Randomised controlled trial combining vitamin E-functionalised chocolate with physical exercise to reduce the risk of protein-energy malnutrition in predementia aged people: study protocol for Choko-Age.

OBJECTIVE: Protein-energy malnutrition and the subsequent muscle wasting (sarcopenia) are common ageing complications. It is knowing to be also associated with dementia. Our programme will test the cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols (PP), in combination with muscle anabolic effect of adequate dietary protein intake and physical exercise to prevent the age-dependent decline of muscle mass and its key underpinning mechanisms including mitochondrial function, and nutrient metabolism in muscle in the elderly. METHODS AND ANALYSIS: In 2020, a 6-month double-blind randomised controlled trial in 75 predementia older people was launched to prevent muscle mass loss, in respond to the 'Joint Programming Initiative A healthy diet for a healthy life'. In the run-in phase, participants will be stabilised on a protein-rich diet (0.9-1.0 g protein/kg ideal body weight/day) and physical exercise programme (high-intensity interval training specifically developed for these subjects). Subsequently, they will be randomised into three groups (1:1:1). The study arms will have a similar isocaloric diet and follow a similar physical exercise programme. Control group (n=25) will maintain the baseline diet; intervention groups will consume either 30 g/day of dark chocolate containing 500 mg total PP (corresponding to 60 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (n=25); or the high polyphenol chocolate without additional vitamin E (n=25). Muscle mass will be the primary endpoint. Other outcomes are neurocognitive status and previously identified biomolecular indices of frailty in predementia patients. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Blood and plasma samples will be analysed for laboratory endpoints including nutrition metabolism and omics. ETHICS AND DISSEMINATION: All the ethical and regulatory approvals have been obtained by the ethical committees of the Azienda Ospedaliera Universitaria Integrata of Verona with respect to scientific content and compliance with applicable research and human subjects' regulation. Given the broader interest of the society toward undernutrition in the elderly, we identify four main target audiences for our research activity: national and local health systems, both internal and external to the project; targeted population (the elderly); general public; and academia. These activities include scientific workshops, public health awareness campaigns, project dedicated website and publication is scientific peer-review journals. TRIAL REGISTRATION NUMBER: NCT05343611.

The impact of life-long strength versus endurance training on muscle fiber morphology and phenotype composition in older men.

Aging is typically associated with decreased muscle strength and rate of force development (RFD), partly explained by motor unit remodeling due to denervation, and subsequent loss of fast-twitch type II myofibers. Exercise is commonly advocated to counteract this detrimental loss. However, it is unclear how life-long strength versus endurance training may differentially affect markers of denervation and reinnervation of skeletal myofibers and, in turn, affect the proportion and morphology of fast-twitch type II musculature. Thus, we compared fiber type distribution, fiber type grouping, and the prevalence of atrophic myofibers (≤1,494 µm2) in strength-trained (OS) versus endurance-trained (OE) master athletes and compared the results to recreationally active older adults (all >70 yr, OC) and young habitually active references (<30 yr, YC). Immunofluorescent stainings were performed on biopsy samples from vastus lateralis, along with leg press maximal strength and RFD measurements. OS demonstrated similar type II fiber distribution (OS: 52.0 ± 16.4%; YC: 51.1 ± 14.4%), fiber type grouping, maximal strength (OS: 170.0 ± 18.9 kg, YC: 151.0 ± 24.4 kg), and RFD (OS: 3,993 ± 894 N·s-1, YC: 3,470 ± 1,394 N·s-1) as young, and absence of atrophic myofibers (OS: 0.2 ± 0.7%; YC: 0.1 ± 0.4%). In contrast, OE and OC exhibited more atrophic fibers (OE: 1.2 ± 1.0%; OC: 1.1 ± 1.4%), more grouped fibers, and smaller proportion of type II fibers (OE: 39.3 ± 11.9%; OC: 35.0 ± 12.4%) than OS and YC (all P < 0.05). In conclusion, strength-trained master athletes were characterized by similar muscle morphology as young, which was not the case for recreationally active or endurance-trained old. These results indicate that strength training may preserve type II fibers with advancing age in older men, likely as a result of chronic use of high contractile force generation.NEW & NOTEWORTHY Aging is associated with loss of fast-twitch type II myofibers, motor unit remodeling, and grouping of myofibers. This study reveals, for the first time, that strength training preserves neural innervation of type II fibers, resulting in similar myofiber type distribution and grouping in life-long strength-trained master athletes as young moderately active adults. In contrast, life-long endurance-trained master athletes and recreationally active old adults demonstrated higher proportion of type I fibers accompanied by more marked grouping of type I myofibers, and more atrophic fibers compared with strength-trained master athletes and young individuals. Thus, strength training should be utilized as a training modality for preservation of fast-twitch musculature, maximal muscle strength, and rapid force capacity (RFD) with advancing age.

Early Maximal Strength Training Improves Leg Strength and Postural Stability in Elderly Following Hip Fracture Surgery.

INTRODUCTION: Hip fractures predominantly occur in the geriatric population and results in increased physical inactivity and reduced independency, largely influenced by a downward spiral of ambulatory capacity, related to loss of skeletal muscle strength and postural stability. Thus, effective postoperative treatment, targeting improvements in muscle strength, is sought after. MATERIALS & METHODS: Twenty-one hip fracture patients (>65 yr) were randomized to 8 weeks of either conventional physiotherapy control group (CG), or leg press and hip abduction maximal strength training (MST) 3 times per week. MST was performed applying heavy loads (85-90% of 1 repetition maximum; 1RM) and 4-5 repetitions in 4 sets. Maximal strength (bi- and unilateral 1RM), postural stability (unipedal stance test; UPS), and DEXA-scan bone mineral content/ density (BMC/BMD) were measured before and after the 8-week rehabilitation. RESULTS: Both MST and conventional physiotherapy improved bilateral leg press 1RM by 41 ± 27 kg and 29 ± 17 kg, respectively (both p < 0.01), while unilateral leg press 1RM only increased after MST (within group and between groups difference: both p < 0.05). MST also resulted in an increase in abduction 1RM in both the fractured (5 kg, 95%CI: 2-7; p < 0.01) and healthy limb (6 kg, 95%CI: 3-9; p < 0.01), while no such improvement was apparent in the CG (between groups difference: p < 0.01). Finally, MST improved UPS of the fractured limb (p < 0.05). No differences were observed in BMC or BMD following the 8 weeks. DISCUSSION: Early postoperative MST improved lower extremities maximal muscle strength more than conventional physiotherapy and was accompanied by improvements in postural stability. CONCLUSION: Implementing MST in early rehabilitation after hip fracture surgery should be considered as a relevant treatment to curtail the downward spiral of reduced ambulatory capacity typical for this patient group, possibly reducing the risk of recuring falls and excess mortality. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03030092.

Heavy Resistance Training in Breast Cancer Patients Undergoing Adjuvant Therapy.

BACKGROUND AND PURPOSE: Adjuvant breast cancer therapy may reduce maximal muscle strength, muscle mass, and functional performance. Although maximal strength training (MST) has the potential to counteract this debilitating outcome and is shown to be superior to low- and moderate-intensity strength training, it is unknown if it can elicit effective adaptations in patients suffering treatment-induced adverse side effects. METHODS: Fifty-five newly diagnosed stage I to III breast cancer patients (49 ± 7 yr) scheduled for adjuvant therapy were randomized to MST or a control group. The MST group performed 4 × 4 repetitions of dynamic leg press at approximately 90% of one-repetition maximum (1RM) twice a week for 12 wk. RESULTS: In the MST group, improvements in 1RM (20% ± 8%; P < 0.001) were accompanied by improved walking economy (9% ± 8%) and increased time to exhaustion during incremental walking (9% ± 8%; both P < 0.01). Moreover, the MST group increased 6-min walking distance (6MWD; 10% ± 7%), and chair rising (30% ± 20%) and stair climbing performance (12% ± 7%; all P < 0.001). All MST-induced improvements were different from the control group (P < 0.01) which reduced their 1RM (9% ± 5%), walking economy (4% ± 4%), time to exhaustion (10% ± 8%), 6MWD (5% ± 5%), chair rising performance (12% ± 12%), and stair climbing performance (6% ± 8%; all P < 0.01). Finally, although MST maintained estimated quadriceps femoris muscle mass, a decrease was observed in the control group (7% ± 10%; P < 0.001). The change in 1RM correlated with the change in walking economy (r = 0.754), time to exhaustion (r = 0.793), 6MWD (r = 0.807), chair rising performance (r = 0.808), and stair climbing performance (r = 0.754; all P < 0.001). CONCLUSIONS: Lower-extremity MST effectively increases lower-extremity maximal muscle strength in breast cancer patients undergoing adjuvant therapy and results in improved work economy, functional performance, and maintenance of muscle mass. These results advocate that MST should be considered in breast cancer treatment.

A comprehensive cardiovascular disease risk profile in patients with schizophrenia.

Patients with schizophrenia are physically inactive and have high prevalence of cardiovascular disease (CVD). Peak oxygen uptake (V̇O2peak ) is one of the strongest predictors for CVD, yet is rarely investigated in this patient population, and how V̇O2peak relates to other conventional CVD risk measures in this population is unclear. We measured treadmill V̇O2peak along with daily physical activity assessed by triaxial accelerometry, body mass index (BMI), waist circumference, blood pressure, lipid profiles, and glucose in 48 outpatients (28 men, 35 ± 10 (SD) years; 20 women, 35 ± 12 years), diagnosed with schizophrenia, schizotypal, or delusional disorders (ICD-10; F20-29). The patients were compared with 48 age- and sex-matched healthy references (±2 years) and normative data from the population. V̇O2peak was 34.5 ± 8.7 mL/kg/min (men) and 26.4 ± 7.0 mL/kg/min (women), which was 27% and 30% lower than healthy references, respectively (both P < 0.01). V̇O2peak was not associated with daily physical activity in men while a weak association was seen in women (steps per day: r2  = 0.26; counts per minute: r2  = 0.25; P < 0.05). BMI (26.0 ± 6.1 kg/m2 ) revealed that patients were moderately overweight with a waist circumference of 103 ± 17 cm. Lipid- and glucose levels, and blood pressure were all within normative range. Our data advocate the utilization of V̇O2peak assessment for CVD risk profile determination in patients with schizophrenia. Daily physical activity was poorly and inconsistently related to V̇O2peak, suggesting increased daily physical activity might not translate into improved V̇O2peak and CVD risk reduction.

Maximal strength training increases muscle force generating capacity and the anaerobic ATP synthesis flux without altering the cost of contraction in elderly.

Aging is associated with a progressive decline in skeletal muscle function, then leading to impaired exercise tolerance. Maximal strength training (MST) appears to be a practical and effective intervention to increase both exercise capacity and efficiency. However, the underlying physiological mechanisms responsible for these functional improvements are still unclear. Accordingly, the purpose of this study was to examine the intramuscular and metabolic adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older individuals (75 ±â€¯9 yrs) by employing a combination of molecular, magnetic resonance 1H-imaging and 31P-spectroscopy, muscle biopsies, motor nerve stimulation, and indirect calorimetry techniques. Dynamic and isometric muscle strength were both significantly increased by MST. The greater torque-time integral during sustained isometric maximal contraction post-MST (P = 0.002) was associated with increased rates of ATP synthesis from anaerobic glycolysis (PRE: 10 ±â€¯7 mM·min-1; POST: 14 ±â€¯7 mM·min-1, P = 0.02) and creatine kinase reaction (PRE: 31 ±â€¯10 mM·min-1; POST: 41 ±â€¯10 mM·min-1, P = 0.006) such that the ATP cost of contraction was not significantly altered. Expression of fast myosin heavy chain, quadriceps muscle volume, and submaximal cycling net efficiency were also increased with MST (P = 0.005; P = 0.03 and P = 0.03, respectively). Overall, MST induced a shift toward a more glycolytic muscle phenotype allowing for greater muscle force production during sustained maximal contraction. Consequently, some of the MST-induced improvements in exercise tolerance might stem from a greater anaerobic capacity to generate ATP, while the improvement in exercise efficiency appears to be independent from an alteration in the ATP cost of contraction.

Reliability of forearm oxygen uptake during handgrip exercise: assessment by ultrasonography and venous blood gas.

Assessment of forearm oxygen uptake (V˙O2 ) during handgrip exercise is a keenly investigated concept for observing small muscle mass metabolism. Although a combination of Doppler ultrasound measurements of brachial artery blood flow (Q˙) and blood gas drawn from a deep forearm vein has been utilized to calculate forearm V˙O2 for more than two decades, the applicability of this experimental design may benefit from a thorough evaluation of its reliability during graded exercise. Therefore, we evaluated the reliability of this technique during incremental handgrip exercise in ten healthy young (24 ± 3(SD) years.) males. V˙O2 and work rate (WR) exhibited a linear relationship (1.0 W: 43.8 ± 10.1 mL·min-1 ; 1.5 W: 53.8 ± 14.1 mL·min-1 ; 2.0 W: 63.4 ± 16.3 mL·min-1 ; 2.5 W: 72.2 ± 17.6 mL·min-1 ; 3.0 W: 79.2 ± 18.6 mL·min-1 ; r = 0.65, P < 0.01). In turn, V˙O2 was strongly associated with Q˙ (1.0 W: 359 ± 86 mL·min-1 ; 1.5 W: 431 ± 112 mL·min-1 ; 2.0 W: 490 ± 123 mL·min-1 ; 2.5 W: 556 ± 112 mL·min-1 ; 3.0 W: 622 ± 131 mL·min-1 ; r = 0.96; P < 0.01), whereas arteriovenous oxygen difference (a-vO2diff ) remained constant following all WRs (123 ± 11-130 ± 10 mL·L-1 ). Average V˙O2 test-retest difference was -0.4 mL·min-1 with ±2SD limits of agreement (LOA) of 8.4 and -9.2 mL·min-1 , respectively, whereas coefficients of variation (CVs) ranged from 4-7%. Accordingly, test-retest Q˙ difference was 11.9 mL·min-1 (LOA: 84.1 mL·min-1 ; -60.4 mL·min-1 ) with CVs between 4 and 7%. Test-retest difference for a-vO2diff was -0.28 mL·dL-1 (LOA: 1.26mL·dL-1 ; -1.82 mL·dL-1 ) with 3-5% CVs. In conclusion, our results revealed that forearm V˙O2 determination by Doppler ultrasound and direct venous sampling is linearly related to WR, and a reliable experimental design across a range of exercise intensities.