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

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)

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.

Study Overview

• Status: Completed
• Conditions: Endogenous Conversion of Alpha Linolenic Acid
• Intervention / Treatment: Dietary supplement: linseed oil

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.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Thuringia
    • Jena, Thuringia, Germany, 07743
      • Friedrich-Schiller-University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Linseed oil plus defined background diet (high linolec acid); Linseed 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)	Dietary supplement: linseed oil; linseed oil and defined background diet
ACTIVE_COMPARATOR: Linseed oil plus defined background diet (low linolec acid); Linseed 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)	Dietary supplement: linseed oil; linseed oil and defined background diet
ACTIVE_COMPARATOR: Linseed oil plus defined background diet (high milk); Linseed 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)	Dietary supplement: linseed oil; linseed oil and defined background diet
PLACEBO_COMPARATOR: Linseed oil without defined background diet; Linseed oil (LO) without defined menu plans (D) Western diet, n = 37)	Dietary supplement: linseed oil; linseed oil and defined background diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of EPA and further n-3 PUFA in plasma and erythrocyte lipids	Percentage of EPA and further n-3 PUFA (ALA, DPA, DHA) in plasma and erythrocyte lipids (available from the gas chromatographic analysis)	change from baseline after 4, 8 and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatty acid distribution in plasma lipids	Fatty acid distribution in plasma lipids (including SFA, MUFA, PUFA, > 90 fatty acids) available from the gas chromatographic analysis)	change from baseline after 4, 8 and 12 weeks
Fatty acid distribution in erythrocyte lipids	Fatty acid distribution in erythrocyte lipids (including SFA, MUFA, PUFA, > 90 fatty acids) available from the gas chromatographic analysis)	change from baseline after 4, 8 and 12 weeks
Anthropometric and physiological data	height, weight, blood pressure, bioelectrical impedance, waist circumstances, heart rate variability	change from baseline after 4, 8 and 12 weeks
Blood lipids	total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerides	change from baseline after 4, 8 and 12 weeks
Inflammatory markers	eicosanoids, docosanoids	change from baseline after 4, 8 and 12 weeks
Diabetes risk markers	Insulin, HbA1c, glucose	change from baseline after 4, 8 and 12 weeks
Clotting markers	alpha prothrombin time, fibrinogen	change from baseline after 4, 8 and 12 weeks
Cardiovascular risk factors	homocysteine; high sensitive c-reactive protein	change from baseline after 4, 8 and 12 weeks
Unbound free fatty acid profiles in plasma	Unbound free fatty acid profiles in plasma	change from baseline after 12 weeks
Futher biomarkers (cardovascular risk factors)	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)	change from baseline after 12 weeks

Collaborators and Investigators

• Sponsor: University of Jena

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 13, 2018
• Primary Completion (ACTUAL): July 22, 2018
• Study Completion (ACTUAL): December 31, 2018

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: June 5, 2018
• First Posted (ACTUAL): June 15, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 7, 2019
• Last Update Submitted That Met QC Criteria: March 6, 2019
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: alpha linolenic acid, linseed oil, eicosapentaenoic acid, docosahexaenoic acid
• Other Study ID Numbers: H6_18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: publication of the study data and results in national and international journals

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No