scholarly journals The PROMOTe study: targeting the gut microbiome with prebiotics to overcome age-related anabolic resistance: protocol for a double-blinded, randomised, placebo-controlled trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mary Ni Lochlainn ◽  
Ayrun Nessa ◽  
Alyce Sheedy ◽  
Rachel Horsfall ◽  
María Paz García ◽  
...  

Abstract Background Loss of skeletal muscle mass and strength occurs with increasing age and is associated with loss of function, disability, and the development of sarcopenia and frailty. Dietary protein is essential for skeletal muscle function, but older adults do not anabolise muscle in response to protein supplementation as well as younger people, so called ‘anabolic resistance’. The aetiology and molecular mechanisms for this are not understood, however the gut microbiome is known to play a key role in several of the proposed mechanisms. Thus, we hypothesise that the gut microbiome may mediate anabolic resistance and therefore represent an exciting new target for ameliorating muscle loss in older adults. This study aims to test whether modulation of the gut microbiome using a prebiotic, in addition to protein supplementation, can improve muscle strength (as measured by chair-rise time) versus protein supplementation alone. Methods The study is a randomised, double-blinded, placebo-controlled trial, with two parallel arms; one will receive prebiotic and protein supplementation, and the other will receive placebo (maltodextrin) and protein supplementation. Participants will be randomised as twin pairs, with one twin from each pair in each arm. Participants will be asked to take supplementation once daily for 12 weeks in addition to resistance exercises. Every participant will receive a postal box, containing their supplements, and the necessary equipment to return faecal, urine, saliva and capillary blood samples, via post. A virtual visit will be performed using online platform at the beginning and end of the study, with measures taken over video. Questionnaires, food diary and cognitive testing will be sent out via email at the beginning and end of the study. Discussion This study aims to provide evidence for the role of the gut microbiome in anabolic resistance to dietary protein. If those who take the prebiotic and protein supplementation have a greater improvement in muscle strength compared with those who take protein supplementation alone, this would suggest that strategies to modify the gut microbiome may reduce anabolic resistance, and therefore potentially mitigate sarcopenia and frailty in older adults. Trial registration Clinicaltrials.gov: NCT04309292. Registered on the 2nd May 2020. 

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 929 ◽  
Author(s):  
Mary Ni Lochlainn ◽  
Ruth Bowyer ◽  
Claire Steves

Muscle mass, strength, and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. Dietary protein is essential for skeletal muscle function. Resistance exercise appears to be the most beneficial form of physical activity for preserving skeletal muscle and a synergistic effect has been noted when this is combined with dietary protein. However, older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis, and response is variable. Thus, the recommended daily amount of protein is greater for older people. The aetiologies and mechanisms responsible for anabolic resistance are not fully understood. The gut microbiota is implicated in many of the postulated mechanisms for anabolic resistance, either directly or indirectly. The gut microbiota change with age, and are influenced by dietary protein. Research also implies a role for the gut microbiome in skeletal muscle function. This leads to the hypothesis that the gut microbiome might modulate individual response to protein in the diet. We summarise the existing evidence for the role of the gut microbiota in anabolic resistance and skeletal muscle in aging people, and introduce the metabolome as a tool to probe this relationship in the future.


Author(s):  
Mary Ni Lochlainn ◽  
Ruth C. E. Bowyer ◽  
Claire J. Steves

Muscle mass, strength and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. These conditions are associated with disability, falls, longer hospital stay, higher readmission rates, institutionalisation, osteoporosis, and death. Moreover, they are associated with reduced quality of life, as well as substantial costs to health services around the world. Dietary protein is essential for skeletal muscle function. Older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis and therefore require higher daily amounts of dietary protein. Research shows that resistance exercise has the most beneficial effect on preserving skeletal muscle. A synergistic effect has been noted when this is combined with dietary protein, yet studies in this area lack consistency. This is due, in part, to the variation that exists within dietary protein, in terms of dose, quality, source, amino acid composition and timing. Research has targeted participants that are replete in dietary protein with negative results. Inconsistent measures of muscle mass, muscle function, physical activity and diet are used. This review attempts to summarise these issues, as well as introduce the possible role of the gut microbiome and its metabolome in this area.


Author(s):  
Nien Xiang Tou ◽  
Shiou-Liang Wee ◽  
Wei Ting Seah ◽  
Daniella Hui Min Ng ◽  
Benedict Wei Jun Pang ◽  
...  

AbstractTranslation of community-based functional training for older adults to reduce frailty is still lacking. We evaluated the effectiveness and implementation of a community-delivered group-based functional power training (FPT) program for frail older adults within their neighborhoods. A two-arm, multicenter assessor-blind stratified randomized controlled trial was conducted at four local senior activity centers in Singapore. Sixty-one community-dwelling older adults with low handgrip strength were randomized to intervention (IG) or control (CG) group. The IG underwent the FPT program (power and balance exercises using simple equipment) delivered by a community service provider. The 12-week program comprised 2 × 60 min sessions/week. CG continued usual activities at the centers. Functional performance, muscle strength, and frailty status were assessed at baseline and 3 months. Program implementation was evaluated using RE-AIM framework. The program was halted due to Coronavirus Disease 2019-related suspension of senior center activities. Results are reported from four centers, which completed the program. IG showed significantly greater improvement in the Short Physical Performance Battery test as compared to CG (p = 0.047). No effects were found for timed up and go test performance, muscle strength, and frailty status. The community program exhibited good reach, effectiveness, adoption, and implementation. Our study demonstrated that FPT was associated with greater improvement in physical function in pre-frail/frail participants as compared to exercise activities offered at local senior activity centers. It is a feasible intervention that can be successfully implemented for frail older adults in their neighborhoods. Trial registration ClinicalTrials.gov, NCT04438876. Registered 19 June 2020–retrospectively registered.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 352
Author(s):  
Rui Nouchi ◽  
Qingqiang Hu ◽  
Toshiki Saito ◽  
Natasha Yuriko dos Santos Kawata ◽  
Haruka Nouchi ◽  
...  

Background: Earlier studies have demonstrated that a single-domain intervention, such as a brain-training (BT) game alone and a sulforaphane (SFN) intake, positively affects cognition. This study examined whether a combined BT and SFN intake intervention has beneficial effects on cognitive function in older adults. Methods: In a 12-week double-blinded randomized control trial, 144 older adults were randomly assigned to one of four groups: BT with SFN (BT-S), BT with placebo (BT-P), active control game (AT) with SFN (AT-S), and active control game with placebo (AT-P). We used Brain Age in BT and Tetris in AT. Participants were asked to play BT or AT for 15 min a day for 12 weeks while taking a supplement (SFN or placebo). We measured several cognitive functions before and after the intervention period. Results: The BT (BT-S and BT-P) groups showed more improvement in processing speed than the active control groups (AT-S and AT-P). The SFN intake (BT-S and AT-S) groups recorded significant improvements in processing speed and working memory performance unlike the placebo intake groups (BT-P and AT-P). However, we did not find any evidence of the combined intervention’s beneficial effects on cognition. Discussion: We discussed a mechanism to improve cognitive functions in the BT and SFN alone interventions.


Author(s):  
Kim Gaffney ◽  
Adam Lucero ◽  
Donia Macartney-Coxson ◽  
Jane Clapham ◽  
Patricia Whitfield ◽  
...  

Skeletal muscle microvascular dysfunction and mitochondrial rarefaction feature in type-2 diabetes mellitus (T2DM) linked to low tissue glucose disposal rate (GDR). Exercise training and milk protein supplementation independently promote microvascular and metabolic plasticity in muscle associated with improved nutrient delivery, but combined effects are unknown. In a randomised-controlled trial, 24 men (55.6 y, SD5.7) with T2DM ingested whey protein drinks (protein/carbohydrate/fat: 20/10/3 g; WHEY) or placebo (carbohydrate/fat: 30/3 g; CON) before/after 45 mixed-mode intense exercise sessions over 10 weeks, to study effects on insulin-stimulated (hyperinsulinemic clamp) skeletal-muscle microvascular blood flow (mBF) and perfusion (near-infrared spectroscopy), and histological, genetic, and biochemical markers (biopsy) of microvascular and mitochondrial plasticity. WHEY enhanced insulin-stimulated perfusion (WHEY-CON 5.6%; 90%CI -0.1, 11.3), while mBF was not altered (3.5%; -17.5, 24.5); perfusion, but not mBF, associated (regression) with increased GDR. Exercise training increased mitochondrial (range of means: 40-90%) and lipid density (20-30%), enzyme activity (20-70%), capillary:fiber ratio (~25%), and lowered systolic (~4%) and diastolic (4-5%) blood pressure, but without WHEY effects. WHEY dampened PGC1α -2.9% (90%CI -5.7, -0.2) and NOS3 -6.4% (-1.4, -0.2) expression, but other mRNA were unclear. Skeletal muscle microvascular and mitochondrial exercise adaptations were not accentuated by whey protein ingestion in men with T2DM. Clinical Trial Registration Number: ACTRN12614001197628 Novelty Bullets: • Chronic whey ingestion in T2DM with exercise altered expression of several mitochondrial and angiogenic mRNA. • Whey added no additional benefit to muscle microvascular or mitochondrial adaptations to exercise. • Insulin-stimulated perfusion increased with whey but was without impact on glucose disposal.


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