Nutrition and Metabolic Adaptation: the Assessment and Impact of Dietary Manipulation on Metabolic and Cellular Perturbation

It is well established that improved nutritional strategies can enhance both health and exercise performance. Scientific developments in recent years have furthered our understanding of cellular metabolism, which in turn, has provided an additional platform to investigate the impact of diet on health and adaptation. The overall aim of this research programme was to build on the current understanding of dietary intake in athletes and the impact dietary manipulation has on cellular and metabolic adaptation at rest and in combination with endurance training. It is postulated that nutrition is the most controllable risk factor impacting long-term health and chronic disease (World-Health-Organization, 2003), and enhanced knowledge of nutrition has been associated with improved dietary choices. A number of nutrition knowledge questionnaires have been developed to assess this; however the validity of each tool is reduced if implemented outside the target population. A valid and reliable general and sport nutrition knowledge questionnaire had not yet been developed. Using a parallel groups repeated measures study design (N = 101) the aim of the first experimental Chapter (Chapter 4) was to develop a new tool to measure general and sport nutrition knowledge in UK track and field athletes. Following the questionnaire design 53 nutrition educated and 48 non-nutrition educated participants completed the questionnaire on two occasions separated by three weeks. The results of the process demonstrated face and construct validity from the development of the question pool, content validity (the nutrition educated group scored > 30% higher that the non-nutrition educated group), reliability (test - retest correlation of 0.98, p 0.7) as such establishing a new tool (Nutrition knowledge Questionnaire for Athletes (NKQA)) for the assessment of general and sport nutrition knowledge in track and field athletes. Athletes’ diets are commonly reported as inadequate and previous work has demonstrated a weak positive relationship between diet quality and nutrition knowledge. Additionally a commercially available tool, the metabolic typing questionnaire, claims to identify individual metabolic function and subsequently prescribe a personalised diet to optimise health. Thus the aim of the second experimental Chapter (Chapter 5) was to quantify nutrition knowledge (using the questionnaire developed in Chapter 4), measure diet intake and quality and investigate the efficacy of the metabolic typing questionnaire in UK track and field athletes. Using a parallel groups repeated measures design participants (UK track and field athletes n = 59, and non-athletic control group n = 29) completed a food diary, the NKQA and the metabolic typing questionnaire at two time points through the year (October and April) to investigate seasonal change. The results of the metabolic typing questionnaire concluded that 94.3% of the participants were the same dietary type and would subsequently have been prescribed the same diet. Athletes possess greater general and sport nutrition knowledge the non-athletes (60.4 ± 2.0 % vs. 48.6 ± 1.5 %) and also had better diet quality (76.8 ± 10.5 % vs. 67.6 ± 2.6 %). However no relationship was observed between individual nutrition knowledge score and diet quality (r2 = 0.003, p = 0.63). No difference in dietary intake was observed between power and endurance athletes; average diet intake consisted of 57.0% carbohydrate, 17.1% protein and 25.9% fat. The metabolic typing diet is based around three different diets: high carbohydrate, high protein and mixed diet. The results from Chapter 5 identified that the metabolic typing questionnaire was not able to differentiate between metabolic function in healthy individuals. Additionally all athletes, independent of event (power vs. endurance), consumed similar diets. With such similarities a clearer understanding of the impact such diets have at a cellular level is required. Therefore for the remainder of the thesis it was decided to investigate the impact of dietary manipulation utilising more robust measures. Mitochondria are responsible for energy production; their quantity and density have been associated with improved health and endurance performance. External stressors such as energy reduction, carbohydrate restriction and exercise are potent stimulators of transcription markers of mitochondrial biogenesis. Thus manipulating carbohydrate and energy availability in vivo may enhance cellular adaptation and limited literature exists on the impact increased protein intake has on this. The aim of Chapter 6 was to investigate the impact of acute (7-day) continuous dietary manipulation on metabolic markers, body composition and resting metabolic rate (RMR). Using a repeated measures parallel group (N = 45) design, participants were randomly assigned one of four diets: high protein hypocaloric, high carbohydrate hypocaloric, high protein eucaloric or high carbohydrate eucaloric. The macronutrient ratio of the high protein diets was 40% protein, 30 % carbohydrate and 30% fat, the high carbohydrate diets were 10% protein, 60% carbohydrate and 30% fat. Energy intake in the hypocaloric diets was matched to resting metabolic rate (RMR). Participants consumed habitual diet for 7-days then baseline measures were collected (skeletal muscle biopsy, dual energy X-ray absorptiometry scan (DXA) and RMR, habitual diet was consumed for a further 7-days and repeat testing was completed (these time points were used as a control), the intervention diet was then consumed for 7-days and post measures were collected. The results of the skeletal muscle biopsy demonstrated no group x time interaction in any marker, however a pre-post time difference subsequent to the high protein hypocaloric diet (the diet which induced the greatest metabolic stress) was observed in four transcriptional markers of mitochondrial biogenesis (pre-post intervention fold increase: PCG1-α 1.27, AMPK 2.09, SIRT1 1.5, SIRT3 1.19, p < 0.05). The results of the DXA scan demonstrated that the high protein hypocaloric group lost significantly more fat mass than the high carbohydrate eucaloric group (-0.99 kg vs. -0.50 kg, p < 0.015). Irrespective of macronutrient ratio, no energy-matched between group difference was observed in lean mass (LM) loss. However when matched for macronutrient ratio the high protein diet attenuated LM loss to a greater extent that the high carbohydrate diet, suggesting an important role of increased protein intake in the maintenance of lean mass. No time point or group difference in RMR was observed. This data suggests that a high protein low carbohydrate hypocaloric diet may provide a stimulus to promote skeletal muscle metabolic adaptation. The aim of the final experimental Chapter (Chapter 7) in this thesis was to explore the impact exercise in combination with a high protein diet on metabolic adaptation, substrate utilisation and exercise performance in well trained runners. Using a parallel groups repeated measures study design the participants (well-trained endurance runners, N = 16) consumed normal habitual diet for 7-days, then 7-days intervention diet (high protein eucaloric or high carbohydrate eucaloric, same dietary ratios as Chapter 6) and finally returned to habitual diet for 7-days, training was consistent throughout. A pre exercise muscle biopsy was taken subsequent to each diet and immediately followed by a 10 km sub-maximal run and a time to exhaustion run (TTE) at 95% of velocity at maximal aerobic capacity (vV̇O2max). Post intervention the high protein group presented significant changes in sub-maximal substrate utilisation with 101% increase in fat oxidation (0.59 g•min-1, p = 0.0001). No changes were observed in substrate utilisation in the high carbohydrate group. A trend towards a reduction in average weekly running speed was observed in the PRO group (-0.9 km•h-1), the high carbohydrate group maintained the same training speed. TTE was decreased (-23.3%, p = 0.0003) in the high protein group subsequent to the intervention, no change was observed in subsequent to the high carbohydrate diet. The high carbohydrate group demonstrated preferential increases in markers of metabolic adaptations (fold increase: AMPK = 1.44 and PPAR = 1.32, p < 0.05) suggesting that training intensity, rather than carbohydrate restriction, may be a more profound driver of metabolic adaptation. All performance measures, in both groups, returned to pre intervention levels once habitual diet was returned; however the increased gene expression observed in the high carbohydrate group remained elevated 7-days post intervention. The increased metabolic stress imposed by reducing carbohydrate intake did not increase transcriptional markers of mitochondrial biogenesis. For continuous endurance training and high intensity endurance performance a high carbohydrate diet is preferential to a high protein diet

An Acute Increase of Dietary Protein Intake Elicits Positive Cellular Metabolic Adaptations in Healthy Males

There is emerging literature demonstrating that restricting dietary carbohydrate (CHO) intake might upregulate cellular markers of mitochondrial biogenesis. Mitochondria quantity and density has been linked with increased endurance performance, reduction in type 2 diabetes and improved insulin sensitivity. A number of transcriptional cellular markers have been identified as key regulators of this process. PURPOSE: To determine the influence of 7 days dietary manipulation on resting metabolic rate (RMR), body composition and transcriptional markers of mitochondrial biogenesis. METHOD: Forty-six healthy male participants (mean ± SD; age (years), body mass (kg), height (cm); 28 ± 5, 75.6 ± 11.1, 178.0 ± 4.9, respectively) were recruited and randomised to one of four conditions: energy matched high protein (PRO-EM), energy restricted high protein (PRO-ER), energy matched high carbohydrate (CHO-EM) or energy restricted high carbohydrate (CHO-ER). Macronutrient ratios (PRO:CHO:FAT) of 40:30:30 and 60:10:30 were used for high protein and high carbohydrate conditions, respectively. Calorific intake for energy restricted groups was matched to RMR. Participants visited the laboratory on 3 occasions across 15 days. On days 0, 7 and 15 participants completed assessments of body composition (DEXA) and RMR (indirect calorimetry), prior to providing a muscle biopsy from the vastus lateralis for later analysis of transcriptional markers via real-time polymerase chain reaction. Between days 1 & 7 and 7 & 14 participants consumed their habitual and prescribed diets, respectively. Laboratory testing was completed following an overnight fast and at the same time of day on each occasion. RESULTS: No difference in RMR was observed in any group across all time points. AMPK, PGC-1a, SIRT1 and PPAR expression was increased in the PRO-ER group (1.32, 1.20, 1.45 and 1.41 fold, respectively). Transcriptional markers were not affected in either CHO group. The CHO-ER group demonstrated a greater loss in lean mass relative to the PRO-EM (-2.22 vs -0.35%,) and body mass loss relative to both CHO-EM and PRO-EM (-2.85 vs -0.95 vs -1.47%) (P < 0.05). CONCLUSION: A restriction energy intake combined with increased protein consumption for 7 days increases transcriptional markers of mitochondrial biogenesis

A valid and reliable nutrition knowledge questionnaire for track and field athletes

Background: Establishing an understanding of an athlete’s nutrition knowledge can inform the coach/practitioner and support the development of the athlete. Thus the purpose of the study was to develop a psychometrically valid and reliable tool to assess general and sport nutrition knowledge. Methods: An 85 question questionnaire was developed in consultation with a panel of experts. Ninety-eight participants from the UK completed the questionnaire, and again 3 weeks later. The participants were classified into two groups:those with nutrition (NUT, n= 53) training (sport nutritionists and dietitians who were either practicing or undertaking a postgraduate qualification in the field), and those without (NONUT,n= 48) training (professionals and postgraduate students with no exposure to any form of nutrition training). The questionnaire was then administered to a pilot cohort of UK based track and field athletes (n= 59) who were requested to time how long it took to complete the questionnaire. Results: Psychometric statistical analysis of the results was completed, resulting in the removal of 23 questions for a total of 62 questions in the final questionnaire. The validated questionnaire was then administered to 58 track and field athletes. Internal consistency was assessed using Chronbach’salpha(α>0.7),Pearson’scorrelation(p< 0.05) was used to assess reliability. Construct validity was evaluated using at-test (p< 0.05). A total test retest correlation of 0.95 was achieved (sub-section range: 0.87–0.97). Internal consistency was accepted in each sub-section (α=0.78–0.92) and the nutrition-trained group scored significantly higher on the overall questionnaire (80.4 vs 49.6%). The overall score for the athletic group was 61.0%. Conclusion: The questionnaire satisfied all psychometric measures and provides a new valid and reliable tool to assess general and sport nutrition knowledge of track and field athlete

Gut Microbial Stability is Associated with Greater Endurance Performance in Athletes Undertaking Dietary Periodization

Dietary manipulation with high-protein or high-carbohydrate content are frequently employed during elite athletic training, aiming to enhance athletic performance. Such interventions are likely to impact upon gut microbial content. This study explored the impact of acute high-protein or high-carbohydrate diets on measured endurance performance and associated gut microbial community changes. In a cohort of well-matched, highly trained endurance runners, we measured performance outcomes, as well as gut bacterial, viral (FVP), and bacteriophage (IV) communities in a double-blind, repeated-measures design randomized control trial (RCT) to explore the impact of dietary intervention with either high-protein or high-carbohydrate content. High-dietary carbohydrate improved time-trial performance by +6.5% (P < 0.03) and was associated with expansion of Ruminococcus and Collinsella bacterial spp. Conversely, high dietary protein led to a reduction in performance by −23.3% (P = 0.001). This impact was accompanied by significantly reduced diversity (IV: P = 0.04) and altered composition (IV and FVP: P = 0.02) of the gut phageome as well as enrichment of both free and inducible Sk1virus and Leuconostoc bacterial populations. Greatest performance during dietary modification was observed in participants with less substantial shifts in community composition. Gut microbial stability during acute dietary periodization was associated with greater athletic performance in this highly trained, well-matched cohort. Athletes, and those supporting them, should be mindful of the potential consequences of dietary manipulation on gut flora and implications for performance, and periodize appropriately

NeuroBench:A Framework for Benchmarking Neuromorphic Computing Algorithms and Systems

Neuromorphic computing shows promise for advancing computing efficiency and capabilities of AI applications using brain-inspired principles. However, the neuromorphic research field currently lacks standardized benchmarks, making it difficult to accurately measure technological advancements, compare performance with conventional methods, and identify promising future research directions. Prior neuromorphic computing benchmark efforts have not seen widespread adoption due to a lack of inclusive, actionable, and iterative benchmark design and guidelines. To address these shortcomings, we present NeuroBench: a benchmark framework for neuromorphic computing algorithms and systems. NeuroBench is a collaboratively-designed effort from an open community of nearly 100 co-authors across over 50 institutions in industry and academia, aiming to provide a representative structure for standardizing the evaluation of neuromorphic approaches. The NeuroBench framework introduces a common set of tools and systematic methodology for inclusive benchmark measurement, delivering an objective reference framework for quantifying neuromorphic approaches in both hardware-independent (algorithm track) and hardware-dependent (system track) settings. In this article, we present initial performance baselines across various model architectures on the algorithm track and outline the system track benchmark tasks and guidelines. NeuroBench is intended to continually expand its benchmarks and features to foster and track the progress made by the research community

The coming decade of digital brain research: a vision for neuroscience at the intersection of technology and computing

In recent years, brain research has indisputably entered a new epoch, driven by substantial methodological advances and digitally enabled data integration and modelling at multiple scales— from molecules to the whole brain. Major advances are emerging at the intersection of neuroscience with technology and computing. This new science of the brain combines high-quality research, data integration across multiple scales, a new culture of multidisciplinary large-scale collaboration and translation into applications. As pioneered in Europe’s Human Brain Project (HBP), a systematic approach will be essential for meeting the coming decade’s pressing medical and technological challenges. The aims of this paper are to: develop a concept for the coming decade of digital brain research, discuss this new concept with the research community at large, to identify points of convergence, and derive therefrom scientific common goals; provide a scientific framework for the current and future development of EBRAINS, a research infrastructure resulting from the HBP’s work; inform and engage stakeholders, funding organisations and research institutions regarding future digital brain research; identify and address the transformational potential of comprehensive brain models for artificial intelligence, including machine learning and deep learning; outline a collaborative approach that integrates reflection, dialogues and societal engagement on ethical and societal opportunities and challenges as part of future neuroscience research

Comparing Acute, High Dietary Protein and Carbohydrate Intake on Transcriptional Biomarkers, Fuel Utilisation and Exercise Performance in Trained Male Runners

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)Manipulating dietary macronutrient intake may modulate adaptive responses to exercise, and improve endurance performance. However, there is controversy as to the impact of short-term dietary modification on athletic performance. In a parallel-groups, repeated measures study, 16 trained endurance runners (maximal oxygen uptake (V˙O2max): 64.2 ± 5.6 mL·kg−1·min−1) were randomly assigned to, and provided with, either a high-protein, reduced-carbohydrate (PRO) or a high-carbohydrate (CHO) isocaloric-matched diet. Participants maintained their training load over 21-consecutive days with dietary intake consisting of 7-days habitual intake (T1), 7-days intervention diet (T2) and 7-days return to habitual intake (T3). Following each 7-day dietary period (T1−T3), a micro-muscle biopsy was taken for assessment of gene expression, before participants underwent laboratory assessment of a 10 km treadmill run at 75% V˙O2max, n treadmill run at 70% vV˙O2max time to exhaustion (TTE) trial. The PRO diet resulted in a modest change (1.37-fold increase, p = 0.016) in AMPK expression, coupled with a significant increase in fat oxidation (0.29 ± 0.05 to 0.59 ± 0.05 g·min−1, p 0.0001). However, a significant reduction of 23.3% (p = 0.0003) in TTE post intervention was observed; this reverted back to pre levels following a return to the habitual diet. In the CHO group, whilst no change in sub-maximal fuel utilisation occurred at T2, a significant 6.5% increase in TTE performance (p = 0.05), and a modest, but significant, increase in AMPK (p = 0.042) and PPAR (p = 0.029) mRNA expression compared to T1 were observed; with AMPK (p = 0.011) and PPAR (p = 0.044) remaining significantly elevated at T3. In conclusion, a 7-day isocaloric high protein diet significantly compromised high intensity exercise performance in trained runners with no real benefit on gene markers of training adaptation. A significant increase in fat oxidation during submaximal exercise was observed post PRO intervention, but this returned to pre levels once the habitual diet was re-introduced, suggesting that the response was driven via fuel availability rather than cellular adaptation. A short-term high protein, low carbohydrate diet in combination with endurance training is not preferential for endurance running performance.Peer reviewedFinal Published versio

Mapping scores from the Strengths and Difficulties Questionnaire (SDQ) to preference-based utility values

Conclusion: This research generated algorithms for translating SDQ scores to utility values and providing researchers with an additional tool for conducting health economic evaluations with child and adolescent mental health data.

Modelling graded semantic effects in lexical decision

Recent studies have shown that the involvement of semantic information in visual lexical decision depends on the nature of nonword foils with semantic effects increased as nonwords become more word-like (Evans, Lambon Ralph &Woollams, 2012). Given that most models of lexical decision focus on orthographic information (Coltheart, Rastle, Perry, Langdon & Ziegler, 2001; Grainger & Jacobs, 1996; Seidenberg & McClelland, 1989), the role of semantics and its interactions with vision, orthography, and phonology has been overlooked. We developed a recurrent connectionist model of single word reading including visual, orthographic, phonological, and semantic processing. The model differentiated words from nonwords by integrating measures of polarity across four key processing layers. The contribution of semantics depended on the type of nonword foils. The model was more reliant on semantic information when the nonword foils were pseudowords and pseudohomophones rather than consonant strings. The results support the view that semantic involvement in lexical decision is graded by the difficulty of the decision task