Novel Approach to Increase EPA and DHA Levels

The Intake of Omega-3 Fatty Acids and the Inhibition of Their Mitochondrial Metabolism Increase EPA and DHA Levels in Healthy Volunteers

The goal of this intervention trial is to evaluate whether combining meldonium therapy with PUFAs (polyunsaturated fatty acids) supplements containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) changes the plasma (blood component) concentration of EPA and DHA, as well as the acylcarnitine (fatty acid metabolite) profile in healthy volunteers. The main questions it aims to answer are:

Does using meldonium together with PUFA supplements increase PUFA (EPA and DHA) concentrations in blood plasma? Does meldonium therapy change change the fatty acid metabolite (acylcarnitine) profile, if used together with PUFA supplements?

Researchers compared plasma metabolic parameters in the beginning, middle and end of study period in a group who received only PUFA supplements, with a group which got PUFA supplements at the beginning, but after one month meldonium therapy was added and a group which got meldonium therapy at the beginning, but after one month PUFA supplements were added.

Participants:

1. Received detailed information about the study and signed an informed consent form.
2. They were assigned to one of three study groups and received PUFAs and/or meldonium for the duration of the study.
3. Plasma samples were collected at the beginning, middle and end of the study period.

Study Overview

• Status: Completed
• Conditions: Supplementation; Lipid Metabolism; Omega-3 Polyunsaturated Fatty Acids
• Intervention / Treatment: Dietary supplement: PUFA supplementation only; Dietary supplement: PUFA + meldonium; Drug: Meldonium + PUFA

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Latvia
  • Riga, Latvia
    • Riga Stradins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy adults (age 18 and older)

Exclusion Criteria:

• Previously diagnosed serious chronic diseases (diabetes mellitus, atherosclerotic cardiovascular diseases, chronic kidney and liver diseases, cancer)
• PUFA supplement usage and/or meldonium therapy at least 6 months before inclusion in the study
• Participation in other clinical drug trials
• Pregnancy and breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: PUFAs supplementation only; Participants received only PUFA supplements, metabolic parameters measured in plasma in the beginning, middle and end of study period	Dietary supplement: PUFA supplementation only; PUFA supplement containing 930 mg EPA and 750 mg DHA for 8 weeks
Experimental: Arm 2: PUFAs followed by PUFAs+ meldonium; Participants received PUFA supplements at the beginning, but after one month meldonium therapy was added to PUFA supplementation. Metabolic parameters measured in plasma in the beginning, middle and end of study period	Dietary supplement: PUFA + meldonium; PUFA supplement (930 mg EPA and 750 mg DHA) for four weeks, followed by an additional four weeks of combined PUFA supplement with 1 g/day meldonium
Experimental: Arm 3: Meldonium followed by meldonium+ PUFAs; Participants received meldonium therapy at the beginning, but after one month PUFAs supplementation was added to meldonium therapy. Metabolic parameters measured in plasma in the beginning, middle and end of study period	Drug: Meldonium + PUFA; Meldonium (1g/day) or four weeks, followed by an additional four weeks of combined meldonium and PUFA (930 mg EPA and 750 mg DHA) supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the plasma concentrations of EPA and DPA		From enrollment moment to the end of 8 week study period
Changes in plasma acetylcarnitine concentrations	Acetylcarnitine contains acyl group with 2 carbon atoms	From the enrollment moment to the end of 8 week study period
Changes in plasma medium-chain acylcarnitine concentration	Medium- chain acylcarnitines are defined as containing acyl groups with 6-12 carbon atoms	From enrollment moment to the end of 8 week study period
Changes in plasma long-chain acylcarnitine concentration	Long-chain acylcarnitines contain acyl groups with 14-18 carbon atoms	Time Frame: From the enrollment moment to the end of 8 week study period

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in plasma meldonium concentration	From the enrollment moment to the end of 8 week study period
Changes in plasma gamma-butyrobetaine (GBB) concentrations	From the enrollment moment to the end of 8 week study period

Collaborators and Investigators

• Sponsor: Riga Stradins University
• Investigators: Principal Investigator: Ilze Konrade, PhD, MD, Riga Stradins University

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2023
• Primary Completion (Actual): June 6, 2023
• Study Completion (Actual): June 6, 2023

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Actual): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: DHA; EPA; PUFA; cardiometabolic health; acylcarnitines; meldonium
• Additional Relevant MeSH Terms: Fatty Acids; Lipids; 3-(2,2,2-trimethylhydrazine)propionate; Fatty Acids, Unsaturated
• Other Study ID Numbers: VPP-2022/1-000-28/2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will deposit individual original measurement results, but not anthropometric data.
• IPD Sharing Time Frame: Available immediately following completion of the study. Study data will be stored indefinitely in accordance with institutional and regulatory requirements
• IPD Sharing Access Criteria: Data will be provided to researchers on request. We will evaluate whether their purpose comply with the consent and ethics approval.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Study Data/Documents

1. Individual Participant Data Set

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No