Vegetarianism, female gender and increasing age, but not CNDP1 genotype, are associated with reduced muscle carnosine levels in humans
Carnosine is found in high concentrations in skeletal muscles, where it is involved in several physiological functions. The muscle carnosine content measured within a population can vary by a factor 4. The aim of this study was to further characterize suggested determinants of the muscle carnosine content (diet, gender and age) and to identify new determinants (plasma carnosinase activity and testosterone). We investigated a group of 149 healthy subjects, which consisted of 94 men (12 vegetarians) and 55 women. Muscle carnosine was quantified in M. soleus, gastrocnemius and tibialis anterior using magnetic resonance proton spectroscopy and blood samples were collected to determine CNDP1 genotype, plasma carnosinase activity and testosterone concentrations. Compared to women, men have 36, 28 and 82% higher carnosine concentrations in M. soleus, gastrocnemius and tibialis anterior muscle, respectively, whereas circulating testosterone concentrations were unrelated to muscle carnosine levels in healthy men. The carnosine content of the M. soleus is negatively related to the subjects’ age. Vegetarians have a lower carnosine content of 26% in gastrocnemius compared to omnivores. In contrast, there is no difference in muscle carnosine content between omnivores with a high or low ingestion of β-alanine. Muscle carnosine levels are not related to the polymorphism of the CNDP1 gene or to the enzymatic activity of the plasma carnosinase. In conclusion, neither CNDP1 genotype nor the normal variation in circulating testosterone levels affects the muscular carnosine content, whereas vegetarianism, female gender and increasing age are the factors associated with reduced muscle carnosine stores.
KeywordsCarnosine Gender Age Vegetarianism CNDP1 genotype Androgens
This study was financially supported by grants from the Research Foundation—Flanders (FWO 1.5.149.08 and G.0046.09) and by the EU-funded specifically targeted project, PREDICTIONS, to identify risk factors for developing diabetic nephropathy (FP6-018733, http://www.predictions-project.eu). Audrey Baguet is a recipient of a PhD-scholarship from the Research Foundation—Flanders. MRS was performed at GIfMI (http://www.gifmi.be). The authors declare that they have no conflict of interest.
- Abe H (2000) Role of histidine-related compounds as intracellular proton buffering constituents in vertebrate muscle. Biochemistry (Mosc) 65:757–765Google Scholar
- Bate Smith EC (1938) The buffering of muscle in rigor: protein, phosphate and carnosine. J Physiol 92:336–343Google Scholar
- Boldyrev AA (2007) Carnosine and oxidative stress in cells and tissues. Nova Science, New YorkGoogle Scholar
- Enette Larson-Meyer D (2006) Vegetarian sports nutrition. Human Kinetics, ChampaignGoogle Scholar
- Freedman BI, Hicks PJ, Sale MM, Pierson ED, Langefeld CD, Rich SS, Xu J, McDonough C, Janssen B, Yard BA, van der Woude FJ, Bowden DW (2007) A leucine repeat in the carnosinase gene CNDP1 is associated with diabetic end-stage renal disease in European Americans. Nephrol Dial Transplant 22:1131–1135PubMedCrossRefGoogle Scholar
- Janssen B, Hohenadel D, Brinkkoetter P, Peters V, Rind N, Fischer C, Rychlik I, Cerna M, Romzova M, de Heer E, Baelde H, Bakker SJ, Zirie M, Rondeau E, Mathieson P, Saleem MA, Meyer J, Koppel H, Sauerhoefer S, Bartram CR, Nawroth P, Hammes HP, Yard BA, Zschocke J, van der Woude FJ (2005) Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1. Diabetes 54:2320–2327PubMedCrossRefGoogle Scholar
- Peters V, Kebbewar M, Jansen E, Jakobs C, Riedl E, Koeppel H, Frey D, Adelmann K, Klingbeil K, Mack M, Hoffmann GF, Janssen B, Zschocke J, Yard BA (2009) Relevance of allosteric conformations and homocarnosine concentration on carnosinase activity 38:1607–1615Google Scholar
- Ponte J, Harris RC, Hill CA, Sale C, Jones GA, Kim HJ, Wise JA (2006) Effect of 14 and 28 days β-alanine supplementation on isometric endurance of the knee extensors. J Sports Sci 25:344Google Scholar
- Teufel M, Saudek V, Ledig JP, Bernhardt A, Boularand S, Carreau A, Cairns NJ, Carter C, Cowley DJ, Duverger D, Ganzhorn AJ, Guenet C, Heintzelmann B, Laucher V, Sauvage C, Smirnova T (2003) Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. J Biol Chem 278:6521–6531PubMedCrossRefGoogle Scholar