Athletes often face sleep disturbances due to strenuous training, leading to decreased REM sleep and increased wakefulness. These sleep impairments can harm exercise performance, hinder recovery, and increase the risk of illness and injury. This article delves into how ketone ester (KE) ingestion can improve sleep efficiency and quality after high-intensity exercise.
The Impact of Exercise on Sleep
Both acute and regular exercises exert positive effects on sleep quality and quantity, as evidenced by improved sleep onset, slow-wave sleep, and sleep efficiency. However, sleep disruptions also frequently occur in athletes, most often resulting in decreased rapid eye movement (REM) sleep and increased wakefulness during the subsequent night. This is particularly common before competition, during intensive training periods, after ultraendurance exercise, as well as after vigorous exercise ending in close proximity to bedtime. Elevated nocturnal sympathetic and adrenergic activity are considered to be an important cause of reduced sleep quality in both athletes and other individuals afflicted by chronic insomnia.
Ketone Bodies and Brain Metabolism
Oxidation of the ketone bodies d-β-hydroxybutyrate (βHB) and acetoacetate (AcAc), which are continuously produced from fatty-acid-derived acetyl-CoA in hepatic mitochondria and astrocytes, supports brain metabolism. Furthermore, the contribution of ketone bodies to brain metabolism has been shown to depend on the level of neuronal activity. Preliminary evidence also indicates that ketone bodies can directly modulate sleep architecture. Intracerebroventricular injection of AcAc, but not βHB, increased slow-wave activity during non-REM (NREM) sleep in a dose-dependent manner and slightly decreased the amount of REM sleep in mice. In contrast, another study observed that elevating blood ketone levels by means of a ketogenic diet increased REM sleep in children with epilepsy. However, because a ketogenic diet elicits a multitude of metabolic changes, it is unclear whether these effects are a direct result of ketosis per se.
The Study: Investigating Ketone Esters and Sleep in Cyclists
Against this background, a study aimed to investigate whether ketone bodies can counteract strenuous exercise-induced disruptions in sleep architecture in well-trained cyclists. Therefore, a strenuous training day was simulated, involving a morning endurance training session and a late-evening high-intensity interval training (HIIT) ending 1 h before sleeping time. After each training session and before sleeping time, the subjects received either a KE or a placebo drink, enabling an investigation into the specific effects of ketone bodies in the absence of other metabolic alterations induced by other ketotic interventions such as fasting or a ketogenic diet. An experimental condition without exercise was also added to investigate the effect of exercise per se on sleep architecture.
Exclusion Criteria and Participant Selection
Before participation, subjects were examined by a qualified physician using a medical questionnaire and a resting electrocardiogram. People working in late-night shifts and extreme morning and evening chronotypes as determined by the Horne and Östberg questionnaire were excluded from participation. Subjects were also free of psychological and neurological disorders, including depression and anxiety, as assessed using the Beck’s Depression and Anxiety questionnaires. None of the subjects had sleep disorders and reported good sleep quality (Pittsburgh Sleep Quality Index score <5), were nonsmokers, and did not take any medication that could interfere with either sleep or exercise performance. None of the subjects followed a high-fat, low-carbohydrate, ketogenic diet or consumed ketotic supplements during the last 3 months before the study. Ten well-trained male cyclists with good sleep quality (age: 23 ± 4 yr (mean ± SD); body mass: 70.7 ± 4.8 kg; height: 1.79 ± 0.05 m; lactate threshold (LT): 267 ± 38 W; V̇O2max: 62.9 ± 7.2 mL·kg−1·min−1) and an average cycling volume of 10.8 ± 4.4 h·wk−1 met the inclusion criteria and signed the written informed consent before participation.
Read also: Easy Low-Carb Cheese Crackers
Pre-Study Assessments
Two weeks before the start of the experimental sessions, subjects completed a maximal graded exercise test on a calibrated cycling ergometer (Cyclus 2; RBM elektronik-automation GmbH, Leipzig, Germany) to determine LT and maximal oxygen uptake rate (V̇O2max). Initial workload was set at 100 W and increased every 8 min with 40 W until volitional exhaustion to determine LT. Heart rate was measured continuously (Polar H10; Polar, Kempele, Finland), and capillary blood samples were obtained every 4 min to determine blood lactate concentration (Lactate Pro2; Arkray, Amstelveen, the Netherlands). LT was defined as the lowest workload corresponding to a 1 mM blood lactate increase from min 4 to 8 within the same stage. Subsequently, the subjects rested for 15 minute before starting the V̇O2max test. The V̇O2max test started at an initial workload of 70 W and was increased by 25 W every 30 s until volitional exhaustion.
Experimental Design
Experiments were conducted according to a double-blinded, placebo-controlled, crossover design. The study consisted of three experimental sessions, each separated by a 1-wk washout period. The order of the three experimental conditions was randomized by a researcher who was otherwise not involved in the study. Two of the three experimental sessions involved a 120-min cycling endurance training session (ET120′) starting 2 h after breakfast and a 90-min HIIT (HIIT90′) ending 1 h before sleeping time. After each training session, and 30 min before sleeping time, the subjects received either 25 g of a KE (EXKE) or a control drink (EXCON). To determine the specific effect of strenuous exercise on sleep, an additional experimental session without exercise (RCON) was added. Except for exercise, RCON followed the exact same protocol as EXCON and EXKE. In the RCON condition, subjects received the control drink at the same time points as during the exercise conditions. Sleep was measured during the subsequent night in each condition using polysomnography (PSG).
Study Protocol and Standardizations
Exactly 1 wk before the first experimental session (see Experimental Sessions section), subjects completed the full protocol, but without nutritional intervention, to become accustomed to the exercise protocol, the sleeping facility, and the sleep recordings. From the familiarization session until the end of the study, subjects had to maintain a regular sleep-wake rhythm with at least 7 h of sleep per night. In order not to deviate from their normal sleep-wake rhythm, subjects were allowed to choose their preferred wake-up time (lights on) and sleeping time (lights off). Adherence to this sleep-wake rhythm was monitored throughout the entire study period using a sleep diary and an actigraphic wristband (ActiGraph wGT3X-BT, ActiGraph, Pensacola, FL). Sleep quality and quantity of each night preceding the experimental sessions were assessed using the St. The evening before each experimental session, the subjects consumed a carbohydrate-rich dinner (~5600 kJ, 69% carbohydrate, 16% fat, 15% protein) at home and went to bed at their predetermined time. The next morning, they woke-up at their predetermined time, consumed a carbohydrate-rich breakfast at home (∼2600 kJ, 72% carbohydrates, 13% protein, 15% fat), and arrived at the exercise and sleeping facility 2 h after waking up. Each subject stayed in a fully equipped, temperature- and ventilation-controlled private room at the research facility (Bakala Academy-Athletic Performance Center, Leuven) during the entire experimental session to standardize light exposure and environmental temperature during the day (21°C) and night (18°C). The exercise training sessions were performed in a separate room within the facility. ET120′ started 2.5 h after waking up and consisted of eight consecutive 15-min intervals during which the exercise intensity alternated between 60% and 80% of LT. One hour after ET120′, subjects received a carbohydrate-rich lunch (~5000 kJ, 69% carbohydrates, 15% protein and 16% fat). In the afternoon, subjects received some free time, but activities (e.g., exercise or naps), food intake, or caffeinated drinks (e.g., coffee) that could interfere with sleep were prohibited. Five hours before sleeping time, subjects received a light evening meal (~1700 kJ, 69% carbohydrates, 15% protein, 16% fat). Two hours later, HIIT90′ was started, which consisted of a 10-min warm-up (70% of LT), 10× 7-min intervals (3 min at 120% of LT-4 min at 50% of LT), and an all-out sprint at 175% of LT. HIIT90′ ended 1 h before sleeping time, after which subjects took a lukewarm shower (38°C). Subsequently, the electrodes for the PSG measurement were attached, and subjects went to bed 5 min before their predetermined sleeping time. Next morning, subjects were woken up at their predetermined time.
Nutritional Interventions
Subjects received 32 g of carbohydrates per hour during ET120′ via an energy cake (650 kJ, 83% carbohydrates, 11% fat, 3% protein; 6D Sports Nutrition, Oudenaarde, Belgium). After each training session or at the same time of the day for the RCON condition, subjects also received 300 mL of a high-dose protein-carbohydrate recovery shake delivering 64 g of carbohydrates and 30 g of proteins (1585 kJ, 67% carbohydrates, 32% protein, 1% fat; 6D Sports Nutrition). In addition, in EXKE, subjects received 25 g of a ketone monoester immediately after each training session and 30 min before sleeping time. (Falls Church, VA). The dosing strategy was based on a previous study by our research group and aimed to increase blood βHB levels to ~3 mM within 30 min postexercise and just before sleeping time. In the EXCON and RCON condition, subjects received a taste-matched placebo drink at the same time points. The placebo drink consisted of collagen Peptan® (12.5% w/v; 6D Sports Nutrition) and 1 mM bitter sucrose octaacetate (Sigma-Aldrich, Bornem, Belgium) dissolved in water. The same control drink was used as in previous studies in which subjects were unable to distinguish the control drink from KE. The total energy content of the three KE supplements was 1468 versus 139 kJ for the three control drinks. An inert low-caloric placebo drink was used to exclude potential effects on sleep from increased carbohydrate intake or slightly increased ketone body production associated with increased fat intake. The supplements were administered in nontransparent tubes to avoid potential visual identification.
Polysomnography (PSG) Measurements
Both familiarization and experimental nights were recorded with a digital amplifier (V-amp; Brain Products GmbH, Gilching, Germany) and digitized at a sampling rate of 1000 Hz. Electroencephalographic (EEG) recordings were made from Fz, Cz, Pz, Oz, C3, C4, A1, and A2 according to the international 10-20 system. The A2 electrode served as the reference electrode, and A1 was used as a backup reference electrode. An electrode applied to the middle of the forehead functioned as the ground electrode. Vertical and horizontal eye movements electrooculography (EOG) were recorded with electrodes above and under the right eye and with electrodes attached to the outer cantus of both eyes. EEG and EOG data were recorded with a 0.1-Hz low cut-off filter and a 30-Hz high cut-off filter. Muscle tone and movements were measured with a bipolar submental electromyogram of the chin with a low cut-off filter of 10 Hz and a high cut-off filter of 200 Hz. A 50-Hz notch filter was used to filter out electrical noise.
Read also: Keto Calorie Counting: A Detailed Guide
Sleep Data Analysis
An independent certified sleep technician (Sleep Well PSG, Canada), who was blinded to the treatment conditions, visually scored night recordings according to the Rechtschaffen and Kales guidelines in conjunction with the American Academy of Sleep Medicine guidelines. PSG data were visually scored in 30-s epochs and 0.3- to 35-Hz, 0.3- to 30-Hz, and 10- to 100-Hz bandpass filters were used for EEG, EOG and electromyogram signals, respectively. The following sleep variables were obtained: (i) total sleep time; (ii) WASO; (iii) total NREM and REM sleep; (iv) total N1, N2, and N3 sleep; (v) sleep onset, sleep onset to N2, N3, and REM sleep; and (vi) sleep efficiency (total sleep time/time in bed). A total of two datasets were lost because of technical issues, one from EXCON and one from EXKE. In one subject, the computer crashed during the night, and in another, all the electrodes had come off during the night. First, EEG data were preprocessed in BrainVision Analyzer (Brain Products GmbH) by applying a 0.1- to 30-Hz bandpass filter and subsequently transferred to the Python environment (version 3.10.5). Detection of slow waves and sleep spindles was performed as previously described by Nicolas et al.
Key Findings: Ketone Esters Improve Sleep
Available evidence indicates that ketone bodies may improve sleep quality. Blood d-β-hydroxybutyrate concentrations transiently increased to ~3 mM postexercise and during the first part of the night in EXKE but not in EXCON or RCON. Exercise significantly reduced rapid eye movement sleep by 26% (P = 0.001 vs RCON) and increased wakefulness after sleep onset by 95% (P = 0.004 vs RCON). Interestingly, KE improved sleep efficiency by 3% (P = 0.040 vs EXCON) and counteracted the exercise-induced decrease in rapid eye movement sleep (P = 0.011 vs EXCON) and the increase in wakefulness after sleep onset (P = 0.009 vs EXCON). This was accompanied by a KE-induced increase in dopamine excretion (P = 0.033 vs EXCON), which plays a pivotal role in sleep regulation. These data indicate that KE ingestion improves sleep efficiency and quality after high-intensity exercise.
Read also: Magnesium Supplements for Keto