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Influence of the Background Diet on Metabolism of Land-based n-3 PUFA

Not Applicable
Completed
Conditions
Endogenous Conversion of Alpha Linolenic Acid
Interventions
Dietary Supplement: linseed oil
Registration Number
NCT03558776
Lead Sponsor
University of Jena
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
148
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Linseed oil plus defined background diet (high milk)linseed oilLinseed oil (LO) plus daily menu plans (total dietary fat intake: 30 En%): 10 En% LO plus menu plan with 20 En% fat: C) 15 ± 2 En% milk fat (n = 37)
Linseed oil plus defined background diet (high linolec acid)linseed oilLinseed oil (LO) plus daily menu plans (total dietary fat intake: 30 En%): 10 En% LO plus menu plan with 20 En% fat: A) 7 ± 2 En% linoleic acid (n = 37)
Linseed oil plus defined background diet (low linolec acid)linseed oilLinseed oil (LO) plus daily menu plans (total dietary fat intake: 30 En%): 10 En% LO plus menu plan with 20 En% fat: B) \< 2.5 En% linoleic acid (n = 37)
Linseed oil without defined background dietlinseed oilLinseed oil (LO) without defined menu plans (D) Western diet, n = 37)
Primary Outcome Measures
NameTimeMethod
Percentage of EPA and further n-3 PUFA in plasma and erythrocyte lipidschange from baseline after 4, 8 and 12 weeks

Percentage of EPA and further n-3 PUFA (ALA, DPA, DHA) in plasma and erythrocyte lipids (available from the gas chromatographic analysis)

Secondary Outcome Measures
NameTimeMethod
Diabetes risk markerschange from baseline after 4, 8 and 12 weeks

Insulin, HbA1c, glucose

Fatty acid distribution in plasma lipidschange from baseline after 4, 8 and 12 weeks

Fatty acid distribution in plasma lipids (including SFA, MUFA, PUFA, \> 90 fatty acids) available from the gas chromatographic analysis)

Unbound free fatty acid profiles in plasmachange from baseline after 12 weeks

Unbound free fatty acid profiles in plasma

Blood lipidschange from baseline after 4, 8 and 12 weeks

total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerides

Inflammatory markerschange from baseline after 4, 8 and 12 weeks

eicosanoids, docosanoids

Cardiovascular risk factorschange from baseline after 4, 8 and 12 weeks

homocysteine; high sensitive c-reactive protein

Futher biomarkers (cardovascular risk factors)change from baseline after 12 weeks

Cotinin (marker for smoking), Cystatin C (marker for kidney function), NT-pro-BNP (marker for cardiac function, volume regulation), Troponin (TnT or TnI, marker for myocardial necrosis), Galektin 3 (marker for fibrosis), Asymmetric dimethylarginine (ADMA), homoarginine, trimethylamine N-oxide (TMAO)

Fatty acid distribution in erythrocyte lipidschange from baseline after 4, 8 and 12 weeks

Fatty acid distribution in erythrocyte lipids (including SFA, MUFA, PUFA, \> 90 fatty acids) available from the gas chromatographic analysis)

Anthropometric and physiological datachange from baseline after 4, 8 and 12 weeks

height, weight, blood pressure, bioelectrical impedance, waist circumstances, heart rate variability

Clotting markerschange from baseline after 4, 8 and 12 weeks

alpha prothrombin time, fibrinogen

Trial Locations

Locations (1)

Friedrich-Schiller-University

🇩🇪

Jena, Thuringia, Germany

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