A Dose Response Investigation of Docosahexaenoic Acid (DHA)

Summary

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA), commonly consumed from fish, that regulates many critical functions within the body including the brain, eye, and heart. While the metabolic precursor to DHA, alpha-linolenic acid (ALA) is considered nutritionally essential and has a set Dietary Reference Intake (DRI), DHA has not yet been deemed essential and does not have a set DRI. Currently, research suggests an intake range of dietary DHA to be anywhere from 0 to over 500mg/d. The aim of our study is to further investigate a feedback mechanism or accumulation that occurs with eicosapentaenoic acid (EPA) as a result of increased dietary DHA to provide insight for potential Recommended Dietary Intake (RDI) values.

Hypothesis: The dietary DHA dose at which blood EPA levels increase is the point at which elongation slows, indicating a significant negative feedback pathway is present.

Objectives: 1: To determine the dose-response for DHA to increase blood EPA levels in a mixed vegetarian and vegan population. 2: Investigate the DHA dose and time at dose that increases EPA using natural abundance delta carbon-13 (δ13C) as a tracer. 3: To measure DHA turnover and loss rates. 4: Provide data for exploratory analyses related to PUFA metabolism and the effect of DHA on disease related biomarkers.

Method: During an 8-week trial, 72 healthy vegan or vegetarian males and females (18-50 years) will be supplemented with 1 of 6 algal-oil based DHA doses: 0, 100, 200, 400, 800 or 1000 mg/d. Blood will be collected at days 0, 3, 7, 14, 28 and 56 and will be analyzed for changes in blood EPA levels as the primary outcome and plasma δ13C EPA signature as the secondary outcome.

Significance: Investigating this negative feedback pathway is of great importance in providing evidence to support n-3 PUFA DRIs. EPA and DHA are ecologically sensitive with their major source coming from unsustainably farmed fish stocks and having a set DRI may help to limit the overconsumption of these nutrients.

Conditions

• Nutrition, Healthy

Interventions

DIETARY_SUPPLEMENT

docosahexaenoic acid (DHA)

72 healthy participants will be divided into 6 groups and receive varying amounts of DHA (0mg, 100mg, 200mg, 400mg, 800mg and 1000mg) over the course of 8 weeks.

DIETARY_SUPPLEMENT

soybean oil placebo

72 healthy participants will be divided into 6 groups and receive varying amounts of DHA (0mg, 100mg, 200mg, 400mg, 800mg and 1000mg) over the course of 8 weeks. The 0mg group will receive only placebos.

Sponsors & Collaborators

• Unity Health Toronto

  collaborator OTHER

• University of Toronto

  lead OTHER

Principal Investigators

• Richard P Bazinet, PhD · University of Toronto

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-02-26

Primary Completion

2025-02-26

Completion

2025-03-26

Countries

• Canada

Study Locations