Fatty Acids, Genetics
Conditions
Keywords
Nutrigenetics
Brief summary
Interactions between genes and environment, are likely to be crucial in the development of the common diseases such as type 2 diabetes. Recently, the investigators have obtained data that genotypes of genes encoding for fatty acid desaturases 1 and 2 (FADS1 and FADS2) are the strongest genes in a genome-wide analysis regulating serum fatty acid profile.The aim of this study is to test if subjects with different genotypes of the FADS2 gene respond differently to a diet supplemented with linoleic acid or alpha-linolenic acid (substrates for FADS2). The study hypothesizes that subjects will be more sensitive to the dietary modifications according to their genotype leading to more robust differences in serum FA profile, tissue inflammation and serum lipids.
Detailed description
Lean and overweight subjects (Body mass index: BMI \>20kg/m2 \<32kg/m2 ) with CC and TT genotypes of FADS1 single nucleotide polymorphism (SNP) from the METabolic Syndrome in Men (METSIM) study, in which currently \>10000 men are included from the population living in Kuopio, will be recruited. Seventy subjects with CC genotype will be selected after matching with the 70 subjects with the TT genotype for age and BMI. After a 4-week run-in period, the subjects within each genotype group will be randomly assigned into two study groups according to medians of BMI, age and fasting plasma glucose concentration: in one group the diet will be enriched with linoleic acid (LA, sunflower oil) and in the other group with alpha-linolenic acid (ALA, camelina oil). The intervention will last for 8 weeks. The sample size calculation is based on the observed change in arachidonic acid (AA) in the cholesterol esthers fraction between CC and TT genotypes (12.14 vs. 4.20 mol%, respectively) after the diet enriched in LA from preliminary data. Considering a β=0.80 and an α=0.025 instead of only 0.05 to account for the fact that we now have two dietary interventions instead of one, 31 participants in each study group would need to be included. Assuming around 15% of dropouts in this trial, a final sample size of 35 for each group is required. The study diet will be isocaloric following the habitual diet of the participants with a supplement of 30-50 ml (25-45 g) sunflower or camelina oil daily depending on body weight. The dose of each oil is not known to cause any side effects or adverse events and even higher doses have been safe. Participants will record their daily oil consumption and 4-day food records will be collected at the beginning and two times during the intervention period to measure daily intake of macronutrients and specifically different fatty acids.
Interventions
DIETARY_SUPPLEMENTLA
The source of linoleic acid (LA) will be sunflower oil (62-63 % LA). The study diets will be isocaloric. The allowed weight change during the study is ± 2-3 %. The amount of supplementary oil will be calculated individually based on the calculated energy expenditure and adjusted, if necessary, during the study based on body weight measurements.
DIETARY_SUPPLEMENTALA
The source of alpha-linolenic acid (ALA) will be camelina sativa oil (30-35 % ALA). The study diets will be isocaloric. The allowed weight change during the study is ± 2-3 %. The amount of supplementary oil will be calculated individually based on the calculated energy expenditure and adjusted, if necessary, during the study based on body weight measurements.
Sponsors
University of Eastern Finland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
50 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants of METSIM study cohort with CC/TT FADS1 rs174547 SNP genotype. * BMI 20-32 kg/m2. * Healthy .
Exclusion criteria
* Diagnosis of type 2 diabetes. * Diagnosis of chronic diseases and conditions, that may hamper the ability to follow the dietary intervention protocol * Chronic liver, thyroid and kidney diseases * Alcohol abuse (\> 40 g/d) * BMI \>32 kg/m2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in fatty acid composition of serum lipid fractions | 8 weeks | Fatty acid composition of serum lipid fractions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose and insulin metabolism response | 8 weeks | Oral glucose tolerance test (OGTT) variables: fasting, 30 min and 120 min glucose and insulin measurements |
| Inflammatory markers response | 8 weeks | Serum circulating levels of high-sensitivity C-reactive protein |
| Adipose tissue biopsies | 8 weeks | Subcutaneous adipose tissue taken by open biopsy to collect 1-5 g of adipose tissue. |
Countries
Finland
Outcome results
None listed