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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1. Sunflower oil | Experimental | Sunflower oil (30 g) |
|
| 2. Caprylic acid | Experimental | Caprylic acid (20 g) + Sunflower oil (10 g) |
|
| 3. Caprylic acid + Glucose | Experimental | Caprylic acid (20 g) + Sunflower oil (10 g) + Glucose (50 g) |
|
| 4. Coconut oil | Experimental | Coconut oil (30 g) |
|
| 5. Coconut oil + Glucose | Experimental | Coconut oil (30 g) + Glucose (50 g) |
|
| 6. Coconut oil + Caprylic acid | Experimental | Coconut oil (30 g) + Caprylic acid (20 g) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Coconut oil | Other | Coconut oil given in coffee with cream |
|
| 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) |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Concentrations of insulin | Not measured at minutes 60, 90 & 120 in arm 1, 2, 4, 6 | 0, 60, 90, 120, 240 (minutes) |
| Concentrations of glucagon | Not measured at minutes 60, 90 & 120 in arm 1, 2, 4, 6 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Miia Kivipelto, Professor | Karolinska Institutet | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karolinska Institutet | Solna | Stockholm County | 17176 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34489682 | Derived | Norgren J, Daniilidou M, Kareholt I, Sindi S, Akenine U, Nordin K, Rosenborg S, Ngandu T, Kivipelto M, Sandebring-Matton A. Serum proBDNF Is Associated With Changes in the Ketone Body beta-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF: Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults. Front Aging Neurosci. 2021 Aug 20;13:716594. doi: 10.3389/fnagi.2021.716594. eCollection 2021. | |
| 32351966 |
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| ID | Term |
|---|---|
| D000074263 | Coconut Oil |
| C031492 | octanoic acid |
| D000074242 | Sunflower Oil |
| D005947 | Glucose |
| ID | Term |
|---|---|
| D004041 | Dietary Fats |
| D005223 | Fats |
| D008055 | Lipids |
| D010938 | Plant Oils |
| D009821 |
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|
| Caprylic acid | Dietary Supplement | Caprylic acid given in coffee with cream |
|
| Sunflower oil | Other | Sunflower oil given in coffee with cream |
|
| Glucose | Other | Glucose dissolved in water |
|
| 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:
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?
If the answer is b, c or d participants are asked to give a short description. | 240 (minutes) |
| 0, 60, 90, 120, 240 (minutes) |
| Concentrations of HbA1c | Only measured at the first testing session | 0 (minutes) |
| Derived |
| Norgren J, Sindi S, Sandebring-Matton A, Kareholt I, Daniilidou M, Akenine U, Nordin K, Rosenborg S, Ngandu T, Kivipelto M. Ketosis After Intake of Coconut Oil and Caprylic Acid-With and Without Glucose: A Cross-Over Study in Healthy Older Adults. Front Nutr. 2020 Apr 15;7:40. doi: 10.3389/fnut.2020.00040. eCollection 2020. |
| Oils |
| D028321 | Plant Preparations |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
| D002241 | Carbohydrates |