The ketogenic diet raises brain oxygen levels, attenuates postictal hypoxia, and protects against learning impairments

Gom, Renaud C.; Bhatt, Dhyey; Villa, Bianca R.; George, Antis G.; Lohman, Alexander W.; Mychasiuk, Richelle; Rho, Jong M.; Teskey, G. Campbell

doi:10.1016/j.nbd.2021.105335

Cited by 9 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be highlighted that pO2 values were obtained using a capillary sampling method, which might underestimate actual arterial pO2. Nevertheless, these data confirm earlier observations showing an increase in arterial, capillary and hippocampal oxygenation [16, 26, 27] upon endogenous and exogenous ketosis. In turn, an increased pO2 can either result from a higher oxygen uptake through increased ventilation or from a decreased cellular oxygen consumption.…”

Section: Discussionsupporting

confidence: 92%

Exogenous ketosis attenuates acute mountain sickness and mitigates high-altitude hypoxemia

Stalmans,

Tominec,

Lauriks

et al. 2023

Preprint

View full text Add to dashboard Cite

BackgroundAcute mountain sickness (AMS) represents a considerable issue for individuals sojourning to high altitudes with systemic hypoxemia known to be intimately involved in its development. Based on recent evidence that ketone ester (KE) intake attenuates hypoxemia, we sought to investigate whether exogenous ketosis might mitigate AMS development and improve hypoxic tolerance.MethodsFourteen healthy, male participants were enrolled in two 29h protocols (simulated altitude of 4,000-4,500m) receiving either KE or a placebo (CON) at regular timepoints throughout the protocol in a randomized, crossover manner. Select physiological responses were characterized after 15min and 4h in hypoxia, and the protocol was terminated prematurely upon development of severe AMS.ResultsAll participants tolerated the protocol equally long (n=6, of which n=5 completed the protocol in both conditions) or longer (n=8) in KE. Overall protocol duration increased by 32% on average with KE, and doubled for AMS-developing participants. KE consistently induced diurnal ketosis, a mild metabolic acidosis, hyperventilation, and relative sympathetic dominance. KE also fully negated the progressive hypoxemia that was observed between 15min and 4h in hypoxia in CON, while concomitantly increasing cerebral oxygenation and capillary pO2within this timeframe. This coincided with a KE-induced reduction in cerebral oxygen supply, suggesting that KE reduced cerebral oxygen consumption under hypoxic conditions.ConclusionsThese data indicate that exogenous ketosis improves hypoxic tolerance in humans and attenuates AMS development. The key underlying mechanisms include improved arterial and cerebral oxygenation, in combination with lowered cerebral blood flow and oxygen demand, and increased sympathetic dominance.SummaryKetone ester intake attenuated the development of acute mountain sickness at a simulated altitude of 4,000-4,500m. This likely resulted from a mitigation of arterial and cerebral hypoxemia, reduced cerebral blood flow and increased sympathetic drive.

show abstract

Section: Discussionsupporting

confidence: 92%

Exogenous ketosis attenuates acute mountain sickness and mitigates high-altitude hypoxemia

Stalmans,

Tominec,

Lauriks

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Data were evaluated using two-way repeated-measures analysis of variance. circulating b-hydroxybutyrate concentration to $2 mM, increased the degree of hippocampal and arterial oxygen saturation (61,62). If such effect also occurred in the conditions of the current study, indeed, it clearly did not translate into improved exercise performance at the moderate altitudes simulated.…”

Section: Discussionmentioning

confidence: 46%

Exogenous ketosis increases blood and muscle oxygenation but not performance during exercise in hypoxia

Poffé

Robberechts

Podlogar

et al. 2021

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Available evidence indicates that elevated blood ketones are associated with improved hypoxic tolerance in rodents. From this perspective, we hypothesized that exogenous ketosis by oral intake of the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) may induce beneficial physiological effects during prolonged exercise in acute hypoxia. As we recently demonstrated KE to deplete blood bicarbonate, which per se may alter the physiological response to hypoxia, we evaluated the effect of KE both in the presence and absence of bicarbonate intake (BIC). Fourteen highly trained male cyclists performed a simulated cycling race (RACE) consisting of 3h intermittent cycling (IMT180') followed by a 15-min time-trial (TT15') and an all-out sprint at 175% of lactate threshold (SPRINT). During RACE, fraction of inspired oxygen (FiO2) was gradually decreased from 18.6 to 14.5%. Before and during RACE, participants received either i) 75g ketone ester (KE), ii) 300 mg/kg body mass bicarbonate (BIC), iii) KE+BIC or iv) a control drink in addition to 60g carbohydrates per h in a randomized, crossover design. KE counteracted the hypoxia-induced drop in blood (SpO2) and muscle oxygenation by ~3%. In contrast, BIC decreased SpO2 by ~2% without impacting muscle oxygenation. Performance during TT15' and SPRINT were similar between all conditions. In conclusion, KE slightly elevated the degree of blood and muscle oxygenation during prolonged exercise in moderate hypoxia without impacting exercise performance. Our data warrant to further investigate the potential of exogenous ketosis to improve muscular and cerebral oxygenation status, and exercise tolerance in extreme hypoxia.

show abstract

“…While SGLT2 inhibitors' mechanism still is not completely understood, one of the main hypotheses is that SGLT2 inhibitors are increasing circulating ketone levels [168]. The improvement of parameters seen in the first use of SGLT2 inhibitors on Fontan patients match the effects of ketone bodies on hypoxia [175] and glomerular filtration rate [176], as reported in non-Fontan studies.…”

Section: Energy Metabolism and The Single Ventricle After Fontan Pall...mentioning

confidence: 86%

“…For certain anatomical variants of a SV, optimizing oxygen consumption might be critical considering altered coronary perfusion. A ketogenic diet improved the cerebral oxygen level in hypoxia after an epileptic event [ 175 ]—the assumed mechanism being altered substrate consumption, reduced glycolysis, and accumulation of lactate [ 246 ]. Exogenous ketones increased blood and muscle oxygenation in hypoxia [ 247 ].…”

Section: Impact Of Ketones Apart From That On the Cardiovascular Syst...mentioning

confidence: 99%

Comparative Metabolomics in Single Ventricle Patients after Fontan Palliation: A Strong Case for a Targeted Metabolic Therapy

Renaud,

Scholl-Bürgi,

Karall

et al. 2023

Metabolites

View full text Add to dashboard Cite

Most studies on single ventricle (SV) circulation take a physiological or anatomical approach. Although there is a tight coupling between cardiac contractility and metabolism, the metabolic perspective on this patient population is very recent. Early findings point to major metabolic disturbances, with both impaired glucose and fatty acid oxidation in the cardiomyocytes. Additionally, Fontan patients have systemic metabolic derangements such as abnormal glucose metabolism and hypocholesterolemia. Our literature review compares the metabolism of patients with a SV circulation after Fontan palliation with that of patients with a healthy biventricular (BV) heart, or different subtypes of a failing BV heart, by Pubmed review of the literature on cardiac metabolism, Fontan failure, heart failure (HF), ketosis, metabolism published in English from 1939 to 2023. Early evidence demonstrates that SV circulation is not only a hemodynamic burden requiring staged palliation, but also a metabolic issue with alterations similar to what is known for HF in a BV circulation. Alterations of fatty acid and glucose oxidation were found, resulting in metabolic instability and impaired energy production. As reported for patients with BV HF, stimulating ketone oxidation may be an effective treatment strategy for HF in these patients. Few but promising clinical trials have been conducted thus far to evaluate therapeutic ketosis with HF using a variety of instruments, including ketogenic diet, ketone esters, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. An initial trial on a small cohort demonstrated favorable outcomes for Fontan patients treated with SGLT2 inhibitors. Therapeutic ketosis is worth considering in the treatment of Fontan patients, as ketones positively affect not only the myocardial energy metabolism, but also the global Fontan physiopathology. Induced ketosis seems promising as a concerted therapeutic strategy.

show abstract

The ketogenic diet raises brain oxygen levels, attenuates postictal hypoxia, and protects against learning impairments

Cited by 9 publications

References 43 publications

Exogenous ketosis attenuates acute mountain sickness and mitigates high-altitude hypoxemia

Exogenous ketosis attenuates acute mountain sickness and mitigates high-altitude hypoxemia

Exogenous ketosis increases blood and muscle oxygenation but not performance during exercise in hypoxia

Comparative Metabolomics in Single Ventricle Patients after Fontan Palliation: A Strong Case for a Targeted Metabolic Therapy

Contact Info

Product

Resources

About