Clinical trial NCT03558776: Influence of the Background Diet on Metabolism of Land-based n-3 PUFA
Official title: Influence of the Background Diet on Metabolism of Land-based n-3 PUFA From Linseed Oil - Focus: Conversion of Alpha Linolenic Acid (ALA; KoALA Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Endogenous Conversion of Alpha Linolenic Acid
Keywords: alpha linolenic acid, linseed oil, eicosapentaenoic acid, docosahexaenoic acid
Lead sponsor: University of Jena
Sponsor class: OTHER
First posted: 2018-06-15
Enrollment: 148
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Blood samples will be taken at the beginning and regularly every four weeks during the 12-weeks intervention period. For all groups, the consumption of additional n-3 PUFA sources is not permitted during the entire intervention period. The study intervention will consist of a daily dose of linseed oil (LO, 10 En%) and prepared daily menu plans determining the background diet, except for the control group D. The fat composition of the developed daily menu plans (fat content 20 En%) will differ between the groups A to C. For groups A to C, the daily menu plans will ensure an adequate intake of energy and nutrients according to the guidelines of the German Society of Nutrition. Group D serves as control because in this group the background diet is not fixed by menu plans. Participants of group D must follow their normal dietary habits, i.e. a typical Western diet (LA intake is about 15 g/d (5-7 En%) / SFA intake ranges from 10 to 15 En%).
Primary purpose: TREATMENT

Brief summary: KoALA study - assessment of the influence of the background diet on the metabolism and the bioavailability of plant n-3 PUFA from linseed oil.

In particular, the study design focusses on the impact of variations in the background diet as confounding factor (e.g. variations in concurrently intake of linoleic acid (n-6)). Further, the influence of a regular intake of milk fat, in particular from free-grazing ruminants, on n-3 PUFA metabolism will be investigated.

Detailed description: The KoALA study focuses on the impact of variations in the background diet as a confounding factor. The intake of linoleic acid (LA, C18:2 n-6) has been suggested to diminish the metabolism of α-linolenic acid (ALA, C18:3 n-3) to eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3).

In this context, the proposed study will be conducted to evaluate the influence of the background diet, in particular the impact of the simultaneous intake of LA on the conversion of ALA into their long-chain (LC) metabolites, the incorporation of n-3 LC-PUFA in human tissues and their metabolism into eicosanoids and docosanoids. Further, the influence of a regular intake of milk fat, in particular from free-grazing ruminants, on n-3 PUFA metabolism will be investigated, because short- and middle-chain fatty acids as well as the branched-chain fatty acids in milk fat may influence the conversion of ALA into n-3 LC-PUFA (hypothesis).

Thus, validated nutrition concepts for increasing n-3 LC-PUFA status from plant sources will be developed to ensure an adequate intake of n-3 PUFA according to the guidelines of nutritional societies and as a contribution to the prevention of cardiovascular diseases.

Eligibility criteria: Inclusion Criteria:

Whether participants meet the inclusion criteria will be evaluated by screening prior the run-in (blood sampling).

* Females (in the menopause) and males (50 % each); age: 40 - 65 years; BMI \< 30 kg/m2
* Subjects must be able and willing to give written informed consent, and to comply with study procedures
* Subjects with moderate elevated LDL cholesterol (\> 3 mmol/l), without lipid-lowering medication
* Persons who consume a traditional "Western diet" composed of meat, sausage, dairy products, cereals, vegetables, fruits etc.
* Precondition: stable eating habits at least one year before enrollment
* Subjects must have adequate fluency in the German language to complete the questionnaires and understand the daily menu plans
* No antihypertensive medication or stable dose for \>3 months prior to start of the study and during the entire study period

Exclusion Criteria:

* Subjects with any acute or chronic disease (tumor, infection, other), gastrointestinal diseases, diabe-tes mellitus (type I and II), chronic renal disease, diseases of the parathyroids, diseases necessitat-ing regular phlebotomies other chronic diseases which could affect the results of the present study
* Use of medication which could affect the results of the present study including systemic glucocorti-coids, lipid-lowering medication
* Hormone replacement therapy
* Use of dietary supplements, incl. multivitamins, fish oil capsules, minerals, and trace elements (three months before and during the entire study period)
* Weight loss or weight gain (\> 3 kg) during the last three months before study begin
* Relevant food allergies (e.g. milk, nuts etc.)
* Pregnancy or lactation
* Transfusion of blood in the last three months before blood sample taking

Primary outcomes:
measure: Percentage of EPA and further n-3 PUFA in plasma and erythrocyte lipids
timeFrame: change from baseline after 4, 8 and 12 weeks
Secondary outcomes:
measure: Fatty acid distribution in plasma lipids
timeFrame: change from baseline after 4, 8 and 12 weeks
measure: Fatty acid distribution in erythrocyte lipids
timeFrame: change from baseline after 4, 8 and 12 weeks
measure: Anthropometric and physiological data
timeFrame: change from baseline after 4, 8 and 12 weeks
measure: Blood lipids
timeFrame: change from baseline after 4, 8 and 12 weeks
measure: Inflammatory markers
timeFrame: change from baseline after 4, 8 and 12 weeks
measure: Diabetes risk markers
timeFrame: change from baseline after 4, 8 and 12 weeks
measure: Clotting markers
timeFrame: change from baseline after 4, 8 and 12 weeks
measure: Cardiovascular risk factors
timeFrame: change from baseline after 4, 8 and 12 weeks
measure: Unbound free fatty acid profiles in plasma
timeFrame: change from baseline after 12 weeks
measure: Futher biomarkers (cardovascular risk factors)
timeFrame: change from baseline after 12 weeks
Other outcomes:
Locations:
city: Jena
country: Germany
facility: Friedrich-Schiller-University
state: Thuringia
Study officials:
References: