Vegetarianism, female gender and increasing age, but not CNDP1 genotype, are associated with reduced muscle carnosine levels in humans
Journal Title (Medline/Pubmed accepted abbreviation): Amino Acids
Year: 2010 Epub ahead of print
Page numbers:
doi: 10.1007/s00726-010-0749-2

Summary of Background and Research Design

Background:Carnosine (ß-alanyl-L-histidine) is a dipeptide found in high concentrations in skeletal muscles and is associated with multiple physiologic functions such as pH buffering, antioxidant effects, increasing sensitivity to Ca2+, and inhibiting protein glycation. Recent studies have shown that elevated muscle carnosine is associated with attenuated fatigue and improved exercise performance in humans. Although the muscle carnosine content can vary greatly between individuals, the intra-individual variation is relatively low (9% to 15% over a 3-month period). The most established determinant of the muscle carnosine content is muscle fiber type. The amount of food from animal sources is likely to contribute to muscle carnosine content as ß-alanine, the rate-limiting precursor in carnosine synthesis, which is exclusively found in meat and fish. Women and the elderly have been suggested to have lower muscle carnosine levels. Finally, polymorphisms in the enzymes responsible for the synthesis (carnosine synthase) and hydrolysis (carnosinase) of carnosine may contribute to muscle carnosine content.

Hypothesis/purpose of study: The aim of this study was to further characterize suggested determinants of muscle carnosine content (diet, sex, and age) and to identify new determinants (plasma carnosinase activity and testosterone).

Subjects: Healthy subjects (N = 149), which consisted of 94 men (12 vegetarians) and 55 women, participated in the study. Vegetarians were either lacto-ovo vegetarians or vegans and were required to have been vegetarian for >= 8 years (mean, 15 ± 9.5 yr).

Experimental design: Observational, non-experimental

Treatments and protocol: Muscle carnosine was quantified in the slow twitch soleus, the fast-twitch gastrocnemius muscle, and the tibialis anterior to determine the possible interaction of various factors within the muscle fiber type. Magnetic resonance proton spectroscopy was used to explore, without the need for biopsy, determinants of the variation in muscle carnosine content. Additionally, blood samples were collected to determine CNDP1 genotype (the gene coding for serum carnosinase enzyme), plasma carnosinase activity, and testosterone concentrations.

Summary of research findings:
  • Men had 36%, 28%, and 82% higher carnosine concentrations in the soleus, gastrocnemius, and tibialis anterior muscle, respectively, compared with women.
  • Circulating testosterone concentrations were unrelated to muscle carnosine levels in healthy men.
  • Carnosine content of the soleus was negatively related to the subjects' age.
  • Vegetarians had a lower carnosine content of 26% in gastrocnemius compared with omnivores.
    • In contrast, there was no difference in muscle carnosine content between omnivores with a high or low ingestion of ß-alanine.
  • Muscle carnosine levels were not related to polymorphism of the CNDP1 gene or to the enzymatic activity of plasma carnosinase.

Interpretation of findings/Key practice applications:

It has been previously demonstrated that an increased availability of ß-alanine results in higher muscle carnosine content. This is the first peer-reviewed study demonstrating that a complete and long-lasting restriction of ß-alanine from the diet results in lower intramuscular carnosine concentrations. In addition, this study confirms the higher muscle carnosine content of males versus females. The data suggest that carnosine content declines 1.2% per year. As the majority of participants were < 30 years of age, this result will need confirmation in an older population of adults. Although this study does not support a correlation between free plasma testosterone and carnosine content, it does not exclude the possibility that more extreme variations such as overt hypogonadism or exogenous testosterone supplementation influence muscle carnosine. Finally, CNDP1 genotype did not affect the muscular carnosine content. However, this study was too small to exclude an association between carnosine and CNDP1 genotype. An important implication from this study is that vegetarian athletes involved in high-intensity exercise may benefit from ß-alanine supplementation.
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