Healthy
Conditions
Keywords
ketone, α-linolenic acid, flaxseed, aging, β-hydroxybutyrate, acetoacetate, omega-3 fatty acids, ketogenesis
Brief summary
Background: As the main alternative fuel to glucose for the brain, increased plasma ketones could potentially help compensate for brain glucose hypometabolism occurring during aging. The precursor long-chain n-3 polyunsaturated fatty acid (PUFA), α-linolenic acid (ALA), is normally mostly β-oxidized and so could potentially be used to stimulate ketogenesis in humans. Objective: To compare the impact of an ALA-rich supplement on the ketogenic response in young and older healthy adults. Design: Ten young and ten older adults will consume a flaxseed oil supplement providing 2 g/d of ALA for 4 weeks. Plasma ketones, free fatty acids, triglycerides, glucose and insulin will be measured over 6 h during two metabolic study days, one before and one at the end of the supplementation. Hypothesis: ALA-rich supplement for 4 weeks will increase ketone production in both groups.
Interventions
DIETARY_SUPPLEMENTalpha-linolenic acid-rich supplement
each participant consumed one 1000 mg capsule of flaxseed oil four times per day for 4 weeks, providing a total of 2 g/d of ALA. The capsules used were a commercially available flaxseed oil supplement containing ALA at 56% of total fatty acids (Jamieson, Toronto, ON, Canada). The other main fatty acids present in flaxseed oil include linoleic acid (18%), oleic acid (16%), palmitic and stearic acid (10% combined).
Sponsors
Université de Sherbrooke
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Dietary Supplement: alpha-linolenic acid-rich supplement
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* aged between 18 and 30 or 65 years and more
Exclusion criteria
* non smoker * pregnancy or breastfeeding * diabetes or insulin resistance * uncontrolled thyroid disease, hepatic or renal disease * uncontrolled high blood pressure * medical treatment influencing lipid or glucide metabolism * ongoing or past severe drug or alcohol abuse * dementia or psychiatric difficulties or depression * chronic immune condition or inflammation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ketone Production | After 4 weeks | Total Ketone (acetoacetate + beta-hydroxybutyrate) concentration in plasma in average during the metabolic study day, measured hourly between 1 and 6h after breakfast |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Glucose | After 4 weeks | Glucose measured in plasma in average during the metabolic study day, measure hourly between 0 and 6 h after breakfast |
| Plasma Triglycerides | After 4 weeks | Triglycerides measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast |
| Plasma Free Fatty Acids | 4 weeks | Free fatty acids measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast |
| Insulin Concentration in Plasma | after 4 weeks | Insulin measured in plasma in average during the metabolic study day, measured hourly between 0 ans 6 h after breakfast |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Young Group 4 Week ALA Treatment Participants will receive the alpha-linolenic acid-rich supplement (1000mg 4 times par day) for 4 weeks
alpha-linolenic acid-rich supplement: each participant consumed one 1000 mg capsule of flaxseed oil four times per day for 4 weeks, providing a total of 2 g/d of ALA. The capsules used were a commercially available flaxseed oil supplement containing ALA at 56% of total fatty acids (Jamieson, Toronto, ON, Canada). The other main fatty acids present in flaxseed oil include linoleic acid (18%), oleic acid (16%), palmitic and stearic acid (10% combined). | 10 |
| Old Group 4 Week ALA Treatment Participants will receive the alpha-linolenic acid-rich supplement (1000mg 4 times par day) for 4 weeks
alpha-linolenic acid-rich supplement: each participant consumed one 1000 mg capsule of flaxseed oil four times per day for 4 weeks, providing a total of 2 g/d of ALA. The capsules used were a commercially available flaxseed oil supplement containing ALA at 56% of total fatty acids (Jamieson, Toronto, ON, Canada). The other main fatty acids present in flaxseed oil include linoleic acid (18%), oleic acid (16%), palmitic and stearic acid (10% combined). | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Old Group 4 Week ALA Treatment | Young Group 4 Week ALA Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 0 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 10 Participants | 10 Participants |
| Age, Continuous | 73 years STANDARD_DEVIATION 7 | 25 years STANDARD_DEVIATION 2.8 | 52 years STANDARD_DEVIATION 25 |
| Region of Enrollment Canada | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Ketone Production
Total Ketone (acetoacetate + beta-hydroxybutyrate) concentration in plasma in average during the metabolic study day, measured hourly between 1 and 6h after breakfast
Time frame: After 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Young Group 4 Week ALA Treatment | Ketone Production | 217.71 µmol/L | Standard Error 24 |
| Old Group 4 Week ALA Treatment | Ketone Production | 187.48 µmol/L | Standard Error 17 |
Secondary
Insulin Concentration in Plasma
Insulin measured in plasma in average during the metabolic study day, measured hourly between 0 ans 6 h after breakfast
Time frame: after 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Young Group 4 Week ALA Treatment | Insulin Concentration in Plasma | 10.48 µIU/mL | Standard Error 1.48 |
| Old Group 4 Week ALA Treatment | Insulin Concentration in Plasma | 14.87 µIU/mL | Standard Error 2.63 |
Secondary
Plasma Free Fatty Acids
Free fatty acids measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Young Group 4 Week ALA Treatment | Plasma Free Fatty Acids | 0.48 mmol/L | Standard Error 0.05 |
| Old Group 4 Week ALA Treatment | Plasma Free Fatty Acids | 0.55 mmol/L | Standard Error 0.04 |
Secondary
Plasma Glucose
Glucose measured in plasma in average during the metabolic study day, measure hourly between 0 and 6 h after breakfast
Time frame: After 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Young Group 4 Week ALA Treatment | Plasma Glucose | 4.75 mmol/L | Standard Error 0.13 |
| Old Group 4 Week ALA Treatment | Plasma Glucose | 5.46 mmol/L | Standard Error 0.19 |
Secondary
Plasma Triglycerides
Triglycerides measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast
Time frame: After 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Young Group 4 Week ALA Treatment | Plasma Triglycerides | 0.97 mmol/L | Standard Error 0.15 |
| Old Group 4 Week ALA Treatment | Plasma Triglycerides | 1.81 mmol/L | Standard Error 0.29 |