Ketoses, Metabolic, Ketogenic Dieting, Alcohol Intoxication, Magnetic Resonance Imaging, Alcohol Drinking
Conditions
Keywords
Ketone supplement
Brief summary
The research study is being conducted in health controls to better understand the effects of ketosis on brain functioning after 3 different, randomly assigned, 3-day dietary interventions and the acute effects of alcohol after consuming about 4-5 alcohol beverages. The labs visits will use magnetic resonance imaging (MRI) scans to study the brain, measuring levels of nicotinamide adenine dinucleotide (NAD), lactate, neurotransmitters glutamate, and Gamma-aminobutyric acid (GABA).
Detailed description
The research study is being conducted to better understand the effects of ketosis on brain functioning and the acute effects of alcohol. Healthy participants will undergo three randomly assigned dietary interventions, each lasting three days, followed by a study lab visit day on day 4. The three interventions are: (1) Eat a ketogenic diet for 3 days, (2) eat a control diet for 3 days with a ketone supplement drink, and (3) eat a control diet for 3 days. The dietary interventions will be spaced 1 week apart. The ketone supplement drink "bis-octanoyl (R)-1,3-butanediol" (Kenetik: Ketone Drink, VitaNav Inc., Washington D.C.) 12.5g of ketones, TID PO (by mouth).) is a dietary supplement that has been extensively studied in humans and is designated by the FDA as Generally Recognized as Safe (GRAS). Its use in this study is experimental. On the day of the 3 labs visits days, magnetic resonance imaging (MRI) will be used to study the brain. Specifically, levels of nicotinamide adenine dinucleotide (NAD) (a coenzyme that is important for energy metabolism), lactate (a metabolite produced during energy metabolism), and neurotransmitters glutamate and GABA. Following the scans, participants will be provided a dose of alcohol that will elevate participants breath alcohol levels to approximately 0.08% to measure the acute effects of alcohol.
Interventions
DIETARY_SUPPLEMENTKetone Supplement
Ketone supplement 3x day with control diet for 3 days.
OTHERControl Diet
Control Diet breakfast, lunch, and dinner for 3 days.
OTHERKetogenic diet
Ketogenic Diet breakfast, lunch, and dinner for 3 days.
DRUGEthanol
After 3 days of diet intervention, participants will receive alcohol drinks that dose-adjusts for body weight and sex differences in pharmacokinetics and calculated to obtain a final breath alcohol concentration of 0.08%
Sponsors
University of Pennsylvania
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Three-way, open-labeled, crossover trial in which participants will undergo three alcohol tolerance tests, each following a 3-days dietary intervention: (1) control diet (\ 50% kcal carbohydrates), (2) ketogenic diet (\ 5-10% kcal carbohydrates), and (3) control diet with 3x daily administration of 10 g Ketone Supplement (KS) drink (30 g/day, Kenetik: ketone Drink, VitaNav Inc., Washington D.C.).
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Willingness to provide signed, informed consent and commit to completing study procedures. 2. Reported on at least one day in the month prior to consent of consuming 2 or more standard alcohol drinks on a single day.
Exclusion criteria
1. Unwilling or unable to refrain from use, within 24 hours of the alcohol lab procedures, psychoactive medications or medication that may affect study results. 2. Current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of any major psychiatric disorder (other than nicotine use disorders, or marijuana use disorders) as identified by clinical examination or structured interview that could interfere with study participation or make it hazardous for the subject. 3. Currently taking medication(s) that could interfere with study participation or make it hazardous for the subject to participate. (e.g. anticholinergics; antipsychotics; lithium; psychotropic drugs not otherwise specified) 4. Positive urine drug screen, positive for all substances but marijuana at screening or study visits (may be repeated once and if the result is negative on repeat, it is not exclusionary). 5. A current, clinically significant physical disease or abnormality on the basis of medical history, or routine laboratory evaluation that can impact brain function, the use of a ketone supplement, administration of ketogenic diet, or the use of alcohol (e.g., epilepsy, diabetes, irritable bowel syndrome, Crohn's disease, liver disease, kidney disease, kidney stones, chronic metabolic acidosis or a cardiomyopathy as determined by history and clinical exam). 6. Currently suffering from or has a history of stroke and/or stroke related spasticity. 7. Head trauma with loss of consciousness for more than 30 minutes or associated with skull fracture, inter-cranial bleeding or abnormal MRI (self-report, medical history). 8. Weight greater than 225lbs (Need to cap amount of alcohol given based on weight to individuals). 9. Females who are pregnant or breast-feeding 10. Contraindication to MRI, including presence of ferromagnetic objects, claustrophobia or fear of enclosed, medical conditions that prevent subjects from lying comfortably flat on his/ her back for up to 2 hrs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in breath alcohol concentration | 3 hours | Breath alcohol concentration measured in mg/L of air. The range is .000 to .400 g/L. Change in breath alcohol concentration, pre to post alcohol consumption after 3 day diet intervention during lab day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in motor agility tasks | 3 hours | Motor agility will be assessed with the grooved pegboard task, in which participants will place pegs onto a metal surface containing 25 keyhole-shaped holes that differ in orientation. Measured in seconds, range 0 to 5 minutes. Change in motor agility tasks pre to post alcohol consumption after 3 day diet intervention. |
| Change in cognitive performance tasks | 3 hours | Cognitive performance will be measured with a cued go/no-go task, in which participants will press a computer keyboard key in response to a "go" target and suppress the action in response to a "no-go" target. Measured in % correct responses 0-100. Pre to post alcohol consumption after 3 day diet intervention. |
Countries
United States
Contacts
CONTACTTimothy S Pond, MPH
PRINCIPAL_INVESTIGATORCorinde Wiers, Ph.D.
University of Pennsylvania
STUDY_DIRECTORHenry Kranzler, MD
University of Pennsylvania
STUDY_DIRECTORKyle Kampman, MD
University of Pennsylvania
Outcome results
None listed