MCT Oil SupplementationNCT03460444
The Effect of Raising Ketones Directly With MCT Oil on Inflammation in Healthy Young Adults
A study testing MCT Oil Supplementation in people with MCT Oil Supplementation, run by University of British Columbia at 1 site in Canada.
Trial summary
Ketogenic diets are gaining support as a method to lower inflammation within the body, but studies have not been able to show the way by which this occurs. Ketones, which are molecules made by the body as a source of energy during carbohydrate restriction, have been shown to have the ability to alter the number and… Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- MCT Oil Supplementation
- What is being tested?
- MCT Oil Supplementation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 20 Mar 2018to 4 Feb 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI between 18.5-29.9 kg/m^2
- Females only: have a regular 28-35 day menstrual cycle
Who cannot join
- Diagnosed metabolic disorder such as diabetes, metabolic syndrome, hypothyroidism, or any other condition known to affect metabolism;
- history of inflammatory disorders such as Rheumatoid Arthritis, Crohn's Disease, Irritable Bowel Syndrome
- Prescribed any anti-inflammatory medication cannot be avoided for the duration of the study;
- current consumption of a very low-carbohydrate diet (e.g., "Atkins", "Protein Power Plan", "Paleo diet", etc.) or have within the previous three months;
- adhere to dietary restrictions such as vegetarianism or veganism;
- unable to abstain from drugs (prescription and recreational) or alcohol for the duration of the study;
- competitive athlete (currently training for an elite sport).
Trial locations and contacts
1 site in 1 country.
Canada1 site
University of British Columbia, Okanagan.
Kelowna, British Columbia, V1V 1V7
About this study
Official title: Impact of Raising B-OHB Directly With MCT Oil on NLPR3 Inflammasome Activation in Healthy, Young Adults
Ketogenic diets are gaining support as a method to lower inflammation within the body, but studies have not been able to show the way by which this occurs. Ketones, which are molecules made by the body as a source of energy during carbohydrate restriction, have been shown to have the ability to alter the number and types of messages that immune cells send to each other, and thus have the potential to lower inflammation. To determine whether raising ketones independent of diet reduce inflammation, 20 healthy, young men and women will follow a 14-day "normal" diet combined with MCT oil supplements. Based on previous research, the investigators expect that raising ketones will reduce immune cell pro-inflammatory signaling.
Read the detailed description
The potential for a ketogenic diet to reduce inflammation has become increasingly popular in recent years, but direct scientific evidence to demonstrate that ketones impact inflammatory mechanisms in humans does not exist. B-hydroxybutyrate (B-OHB) is the most abundant circulating ketone and recent evidence indicates that B-OHB may be able to act as a direct signal to inhibit cellular pathways involved in inflammation.
B-OHB can be raised naturally by induction of nutritional ketosis, which is a normal physiological response to severe reductions in carbohydrate or caloric intake. In this state, free fatty acids are converted to ketone bodies (primarily B-hydroxybutyrate [B-OHB]) by the liver in order to provide essential fuel for metabolically active tissues. However, determining the direct effects of B-OHB in human ketogenic diet studies is difficult due to the numerous metabolic adaptations that occur in nutritional ketosis (e.g., reduced insulin, elevated free fatty acids, stable glucose) and the propensity for participants to lose body and fat mass over longer period.
B-OHB can also be raised independent of diet by supplementation with medium chain triglyceride (MCT) oil, allowing for induction of ketosis without the additional metabolic adaptations. In addition to being an important fuel source, recent interest has focused on a potential signaling role for B-OHB with cell culture and animal studies describing anti-inflammatory, anti-oxidant, and anti-cancer effects. The cellular pathways through which B-OHB is proposed to reduce inflammation, include the NLPR3 inflammasome and histone deacetylases (HDACs), both of which play important roles in regulating cellular inflammation. The NLRP3 inflammasome pathway is an immune complex which, upon activation, initiates downstream pro-inflammatory cascades including the activation of caspase-1 and interleukin (IL)-1B. These pro-inflammatory cascades have been implicated in the propagation of sterile inflammation, which has been identified as a major contributor to certain chronic inflammatory diseases such as type 2 diabetes and atherosclerosis. HDACs are enzymes typically found within the nucleus and have the ability to regulate signaling through innate immune pathways. B-OHB has been shown to have the ability to inhibit HDACs, and consequently has the potential to decrease oxidative stress and inflammation. The NLRP3 inflammasome and HDACs are responsive to the intracellular nutritional milieu and thus their activity may be able to be modulated through increases in B-OHB.
The use of MCT oil supplements will allow the investigators to raise blood B-OHB independent of diet, and thus directly test the immunomodulatory effects of B-OHB in healthy, adult males. This fundamental research is needed to understand whether ketones have direct immunomodulatory effects or if it is the widespread systemic metabolic adaptation to a ketogenic diet that might impact inflammatory processes.
The overall objective of this pilot study is to determine if directly raising B-OHB through supplementation with MCT oil impacts innate immune cell function and/or phenotype. Based on previous cell culture and animal research showing that B-OHB can reduce pro-inflammatory signaling, it is hypothesized that raising B-OHB with MCT oil supplementation will result in a attenuation of caspase-1 activation and mature IL-1B secretion, both markers of NLRP3 inflammasome activation. Additionally, it is hypothesized that raised B-OHB will result in greater histone acetylation, as B-OHB has been shown to be an HDAC inhibitor.
- Conditions
- MCT Oil Supplementation
- Being tested
- MCT Oil Supplementation
- Keywords
- NLR Family, Pyrin Domain-Containing 3 Protein, Caspase 1, 3-Hydroxybutyric Acid, Histone Deacetylase Inhibitors, MCT Oil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MCT Oil SupplementationDietary supplement
Participants consume MCT oil (97-99% octanoic acid) twice per day for 14 days. Dosing will begin at 5ml/dose for Days 1-2, 10ml for Days 3-4, and 15ml for the remainder of the intervention.
| Study group | Role | What they receive |
|---|---|---|
| MCT Oil Supplementation | Experimental | Participants consume MCT oil (97-99% octanoic acid) twice per day for 14 days while consuming a diet similar to the recommended health guidelines (40-50% carbohydrate; 30-40% fat; 20-25% protein). Receives: Dietary Supplement: MCT Oil Supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline Caspase-1 Activation at 14 days
Caspase-1 activation will be quantified by flow cytometry. The fluorescent inhibitor probe FAM-YVAD-FMK binds covalently to activated caspase-1 and emits at 530nm.
Measured: Measured the day before the first dose of MCT oil (baseline) and the last day of the 14 day trial (post).
Secondary outcomes (3)
Change from Baseline Histone H3 Acetylation at 14 days
Histone H3 acetylation status will be quantified by flow cytometry using the conjugated acetyl-histone H3 antibody specific for Lys9 (Pacific Blue 455) and the conjugated acetyl-histone H3 antibody specific for Lys14 (Alexa Fluor 488).
Measured: Measured the day before the first dose of MCT oil (baseline) and the last day of the 14 day trial (post).
Change from Baseline Interleukin(IL)-1beta at 14 days
Mature IL-1beta secretion will be quantified by enzyme-linked immunosorbent assay run in duplicate.
Measured: Measured the day before the first dose of MCT oil (baseline) and the last day of the 14 day trial (post).
Change from Baseline Blood beta-hydroxybutyrate at 14 days
Blood beta-hydroxybutyrate will be quantified in whole blood using FreeStyle Precision Blood β-Ketone Test Strips (Abbott, Abbot Park, IL, USA) with the FreeStyle Precision Neo Blood Ketone Monitoring System (Abbott).
Measured: Measured the day before the first dose of MCT oil (baseline), 1 and 2 hours after each meal on Day 1, 2, 13, and 14, as well as once every 2 days at a time which is convenient for the participant (i.e. on Day 4, 6, 8, 10, & 12).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2018
- Study start20 Mar 2018
- Primary completion4 Feb 2019
- Study completion4 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MCT Oil SupplementationStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants complete the supplementation condition.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jonathan Little, University of British Columbia
- Investigators
- Jonathan Little, PhD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03460444
- Sponsor's protocol ID
- H17-03258
- Status last verified
- Apr 2019
- First submitted
- 23 Feb 2018
- Last updated
- 18 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Raising B-OHB Directly With MCT Oil on NLPR3 Inflammasome Activation in Healthy, Young Adults
- ClinicalTrials.gov ID
- NCT03460444
- Acronym / sponsor ID
- H17-03258
- Conditions
- MCT Oil Supplementation
- Keywords
- NLR Family, Pyrin Domain-Containing 3 Protein, Caspase 1, 3-Hydroxybutyric Acid, Histone Deacetylase Inhibitors, MCT Oil
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 20 Mar 2018 (actual)
- Primary completion
- 4 Feb 2019 (actual)
- Study completion
- 4 Feb 2019 (actual)
- First posted
- 9 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ketogenic diets are gaining support as a method to lower inflammation within the body, but studies have not been able to show the way by which this occurs. Ketones, which are molecules made by the body as a source of energy during carbohydrate restriction, have been shown to have the ability to alter the number and types of messages that immune cells send to each other, and thus have the potential to lower inflammation. To determine whether raising ketones independent of diet reduce inflammation, 20 healthy, young men and women will follow a 14-day "normal" diet combined with MCT oil supplements. Based on previous research, the investigators expect that raising ketones will reduce immune cell pro-inflammatory signaling.
Detailed description
The potential for a ketogenic diet to reduce inflammation has become increasingly popular in recent years, but direct scientific evidence to demonstrate that ketones impact inflammatory mechanisms in humans does not exist. B-hydroxybutyrate (B-OHB) is the most abundant circulating ketone and recent evidence indicates that B-OHB may be able to act as a direct signal to inhibit cellular pathways involved in inflammation.
B-OHB can be raised naturally by induction of nutritional ketosis, which is a normal physiological response to severe reductions in carbohydrate or caloric intake. In this state, free fatty acids are converted to ketone bodies (primarily B-hydroxybutyrate [B-OHB]) by the liver in order to provide essential fuel for metabolically active tissues. However, determining the direct effects of B-OHB in human ketogenic diet studies is difficult due to the numerous metabolic adaptations that occur in nutritional ketosis (e.g., reduced insulin, elevated free fatty acids, stable glucose) and the propensity for participants to lose body and fat mass over longer period.
B-OHB can also be raised independent of diet by supplementation with medium chain triglyceride (MCT) oil, allowing for induction of ketosis without the additional metabolic adaptations. In addition to being an important fuel source, recent interest has focused on a potential signaling role for B-OHB with cell culture and animal studies describing anti-inflammatory, anti-oxidant, and anti-cancer effects. The cellular pathways through which B-OHB is proposed to reduce inflammation, include the NLPR3 inflammasome and histone deacetylases (HDACs), both of which play important roles in regulating cellular inflammation. The NLRP3 inflammasome pathway is an immune complex which, upon activation, initiates downstream pro-inflammatory cascades including the activation of caspase-1 and interleukin (IL)-1B. These pro-inflammatory cascades have been implicated in the propagation of sterile inflammation, which has been identified as a major contributor to certain chronic inflammatory diseases such as type 2 diabetes and atherosclerosis. HDACs are enzymes typically found within the nucleus and have the ability to regulate signaling through innate immune pathways. B-OHB has been shown to have the ability to inhibit HDACs, and consequently has the potential to decrease oxidative stress and inflammation. The NLRP3 inflammasome and HDACs are responsive to the intracellular nutritional milieu and thus their activity may be able to be modulated through increases in B-OHB.
The use of MCT oil supplements will allow the investigators to raise blood B-OHB independent of diet, and thus directly test the immunomodulatory effects of B-OHB in healthy, adult males. This fundamental research is needed to understand whether ketones have direct immunomodulatory effects or if it is the widespread systemic metabolic adaptation to a ketogenic diet that might impact inflammatory processes.
The overall objective of this pilot study is to determine if directly raising B-OHB through supplementation with MCT oil impacts innate immune cell function and/or phenotype. Based on previous cell culture and animal research showing that B-OHB can reduce pro-inflammatory signaling, it is hypothesized that raising B-OHB with MCT oil supplementation will result in a attenuation of caspase-1 activation and mature IL-1B secretion, both markers of NLRP3 inflammasome activation. Additionally, it is hypothesized that raised B-OHB will result in greater histone acetylation, as B-OHB has been shown to be an HDAC inhibitor.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants complete the supplementation condition.
| Arm | Type | Receives |
|---|---|---|
| MCT Oil Supplementation | Experimental | Dietary Supplement: MCT Oil SupplementationParticipants consume MCT oil (97-99% octanoic acid) twice per day for 14 days while consuming a diet similar to the recommended health guidelines (40-50% carbohydrate; 30-40% fat; 20-25% protein). |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- BMI between 18.5-29.9 kg/m^2
- Females only: have a regular 28-35 day menstrual cycle
Key exclusion criteria (7 listed)
- Diagnosed metabolic disorder such as diabetes, metabolic syndrome, hypothyroidism, or any other condition known to affect metabolism;
- history of inflammatory disorders such as Rheumatoid Arthritis, Crohn's Disease, Irritable Bowel Syndrome
- Prescribed any anti-inflammatory medication cannot be avoided for the duration of the study;
- current consumption of a very low-carbohydrate diet (e.g., "Atkins", "Protein Power Plan", "Paleo diet", etc.) or have within the previous three months;
- adhere to dietary restrictions such as vegetarianism or veganism;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MCT Oil SupplementationParticipants consume MCT oil (97-99% octanoic acid) twice per day for 14 days. Dosing will begin at 5ml/dose for Days 1-2, 10ml for Days 3-4, and 15ml for the remainder of the intervention. | Dietary supplement | MCT Oil Supplementation |
Primary outcome
Change from Baseline Caspase-1 Activation at 14 days
Time frame: Measured the day before the first dose of MCT oil (baseline) and the last day of the 14 day trial (post).
Caspase-1 activation will be quantified by flow cytometry. The fluorescent inhibitor probe FAM-YVAD-FMK binds covalently to activated caspase-1 and emits at 530nm.
3 secondary outcomes
Change from Baseline Histone H3 Acetylation at 14 days
Time frame: Measured the day before the first dose of MCT oil (baseline) and the last day of the 14 day trial (post).
Change from Baseline Interleukin(IL)-1beta at 14 days
Time frame: Measured the day before the first dose of MCT oil (baseline) and the last day of the 14 day trial (post).
Change from Baseline Blood beta-hydroxybutyrate at 14 days
Time frame: Measured the day before the first dose of MCT oil (baseline), 1 and 2 hours after each meal on Day 1, 2, 13, and 14, as well as once every 2 days at a time which is convenient for the participant (i.e. on Day 4, 6, 8, 10, & 12).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2019.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Little, PhD principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MCT Oil Supplementation in people with MCT Oil Supplementation, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline Caspase-1 Activation at 14 days (time frame: Measured the day before the first dose of MCT oil (baseline) and the last day of the 14 day trial (post).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2019.