Diverse neurological disorders are associated with a deficit in brain energy metabolism, often characterized by acute or chronic glucose hypometabolism. Ketones serve as the brain's only significant alternative fuel and can even become the primary fuel in conditions of limited glucose availability. Thus, dietary supplementation with exogenous ketones represents a promising novel therapeutic strategy to help meet the energetic needs of the brain in an energy crisis. Preliminary evidence suggests ketosis induced by exogenous ketones may attenuate damage or improve cognitive and motor performance in neurological conditions such as seizure disorders, mild cognitive impairment, Alzheimer's disease, and neurotrauma.
Human adaptation to extreme environments has been explored for over a century to understand human psychology, integrated physiology, comparative pathologies, and exploratory potential. It has been demonstrated that these environments can provide multiple external stimuli and stressors, which are sufficient to disrupt internal homeostasis and induce adaptation processes. Multiday hyperbaric and/or saturated (HBS) environments represent the most understudied of environmental extremes due to inherent experimental, analytical, technical, temporal, and safety limitations. National Aeronautic Space Agency (NASA) Extreme Environment Mission Operation (NEEMO) is a space-flight analog mission conducted within Florida International University’s Aquarius Undersea Research Laboratory (AURL), the only existing operational and habitable undersea saturated environment. To investigate human objective and subjective adaptations to multiday HBS, we evaluated aquanauts living at saturation for 9–10 days via NASA NEEMO 22 and 23, across psychologic, cardiac, respiratory, autonomic, thermic, hemodynamic, sleep, and body composition parameters. We found that aquanauts exposed to saturation over 9–10 days experienced intrapersonal physical and mental burden, sustained good mood and work satisfaction, decreased heart and respiratory rates, increased parasympathetic and reduced sympathetic modulation, lower cerebral blood flow velocity, intact cerebral autoregulation and maintenance of baroreflex functionality, as well as losses in systemic bodyweight and adipose tissue. Together, these findings illustrate novel insights into human adaptation across multiple body systems in response to multiday hyperbaric saturation.
Objectives 70.7% of Americans over 20 years of age are overweight or obese. Currently, the main strategy for weight loss is caloric restriction. Ketone bodies have been shown to facilitate voluntary caloric restriction through altering the appetite stimulating hormone ghrelin. However, these non-toxic ketone bodies have not been evaluated as weight loss supplements. C57BL6J mice were used to determine the weight loss efficacy of exogenous ketones by adding synthetic (R/S 1,3-Butanediol Acetoacetate Diester and 1,3-Butanediol) and natural (Beta-hydroxybutyrate and Beta-hydroxybutyrate + Medium Chain Triglycerides) ketogenic agents to standard rodent chow ab-libitum. Methods Six groups (R/S 1,3-butanediol acetoacetate diester, 1,3-butanediol, beta-hydroxybutyrate, beta-hydroxybutyrate + medium chain triglycerides, caloric restriction, standard diet ad-libitum) were housed 2–5 animals per cage and monitored to ensure appropriate acclimation prior to intervention. Mice were treated for two weeks with ketogenic agents, adjusting % of agent daily to ensure 20% weight loss was achieved. Results All ketogenic agents induced weight loss and voluntary caloric restriction. Weight loss for beta-hydroxybutyrate and beta-hydroxybutyrate + medium chain triglycerides was explained by caloric restriction alone. However, R/S 1,3-butanediol acetoacetate diester induced weight loss at lower dosages which could not be explained by caloric restriction alone. Conclusions Taken together, all ketogenic agents may assist in weight loss. However, R/S 1,3-butanediol acetoacetate diester appears to be a more potent non-toxic ketogenic supplement that facilitates weight loss via both voluntary caloric restriction and caloric restriction-independent mechanisms. Future studies should explore caloric-restriction independent weight loss mechanisms of R/S 1,3-butanediol acetoacetate diester. Funding Sources Disruptive Nutrition.
Background Kabuki Syndrome is a rare genetic disorder that leads to many developmental abnormalities, and is caused by a heterozygous mutation in either KMT2D (Type 1) or KDM6A (Type 2) that leads to a loss of function. Both genes play a role in gene regulation via histone modification. KMT2D is a gene that codes for the protein kmt2d, a lysine methyltransferase responsible for methylating H3K4. The KDM6A gene encodes the protein kdm6a, a demethylase responsible for demethylating H3K27. Both gene functions contribute to the opening of the chromatin. When either of these two proteins are deficient, craniofacial, skeletal, mental, and dermatologic development are severely impacted. Other developmental processes are impacted, but to varying degrees across patients. The endogenous ketone metabolite beta‐hydroxybutyrate (βHB) is a known epigenetic modifier, functioning as a class I and IIa histone deacetylase inhibitor. Previous research has shown that the ketogenic diet increases H3K4 acetylation and methylation rates, making βHB a potential therapeutic intervention for Kabuki syndrome. Additionally, H3K4 is a beta‐hydroxybutyrylation site, further underlying the potential for βHB to affect the epigenetic modifications observed in the disease. However, there is no current research on beta‐hydroxybutyrylation in Kabuki, nor on the effects of continuous exogenous βHB supplementation in the disorder. Methods Kmt2d+/βGeo (Type 1 Kabuki syndrome model) mice were fed standard diet with or without 15% BHB‐MCT supplementation for 12–15 weeks. Blood ketones, glucose, and body weight were monitored during the treatment period. Open field, Elevated Plus Maze, Novel Object Recognition, and Grip Strength behavioral tests were performed at the end of treatment. Various tissues were harvested, including the brain, for ongoing ex vivo analysis of markers associated with learning, memory, and development. Conclusions The 15% BHB‐MCT supplementation is sufficient to raise blood ketone levels in Kmt2d+/βGeo mice. Behavioral and molecular analysis is ongoing. Support or Funding Information Disruptive Nutrition, Florida high Tech Corridor
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.