Impact of Exogenous Ketones on Indices of Keto-Adaptation in Obese Subjects on Weight Reducing Diets.

NCT ID: NCT06449287

Last Updated: 2024-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-05

Study Completion Date

2019-08-21

Brief Summary

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This project will be a three-group controlled 6-wk feeding study where all meals are prepared and provided to obese participants. All participants will be fed a 25% energy-restricted diet. Two diets will be very low in carbohydrate (i.e., ketogenic diets) designed to induce nutritional ketosis and fat loss. Another diet will be low in fat and saturated fat but contain the same total calories. Participants will be randomly assigned to a Ketone Supplement group who are provided an exogenous pre-formed source of beta-hydroxybutyrate (BOHB) or a Control group that only receives the standard ketogenic diet. Randomization will be stratified based on insulin resistance, sex, and body composition to ensure balanced group assignment. Because of timing of recruitment (i.e., after most of the ketogenic groups have already completed the study), the low-fat group will not be randomized. Outcome measurements will be made at various intervals over the 6-wk intervention.

Detailed Description

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This project will be a three-group controlled 6-wk feeding study where all meals are prepared and provided to obese participants. All participants will be fed a 25% energy-restricted diet. Two diets will be very low in carbohydrate (i.e., ketogenic diets) designed to induce nutritional ketosis and fat loss. Another diet will be low in fat and saturated fat but contain the same total calories. Participants will be randomly assigned to a Ketone Supplement group (n=12) who are provided an exogenous pre-formed source of beta-hydroxybutyrate (BOHB) or a Control group (n=12) that only receives the standard ketogenic diet. Randomization will be stratified based on insulin resistance, sex, and body composition to ensure balanced group assignment. Because of timing of recruitment (i.e., after most of the ketogenic groups have already completed the study), the low-fat group will not be randomized. Outcome measurements will be made at various intervals over the 6-wk intervention. Key outcome variables will include: 1) Markers of Ketosis/Keto-Adaptation: a. Daily measures of BOHB (capillary blood) b. Fasting serum BOHB and total ketones (venous blood) c. Diurnal capillary blood ketones and urinary loss of BOHB and total ketones 2) Energy Balance and Body Composition: a. Body mass (scale) b. Whole body and regional composition (DXA) c. Nitrogen balance (daily nitrogen intake - 24-hr urinary nitrogen loss) d. Resting energy expenditure and substrate oxidation (indirect calorimetry) e. Adiposity (myocardial/epicardial fat, liver fat, visceral fat, skeletal muscle fat by MRI) f. Microbiome (stool collection to observe microbiota and the response to diet alteration) 3) Cognitive and Behavioral: a. Computer-based cognitive function (ANAM) b. Behavioral responses (surveys) 4) Cardio-Metabolic Risk: a. Metabolic panel b. Circulating lipid panel (total cholesterol, LDL-C, HDL-C, TG) c. Glucose, insulin, HOMA

Conditions

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Ketogenic Diet Weight Loss

Keywords

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ketones metabolism weight loss

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Ketogenic Diet

Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans.

Group Type EXPERIMENTAL

Diet

Intervention Type OTHER

The diet intervention will start after all baseline testing is complete

Blood Draw

Intervention Type BIOLOGICAL

Blood samples will be collected biweekly.

Ketone/Glucose Monitoring

Intervention Type BIOLOGICAL

Hand-held glucometer will be used daily to monitor dietary intervention adherence.

Body Composition

Intervention Type OTHER

DEXA Scanning will be done pre-, mid-, and post- intervention.

Urine Analysis

Intervention Type BIOLOGICAL

24 hour urine collection will be done biweekly.

Neuropsychological Measures - ANAM

Intervention Type BEHAVIORAL

The first cognitive assessment will be done via Automated Neuropsychological Assessment Metrics (ANAM). This cognitive battery is a library of computer-based tests of domains including attention, concentration, reaction time, memory, processing speed, decision-making, and executive function.

Ketogenic Diet + Ketone Salt

Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans. This group will also be provided a ketone salt supplement to take x2 daily.

Group Type EXPERIMENTAL

Diet

Intervention Type OTHER

The diet intervention will start after all baseline testing is complete

Blood Draw

Intervention Type BIOLOGICAL

Blood samples will be collected biweekly.

Ketone/Glucose Monitoring

Intervention Type BIOLOGICAL

Hand-held glucometer will be used daily to monitor dietary intervention adherence.

Body Composition

Intervention Type OTHER

DEXA Scanning will be done pre-, mid-, and post- intervention.

Urine Analysis

Intervention Type BIOLOGICAL

24 hour urine collection will be done biweekly.

Neuropsychological Measures - ANAM

Intervention Type BEHAVIORAL

The first cognitive assessment will be done via Automated Neuropsychological Assessment Metrics (ANAM). This cognitive battery is a library of computer-based tests of domains including attention, concentration, reaction time, memory, processing speed, decision-making, and executive function.

Low Fat Diet +Placebo

The low-fat comparison group will also be provided all their food. Their diet will also be restricted in calories and have the same level of protein, but it will be lower in fat and higher in carbohydrate. The low-fat diet will consist of approximately 25% fat, with the remaining calories coming from carbohydrates (approximately 55% after accounting for protein at around 20%). Added sugars will be kept relatively low (less than 25 g/day) with a focus on unprocessed carbohydrate-rich foods. Saturated fat will be limited to less than 10% of total energy, with a focus on unsaturated fat sources.

Group Type ACTIVE_COMPARATOR

Diet

Intervention Type OTHER

The diet intervention will start after all baseline testing is complete

Blood Draw

Intervention Type BIOLOGICAL

Blood samples will be collected biweekly.

Ketone/Glucose Monitoring

Intervention Type BIOLOGICAL

Hand-held glucometer will be used daily to monitor dietary intervention adherence.

Body Composition

Intervention Type OTHER

DEXA Scanning will be done pre-, mid-, and post- intervention.

Urine Analysis

Intervention Type BIOLOGICAL

24 hour urine collection will be done biweekly.

Neuropsychological Measures - ANAM

Intervention Type BEHAVIORAL

The first cognitive assessment will be done via Automated Neuropsychological Assessment Metrics (ANAM). This cognitive battery is a library of computer-based tests of domains including attention, concentration, reaction time, memory, processing speed, decision-making, and executive function.

Interventions

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Diet

The diet intervention will start after all baseline testing is complete

Intervention Type OTHER

Blood Draw

Blood samples will be collected biweekly.

Intervention Type BIOLOGICAL

Ketone/Glucose Monitoring

Hand-held glucometer will be used daily to monitor dietary intervention adherence.

Intervention Type BIOLOGICAL

Body Composition

DEXA Scanning will be done pre-, mid-, and post- intervention.

Intervention Type OTHER

Urine Analysis

24 hour urine collection will be done biweekly.

Intervention Type BIOLOGICAL

Neuropsychological Measures - ANAM

The first cognitive assessment will be done via Automated Neuropsychological Assessment Metrics (ANAM). This cognitive battery is a library of computer-based tests of domains including attention, concentration, reaction time, memory, processing speed, decision-making, and executive function.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* BMI \>27 and =35 kg/m2

Exclusion Criteria

* have diabetes, liver, kidney, or other metabolic or endocrine dysfunction, or using diabetic medications.
* Currently consuming a low-carbohydrate diet
* Weight loss of \>10% in past 6 months -Currently pregnant or nursing, or planning to become pregnant during the study
* Major psychiatric disorder (e.g., schizophrenia, bipolar disorder)
* Excessive alcohol intake (acute or chronic) defined as average consumption of 3 or more alcohol-containing beverages daily or consumption of more than 14 alcoholic beverages per week
Minimum Eligible Age

21 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Ohio State University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeff Volek, PhD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

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The Ohio State University

Columbus, Ohio, United States

Site Status

Countries

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United States

References

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Kackley ML, Brownlow ML, Buga A, Crabtree CD, Sapper TN, O'Connor A, Volek JS. The effects of a 6-week controlled, hypocaloric ketogenic diet, with and without exogenous ketone salts, on cognitive performance and mood states in overweight and obese adults. Front Neurosci. 2022 Sep 30;16:971144. doi: 10.3389/fnins.2022.971144. eCollection 2022.

Reference Type RESULT
PMID: 36248655 (View on PubMed)

Belany P, Kackley ML, Zhao S, Kluwe B, Buga A, Crabtree CD, Nedungadi D, Kline D, Brock G, Simonetti OP, Volek JS, Joseph JJ. Effects of Hypocaloric Low-Fat, Ketogenic, and Ketogenic and Ketone Supplement Diets on Aldosterone and Renin. J Clin Endocrinol Metab. 2023 Jun 16;108(7):1727-1739. doi: 10.1210/clinem/dgad009.

Reference Type RESULT
PMID: 36629058 (View on PubMed)

Buga A, Kackley ML, Crabtree CD, Bedell TN, Robinson BT, Stoner JT, Decker DD, Hyde PN, LaFountain RA, Brownlow ML, O'Connor A, Krishnan D, McElroy CA, Kraemer WJ, Volek JS. Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts. Clin Nutr ESPEN. 2023 Apr;54:277-287. doi: 10.1016/j.clnesp.2023.01.030. Epub 2023 Feb 4.

Reference Type RESULT
PMID: 36963874 (View on PubMed)

Other Identifiers

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2017H0395

Identifier Type: -

Identifier Source: org_study_id