Cocoa-flavanols enhance moderate-intensity pulmonary $$\dot{V}{\text{O}}_{2}$$ V ˙ O 2 kinetics but not exercise tolerance in sedentary middle-aged adults

European Journal of Applied Physiology (2021) 121:2285–2294 https://doi.org/10.1007/s00421-021-04682-9 ORIGINAL ARTICLE Cocoa‑flavanols enhance moderate‑intensity pulmonary V̇ O2 kinetics but not exercise tolerance in sedentary middle‑aged adults Daniel G. Sadler1 · Richard Draijer3 · Claire E. Stewart1 · Helen Jones1 · Simon Marwood2 · Dick H. J. Thijssen1 Received: 20 January 2021 / Accepted: 4 April 2021 / Published online: 10 May 2021 © The Author(s) 2021 Abstract Introduction Cocoa flavanols (CF) may exert health benefits through their potent vasodilatory effects, which are perpetuated by elevations in nitric oxide (NO) bioavailability. These vasodilatory effects may contribute to improved delivery of blood and oxygen (O2) to exercising muscle. ̇ 2) Purpose Therefore, the objective of this study was to examine how CF supplementation impacts pulmonary O 2 uptake (VO kinetics and exercise tolerance in sedentary middle-aged adults. Methods We employed a double-blind cross-over, placebo-controlled design whereby 17 participants (11 male, 6 female; mean ± SD, 45 ± 6 years) randomly received either 7 days of daily CF (400 mg) or placebo (PL) supplementation. On day 7, ̇ 2 kinetics. participants completed a series of ‘step’ moderate- and severe-intensity exercise tests for the determination of VO ̇ ̇ Results During moderate-intensity exercise, the time constant of the phase II VO2 kinetics (𝜏 VO2 ) was decreased by 15% ̇ 2 in CF as compared to PL (mean ± SD; PL 40 ± 12 s vs. CF 34 ± 9 s, P = 0.019), with no differences in the amplitude of VO −1 −1 ̇ ̇ (AVO2 ; PL 0.77 ± 0.32 l min vs. CF 0.79 ± 0.34 l min , P = 0.263). However, during severe-intensity exercise, 𝜏 VO2 , ̇ 2 ) and exercise tolerance (PL 435 ± 58 s vs. CF 424 ± 47 s, P = 0.480) were the amplitude of the slow component (SCVO unchanged between conditions. ̇ 2 kinetics during moderate-, but not severe-intensity Conclusion Our data show that acute CF supplementation enhanced VO exercise in middle-aged participants. These novel effects of CFs, in this demographic, may contribute to improved tolerance of moderate-activity physical activities, which appear commonly present in daily life. Trial registration Registered under ClinicalTrials.gov Identifier no. NCT04370353, 30/04/20 retrospectively registered Keywords Flavanols · Oxygen uptake kinetics · Heart rate · Exercise tolerance · Middle-age Abbreviations AHR Amplitude of the fundamental heart rate response ̇ 2 Amplitude of the phase II oxygen uptake AVO response CF Cocoa flavanol GET Gas exchange threshold Communicated by Michalis G Nikolaidis . * Dick H. J. Thijssen 1 School of Sport and Exercise Science, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK 2 School of Health Sciences, Liverpool Hope University, Liverpool, UK 3 Unilever Research & Development, Olivier van Noortlaan 120, 3133 AT Vlaardingen, The Netherlands HR Heart rate HRb Baseline heart rate τHR Time constant of the fundamental heart rate response NO Nitric oxide O2 Oxygen PL Placebo ̇ Magnitude of the slow component SCVO ̇ 2 Time constant of the phase II response 𝜏 VO ̇ 2 slow component TDSCVO ̇ 2 Time delay of the VO ̇ 2 Time delay of the phase II response TDVO Tlim Limit of exercise tolerance ̇ 2 Oxygen uptake VO ̇ 2b Baseline oxygen uptake VO 13 Vol.:(0123456789) 2286 Introduction ̇ 2 contraction and force production form Skeletal muscle VO the basis for the ability to perform physical activity, both for daily life activities as well as during sports-related events. Repeated muscle contractions require continuous regeneration of adenosine triphosphate (ATP). The production of ATP during (prolonged) physical activity is driven through the mechanism of oxidative phosphorylation, which depends on sufficient availability of oxygen ( O 2) amongst other key substrates (Poole et al. 2008). Impairment to pathways involved in the delivery of O 2 to working skeletal muscle, like that observed in older and physically inactive adults, leads to slower rates ̇ 2 ) and therefore greater O of pulmonary O 2 uptake (VO 2 deficit (Cunningham and Paterson 1994; DeLorey et al. 2004a; Dumanoir et al. 2010; Whipp and Rossiter 2013; ̇ 2 kinetics in response to George et al. 2018). Slower VO physical activity are associated with lower exercise tolerance (Grassi et al. 2011; Goulding et al. 2017, 2018), and may affect the capacity to perform daily life activities that require moderate-intensity physical activity. ̇ 2 across a metaThe slower dynamic adjustment of VO bolic transient observed in older adults is thought to be due to a mismatch of O2 delivery to O2 utilisation (Murias et al. 2010; Murias and Paterson 2015; George et al. 2018). Indeed, attenuations in microvascular blood flow supply and distribution (and thus O2 delivery) within aged skeletal muscle are well documented (Muller-Delp et al. 2002; Musch et al. 2004; Behnke and Delp 2010; Dumanoir et al. 2010). These reductions in O 2 delivery to active skeletal muscle are likely caused by impaired vascular endothelial function and diminished nitric oxide (NO) bioavailability (Muller-Delp et al. 2002; Woodman et al. 2002; Spier et al. 2004; Sindler et al. 2009). Interestingly, lifestyle interventions, such as exercise training and dietary strategies (Vanhatalo et al. 2010; Schreuder et al. 2015), have demonstrated potent effects to enhance NO bioavailability and improve endothelial function. Consequently, a number ̇ 2 kinetics in concert with of studies have shown faster VO increased O2 availability (Murias et al. 2010; Bailey et al. 2015; Goulding et al. 2017). Cocoa flavanols (CFs) represent a group of flavonoids present in cocoa derived from seeds of the fruit of the Theobroma cacao tree. Previous studies have found CFs (700–900 mg range) act primarily through the monomer (−)-epicatechin, to stimulate NO production, resulting in improved vasodilation and endothelial function in healthy adults (Schroeter et al. 2006; Davison et al. 2008; Berry et al. 2010). Given the direct impact of CFs on NO production and vascular endothelial function, and the negȧ 2 tive effects of sedentary ageing on O 2 delivery and VO 13 European Journal of Applied Physiology (2021) 121:2285–2294 kinetics at the onset of exercise, our objective was to test the hypothesis that, compared with placebo (PL), CF suṗ 2 kinetics during moderplementation speeds phase II VO ate-intensity physical activity and increases exercise tolerance in healthy middle-aged individuals. Methodology Participants Seventeen healthy middle-aged adults (11 male: mean ± SD, age 45 ± 6 years; body mass 87.7 ± 13.5 kg; height 1.75 ± 0.07 m; and 6 female: aged 47 ± 5 years; body mass 68.2 ± 17.7 kg; height 1.62 ± 0.09 m) volunteered and gave written informed consent to participate in the study (see Fig. 1). All procedures conformed to the Declaration of Helsinki and were approved by Liverpool John Moores University Research Ethics Committee (approv (...truncated)