Metabolic Differences of an Oral and Intravenous Dose of 3-hydroxybutyrate (3-OHB).

Study Overview
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Brief Summary
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An open-labeled intervention study testing healthy, lean, and male volunteers on two separate occasions: blood sampling after consuming 36 gram 3-Hydroxybutyrate (3-OHB) salt. blood sampling while given a variable rate of 3-OHB salt intravenously to replicate the concentrations seen during oral consumption. The primary outcome is differences in insulin concentrations (incremental AUC) 180 minutes after 3-OHB consumed orally vs. intravenously. Secondary outcomes includes iAUC for other gastrointestinal hormones and substrates (Glucagon, GLP-1, GIP, glucose, and 3-OHB) Gastric emptying will be evaluated using 1500 mg Paracetamol consumption before each intervention day. Urine will be analyzed for ketone concentrations/excretion rates.

Detailed Description
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An open-labeled intervention study testing healthy, lean, and male volunteers on two separate occasions with at least 48 hours apart. blood sampling after consuming 36 gram 3-Hydroxybutyrate (3-OHB) salt. blood sampling while given a variable rate of 3-OHB salt intravenously to replicate the concentrations seen during oral consumption. The primary outcome is differences in insulin concentrations (incremental AUC) 180 minutes after 3-OHB consumed orally vs. intravenously. Secondary outcomes includes iAUC for other gastrointestinal hormones and substrates (Glucagon, GLP-1, GIP, glucose, and 3-OHB) Gastric emptying will be evaluated using 1500 mg Paracetamol consumption before each intervention day. Urine will be analyzed for ketone concentrations/excretion rates.

Official Title
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Metabolic Differences of an Oral and Intravenous Dose of 3-hydroxybutyrate (3-OHB).

Conditions
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Healthy, Incretin Effect, Ketosis

Intervention / Treatment
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* Dietary Supplement: 3-OHB salt (NaCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy 19<BMI<30 written og oral consent No allergies to paracetamol Exclusion Criteria: Chronic disease or daily medical treatment Daily intake of ketones or ketogenic diets Speaks and understands Danish Screening blood sample abnormalities

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3-OHB orally<br>36 gram 3-OHB salt consumed orally | Dietary Supplement: 3-OHB salt (NaCl)<br>* 36 gram 3-OHB salt diluted in 500 ml sterile water<br>|
| Active Comparator: 3-OHB intravenously<br>Variable amounts of 3-OHB salt given i order to replicate the same individual plasma concentrations measured during the experimental arm. | Dietary Supplement: 3-OHB salt (NaCl)<br>* 36 gram 3-OHB salt diluted in 500 ml sterile water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma insulin | incremental area under the curve (iAUC) for plasma insulin concentrations {pmol/l} | 180 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Glucagon | iAUC and concentrations of (Glucagon {pg/ml} | 180 minutes | 
| Gastric emptying | Paracetamol test, 1500 mg following interventions and measuring plasma paracetamol {micromol/l} | 180 minutes | 
| Urine 3-OHB | Excretion rates {gram/hour} will be estimated as = urine output {L} x urine 3-OHB concentration {mmol/l} x 0.1041 {g/mmol}/180 minutes | 180 minutes | 
| Plasma GLP1 | iAUC and concentrations of GLP-1 {pmol/l}, | 180 minutes | 
| Plasma GIP | iAUC and concentrations of GIP {pmol/l}, | 180 minutes | 
| Plasma glucose | iAUC and concentrations of glucose {mmol/l}, | 180 minutes | 
| Plasma free fatty acids | iAUC and concentrations of free fatty acids {mmol/l}, | 180 minutes | 
| Plasma 3-OHB | iAUC and concentrations of 3-OHB {mmol/l}) | 180 minutes | 
| Plasma Ghrelin | iAUC and concentrations of Ghrelin {ng/l}) | 180 minutes | 
| Plasma PYY | iAUC and concentrations of PYY {pg/ml}) | 180 minutes | 
| height | height {meters} | at time 0 minutes | 
| weight | weight {kg} | at time 0 minutes | 
| BMI | Body mass index = weight/height^2 | time 0 minutes | 
| Blood pressure | Arm blood pressure | time 0 minutes and 180 minutes | 
| Satiety questionnaire (Blundell et al. 2010) | VAS/NRS-score of hunger, fullness, satiety, desire, and prospective consumption | At 0, 60, 120, and 180 minutes | 
| Ad libitum food intake | gram (and kcal) intake of an ad libitum meal (sandwich) | at time = 180 minutes |