Muscular carnosine is a marker for cardiorespiratory fitness and cardiometabolic risk factors in men with type 1 diabetes.

PURPOSE: Muscle is an essential organ for glucose metabolism and can be influenced by metabolic disorders and physical activity. Elevated muscle carnosine levels have been associated with insulin resistance and cardiometabolic risk factors. Little is known about muscle carnosine in type 1 diabetes (T1D) and how it is influenced by physical activity. The aim of this study was to characterize muscle carnosine in vivo by proton magnetic resonance spectroscopy (1H MRS) and evaluate the relationship with physical activity, clinical characteristics and lipoprotein subfractions. METHODS: 16 men with T1D (10 athletes/6 sedentary) and 14 controls without diabetes (9/5) were included. Body composition by DXA, cardiorespiratory capacity (VO2peak) and serum lipoprotein profile by proton nuclear magnetic resonance (1H NMR) were obtained. Muscle carnosine scaled to water (carnosineW) and to creatine (carnosineCR), creatine and intramyocellular lipids (IMCL) were quantified in vivo using 1H MRS in a 3T MR scanner in soleus muscle. RESULTS: Subjects with T1D presented higher carnosine CR levels compared to controls. T1D patients with a lower VO2peak presented higher carnosineCR levels compared to sedentary controls, but both T1D and control groups presented similar levels of carnosineCR at high VO2peak levels. CarnosineW followed the same trend. Integrated correlation networks in T1D demonstrated that carnosineW and carnosineCR were associated with cardiometabolic risk factors including total and abdominal fat, pro-atherogenic lipoproteins (very low-density lipoprotein subfractions), low VO2peak, and IMCL. CONCLUSIONS: Elevated muscle carnosine levels in persons with T1D and their effect on atherogenic lipoproteins can be modulated by physical activity.

Beta-alanine did not improve high-intensity performance throughout simulated road cycling.

This study investigated the effect of beta-alanine supplementation on short-duration sprints and final 4-km simulated uphill cycling time-trial performance during a comprehensive and novel exercise protocol representative of the demands of road-race cycling, and determined if changes were related to increases in muscle carnosine content. Seventeen cyclists (age 38 ± 9 y, height 1.76 ± 0.07 m, body mass 71.4 ± 8.8 kg, V̇O2max 52.4 ± 8.3 ml·kg-1·min-1) participated in this placebo-controlled, double-blind study. Cyclists undertook a prolonged intermittent cycling protocol lasting 125 min, with a 10-s sprint every 20 min, finishing with a 4-km time-trial at 5% simulated incline. Participants completed two familiarization sessions, and two main sessions, one pre-supplementation and one post-supplementation following 28 days of 6.4 g·day-1 of beta-alanine (N=11) or placebo (N=6; maltodextrin). Muscle biopsies obtained pre- and post-supplementation were analysed for muscle carnosine content. There were no main effects on sprint performance throughout the intermittent cycling test (all P>0.05). There was no group (P=0.69), time (P=0.50) or group x time interaction (P=0.26) on time-to-complete the 4-km time-trial. Time-to-completion did not change from pre- to post-supplementation for BA (-19.2 ± 45.6 s, P=0.43) or PL (+2.8 ± 31.6 s, P=0.99). Beta-alanine supplementation increased muscle carnosine content from pre- to post-supplementation (+9.4 ± 4.0 mmol·kg-1dm; P<0.0001) but was not related to performance changes (r=0.320, P=0.37). Chronic beta-alanine supplementation increased muscle carnosine content but did not improve short-duration sprint performance throughout simulated road race cycling, nor 4-km uphill time-trial performance conducted at the end of this cycling test.HighlightsPerformance during prolonged cycling events often depends on the ability to maintain an increased power output during higher intensity periods. Thus, cyclists are likely heavily dependent on their ability to resist fatigue during these periods of high-intensity activity.Meta-analytical data show beta-alanine to be an effective supplement to improve exercise outcomes, but little work exists on its efficacy during dynamic actions that are common during prolonged cycling.Beta-alanine supplementation increased muscle carnosine content but did not generate improvements in the performance of high-intensity cycling (10-s sprints or 4-km uphill time-trial) during a simulated road race cycling protocol.These data suggest that short duration sprints (≤10 s) and longer duration (>10 min) high-intensity activity throughout endurance cycling may not be improved with beta-alanine supplementation despite increases in muscle carnosine content.

Beta-alanine Supplementation for Four Weeks Increases Volume Index and Reduces Perceived Effort of Resistance-trained Men: A Pilot Study.

The aim of the present study was to assess the short-term effects of four weeks of beta-alanine supplementation (BA) (6.4 g/day) on the total volume performed and perceived effort of resistance-trained individuals. Sixteen trained men (age: 27.3 ± 5.0 years, height: 1.78 ± 0.1 cm, total body mass: 84.3 ± 8.4 kg, RT experience: 5.9 ± 3.3 years) were allocated in one of the following groups: BA or Placebo (PLA). In addition, during the same period, participants were submitted to a resistance training program. Volume index (VI) and the rate of perceived exertion (RPE) were collected during the experimental period for both groups. Significant increases from the first to the last intervention week in VI were observed only for BA (+6.5%, d = 0.61, p = 0.04). In addition, supplementation induced a lower mean RPE (BA: 8.8 ± 0.5 AU vs. PLA: 9.4 ± 0.3 AU, p = 0.02). In conclusion, four weeks of BA supplementation were able to increase resistance-training volume without affecting the perceived effort of trained men.

Effect of ß-alanine supplementation during high-intensity interval training on repeated sprint ability performance and neuromuscular fatigue.

The study investigated the influence of ß-alanine supplementation during a high-intensity interval training (HIIT) program on repeated sprint ability (RSA) performance. This study was randomized, double-blinded, and placebo controlled. Eighteen men performed an incremental running test until exhaustion (TINC) at baseline and followed by 4-wk HIIT (10 × 1-min runs 90% maximal TINC velocity [1-min recovery]). Then, participants were randomized into two groups and performed a 6-wk HIIT associated with supplementation of 6.4 g/day of ß-alanine (Gß) or dextrose (placebo group; GP). Pre- and post-6-wk HIIT + supplementation, participants performed the following tests: 1) TINC; 2) supramaximal running test; and 3) 2 × 6 × 35-m sprints (RSA). Before and immediately after RSA, neuromuscular function was assessed by vertical jumps, maximal isometric voluntary contractions of knee extension, and neuromuscular electrical stimulations. Muscle biopsies were performed to determine muscle carnosine content, muscle buffering capacity in vitro (ßmin vitro), and content of phosphofructokinase (PFK), monocarboxylate transporter 4 (MCT4), and hypoxia-inducible factor-1α (HIF-1α). Both groups showed a significant time effect for maximal oxygen uptake (Gß: 6.2 ± 3.6% and GP: 6.5 ± 4.2%; P > 0.01); only Gß showed a time effect for total (-3.0 ± 2.0%; P = 0.001) and best (-3.3 ± 3.0%; P = 0.03) RSA times. A group-by-time interaction was shown after HIIT + Supplementation for muscle carnosine (Gß: 34.4 ± 2.3 mmol·kg-1·dm-1 and GP: 20.7 ± 3.0 mmol·kg-1·dm-1; P = 0.003) and neuromuscular voluntary activation after RSA (Gß: 87.2 ± 3.3% and GP: 78.9 ± 12.4%; P = 0.02). No time effect or group-by-time interaction was shown for supramaximal running test performance, ßm, and content of PFK, MCT4, and HIF-1α. In summary, ß-alanine supplementation during HIIT increased muscle carnosine and attenuated neuromuscular fatigue, which may contribute to an enhancement of RSA performance.NEW & NOTEWORTHY ß-Alanine supplementation during a high-intensity interval training program increased repeated sprint performance. The improvement of muscle carnosine content induced by ß-alanine supplementation may have contributed to an attenuation of central fatigue during repeated sprint. Overall, ß-alanine supplementation may be a useful dietary intervention to prevent fatigue.

Can the Skeletal Muscle Carnosine Response to Beta-Alanine Supplementation Be Optimized?

Carnosine is an abundant histidine-containing dipeptide in human skeletal muscle and formed by beta-alanine and L-histidine. It performs various physiological roles during exercise and has attracted strong interest in recent years with numerous investigations focused on increasing its intramuscular content to optimize its potential ergogenic benefits. Oral beta-alanine ingestion increases muscle carnosine content although large variation in response to supplementation exists and the amount of ingested beta-alanine converted into muscle carnosine appears to be low. Understanding of carnosine and beta-alanine metabolism and the factors that influence muscle carnosine synthesis with supplementation may provide insight into how beta-alanine supplementation may be optimized. Herein we discuss modifiable factors that may further enhance the increase of muscle carnosine in response to beta-alanine supplementation including, (i) dose; (ii) duration; (iii) beta-alanine formulation; (iv) dietary influences; (v) exercise; and (vi) co-supplementation with other substances. The aim of this narrative review is to outline the processes involved in muscle carnosine metabolism, discuss theoretical and mechanistic modifiable factors which may optimize the muscle carnosine response to beta-alanine supplementation and to make recommendations to guide future research.