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

Abstract

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.