Clinical trial NCT03572205: Fatty Acid Desaturase Gene Locus Interactions With Diet (FADSDIET2)
Official title: Fatty Acid Desaturase Gene Locus Interactions With Diet (FADSDIET2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fatty Acids
Genetics
Keywords: Nutrigenetics
Lead sponsor: University of Eastern Finland
Sponsor class: OTHER
First posted: 2018-06-28
Enrollment: 140
Sex: MALE
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in fatty acid composition of serum lipid fractions
timeFrame: 8 weeks
Secondary outcomes:
measure: Glucose and insulin metabolism response
timeFrame: 8 weeks
measure: Inflammatory markers response
timeFrame: 8 weeks
measure: Adipose tissue biopsies
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Kuopio
country: Finland
facility: University of Eastern Finland
Study officials:
affiliation: University of Eastern Finland
name: Jussi Pihlajamäki, MD
role: PRINCIPAL_INVESTIGATOR
References: