Browsing by Author "Thies, Dakkota"

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    Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction
    (Elsevier, 2017) Coggan, Andrew R.; Broadstreet, Seth R.; Mahmood, Kiran; Mikhalkova, Deana; Madigan, Michael; Bole, Indra; Park, Soo; Leibowitz, Joshua L.; Kadkhodayan, Ana; Thomas, Deepak P.; Thies, Dakkota; Peterson, Linda R.; Kinesiology, School of Physical Education and Tourism Management
    Background Patients with heart failure with reduced ejection fraction (HFrEF) exhibit lower efficiency, dyspnea, and diminished peak oxygen uptake (VO2peak) during exercise. Dietary nitrate (NO3−), a source of nitric oxide (NO), has improved these measures in some studies of other populations. We determined the effects of acute NO3− ingestion on exercise responses in 8 patients with HFrEF using a randomized, double-blind, placebo-controlled, crossover design. Methods and Results Plasma NO3−, nitrite (NO2−), and breath NO were measured at multiple time points and respiratory gas exchange was determined during exercise after ingestion of beetroot juice containing or devoid of 11.2 mmol of NO3−. NO3− intake increased (P < .05–0.001) plasma NO3− and NO2− and breath NO by 1469 ± 245%, 105 ± 34%, and 60 ± 18%, respectively. Efficiency and ventilation during exercise were unchanged. However, NO3− ingestion increased (P < .05) VO2peak by 8 ± 2% (ie, from 21.4 ± 2.1 to 23.0 ± 2.3 mL.min−1.kg−1). Time to fatigue improved (P < .05) by 7 ± 3 % (ie, from 582 ± 84 to 612 ± 81 seconds). Conclusions Acute dietary NO3− intake increases VO2peak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO3− also improves muscle contractile function, suggest that dietary NO3− supplementation may be a valuable means of enhancing exercise capacity in this population.
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    Dietary nitrate-induced increases in human muscle power: high versus low responders
    (Wiley, 2018-01) Coggan, Andrew R.; Broadstreet, Seth R.; Mikhalkova, Deana; Bole, Indra; Leibowitz, Joshua L.; Kadkhodayan, Ana; Park, Soo; Thomas, Deepak P.; Thies, Dakkota; Peterson, Linda R.; Kinesiology, School of Physical Education and Tourism Management
    Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO3- ), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22-79 year of age and weighing 52.1-114.9 kg were studied using a randomized, double-blind, placebo-controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO3- . Plasma NO3- and nitrite (NO2- ) were measured as indicators of NO bioavailability and maximal knee extensor speed (Vmax ), power (Pmax ), and fatigability were determined via isokinetic dynamometry. On average, dietary NO3- increased (P < 0.05) Pmax by 4.4 ± 8.1%. Individual changes, however, ranged from -9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO3- dose per kg), body mass index (surrogate for body composition) or placebo trial Vmax or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO2- concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO3- -induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO2- and possibly female sex.
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    Dietary nitrate‐induced increases in human muscle power: high versus low responders
    (Wiley, 2018-01-25) Coggan, Andrew R.; Broadstreet, Seth R.; Mikhalkova, Deana; Bole, Indra; Leibowitz, Joshua L.; Kadkhodayan, Ana; Park, Soo; Thomas, Deepak P.; Thies, Dakkota; Peterson, Linda R.; Kinesiology, School of Health and Human Sciences
    Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO 3 −), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22–79 year of age and weighing 52.1–114.9 kg were studied using a randomized, double‐blind, placebo‐controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO 3 −. Plasma NO 3 − and nitrite (NO 2 −) were measured as indicators of NO bioavailability and maximal knee extensor speed (V max), power (P max), and fatigability were determined via isokinetic dynamometry. On average, dietary NO 3 − increased (P < 0.05) P max by 4.4 ± 8.1%. Individual changes, however, ranged from −9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO 3 − dose per kg), body mass index (surrogate for body composition) or placebo trial V max or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO 2 − concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO 3 −‐induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO 2 − and possibly female sex.
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    Simultaneous Pharmacokinetic Analysis of Nitrate and its Reduced Metabolite, Nitrite, Following Ingestion of Inorganic Nitrate in a Mixed Patient Population
    (SpringerLink, 2020-11) Coggan, Andrew R.; Racette, Susan B.; Thies, Dakkota; Peterson, Linda R.; Stratford, Robert E., Jr.; Kinesiology, School of Health and Human Sciences
    Purpose: The pharmacokinetic properties of plasma NO3- and its reduced metabolite, NO2-, have been separately described, but there has been no reported attempt to simultaneously model their pharmacokinetics following NO3- ingestion. This report describes development of such a model from retrospective analyses of concentrations largely obtained from primary endpoint efficacy trials. Methods: Linear and non-linear mixed effects analyses were used to statistically define concentration dependency on time, dose, as well as patient and study variables, and to integrate NO3- and NO2- concentrations from studies conducted at different times, locations, patient groups, and several studies in which sample range was limited to a few hours. Published pharmacokinetic studies for both substances were used to supplement model development. Results: A population pharmacokinetic model relating NO3- and NO2- concentrations was developed. The model incorporated endogenous levels of the two entities, and determined these were not influenced by exogenous NO3- delivery. Covariate analysis revealed intersubject variability in NO3- exposure was partially described by body weight differences influencing volume of distribution. The model was applied to visualize exposure versus response (muscle contraction performance) in individual patients. Conclusions: Extension of the present first-generation model, to ultimately optimize NO3- dose versus pharmacological effects, is warranted.
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    A Single Dose of Dietary Nitrate Increases Maximal Knee Extensor Angular Velocity and Power in Healthy Older Men and Women
    (Oxford, 2019-07-22) Coggan, Andrew R; Hoffman, Richard L; Gray, Derrick A; Moorthi, Ranjani N; Thomas, Deepak P; Leibowitz, Joshua L; Thies, Dakkota; Peterson, Linda R; Kinesiology, School of Physical Education and Tourism Management
    Background Aging results in reductions in maximal muscular strength, speed, and power, which often lead to functional limitations highly predictive of disability, institutionalization, and mortality in elderly adults. This may be partially due to reduced nitric oxide (NO) bioavailability. We, therefore, hypothesized that dietary nitrate (NO3−), a source of NO via the NO3− → nitrite (NO2−) → NO enterosalivary pathway, could increase muscle contractile function in older subjects. Methods Twelve healthy older (age 71 ± 5 years) men and women were studied using a randomized, double-blind, placebo-controlled, crossover design. After fasting overnight, subjects were tested 2 hours after ingesting beetroot juice containing or devoid of 13.4 ± 1.6 mmol NO3−. Plasma NO3− and NO2− and breath NO were measured periodically, and muscle function was determined using isokinetic dynamometry. Results NO3− ingestion increased (p < .001) plasma NO3−, plasma NO2−, and breath NO by 1,051% ± 433%, 138% ± 149%, and 111% ± 115%, respectively. Maximal velocity of knee extension increased (p < .01) by 10.9% ± 12.1%. Maximal knee extensor power increased (p < .05) by 4.4% ± 7.8%. Conclusions Acute dietary NO3− intake improves maximal knee extensor angular velocity and power in older individuals. These findings may have important implications for this population, in whom diminished muscle function can lead to functional limitations, dependence, and even premature death.