Quantification of Ketosis After Intake of Coconut Oil and Caprylic Acid-With and Without Glucose-After a 12-hour Fast

Study Overview
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Brief Summary
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In a cross-over design, 15 participants, age 65-75, will be tested in six different arms in a randomised order. After a 12-hour fast participants will be served 2.5 dl coffee with 15 g cream + 30-50 g of different fatty acids, with or without 50 g glucose. Blood ketones and other biomarkers will be measured during 4 hours.

Detailed Description
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In the metabolic state ketosis, beta-hydroxybutyrate (BHB) and acetoacetate are synthesised from fatty acids in the liver, resulting in higher circulating levels. Ketosis can be induced by fasting or adherence to a low-carb-high-fat diet, but also by intake of-at least some-medium-chain-triglycerides (MCT). MCT are built from fatty acids with a chain of 6-12 carbon atoms. Caprylic acid (C8) is well known to be ketogenic, but the effect of lauric acid (C12)-constituting about 50% of coconut oil-is less clear. The aim of this study is to assess ketosis, as a combined effect of an extended overnight fast, and intake of coconut oil or C8, and to study how ketosis is affected by simultaneous glucose intake. Sunflower oil is used as control, expected to not break fasting ketosis, although not being ketogenic in itself. Some sunflower oil is also added to C8 to make that arm isocaloric with coconut oil, with a roughly similar proportion of MCT. Coffee with cream will be used as a vehicle, and although coffee has been reported to be mildly ketogenic, this effect is expected to be negligible and equally distributed between arms.

Official Title
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Quantification of Ketosis After Intake of Coconut Oil and Caprylic Acid-With and Without Glucose-After a 12-hour Fast: A 6-way Cross-over Study in Healthy Older Adults

Conditions
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Aged

Intervention / Treatment
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* Other: Coconut oil
* Dietary Supplement: Caprylic acid
* Other: Sunflower oil
* Other: Glucose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Daily consumption of coffee Written informed consent Exclusion Criteria: Smoker Weight <50 kg Diagnosed diabetes History of heart disease History of disease related to internal organs or metabolism Experience of sensitive gut, or known intolerance to the test ingredients Medication expected to affect glucose- or lipid-metabolism Fasting during study or one month before High intensity physical activity > 3 times/week Dementia Severe psychiatric conditions Hb<125 g/L Participation in other lifestyle intervention last 6 months

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. Sunflower oil<br>Sunflower oil (30 g) | Other: Sunflower oil<br>* Sunflower oil given in coffee with cream<br>|
| Experimental: 2. Caprylic acid<br>Caprylic acid (20 g) + Sunflower oil (10 g) | Dietary Supplement: Caprylic acid<br>* Caprylic acid given in coffee with cream<br>Other: Sunflower oil<br>* Sunflower oil given in coffee with cream<br>|
| Experimental: 3. Caprylic acid + Glucose<br>Caprylic acid (20 g) + Sunflower oil (10 g) + Glucose (50 g) | Dietary Supplement: Caprylic acid<br>* Caprylic acid given in coffee with cream<br>Other: Sunflower oil<br>* Sunflower oil given in coffee with cream<br>Other: Glucose<br>* Glucose dissolved in water<br>|
| Experimental: 4. Coconut oil<br>Coconut oil (30 g) | Other: Coconut oil<br>* Coconut oil given in coffee with cream<br>|
| Experimental: 5. Coconut oil + Glucose<br>Coconut oil (30 g) + Glucose (50 g) | Other: Coconut oil<br>* Coconut oil given in coffee with cream<br>Other: Glucose<br>* Glucose dissolved in water<br>|
| Experimental: 6. Coconut oil + Caprylic acid<br>Coconut oil (30 g) + Caprylic acid (20 g) | Other: Coconut oil<br>* Coconut oil given in coffee with cream<br>Dietary Supplement: Caprylic acid<br>* Caprylic acid given in coffee with cream<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of BHB, area under the curve, 0-4 h | BHB, measured in venous whole blood with a point-of-care meter | 0, 15, 30, 45, 60, 75, 90, 120, 150, 180, 210, 240 (minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of total ketones | BHB + acetoacetate, laboratory analyses from plasma | 0, 30, 60, 120 (minutes) | 
| Concentrations of BHB (capillary) | BHB, measured in capillary whole blood with a point-of-care meter, for exploratory comparisons. (not measured in arm 3 & 5) | 30, 60, 120 (minutes) | 
| Concentrations of BDNF / pro-BDNF | Brain-derived neurotrophic factor (BDNF) & pro-BDNF in serum (not measured in arm 2, 3 & 5) | 0, 60, 120, 240 (minutes) | 
| Concentrations of glucose | Glucose, laboratory analysis | 0, 60, 120, 180, 240 (minutes) | 
| Self-rated satiety | Assessed by a 5-grade categorical hunger-scale in a questionnaire at the end of each testing session. Participants will be instructed to choose the most suitable description of their hunger: Not hungry at all. Modestly hungry. Lunch can wait. It feels like the right time for lunch. Hunger appeared during the last hour. Very hungry. Hunger appeared during the last hour. Hungry or very hungry. Hunger has been palpable for more than one hour. Answers a, b & c will be interpreted as sufficient satiety. | 240 (minutes) | 
| Self-rated tolerance of beverage | Assessed by a 4-grade categorical scale in a questionnaire at the end of each testing session: Did you experience any inconvenience (i.e. nausea, upset stomach), which you attribute to the beverage you were served today? No Yes, minor inconvenience. Yes, moderate inconvenience. Yes, major inconvenience. If the answer is b, c or d participants are asked to give a short description. | 240 (minutes) |