Carnosine increases insulin-stimulated glucose uptake and reduces methylglyoxal-modified proteins in type-2 diabetic human skeletal muscle cells.

Type-2 diabetes (T2D) is characterised by a dysregulation of metabolism, including skeletal muscle insulin resistance, mitochondrial dysfunction, and oxidative stress. Reactive species, such as methylglyoxal (MGO) and 4-hydroxynonenal (4-HNE), positively associate with T2D disease severity and can directly interfere with insulin signalling and glucose uptake in skeletal muscle by modifying cellular proteins. The multifunctional dipeptide carnosine, and its rate-limiting precursor ß-alanine, have recently been shown to improve glycaemic control in humans and rodents with diabetes. However, the precise mechanisms are unclear and research in human skeletal muscle is limited. Herein, we present novel findings in primary human T2D and lean healthy control (LHC) skeletal muscle cells. Cells were differentiated to myotubes, and treated with 10 mM carnosine, 10 mM ß-alanine, or control for 4-days. T2D cells had reduced ATP-linked and maximal respiration compared with LHC cells (p = 0.016 and p = 0.005). Treatment with 10 mM carnosine significantly increased insulin-stimulated glucose uptake in T2D cells (p = 0.047); with no effect in LHC cells. Insulin-stimulation increased MGO-modified proteins in T2D cells by 47%; treatment with carnosine attenuated this increase to 9.7% (p = 0.011). There was no effect treatment on cell viability or expression of other proteins. These findings suggest that the beneficial effects of carnosine on glycaemic control may be explained by its scavenging actions in human skeletal muscle.

Patterns of weight cycling in youth Olympic combat sports: a systematic review.

BACKGROUND: Patterns of weight cycling in adult combat sports have been extensively studied, yet data on this matter in youth combat athletes is rather scarce. METHODS: PubMed, EBSCOhost and Web of Science were used to retrieve relevant data. Eligible studies had to record the methods used to elicit rapid weight loss (RWL) and/or record the oscillations in bodyweight during the RWL phase. Only studies conducted in the context of an official competition were considered for inclusion in the present review. RESULTS: RWL is highly prevalent in children and adolescent combat athletes, ranging from 25 to 94% depending on the type of combat sport, age and level of competition. These athletes regularly prompt RWL by increasing exercise frequency and intensity, decreasing fluid and food intake, training in impermeable suits and using sauna frequently. Overall, the magnitude of RWL was ranging from ~ 1% to 6.3 ± 3.7% with significant RWL variations within individual studies and individuals within those studies. CONCLUSION: Acquired data indicated that RWL patterns in young combat athletes are similar to those found in their adult counterparts. Knowing that childhood and adolescence are critical periods for growth and development, RWL needs to be stringently regulated and ideally banned in this population.

Effect of menstrual cycle phase, menstrual irregularities and hormonal contraceptive use on anterior knee laxity and non-contact anterior cruciate ligament injury occurrence in women: a protocol for a systematic review and meta-analysis.

Exercising women report three to six times more ACL tears than men, which happen, in the majority of cases, with a non-contact mechanism. This sex disparity has, in part, been attributed to the differences in reproductive hormone profiles between men and women. Many studies have shown that anterior knee (AK) laxity and the rate of non-contact ACL injuries vary across the menstrual cycle, but these data are inconsistent. Similarly, several studies have investigated the potential protective effect of hormonal contraceptives on non-contact ACL injuries, but their conclusions are also variable. The purpose of this systematic review and meta-analysis is to, identify, evaluate and summarise the effects of endogenous and exogenous ovarian hormones on AK laxity (primary outcome) and the occurrence of non-contact ACL injuries (secondary outcome) in women. We will perform a systematic search for all observational studies conducted on this topic. Studies will be retrieved by searching electronic databases, clinical trial registers, author's personal files and cross-referencing selected studies. Risk of bias will be assessed using the Newcastle Ottawa Quality Assessment Scale for Cohort and Case-Control Studies. Certainty in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The meta-analyses will use a Bayesian approach to address specific research questions in a more intuitive and probabilistic manner. This review is registered on the international database of prospectively registered systematic reviews (PROSPERO; CRD42021252365).

Effect of Carnosine or ß-Alanine Supplementation on Markers of Glycemic Control and Insulin Resistance in Humans and Animals: A Systematic Review and Meta-analysis.

There is growing evidence that supplementation with carnosine, or its rate-limiting precursor ß-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and its related conditions. The purpose of this systematic review and meta-analysis was to evaluate the effect of carnosine or ß-alanine supplementation on markers of glycemic control and insulin resistance in humans and animals. We performed a systematic search of 6 electronic databases up to 31 December 2020. Primary outcomes were changes in 1) fasting glucose, 2) glycated hemoglobin (HbA1c), and 3) 2-h glucose following a glucose-tolerance test. A set of additional outcomes included fasting insulin and homeostatic model assessment of ß-cell function (HOMA-ß) and insulin resistance (HOMA-IR). We assessed risk of bias using the Cochrane risk of bias (RoB) 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) RoB (animal studies) tools; and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess certainty. We used Bayesian hierarchical random-effects models, with informative priors for human data and noninformative priors for animal data. Inferences were made on posterior samples generated by Hamiltonian Markov Chain Monte Carlo using 90% credible intervals (90% CrI) and calculated probabilities. Twenty studies (n = 4 human, n = 16 rodent) were included, providing data for 2 primary outcomes (fasting glucose and HbA1c) and 3 additional outcomes (fasting insulin, HOMA-ß, and HOMA-IR). The model provides evidence that supplementation decreases fasting glucose [humans: mean difference (MD)0.5 = -0.95 mmol · L-1 (90% CrI: -2.1, 0.08); rodent: MD0.5 = -2.26 mmol · L-1 (90% CrI: -4.03, -0.44)], HbA1c [humans: MD0.5 = -0.91% (90% CrI: -1.46, -0.39); rodents: MD0.5 = -1.05% (90% CrI: -1.64, -0.52)], HOMA-IR [humans: standardized mean difference (SMD)0.5 = -0.41 (90% CrI: -0.82, -0.07); rodents: SMD0.5 = -0.63 (90% CrI: -1.98, 0.65)], and fasting insulin [humans: SMD0.5 = -0.41 (90% CrI: -0.77, -0.07)]. GRADE assessment showed our certainty in the effect estimate of each outcome to be moderate (human outcomes) or very low (rodent outcomes). Supplementation with carnosine or ß-alanine may reduce fasting glucose, HbA1c, and HOMA-IR in humans and rodents, and fasting insulin in humans; both compounds show potential as therapeutics to improve glycemic control and insulin resistance. This review was registered at PROSPERO as CRD42020191588.

ACSM Expert Consensus Statement on Weight Loss in Weight-Category Sports.

ABSTRACT: Weight-category sports are defined by the requirement of a weigh-in before competition to provide performance equity and reduced injury risks by eliminating size discrepancies. Athletes in these sports try to gain a theoretical advantage by competing in weight divisions that are lower than their day-to-day body mass (BM), using a combination of chronic strategies (body-fat losses) and acute manipulations over a period of hours to days before weigh-in ("making weight"). Strategies to support safer practices include minimal competition weight classification based on preseason body composition, reductions in the period between weigh-in and competition, and prohibition of unhealthy weight loss techniques. At an individual level, expert guidance by a sports nutrition professional can help an athlete to establish a pragmatic and long-term approach to BM management, recognizing the nuances of their sport, to achieve favorable outcomes for both health and performance.

The effect of carnosine or ß-alanine supplementation on markers of glycaemic control and insulin resistance in human and animal studies: a protocol for a systematic review and meta-analysis.

BACKGROUND: Diabetes is a major public health issue and there is a need to develop low-cost, novel interventions to prevent or reduce disease progression. Growing evidence shows that supplementation with carnosine, or its rate-limiting precursor ß-alanine, can ameliorate aspects of the metabolic dysregulation that occurs in diabetes. There is, however, a need to develop a better understanding of the magnitude of effect and the factors associated with positive outcomes. The purpose of this systematic review and meta-analysis is to evaluate the effect of carnosine or ß-alanine supplementation on markers of glycaemic control and insulin resistance in humans and animals. METHODS: We will perform a systematic search for randomised and non-randomised controlled trials. Studies will be retrieved by searching electronic databases, clinical trial registers, author review, and cross-referencing. Primary outcomes include changes in (i) fasting glucose, (ii) glycated haemoglobin, and (iii) 2-h glucose following a glucose tolerance test. A set of additional outcomes includes other markers of glycaemic control and insulin resistance. Risk of bias (RoB) will be assessed using the Cochrane RoB 2.0 tool (human studies) and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) RoB tool (animal studies). Confidence in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. All meta-analyses will be conducted within a Bayesian framework, providing a flexible modelling approach to account for uncertainty in model parameters and underlying structures within the data. DISCUSSION: By including all available human and animal data, we will provide the most comprehensive overview on the topic to date. The results will have implications for those working in prediabetes, diabetes, and metabolic health in general and may lead to the development of new treatment approaches. DISSEMINATION: Study results will be presented at a professional conference and published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: CRD42020191588.

The Physiological Roles of Carnosine and ß-Alanine in Exercising Human Skeletal Muscle.

Carnosine (ß-alanyl-L-histidine) plays an important role in exercise performance and skeletal muscle homeostasis. Dietary supplementation with the rate-limiting precursor ß-alanine leads to an increase in skeletal muscle carnosine content, which further potentiates its effects. There is significant interest in carnosine and ß-alanine across athletic and clinical populations. Traditionally, attention has been given to performance outcomes with less focus on the underlying mechanism(s). Putative physiological roles in human skeletal muscle include acting as an intracellular pH buffer, modulating energy metabolism, regulating Ca handling and myofilament sensitivity, and scavenging of reactive species. Emerging evidence shows that carnosine could also act as a cytoplasmic Ca-H exchanger and form stable conjugates with exercise-induced reactive aldehydes. The enigmatic nature of carnosine means there is still much to learn regarding its actions and applications in exercise, health, and disease. In this review, we examine the research relating to each physiological role attributed to carnosine, and its precursor ß-alanine, in exercising human skeletal muscle.

The Magnitude of Rapid Weight Loss and Rapid Weight Gain in Combat Sport Athletes Preparing for Competition: A Systematic Review.

Combat sport athletes typically engage in a process called making weight, characterized by rapid weight loss (RWL) and subsequent rapid weight gain (RWG) in the days preceding competition. These practices differ across each sport, but no systematic comparison of the size of the changes in body mass exists. The aim was to determine the magnitude of RWL and RWG in combat sport athletes preparing for competition. The review protocol was preregistered with PROSPERO (CRD42017055279). In eligible studies, athletes prepared habitually with a RWL period ≤7 days preceding competition. An electronic search of EBSCOhost (CINAHL Plus, MEDLINE, and SPORTDiscus) and PubMed Central was performed up to July 2018. Sixteen full-text studies (total 4,432 participants; 156 females and 4,276 males) were included, providing data from five combat sports (boxing, judo, mixed martial arts, taekwondo, and wrestling). Three studies reported RWL and 14 studies reported RWG. Duration permitted for RWG ranged 3-32 hr. The largest changes in body mass occurred in two separate mixed martial arts cohorts (RWL: 7.4 ± 1.1 kg [∼10%] and RWG: 7.4 ± 2.8 kg [11.7% ± 4.7%]). The magnitude of RWG appears to be influenced by the type of sport, competition structure, and recovery duration permitted. A cause for concern is the lack of objective data quantifying the magnitude of RWL. There is insufficient evidence to substantiate the use of RWG as a proxy for RWL, and little data are available in females. By engaging in RWG, athletes are able to exploit the rules to compete up to three weight categories higher than at the official weigh-in.

Control of tubercular haemoptysis by bronchial artery embolization.

Thirty-seven patients presenting with massive or recurrent haemoptysis secondary to tuberculous aetiology were subjected to bronchial artery angiography. Of these, failure, to catheterize the bleeding vessel occurred in two patients while embolization was withheld in two patients due to the presence of anterior spinal artery arising from a common intercosto-bronchial trunk. Immediate arrest of bleeding was performed in the remaining 33 patients by selective embolization of the abnormal bronchial arteries with a resorbable material (Gelfoam). Regular follow up for a duration of 6 months after the procedure revealed relapse of haemoptysis in four patients; three were treated by re-embolization of the abnormal bleeding vessels while one patient died due to aspiration immediately on admission. No recurrence of bleeding was seen in the remaining 29 patients. It is concluded that bronchial artery embolization is an effective treatment for immediate control of life-threatening haemoptysis.