Pete Cox

• MBChB, DPhil, FRCR
• Fellow at Oxford University Hospitals NHS Trust

Elevating blood ketones may enhance exercise capacity and modulate adaptations to exercise training; however, these effects may depend on whether hyperketonemia is induced endogenously through dietary carbohydrate restriction, or exogenously through ketone supplementation. To determine this, we compared the effects of endogenously‐ and exogenously‐...

Iron deficiency impairs skeletal muscle metabolism. The underlying mechanisms are incompletely characterised, but animal and human experiments suggest the involvement of signalling pathways co-dependent upon oxygen and iron availability, including the pathway associated with hypoxia-inducible factor (HIF). We performed a prospective, case–control,...

Purpose: In this study, we determined ketone oxidation rates in athletes under metabolic conditions of high and low carbohydrate (CHO) and fat availability. Methods: Six healthy male athletes completed 1 h of bicycle ergometer exercise at 75% maximal power (WMax) on three occasions. Prior to exercise, participants consumed 573 mg·kg bw ⁻¹ of a keto...

Introduction: Exogenous ketones potentially provide an alternative, energetically advantageous fuel to power exercising skeletal muscle. However, there is limited evidence regarding their relative contribution to energy expenditure during exercise. Furthermore, the effect of blood ketone concentration and exercise intensity on exogenous ketone oxi...

Background Glycogen storage disease type IIIa (GSDIIIa) is an inborn error of carbohydrate metabolism caused by a debranching enzyme deficiency. A subgroup of GSDIIIa patients develops severe myopathy. The purpose of this study was to investigate whether acute nutritional ketosis (ANK) in response to ketone‐ester (KE) ingestion is effective to deli...

Background While anatomic features associated with the risk of posterior communicating artery (PcoA) occlusion after embolization of aneurysms of the PcoA segment of the internal carotid artery (ICA) are well known, the link between perforator origin and perforator infarction has only been reported following neurosurgical clipping. The aim of this...

Background: A maladaptive shift from fat to carbohydrate (CHO) oxidation during exercise is thought to underlie myopathy and exercise-induced rhabdomyolysis in patients with fatty acid oxidation (FAO) disorders. We hypothesized that ingestion of a ketone ester (KE) drink prior to exercise could serve as an alternative oxidative substrate supply to...

Exogenous ketone drinks may improve athletic performance and recovery, but information on their gastrointestinal tolerability is limited. Studies to date have used a simplistic reporting methodology that inadequately represents symptom type, frequency, and severity. Herein, gastrointestinal symptoms were recorded during three studies of exogenous k...

Purpose: Ketosis, achieved through ingestion of ketone esters, may influence endurance exercise capacity by altering substrate metabolism. However, the effects of ketone consumption on acid-base status and subsequent metabolic and respiratory compensations are poorly described. Methods: Twelve athletically trained individuals completed an increment...

Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter “stressed saturation transfer” (StreST) extension to the...

AimSubjective perceptions of exercising exertion are integral to maintaining homeostasis. Traditional methods have utilized scores of ‘rating of perceived exertion’ (RPE) to quantify these subjective perceptions, and here we aimed to test whether RPE may encompass identifiable localized perceptions from the lungs (breathlessness) and legs (leg disc...

Athletes regularly endure large increases in ventilation and accompanying perceptions of breathlessness. Whilst breathing perceptions often correlate poorly with objective measures of lung function in both health and clinical populations, we have previously demonstrated closer matching between subjective breathlessness and changes in ventilation in...

Apart from acting as an alternative energy source in oxidative tissues, including muscle, ketone bodies regulate the metabolism of other substrates, but are cataplerotic. Glycogen can be mobilised for anaplerosis, regenerating Krebs cycle intermediates, thus glycogen availability may affect the hearts’ ability to oxidise ketone bodies. We hypothesi...

Rationale The oxidation of ketone bodies plus glucose improves the efficiency of the working rat heart by ~30% compared to glucose alone.¹ However, perfusions of hearts with ketones alone led to gradual functional decline with reduced flux through α-ketoglutarate dehydrogenase.² We have shown that that the rate of d-β-hydroxybutyrate (βHB) oxidatio...

Athletes regularly endure large increases in ventilation, and accompanying perceptions of breathlessness. While breathing perceptions often correlate poorly with objective measures of lung function in both health and clinical populations, we have previously demonstrated closer matching between subjective breathlessness and changes in ventilation in...

Objective: The ketones d-β-hydroxybutyrate (BHB) and acetoacetate are elevated during prolonged fasting or during a "ketogenic" diet. Although weight loss on a ketogenic diet may be associated with decreased appetite and altered gut hormone levels, it is unknown whether such changes are caused by elevated blood ketones. This study investigated the...

Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrat...

Purpose: Breathlessness is a complex set of symptoms that are comprised of both sensory and affective (emotional) dimensions. While ventilation is now understood to be a potential limiter to performance in highly-trained individuals, the contribution of breathlessness-anxiety in those nearing maximal ventilation during intense exercise has not yet...

Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition with...

Background: Patients with treated HIV infection have clear survival benefits although with increased cardiac morbidity and mortality. Mechanisms of heart disease may be partly related to untreated chronic inflammation. Cardiovascular magnetic resonance imaging allows a comprehensive assessment of myocardial structure, function, and tissue characte...

The administration of ketones to induce a mild ketosis is of interest for the alleviation of symptoms associated with various neurological disorders. This study aimed to understand the pharmacokinetics (PK) of d-β-hydroxybutyrate (BHB) and quantify the sources of variability following a dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (ketone monoe...

Ketone bodies acetoacetate (AcAc) and D-β-hydroxybutyrate (βHB) may provide an alternative carbon source to fuel exercise when delivered acutely in nutritional form. The metabolic actions of ketone bodies are based on sound evolutionary principles to prolong survival during caloric deprivation. By harnessing the potential of these metabolic actions...

Obesity is linked to a wide variety of cardiac changes, from subclinical diastolic dysfunction to end-stage systolic heart failure. Obesity causes changes in cardiac metabolism, which make ATP production and utilization less efficient, producing functional consequences that are linked to the increased rate of heart failure in this population. As a...

To determine the effects of short-term exercise training on cardiac function and metabolism during rest and physical exercise in patients with heart failure from dilated cardiomyopathy (DCM). Patients with DCM (n=15, age 58±2 years, NYHA class I-III) were studied before and after 8 weeks of cycle exercise for 20 min, five times per week. Cardiac vo...

BACKGROUND The failing heart is characterised by impaired myocardial energetics and a compensatory shift from fatty acid to glucose metabolism. Cardiac steatosis has been implicated in ventricular contractile dysfunction, hypertrophy, inflammation and arrhythmias.Therefore we assessed cardiac steatosis using 1H magnetic resonance spectroscopy in hy...

Objective To determine the effects of short term exercise training on cardiac metabolism and function, during rest and exercise, in patients with dilated cardiomyopathy (DCM). Background Exercise training may play a beneficial role in patients with DCM, however the effects on cardiac function at rest and during exercise have not been defined. Metho...