Carnosine and skeletal muscle dysfunction in a rodent multiple sclerosis model.

Muscle weakness and fatigue are primary manifestations of multiple sclerosis (MS), a chronic disease of the central nervous system. Interventions that enhance muscle function may improve overall physical well-being of MS patients. Recently, we described that levels of carnosine, an endogenous muscle dipeptide involved in contractile function and fatigue-resistance, are reduced in muscle tissue from MS patients and a monophasic rodent MS model (experimental autoimmune encephalomyelitis, EAE). In the present study, we aimed to (1) confirm this finding in a chronic EAE model, along with the characterization of structural and functional muscle alterations, and (2) investigate the effect of carnosine supplementation to increase/restore muscle carnosine levels and improve muscle function in EAE. We performed muscle immunohistochemistry and ex vivo contractility measurements to examine muscle structure and function at different stages of EAE, and following nutritional intervention (oral carnosine: 3, 15 or 30 g/L in drinking water). Immunohistochemistry revealed progressively worsening muscle fiber atrophy and a switch towards a fast-twitch muscle phenotype during EAE. Using ex vivo muscle contractility experiments, we observed reductions in muscle strength and contraction speed, but no changes in muscle fatigability of EAE mice. However, carnosine levels were unaltered during all stages of EAE, and even though oral carnosine supplementation dose-dependently increased muscle carnosine levels up to + 94% after 56 days EAE, this did not improve muscle function of EAE mice. In conclusion, EAE mice display significant, yet time-dependent, muscular alterations, and carnosine intervention does not improve muscle function in EAE.

Lifestyle interventions to reduce sedentary behaviour in clinical populations: A systematic review and meta-analysis of different strategies and effects on cardiometabolic health.

Cardiometabolic comorbidities are highly prevalent in clinical populations, and have been associated (partly) with their sedentary lifestyle. Although lifestyle interventions targeting sedentary behaviour (SB) have been studied extensively in the general population, the effect of such strategies in clinical populations is not yet clear. Therefore, this systematic review and meta-analysis evaluated the effect of different lifestyle interventions on SB and cardiometabolic health in clinical populations. Randomised controlled trials were collected from five bibliographic databases (PubMed, Embase, Web of Science, The Cochrane Central Register of Controlled Trials, and Scopus). Studies were eligible for inclusion if they evaluated a lifestyle intervention to reduce objectively measured SB, in comparison with a control intervention among persons with a clinical condition. Data were pooled using a random-effects meta-analysis. In total, 7094 studies were identified. Eighteen studies met the inclusion criteria and were categorised in five population groups: overweight/obesity, type 2 diabetes mellitus, cardiovascular, neurological/cognitive and musculoskeletal diseases. Participants reduced their SB by 64 min/day (95%CI: [-91, -38] min/day; p < 0.001), with larger within-group differences of multicomponent behavioural interventions including motivational counselling, self-monitoring, social facilitation and technologies (-89 min/day; 95%CI: [-132, -46] min/day; p < 0.001). Blood glycated haemoglobin concentration (-0.17%; 95% CI: [-0.30, -0.04]%; p = 0.01), fat percentage (-0.66%; 95% CI: [-1.26, -0.06]%, p = 0.03) and waist circumference (-1.52 cm; 95%CI: [-2.84, -0.21] cm; p = 0.02) were significantly reduced in the intervention groups compared to control groups. Behavioural lifestyle interventions reduce SB among clinical populations and improve cardiometabolic risk markers such as waist circumference, fat percentage, and glycaemic control. Sedentary behaviour, Cardiometabolic health, Clinical populations.

Replacing sitting with light-intensity physical activity throughout the day versus 1 bout of vigorous-intensity exercise: similar cardiometabolic health effects in multiple sclerosis. A randomised cross-over study.

PURPOSE: Persons with Multiple Sclerosis (PwMS) are physically inactive and spend more time in sedentary behaviours than healthy persons, which increases the risk of developing cardiometabolic diseases. In this randomised crossover study, the cardiometabolic health effects of replacing sitting with light-intensity physical activity (LIPA) and exercise (EX) were investigated. MATERIALS AND METHODS: Twenty-eight mildly disabled PwMS performed four 4-day activity regimens in free-living conditions; CONTROL (habitual activity), SIT, LIPA, and EX. Plasma glucose and insulin (oral glucose tolerance test), plasma lipids, inflammation, resting heart rate, blood pressure, body weight, and perceived exertion were measured (clinical-trials.gov: NCT03919058). RESULTS: CONTROL: 9.7 h sitting/day, SIT: 13.3 h sitting/day, LIPA: 8.3 h sitting, 4.7 h standing, and 2.7 h light-intensity walking/day, and EX: 11.6 h sitting/day with 1.3 h vigorous-intensity cycling. Compared to SIT, improvements (p < 0.001) after LIPA and EX were found for insulin total area under the curve (-17 019 ± 5708 and -23 303 ± 7953 pmol/L*min), insulin sensitivity (Matsuda index +1.8 ± 0.3 and +1.9 ± 0.4) and blood lipids (triglycerides: -0.4 ± 0.1 and -0.5 ± 0.1 mmol/L; non-high-density lipoprotein cholesterol: -0.3 ± 0.1 and -0.5 ± 0.1 mmol/L), with no difference between LIPA and EX. Perceived exertion was higher after EX compared to LIPA (Borg score [6-20]: +2.6 ± 3.3, p = 0.002). CONCLUSION: Replacing sitting with LIPA throughout the day exerts similar cardiometabolic health effects as a vigorous-intensity exercise in PwMS.IMPLICATIONS FOR REHABILITATIONIncreasing light-intensity physical activity (LIPA) throughout the day improves cardiometabolic health to the same extent as one vigorous-intensity exercise sessionIncreasing LIPA induces less exertion than performing a vigorous-intensity exercise.

Periodized home-based training: A new strategy to improve high intensity exercise therapy adherence in mildly affected patients with Multiple Sclerosis.

INTRODUCTION: Although high intensity exercise therapy (HIT) in Multiple Sclerosis (MS) induces substantial effects, longer term compliance to such a training program is not evident. When embedded in a periodized, home-based training strategy, high intensity exercise therapy adherence may improve. This is explored first in mildly affected persons with MS. METHODS: Exercise capacity (maximal exercise test) and body composition (DEXA) of healthy controls (n = 22) and persons with MS (n = 23, EDSS: 1.9 ±â€¯1.1) were assessed at baseline (PRE). Next and within the context of an MS awareness project (climbing the Mont Ventoux, France), all participants were enrolled in a 6 m home-based periodized HIT oriented cycling program with remote (Polar® M200 activity tracker) supervision. Hereafter, POST measurements were performed similar to baseline. RESULTS: Six months of periodized and home-based HIT oriented training induced improvements in body weight (-3%, p = 0.008), BMI (-3%, p = 0.01), total mass (-2%, p = 0.023), VO2max (+ 5%, p = 0.016), workload (+ 11%, p = 0.001), time until exhaustion (+ 14%, p = 0.001), recovery heart rate (+ 4%, p = 0.04), lactate peak (+ 16%, p = 0.03) and RER (+ 4%, p = 0.04) in MS. Furthermore, all persons with MS safely reached the top of the Mont Ventoux, except for two. CONCLUSION: The applied 6 m periodized, home-based and HIT-oriented cycling program provided good therapy adherence with similar improvements in exercise capacity compared to healthy controls. Furthermore, this exercise regimen trained mildly-affected persons with MS adequately to climb the Mont Ventoux.