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Strategies to Augment Ketosis: Optimization of Ketone Delivery Strategies
Sponsor: Ohio State University
Summary
One important difference between KE compounds is the ketone-promoting components, which determines the circulating ratio of blood ketone bodies, BHB and AcAc, and may in turn lead to important metabolic and signaling differences. Whereas some actions of the ketone bodies BHB and AcAc are shared, R-BHB has a broad range of signaling functions that are distinct from AcAc, some of which are shared by the non-circulating, non-oxidizable enantiomer, S-BHB. AcAc also has metabolic and signaling actions that are independent of BHB and is selectively oxidized in some cells that cannot oxidize BHB. Furthermore, responses to different ketone bodies vary between tissue types. A second difference between KE arises from the balance between direct delivery of ketones compared to indirectly elevating ketone concentration via metabolism of non-classical or classical ketogenic precursors. Classical ketogenesis itself may drive adaptation and some of the functional benefits associated with ketosis. BDO is included in all of the KE compounds, but it is currently unknown how consumption of BDO alone, and its metabolism via non-classical ketogenesis acutely affects metabolism. Additionally, ketogenesis is now understood to occur in certain cells outside the liver with important local biological effects, for example ketogenesis driven by medium chain fatty acids has been reported in astrocytes in vitro. Provision of systemic BHB by a KE may elicit different biological effects in some tissues such as the brain versus promoting in situ ketogenesis in that tissue. Overall, not only are functional effects of KE incompletely defined, but also it is unknown which effects are common to all KE versus which are specific to an individual KE compound (i.e., BHB Monoester vs AcAc Diester) or which may be attributable to the BDO precursor common to all of the KE. This study will be the first comparative full crossover study of all available KE and the precursor BDO at two serving sizes. Outcomes will focus on established effects of the BHB Monoester (including the effects on ketones, glucose and acid-base balance) and compare these with the effects of the AcAc Diester, C8 Ketonef Diester and BDO.
Key Details
Gender
MALE
Age Range
20 Years - 30 Years
Study Type
INTERVENTIONAL
Enrollment
14
Start Date
2023-06-05
Completion Date
2027-09
Last Updated
2025-05-29
Healthy Volunteers
Yes
Conditions
Interventions
Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) \& 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at \~2- week intervals during the study. The sensor will be removed at the end of the final test day
DXA
Lean Body Mass will be assessed once via DXA
Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting \<1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis
Locations (1)
The Ohio State University
Columbus, Ohio, United States