19To defend against hydrogen cation accumulation and muscle fatigue during exercise, sodium 20 bicarbonate (NaHCO3) ingestion is commonplace. The individualised dose-response relationship 21 between NaHCO3 ingestion and blood biochemistry is unclear. The present study investigated the 22 bicarbonate, pH, base excess and sodium responses to NaHCO3 ingestion. Sixteen healthy males (23±2 23 years; 78.6±15.1 kg) attended three randomised order-balanced, non-blinded sessions, ingesting a single 24

Carnosine was originally discovered in skeletal muscle, where it exists in larger amounts than in other tissues. The majority of research into the physiological roles of carnosine have been conducted on skeletal muscle. Given this and the potential for muscle carnosine content to be increased with supplementation, there is now a large body of research examining the ergogenic effects (or otherwise) of carnosine. More recent research, however, points towards a potential for carnosine to exert a wider range of physiological effects in other tissues, including the brain, heart, pancreas, kidney and cancer cells. Taken together, this is suggestive of a potential for carnosine to have therapeutic benefits in health and disease, although this is by no means without complication. Herein, we will provide a review of the current literature relating to the potential therapeutic effects of carnosine in health and disease.

PurposeIn fresh muscle, supplementation with the rate-limiting precursor of carnosine, β-alanine (BA), results in a decline in muscle half-relaxation time (HRT) potentially via alterations to calcium (Ca2+) handling. Accumulation of hydrogen cation (H+) has been shown to impact Ca2+ signalling during muscular contraction, carnosine has the potential to serve as a cytoplasmic regulator of Ca2+ and H+ coupling, since it binds to both ions. The present study examined the effect of BA supplementation on intrinsic in-vivo isometric knee extensor force production and muscle contractility in both fresh and fatigued human skeletal muscle assessed during voluntary and electrically evoked (nerve and superficial muscle stimulation) contractions.MethodsTwenty-three males completed two experimental sessions, pre- and post- 28 day supplementation with 6.4 g.day−1 of BA (n = 12) or placebo (PLA; n = 11). Isometric force was recorded during a series of voluntary and electrically evoked knee extensor contractions.ResultsBA supplementation had no effect on voluntary or electrically evoked isometric force production, or twitch electromechanical delay and time-to-peak tension. There was a significant decline in muscle HRT in fresh and fatigued muscle conditions during both resting (3 ± 13%; 19 ± 26%) and potentiated (1 ± 15%; 2 ± 20%) twitch contractions.ConclusionsThe mechanism for reduced HRT in fresh and fatigued skeletal muscle following BA supplementation is unclear. Due to the importance of muscle relaxation on total energy consumption, especially during short, repeated contractions, BA supplementation may prove to be beneficial in minimising contractile slowing induced by fatigue.Trial registrationThe trial is registered with Clinicaltrials.gov, ID number NCT02819505.

We describe a case of obscure gastrointestinal bleeding in a male with noncirrhotic portal hypertension who required multiple admissions and repeated blood transfusions over a 5-month period. Upper and lower gastrointestinal endoscopy failed to establish a cause for bleeding which was eventually ascribed to universal portal hypertensive stigmata in stomach, small bowel and colon, which were not amenable to endoscopic therapy. On account of extensive venous thrombosis, neither surgical shunting nor interventional radiology was an option. Initial management with prothrombotic agents failed. Our patient was successfully stabilized on long-acting somatostatin (SMS) analogue therapy using lanreotide, resulting in avoidance of further admissions and blood transfusion and restoration of his independence and quality of life. The use of short-acting SMS analogues is recognised in acute variceal haemorrhage secondary to portal hypertension in cirrhosis, and long-acting SMS analogue therapy has been described in obscure gastrointestinal bleeding though secondary to angiodysplasia. However, the potential role of long-term SMS analogues in noncirrhotic portal hypertensive bleeding of this type has not been reported earlier. This case supports its use in this scenario in the absence of surgical options and when only palliative approaches are available.

Lower limb muscle dysfunction is a key driver for impaired physical capacity and frailty status, both characteristics of sarcopenia. Sarcopenia is the key pathway between frailty and disability. Identifying biological markers for early diagnosis, treatment, and prevention may be key to early intervention and prevention of disability particularly mobility issues. To identify biological markers associated with lower limb muscle (dys)function in adults with sarcopenia, a systematic literature search was conducted in AMED, CINAHL, Cochrane Library, EMBASE, Medline, PubMed, Scopus, SPORTDiscus, and Web of Science databases from inception to 17 November 2021. Title, abstract, and full-text screening, data extraction, and methodological quality assessment were performed by two reviewers independently and verified by a third reviewer. Depending on available data, associations are reported as either Pearson's correlations, regression R 2 or partial R 2 , P value, and sample size (n). Twenty eligible studies including 3306 participants were included (females: 79%, males: 15%, unreported: 6%; mean age ranged from 53 to 92 years) with 36% in a distinct sarcopenic subgroup (females: 73%, males: 19%, unreported: 8%; mean age range 55-92 years). A total of 119 biomarkers were reported, categorized into: genetic and microRNAs (n = 64), oxidative stress (n = 10), energy metabolism (n = 18), inflammation (n = 7), enzyme (n = 4), hormone (n = 7), bone (n = 3), vitamin (n = 2), and cytokine (n = 4) markers) and seven lower limb muscle measures predominately focused on strength. Seven studies reported associations between lower limb muscle measures including (e.g. power, force, and torque) and biomarkers. In individuals with sarcopenia, muscle strength was positively associated with free testosterone (r = 0.40, P = 0.01; n = 46). In analysis with combined sarcopenic and non-sarcopenic individuals, muscle strength was positively associated with combined genetic and methylation score (partial R 2 = 0.122, P = 0.03; n = 48) and negatively associated with sarcopenia-driven methylation score (partial R 2 = 0.401, P < 0.01; n = 48). Biomarkers related to genetics (R 2 = 0.001-0.014, partial R 2 = 0.013-0.122, P > 0.05; n = 48), oxidative stress (r = 0.061, P > 0.05; n ≥ 77), hormone (r = 0.01, ρ = 0.052 p > 0.05, n ≥ 46) and combined protein, oxidative stress, muscle performance, and hormones (R 2 = 22.0, P > 0.05; n ≥ 82) did not report significant associations with lower limb muscle strength. Several biomarkers demonstrated associations with lower limb muscle dysfunction. The current literature remains difficult to draw clear conclusions on the relationship between biomarkers and lower limb muscle dysfunction in adults with sarcopenia. Heterogeneity of biomarkers and lower limb muscle function precluded direct comparison. Use of international classification of sarcopenia and a set of core standardized outcome measures should be adopted to aid future investigation and recommendations to be made.