Carnosine loading and washout in human skeletal muscles

Abstract

Carnosine (beta-alanyl-L-histidine) is present in high concentrations in human skeletal muscles. The oral ingestion of beta-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle carnosine content both in trained and untrained humans. Little human data exist about the dynamics of the muscle carnosine content, its metabolic regulation, and its dependence on muscle fiber type. The present study aimed to investigate in three skeletal muscle types the supplementation-induced amplitude of carnosine synthesis and its subsequent elimination on cessation of supplementation (washout). Fifteen untrained males participated in a placebo-controlled double-blind study. They were supplemented for 5-6 wk with either 4.8 g/day beta-alanine or placebo. Muscle carnosine was quantified in soleus, tibialis anterior, and medial head of the gastrocnemius by proton magnetic resonance spectroscopy (MRS), before and after supplementation and 3 and 9 wk into washout. The beta-alanine supplementation significantly increased the carnosine content in soleus by 39%, in tibialis by 27%, and in gastrocnemius by 23% and declined post-supplementation at a rate of 2-4%/wk. Average muscle carnosine remained increased compared with baseline at 3 wk of washout (only one-third of the supplementation-induced increase had disappeared) and returned to baseline values within 9 wk at group level. Following subdivision into high responders (+55%) and low responders (+15%), washout period was 15 and 6 wk, respectively. In the placebo group, carnosine remained relatively constant with variation coefficients of 9-15% over a 3-mo period. It can be concluded that carnosine is a stable compound in human skeletal muscle, confirming the absence of carnosinase in myocytes. The present study shows that washout periods for crossover designs in supplementation studies for muscle metabolites may sometimes require months rather than weeks.

Effect of β-alanine supplementation on 20 km cycling time trial performance

“…As such, we cannot con rm in the present study that muscle carnosine contents were signi cantly increased and, if so, what the magnitude of this increase was. However, supplementation with β-alanine at this level has consistently been shown to increase muscle carnosine concentrations by over 60% 8,11 , with others reporting no non-responders to β-alanine supplementation 11,21,31 . Indeed, only one participant from the series of muscle studies to-date has failed to respond to β-alanine supplementation with an increase in muscle carnosine 8 .…”

“…In order to determine the reliability of the 20 km time trial, we used the data from trials 1 and 2 on 21 participants (age 35 ± 8 y, height 1.82 ± 0.05 prior to the study due to the long washout period for muscle Carnosine 21 . Participants verbally agreed to maintain similar levels of physical activity and dietary intake for the duration of the study and compliance with this request was verbally con rmed with participants prior to each testing session.…”

Muscle Carnosine Metabolism and β-Alanine Supplementation in Relation to Exercise and Training

“…Instead, synthesized carnosine either remains present in the muscle cells for long periods, or it is secreted into the circulation through a regulated transport process. Evidence for the former was recently shown by Baguet et al [2], who showed that a highly increased concentration of carnosine in human calf muscles following beta-alanine supplementation can remain present for >9 weeks following cessation of supplementation. Evidence for the regulated carnosine release from muscle into the circulation is fragmentary at present.…”

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“…Oral administration of β-alanine, the rate limiting amino acid for the biosynthesis of carnosine [48], to healthy volunteers during 4 weeks resulted in reduced fatigue after physical exercise and in 30-50% increase of carnosine storage in peripheral muscle tissue, as determined again by proton-MRS [52]. Interestingly, this accumulation is followed by a slow clearance of carnosine during 3-6 months, suggesting a prolonged efficacy of short-term intervention [49,53]. Next, the latter mentioned study also showed that in humans the histidinecontaining dipeptides increase with increasing obesity and glucose intolerance in male individuals.…”