Cell. 2013; 12:672–81.

6. Rinschen MM, Ivanisevic J, Giera M, Siuzdak G. Identification of bioactive metabolites using activity metabolomics. Nat Rev Mol Cell Biol. 2019; 20:353–67.

7. Crentsil V. Mechanistic contribution of carnitine deficiency to geriatric frailty. Ageing Res Rev. 2010; 9:265–8.

8. Flanagan JL, Simmons PA, Vehige J, Willcox MD, Garrett Q. Role of carnitine in disease. Nutr Metab (Lond). 2010; 7:30.

9. Gnoni A, Longo S, Gnoni GV, Giudetti AM. Carnitine in human muscle bioenergetics: can carnitine supplementation improve physical exercise? Molecules. 2020; 25:182.

10. Ahmad S. L-carnitine in dialysis patients. Semin Dial. 2001; 14:209–17.

11. Kemp PR, Paul R, Hinken AC, Neil D, Russell A, Griffiths MJ. Metabolic profiling shows pre-existing mitochondrial dysfunction contributes to muscle loss in a model of ICU-acquired weakness. J Cachexia Sarcopenia Muscle. 2020; 11:1321–35.

12. Patel SS, Molnar MZ, Tayek JA, Ix JH, Noori N, Benner D, et al. Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross-sectional study and review of literature. J Cachexia Sarcopenia Muscle. 2013; 4:19–29.

13. Silverio R, Laviano A, Rossi Fanelli F, Seelaender M. l-Carnitine and cancer cachexia: clinical and experimental aspects. J Cachexia Sarcopenia Muscle. 2011; 2:37–44.

14. Takagi A, Hawke P, Tokuda S, Toda T, Higashizono K, Nagai E, et al. Serum carnitine as a biomarker of sarcopenia and nutritional status in preoperative gastrointestinal cancer patients. J Cachexia Sarcopenia Muscle. 2022; 13:287–95.

15. Kinugasa Y, Sota T, Nakamura K, Hirai M, Kato M, Yamamoto K. Association of carnitine insufficiency with sarcopenia and dynapenia in patients with heart failure. Geriatr Gerontol Int. 2023; 23:524–30.

16. Lustgarten MS, Price LL, Chale A, Phillips EM, Fielding RA. Branched chain amino acids are associated with muscle mass in functionally limited older adults. J Gerontol A Biol Sci Med Sci. 2014; 69:717–24.

17. Murphy RA, Moore SC, Playdon M, Meirelles O, Newman AB, Milijkovic I, et al. Metabolites associated with lean mass and adiposity in older Black men. J Gerontol A Biol Sci Med Sci. 2017; 72:1352–9.

18. Meng L, Yang R, Wang D, Wu W, Shi J, Shen J, et al. Specific lysophosphatidylcholine and acylcarnitine related to sarcopenia and its components in older men. BMC Geriatr. 2022; 22:249.

19. Caballero FF, Struijk EA, Lana A, Buno A, Rodriguez-Artalejo F, Lopez-Garcia E. Plasma acylcarnitines and risk of lower-extremity functional impairment in older adults: a nested case-control study. Sci Rep. 2021; 11:3350.

20. Lum H, Sloane R, Huffman KM, Kraus VB, Thompson DK, Kraus WE, et al. Plasma acylcarnitines are associated with physical performance in elderly men. J Gerontol A Biol Sci Med Sci. 2011; 66:548–53.

21. Xie WQ, He M, Yu DJ, Wu YX, Wang XH, Lv S, et al. Mouse models of sarcopenia: classification and evaluation. J Cachexia Sarcopenia Muscle. 2021; 12:538–54.

22. Kim YA, Lee SH, Koh JM, Kwon SH, Lee Y, Cho HJ, et al. Fatty acid amides as potential circulating biomarkers for sarcopenia. J Cachexia Sarcopenia Muscle. 2023; 14:1558–68.

23. Mihalik SJ, Goodpaster BH, Kelley DE, Chace DH, Vockley J, Toledo FG, et al. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity (Silver Spring). 2010; 18:1695–700.

24. Bae JH, Han KD, Ko SH, Yang YS, Choi JH, Choi KM, et al. Diabetes fact sheet in Korea 2021. Diabetes Metab J. 2022; 46:417–26.