Prevention is Better Than Cure: Cardio-Metabolic Responses to Montmorency Tart Cherry Supplementation With and Without Exercise

Globally, cardio-metabolic diseases and their associated complications are the leading cause of mortality and morbidity, and also the single largest contributor to health care expenditure (World Health Organisation, 2017). Hitherto, much effort has been placed on attempting to cure rather than prevent these diseases; hence rates are projected to increase over the next 25 years (Cho et al., 2018). Consequently, a change in approach towards prevention would be more effective at minimising the burden of these diseases. Hence, this thesis focussed on implementing lifestyle interventions, Montmorency tart cherries (MTC) (Prunus cerasus L.) and FATMAX exercise, to improve biomarkers associated with Metabolic Syndrome (MetS), the precursor to developing cardiovascular disease and type II diabetes (Wilson et al., 2005). Tart cherries are a dietary source rich in many polyphenolic compounds, particularly anthocyanins, which have been increasingly investigated for their ability to optimise health over the past 20 years (Wang, 1998; Seeram et al., 2001; Bell et al., 2014a; Kelley, Adkins and Laugero, 2018). In vitro (Wang, 1998; Seeram et al., 2001; Keane et al., 2016a) and animal (Seymour et al., 2008, 2009) models have provided strong evidence for the anti-oxidative, anti-inflammatory, anti-diabetic and cardio-protective properties of tart cherries. Inconsistent findings from human trials limit the conclusions that can be drawn, however positive results relating to improved cardio-metabolic function (Ataie‐Jafari et al., 2008; Martin et al., 2010; Keane et al., 2016b; Keane et al., 2016c; Chai et al., 2018) and recovery from exercise (Howatson et al., 2010; Bell et al., 2014d) have been reported. These cardio-metabolic responses were observed in various human populations, but never in a MetS cohort, and mechanisms of observed effects have not been delineated. Consequently, the overarching aim of this thesis was to establish whether MTC supplementation with and without FATMAX exercise could improve biomarkers associated with cardio-metabolic health; and delineate potential mechanisms of action. The results from this thesis have corroborated previous literature but also identified novel and clinically relevant findings. The first study (Chapter 4), examined health responses to a combination of MTC juice supplementation with exercise for the first time. However, no significant improvements on cardio-metabolic biomarkers with MTC consumption were observed in healthy humans. Additionally, based on hormesis, chapter 4 also suggested short-term MTC supplementation may be most effective. The next investigation (Chapter 5) was the first to assess cardio-metabolic responses to MTC consumption, in humans with MetS. Results indicated acute supplementation of MTC capsules and juice reduced insulin concentrations; demonstrating a health benefit of MTC capsules for the first time in any human population. However, responses between MTC juice and capsules were not different. Corroborating previous research, MTC juice reduced systolic blood pressure acutely, by a clinically relevant margin. Similarly, and arguably the most clinically important finding of this thesis was reported in chapter 6, as 7 days MTC juice consumption significantly reduced 24-hour ambulatory blood pressure in a population of individuals with MetS. Hence, these findings indicate MTC juice may be used as an anti-hypertensive intervention. Moreover, chapter 6 revealed for the first time an MTC intervention improved fasting glucose, total cholesterol, TC:HDL ratio and lowered resting RER in any human population, after 6 days of MTC juice supplementation compared to a control group. The last experimental study attempted to elucidate the mechanistic pathways for observed responses with MTC (Chapter 7). Findings demonstrated dilutions of MTC concentrate extended lifespan in Caenorhabditis elegans; and identified MTC may act as a calorie restriction mimetic via the PPAR signalling pathway. Together these observations promote the integration of MTC, as a safe, pragmatic, naturally-occurring dietary intervention, into habitual consumption for the prevention and amelioration of cardio-metabolic dysfunction. Substantiation of these results from future, well-designed clinical trials is necessitated to support the implementation of MTC in practice

The effects of Montmorency tart cherry juice supplementation and FATMAX exercise on fat oxidation rates and cardio-metabolic markers in healthy humans

Montmorency tart cherries (Prunus cerasus L.) are rich in anthocyanins, compounds capable of augmenting fat oxidation and regulating metabolic dysfunction. The present study examined whether Montmorency tart cherry juice (MTCJ) supplementation could augment fat oxidation rates at rest and during FATMAX exercise, thus improve cardio-metabolic health. Eleven, healthy participants consumed MTCJ or placebo (PLA) twice daily, in a randomised, counterbalanced order for 20 days. Participants cycled at FATMAX for 1-h pre-, mid- (10 days) and post-supplementation whilst substrate oxidation rates were measured. Before exercise anthropometrics and resting metabolic rate were measured. Blood pressure, serum triglycerides, cholesterol, HDL, total antioxidant status (TAS) and glucose were measured immediately before and after exercise. No significant differences between conditions or interactions were observed for any functional and blood-based cardio-metabolic markers or fat oxidation during exercise or rest (P > 0.05). Pre-exercise TAS (P = 0.036) and HDL (P = 0.001) were significantly reduced from mid- to post-supplementation with MTCJ only. Twenty days’ MTCJ supplementation had no effect on fat oxidation; therefore, it is unnecessary for individuals in this participant cohort to consume MTCJ with exercise to improve cardio-metabolic biomarkers.Peer reviewedFinal Accepted Versio

THE EFFECTS OF MONTMORENCY TART CHERRY JUICE SUPPLEMENTATION AND FATMAX EXERCISE ON CARDIO-METABOLIC MARKERS IN HEALTHY HUMANS

Peer reviewe

Immunosurveillance associated with upper respiratory symptoms in elite swimmers: 8-month period leading into Commonwealth Games

Most research suggests that a greater degree of immune suppression and subsequent increased illness risk occurs during winter and the heaviest training periods. Monitoring an individual’s change in salivary Immunoglobulin A (sIgA) throughout a training programme, could help identify athletes at risk of illness; promoting the use of individual athlete monitoring. Epstein Barr Virus (EBV) has been identified as one of the most likely causes of illness symptoms (Reid et al., 2004). An association has been found between short sleep duration (< 7 hours) and increased number of illnesses, including cold and flu (Orzech et al., 2014). These findings are empirical because athletes do not obtain enough sleep, regularly sleeping less than the NR of 7-9hours of sleep per night.Peer reviewe

The relationship between the elevation of haemoglobin A1c level, sleep quality and sleep duration in clinically diagnosed pre-diabetic patients in a nationally representative sample

© The Author(s) 2022. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/).Background/objectives: Type 2 diabetes mellitus (T2DM) is one of the most common chronic illnesses in the United Kingdom accounting for approximately 15% of deaths per year. Growing evidence suggests that sleep duration and quality contributes towards this. This study aimed to determine whether there was a significant relationship between the elevation of haemoglobin A1c (HbA1c) level, sleep quality (SQ) and sleep duration (SD) in clinically diagnosed pre-diabetic patients.  Subjects/methods: Following referral from a relevant healthcare professional, participants (n = 40) were registered on the National Health Service England, funded Healthier You: National Diabetes Prevention Programme and completed a Pittsburgh Sleep Quality Index questionnaire to evaluate SQ and SD. Results: A Spearman’s correlation showed an association between HbA1c, SQ and SD measures. A simple linear regression showed a significant large positive association (rs = 0.913, p < 0.001) and significant regression (F (1) = 39, p < 0.001) with an R2 of 0.842 between HbA1c level and SQ. Additionally, a significant large negative association (rs = 0.757, p < 0.001) and significant regression was found (F (1) = 39, p < 0.001) with an R2 of 0.570 between HbA1c and SD.  Conclusions: This study suggests a relationship between SQ, SD and the elevation of HbA1c which may contribute towards prevalence of T2DM and may help to increase adherence to diabetes prevention programmes.Peer reviewedFinal Published versio

Observing Longitudinal Physical Activity and Sitting Patterns Throughout COVID-19 Restrictions Amongst UK Adults

© 1996 - 2023 CTI Meeting Technology - All rights reserved.Purpose: The COVID-19 global pandemic presented an insight into observing the changes in physical activity (PA) and sitting patterns of free-living adults during a unique period of intermittent enforced home confinement and free-living conditions. Evidence unequivocally indicates physical inactivity, facilitated by home confinement, is associated with greater risk of disease and mortality. This study aimed to monitor longitudinal PA and sitting patterns throughout the enforced COVID-19 restrictions, uniquely including all three UK national lockdowns between April 2020 and January 2021. Methods: 580 adults (41 ±21 y; 22% ♂ / 77% ♀ / 1% Other) participated in a longitudinal, observational study, encompassing all three UK national lockdowns between 19/4/20 – 23/1/21, using self-reported online surveys either daily or weekly for 6 months, then monthly to reduce survey fatigue. Pre-COVID data was based on the week prior to the first national lockdown. Participants recalled time engaging in PA and sitting per day for each diary completed throughout the study. Data was used to calculate MET-mins/week for total, low, moderate and vigorous activity, then averaged for each month. Friedman’s ranking test analysed differences between months for PA and sitting time. Results: Total, low, moderate and vigorous MET-mins/wk were significantly different across months (p < 0.001) and tended to decline month-on-month. PA levels were similar between lockdowns 2 and 3. Sitting time significantly increased (χ2(8) = 18, p = 0.02) across lockdowns 1-3, but decreased when restrictions were lifted. Conclusions: To avert the negative health impacts of ‘twindemics’ linking future disease pandemics and the physical inactivity pandemic, strict movement restrictions should be carefully considered in future given our data shows increased physical inactivity.Peer reviewe

Changes to Physical Activity, Sitting Time, Eating Behaviours and Barriers to Exercise during the First COVID-19 ‘Lockdown’ in an English Cohort

© 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/)This study aimed to determine the effect of the first English national COVID-19 lockdown on physical activity (PA), sitting time, eating behaviours and body mass in an adult cohort. This was further examined to determine whether conforming to recommended guidelines on PA and sedentary behaviour was improved. Based on an online survey (n = 818) incorporating the International Physical Activity Questionnaire Short Form (IPAQ-SF), self-reported body mass change showed that in 32.2% of participants body mass increased, with 39.1% reporting an increase in food intake. Never exercising at the gym or undertaking an exercise class (online or live), increased by 50.8% during lockdown, with 53.5% changing from exercising frequently to never exercising, suggesting a lack of engagement with online and home workouts. However, outdoor running and cycling >2 times/week increased by 38% during lockdown. Walking at least 30 min continuously on >2 occasions/week increased by 70% during lockdown with minimum 10-min walks on 7 days per week increasing by 23%. The lockdown had a negative impact on sitting time (>8 h a day), which increased by 43.6% on weekdays and 121% at weekends. Furthermore, sitting 4 h/day decreased during lockdown (46.5% and 25.6% for weekdays and weekends, respectively). Those citing tiredness or lack of time as a barrier to exercise reduced by 16% and 60%, respectively, from pre-lockdown to during lockdown. More of the sedentary group met the Public Health England PA recommendations, however most participants still did not meet the UK Government guidelines for PA. Improvements in health per additional minutes of physical activity will be proportionately greater in those previously doing 30 min/week, the area where most improvements were found although, conversely sitting time was greatly increased. This study may assist in informing whether future lifestyle changes could improve the health of the population.Peer reviewedFinal Published versio

Heart Rate Recovery Assessed by Cardiopulmonary Exercise Testing in Patients with Cardiovascular Disease: Relationship with Prognosis

© 2023 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/).Background: The use of exercise testing has expanded in recent decades and there is a wealth of information examining the prognostic significance of exercise variables, such as peak oxygen consumption or ventilatory measures whilst exercising. However, a paucity of research has investigated the use of recovery-derived parameters after exercise cessation. Heart rate recovery (HRR) has been considered a measure of the function of the autonomic nervous system and its dysfunction is associated with cardiovascular risk. Objectives: We aim to provide an overview of the literature surrounding HRR and its prognostic significance in patients with cardiovascular disease undertaking an exercise test. Data Sources: In December 2020, searches of PubMed, Scopus, and ScienceDirect were performed using key search terms and Boolean operators. Study Selection: Articles were manually screened and selected as per the inclusion criteria. Results: Nineteen articles met inclusion criteria and were reviewed. Disagreement exists in methodologies used for measuring and assessing HRR. However, HRR provides prognostic mortality information for use in clinical practice. Conclusions: HRR is a simple, non-invasive measure which independently predicts mortality in patients with heart failure and coronary artery disease; HRR should be routinely incorporated into clinical exercise testing.Peer reviewe

Effects of Short-Term Continuous Montmorency Tart Cherry Juice Supplementation in Participants with Metabolic Syndrome

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s00394-020-02355-5Purpose: Metabolic Syndrome (MetS) augments the incidence of cardiovascular disease by two-fold and type II diabetes mellitus by five-fold. Montmorency tart cherries are rich in phytochemicals shown to improve biomarkers related to cardio-metabolic health in humans. This study aimed to examine cardio-metabolic responses after 7-days Montmorency tart cherry juice (MTCJ) supplementation and also acute on short-term supplementation responses to a single bolus, in humans with MetS. Methods: In a randomised, single-blind, placebo-controlled, crossover trial, 12 participants with MetS (50 ± 10 years; 6M/6F), consumed MTCJ or placebo (PLA) for 7 days. Blood-based and functional cardio-metabolic biomarkers were measured pre- and post-supplementation, and acute responses measured pre-bolus and up to 5 h post-bolus on the 7th day. Results: 24-h ambulatory systolic (P = 0.016), diastolic (P = 0.009) blood pressure and mean arterial pressure (P = 0.041) were significantly lower after 7-days MTCJ supplementation compared to PLA. Glucose (P = 0.038), total cholesterol (P = 0.036), LDL (P = 0.023) concentrations, total cholesterol:HDL ratio (P = 0.004) and respiratory exchange ratio values (P = 0.009) were significantly lower after 6-days MTCJ consumption compared to PLA. Conclusions: This study revealed for the first time in humans that MTCJ significantly improved 24-h BP, fasting glucose, total cholesterol and total cholesterol:HDL ratio, and also lowered resting respiratory exchange ratio compared to a control group. Responses demonstrated clinically relevant improvements on aspects of cardio-metabolic function, emphasising the potential efficacy of MTCJ in preventing further cardio-metabolic dysregulation in participants with MetS. Registered at clinicaltrials.gov (NCT03619941).Peer reviewedFinal Accepted Versio

The relationship between the elevation of Haemoglobin A1c level, sleep quality and sleep duration in clinically diagnosed pre-diabetic patients in a nationally representative sample

Participants were recruited from the National Health Service England (NHSE) funded Healthier You: National Diabetes Prevention Programme (NDPP). Forty participants took part in the study. Potential participants were approached, by phone call once they were referred and registered on the NHSE NDPP. These programme participants were recruited through healthcare professional referrals (nurses and GPs) and self-referrals. Participants were eligible if aged 18 years and over; had an HbA1c referral reading of between 42-47mmol/mol within the last 12 months; and were registered on the NHSE NDPP. Exclusion criteria included participants with a severe debilitating disease which may have interfered with the study participation, under the age of 18 years, over the age of 65 years and/or pregnant. Participants received a pre-program information pack in conjunction with a SQ (sleep quality) and SD (sleep duration) questionnaire at the end of their 1:1 initial appointments for the NHSE NDPP. Participants were given prepaid envelopes to send their anonymised questionnaires back to the researcher once completed after their 1:1 appointment