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

NCT06449287 | Completed

• 1 other identifier: 2017H0395
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ketogenic Diet; Weight Loss

Keywords

ketones; metabolism; weight loss

Outcome Measures

Primary Outcomes (6)

• Daily Ketone/Glucose Monitoring

  Daily fasting glucose/ketones will be assessed using capillary finger stick lancing. A small drop of blood will be obtained once daily, while fasting, using enzymatic strips fitted for a handheld analyzer (KetoMojo). All the data will be stored in the device's internal memory.

  Up to 6 weeks

• Cholesterol (mg/dl)

  Fasting venous blood will be collected biweekly to measure cholesterol.

  up to six weeks

• Insulin (mIU/L)

  Fasting venous blood will be collected biweekly.

  up to six weeks

• Glucose (mg/dL)

  Fasting venous blood will be collected biweekly.

  up to six weeks

• Lean Mass (kg)

  DEXA Scanning will be biweekly to assess lean mass

  up to six weeks

• Fat Mass (kg)

  DEXA Scanning will be biweekly to assess fat mass

  up to six weeks

Secondary Outcomes (4)

• Neuropsychological Outcome 1 - Reaction time (Throughput)

  up to six weeks

• Neuropsychological Outcome 1 - Visual Short Term Memory (Throughput)

  up to six weeks

• Neuropsychological Outcome 1 - Spatial Processing (Throughput)

  up to six weeks

• Urine Chemistries

  up to 6 weeks

Study Arms (3)

Ketogenic Diet

EXPERIMENTAL

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.

Other: Diet; Biological: Blood Draw; Biological: Ketone/Glucose Monitoring; Other: Body Composition; Biological: Urine Analysis; Behavioral: Neuropsychological Measures - ANAM

Ketogenic Diet + Ketone Salt

EXPERIMENTAL

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.

Other: Diet; Biological: Blood Draw; Biological: Ketone/Glucose Monitoring; Other: Body Composition; Biological: Urine Analysis; Behavioral: Neuropsychological Measures - ANAM

Low Fat Diet +Placebo

ACTIVE COMPARATOR

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.

Other: Diet; Biological: Blood Draw; Biological: Ketone/Glucose Monitoring; Other: Body Composition; Biological: Urine Analysis; Behavioral: Neuropsychological Measures - ANAM

Interventions

Diet OTHER

The diet intervention will start after all baseline testing is complete

Ketogenic Diet; Ketogenic Diet + Ketone Salt; Low Fat Diet +Placebo

Blood Draw BIOLOGICAL

Blood samples will be collected biweekly.

Ketogenic Diet; Ketogenic Diet + Ketone Salt; Low Fat Diet +Placebo

Ketone/Glucose Monitoring BIOLOGICAL

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

Ketogenic Diet; Ketogenic Diet + Ketone Salt; Low Fat Diet +Placebo

Body Composition OTHER

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

Ketogenic Diet; Ketogenic Diet + Ketone Salt; Low Fat Diet +Placebo

Urine Analysis BIOLOGICAL

24 hour urine collection will be done biweekly.

Ketogenic Diet; Ketogenic Diet + Ketone Salt; Low Fat Diet +Placebo

Neuropsychological Measures - ANAM 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; Ketogenic Diet + Ketone Salt; Low Fat Diet +Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI \>27 and =35 kg/m2

You may not qualify if:

• 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

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (3)

• 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.

  PMID: 36248655 RESULT

• 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.

  PMID: 36629058 RESULT

• 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.

  PMID: 36963874 RESULT

MeSH Terms

Conditions

Weight Loss; Ketosis

Interventions

Diet; Blood Specimen Collection; Ketones; Body Composition; Urinalysis

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Organic Chemicals; Biochemical Phenomena; Chemical Phenomena; Metabolism; Body Constitution; Clinical Chemistry Tests; Diagnostic Techniques, Urological

Study Officials

• Jeff Volek, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 10, 2024
• Study Start: July 5, 2018
• Primary Completion: March 1, 2019
• Study Completion: August 21, 2019
• Last Updated: December 19, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)