24-Week ß-alanine ingestion does not affect muscle taurine or clinical blood parameters in healthy males.

PURPOSE: To investigate the effects of chronic beta-alanine (BA) supplementation on muscle taurine content, blood clinical markers and sensory side-effects. METHODS: Twenty-five healthy male participants (age 27 ± 4 years, height 1.75 ± 0.09 m, body mass 78.9 ± 11.7 kg) were supplemented with 6.4 g day-1 of sustained-release BA (N = 16; CarnoSyn™, NAI, USA) or placebo (PL; N = 9; maltodextrin) for 24 weeks. Resting muscle biopsies of the m. vastus lateralis were taken at 0, 12 and 24 weeks and analysed for taurine content (BA, N = 12; PL, N = 6) using high-performance liquid chromatography. Resting venous blood samples were taken every 4 weeks and analysed for markers of renal, hepatic and muscle function (BA, N = 15; PL, N = 8; aspartate transaminase; alanine aminotransferase; alkaline phosphatase; lactate dehydrogenase; albumin; globulin; creatinine; estimated glomerular filtration rate and creatine kinase). RESULTS: There was a significant main effect of group (p = 0.04) on muscle taurine, with overall lower values in PL, although there was no main effect of time or interaction effect (both p > 0.05) and no differences between specific timepoints (week 0, BA: 33.67 ± 8.18 mmol kg-1 dm, PL: 27.75 ± 4.86 mmol kg-1 dm; week 12, BA: 35.93 ± 8.79 mmol kg-1 dm, PL: 27.67 ± 4.75 mmol kg-1 dm; week 24, BA: 35.42 ± 6.16 mmol kg-1 dm, PL: 31.99 ± 5.60 mmol kg-1 dm). There was no effect of treatment, time or any interaction effects on any blood marker (all p > 0.05) and no self-reported side-effects in these participants throughout the study. CONCLUSIONS: The current study showed that 24 weeks of BA supplementation at 6.4 g day-1 did not significantly affect muscle taurine content, clinical markers of renal, hepatic and muscle function, nor did it result in chronic sensory side-effects, in healthy individuals. Since athletes are likely to engage in chronic supplementation, these data provide important evidence to suggest that supplementation with BA at these doses for up to 24 weeks is safe for healthy individuals.

The molecular structure of ß-alanine is resistant to sterilising doses of gamma radiation.

ß-alanine is the rate-limiting point for the endogenous synthesis of carnosine in skeletal muscle. Carnosine has a wide range of implications for health, normal function and exercise performance. Whilst the physiological relevance of carnosine to different tissues remains enigmatic, ß-alanine administration is a useful strategy to investigate the physiological roles of carnosine in humans. Intravenous administration of ß-alanine is an interesting approach to study carnosine metabolism. However, sterilisation is mandatory due to the nature of the administration route. We evaluated whether sterilising doses of gamma radiation damages the molecular structure and leads to the loss of functional characteristics of ß-alanine. Pure ß-alanine was sterilised by gamma radiation in sealed glass vials using a 60Co multipurpose irradiator at a dose rate of 8.5 kGy.hour-1 totalising 10, 20, 25 30 and 40 kGy. The molecular integrity was assessed by X-ray Diffraction and changes in content were determined by High Performance Liquid Chromatography (UV-HPLC) and Triple Quadrupole Mass Spectrometer (HPLC/MS-MS). Sterility assurance was evaluated by inoculation assay. To examine whether functional properties were preserved, ß-alanine was infused in one participant, who rated the level of paraesthesia on the skin using a 0-3 scale. Urinary ß-alanine was quantified before and 24-h following ß-alanine infusion using HPLC-ESI+-MS/MS. Irradiation resulted in no change in the crystal structure of ß-alanine, no degradation, and no new peaks were identified in the dose range assayed. The inoculation assay showed the absence of viable microorganisms in all ß-alanine samples, including those that did not undergo irradiation. Intravenous infusion of ß-alanine resulted in paraesthesia and it detected in the urine as per normal. We conclude that gamma radiation is a suitable technique for the sterilisation of ß-alanine. It does not lead to degradation, damage to the ß-alanine structure, content or loss of function within the evaluated irradiation conditions.

High-Intensity Interval Training Augments Muscle Carnosine in the Absence of Dietary Beta-alanine Intake.

PURPOSE: Cross-sectional studies suggest that training can increase muscle carnosine (MCarn), although longitudinal studies have failed to confirm this. A lack of control for dietary ß-alanine intake or muscle fiber type shifting may have hampered their conclusions. The purpose of the present study was to investigate the effects of high-intensity interval training (HIIT) on MCarn. METHODS: Twenty vegetarian men were randomly assigned to a control (CON) (n = 10) or HIIT (n = 10) group. High-intensity interval training was performed on a cycle ergometer for 12 wk, with progressive volume (6-12 series) and intensity (140%-170% lactate threshold [LT]). Muscle carnosine was quantified in whole-muscle and individual fibers; expression of selected genes (CARNS, CNDP2, ABAT, TauT, and PAT1) and muscle buffering capacity in vitro (ßmin vitro) were also determined. Exercise tests were performed to evaluate total work done, V˙O2max, ventilatory thresholds (VT) and LT. RESULTS: Total work done, VT, LT, V˙O2max, and ßmin vitro were improved in the HIIT group (all P < 0.05), but not in CON (P > 0.05). MCarn (in mmol·kg dry muscle) increased in the HIIT (15.8 ± 5.7 to 20.6 ± 5.3; P = 0.012) but not the CON group (14.3 ± 5.3 to 15.0 ± 4.9; P = 0.99). In type I fibers, MCarn increased in the HIIT (from 14.4 ± 5.9 to 16.8 ± 7.6; P = 0.047) but not the CON group (from 14.0 ± 5.5 to 14.9 ± 5.4; P = 0.99). In type IIa fibers, MCarn increased in the HIIT group (from 18.8 ± 6.1 to 20.5 ± 6.4; P = 0.067) but not the CON group (from 19.7 ± 4.5 to 18.8 ± 4.4; P = 0.37). No changes in gene expression were shown. CONCLUSIONS: In the absence of any dietary intake of ß-alanine, HIIT increased MCarn content. The contribution of increased MCarn to the total increase in ßmin vitro appears to be small.

Twenty-four Weeks of ß-Alanine Supplementation on Carnosine Content, Related Genes, and Exercise.

INTRODUCTION: Skeletal muscle carnosine content can be increased through ß-alanine (BA) supplementation, but the maximum increase achievable with supplementation is unknown. No study has investigated the effects of prolonged supplementation on carnosine-related genes or exercise capacity. PURPOSE: This study aimed to investigate the effects of 24 wk of BA supplementation on muscle carnosine content, gene expression, and high-intensity cycling capacity (CCT110%). METHODS: Twenty-five active males were supplemented with 6.4 g·d of sustained release BA or placebo for a 24 wk period. Every 4 wk participants provided a muscle biopsy and performed the CCT110%. Biopsies were analyzed for muscle carnosine content and gene expression (CARNS, TauT, ABAT, CNDP2, PHT1, PEPT2, and PAT1). RESULTS: Carnosine content was increased from baseline at every time point in BA (all P < 0.0001; week 4 = +11.37 ± 7.03 mmol·kg dm, week 8 = +13.88 ± 7.84 mmol·kg dm, week 12 = +16.95 ± 8.54 mmol·kg dm, week 16 = +17.63 ± 8.42 mmol·kg dm, week 20 = +21.20 ± 7.86 mmol·kg dm, and week 24 = +20.15 ± 7.63 mmol·kg dm) but not placebo (all P > 0.05). Maximal increases were +25.66 ± 7.63 mmol·kg dm (range = +17.13 to +41.32 mmol·kg dm), and absolute maximal content was 48.03 ± 8.97 mmol·kg dm (range = 31.79 to 63.92 mmol·kg dm). There was an effect of supplement (P = 0.002) on TauT; no further differences in gene expression were shown. Exercise capacity was improved in BA (P = 0.05) with possible to almost certain improvements across all weeks. CONCLUSIONS: Twenty-four weeks of BA supplementation increased muscle carnosine content and improved high-intensity cycling capacity. The downregulation of TauT suggests it plays an important role in muscle carnosine accumulation with BA supplementation, whereas the variability in changes in muscle carnosine content between individuals suggests that other determinants other than the availability of BA may also bear a major influence on muscle carnosine content.

Endocrine disruption effects of p,p'-DDE on juvenile zebrafish.

The persistent organic pollutant p,p'-DDE, the major metabolite of the insecticide DDT, has displayed evidence of endocrine disruption through the inhibition of androgen binding to androgen receptors in different species. Although p,p'-DDE was continuously detected in wild fish with abnormal gonad development such as intersex, little is known about its mode of action during gonad development in fish. To elucidate the potential endocrine effects of this pollutant in zebrafish (Danio rerio), juveniles (30 days post hatch) were exposed to p,p'-DDE during the critical window of sexual differentiation. Fish were exposed to sublethal concentrations ranging from 0.01 to 20 µg l(-1) over 14 days and were maintained in control water for an additional 4 months. As core endpoints, the vitellogenin (vtg) concentration was measured at the end of exposure, and sex ratio and the gonadosomatic index were assessed 4 months after the end of exposure. An increase in vtg production in whole body homogenate was observed in fish exposed to 0.2 and 2.0 µg l(-1) p,p'-DDE. No significant differences were displayed in morphological parameters such as the gonadosomatic index of males and females or sex ratio. However, exposed females presented histopathological changes that include the reduction of the number of mature oocytes, which might impair their successful reproduction. These results demonstrate the ability of p,p'-DDE to cause endocrine disruption in zebrafish exposed during gonad differentiation of juvenile specimens. Furthermore, vtg induction by p,p'-DDE in juvenile zebrafish arises as a predictive marker for adverse effects of this DDT metabolite on the ovarian function of female zebrafish.