Variations in Ketone Metabolism
STAK-VKM
Strategies to Augment Ketosis- Variations in Ketone Metabolism
2 other identifiers
interventional
400
1 country
2
Brief Summary
This outcome of this study will elucidate how the phenotype of the individual modulates the KE metabolic effect. Most studies of KE have been in homogenous populations, usually young, male athletes. However, two striking experiments using identical, body weight adjusted KE doses in healthy and obese individuals found that BHB area under the curve (AUC) and removal was reduced by obesity and poor metabolic health. Similarly, ketone infusion experiments found that diabetes, obesity, and insulin resistance alter BHB metabolism. It is important to determine how obesity affects KE 'sensitivity' (i.e., breakdown and oxidation) because the increasing prevalence of obesity as a function of age. Age may be another important source of variation in ketone metabolism. The genes that control the ketone system are regulated by a cascade of transcription factors and hormones including PPARα and FGF21, which are themselves known to be affected by aging and dietary status, and the cellular protein sensor target of rapamycin (TOR). Aberrant hyperactivation of TOR with aging may reduce ketogenesis, while it was observed that a long-term ketogenic diet specifically up-regulated PPARα activity. Preliminary work revealed substantial changes across mouse lifespan in the expression of ketone-related genes in the liver such as Hmgcs2 (rate limiting for ketone production) and Bdh1 (rate limiting for BHB oxidation) between young, middle-aged, and old mice, with a nadir of gene expression in middle age before increasing again late in life. Substantial age differences were found in response to matched doses of oral KE in mice and in rats. These data may have important implications for treating people of different ages and for translating KE technologies into the Department of VA. Therefore, this project plans to study individual responses to KE ingestion across the lifespan, against the background of varying metabolic health
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Jun 2023
Longer than P75 for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 20, 2023
CompletedStudy Start
First participant enrolled
June 20, 2023
CompletedFirst Posted
Study publicly available on registry
June 29, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2027
ExpectedMay 29, 2025
May 1, 2025
2.5 years
June 20, 2023
May 28, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Capillary d-BHB
Difference in ketone appearance across metabolic statuses
4 hours
Secondary Outcomes (5)
Ketone Excretion
up to ~5 hours
Satiety Visual Analogue Scale
Up to 4 hours
Beverage tolerability questionnaire (BTQ)
up to 4 hours
Insulin
up to 4 hours
Capillary glucose concentrations
up to 5 hours
Study Arms (1)
C8 Ketone Supplement
EXPERIMENTAL360mg/kg of supplement will be given on a singular testing day.
Interventions
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
IV cannula will be inserted at the start of Test Day, and removed at the end of Test Day. Blood samples will be collected at 7 timepoints (possibly 1 more). Cannula will be flushed with a small volume of saline after each sample to maintain patency.
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
Eligibility Criteria
You may qualify if:
- Ages 20 - 70 years
- Participant is willing and able to comply with all study procedures including the following prior to Test Day: fasting (\>10 h; water only), no alcohol (\>24 h), no exercise (\>24 h), no acute illness and controlled feeding before the Test Day, maintain diet, exercise, medication, and supplement habits throughout the study.
- Participant has no health conditions that would prevent completion of the study requirements as judged by the Investigator based on health history.
- Participant understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Investigator.
You may not qualify if:
- Participant follows a low-carbohydrate diet (\<30% energy from carbohydrate) or have used exogenous ketone supplements within 4-months of study participation.
- Participant has a Primary Care Physician diagnosed history or presence of uncontrolled and/or clinically important hypertension (blood pressure \>150/95 mmHg), pulmonary, cardiac, hepatic, renal, endocrine (including type 1 and 2 diabetes), hematologic, immunologic, neurologic (e.g., Alzheimer's or Parkinson's diseases), psychiatric (including unstable depression and/or anxiety disorders) or biliary disorders.
- Participant has a known allergy, intolerance, or sensitivity to any of the ingredients in the study beverages, including soy and milk protein, wheat, shellfish, fin fish, eggs, tree nuts or peanuts (production facility handles nuts).
- Participant has unstable use of a medication or supplement that the Investigator considers may affect the outcomes of the trial.
- Consumption of alcohol more than 3 drinks per day or more than 18 drinks per week.
- Consumption of tobacco.
- Consumption of cannabis.
- Participant is currently in another research study or has been in the 14 days before screening.
- Participant has had a blood draw or donation in the last 8 weeks.
- Participant has a clinically important gastrointestinal (GI) condition that would potentially interfere with the evaluation of the study beverage \[e.g., inflammatory bowel disease, irritable bowel syndrome, chronic constipation, severe constipation (in the opinion of the Investigator), history of frequent diarrhea, history of surgery for weight loss, gastroparesis, systemic disease that might affect gut motility according to the Investigator, medication managed reflux and/or clinically important lactose intolerance\].
- Participant has a condition the Investigator believes would interfere with his ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results, or put the participant at undue risk.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ohio State Universitylead
- Buck Institute for Research on Agingcollaborator
Study Sites (2)
The Buck Institute
Novato, California, 94945, United States
The Ohio State University
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jeff Volek, PhD
Ohio State University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 20, 2023
First Posted
June 29, 2023
Study Start
June 20, 2023
Primary Completion
January 1, 2026
Study Completion (Estimated)
January 1, 2027
Last Updated
May 29, 2025
Record last verified: 2025-05