protocolSection identificationModule nctId: NCT06294067, orgStudyIdInfo id: 43261, briefTitle: A Dose Response Investigation of Docosahexaenoic Acid (DHA), acronym: DRI-DHA, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-03, primaryCompletionDateStruct date: 2025-04, completionDateStruct date: 2025-09, studyFirstPostDateStruct date: 2024-03-05, lastUpdatePostDateStruct date: 2024-03-27, sponsorCollaboratorsModule leadSponsor name: University of Toronto, class: OTHER, collaborators name: Unity Health Toronto, descriptionModule briefSummary: 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., conditionsModule conditions: Nutrition, Healthy, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Double blinded, randomized, control, dose-response supplementation trial, primaryPurpose: BASIC_SCIENCE, maskingInfo masking: DOUBLE, maskingDescription: For randomization we will use the Research Electronic Data Capture (REDCap) program. Following successful completion of informed consent, the questionnaire and anthropometric assessment participants will be randomized into groups, of a possible six, using a blocked (Latin squares) randomization. These groups will represent DHA0 (0mg/d), DHA1 (100mg/d), DHA2 (200mg/d), DHA3 (400mg/d), DHA4 (800mg/d), and DHA5 (1000mg/d) groups. The Latin square sequences will be randomly allocated to participants with a similar number of participants allocated to each treatment sequence. The participants will only be randomized once all information is collected, informed consent has been obtained and questionnaires have been filled out following the first study call/zoom meeting. Then following their first study in person visit and post blood sample extraction they will be given their DHA capsules, which have been organized by a lab member not directly involved in the study., whoMasked: PARTICIPANT, whoMasked: INVESTIGATOR, enrollmentInfo count: 72, type: ESTIMATED, armsInterventionsModule interventions name: docosahexaenoic acid (DHA), interventions name: soybean oil placebo, outcomesModule primaryOutcomes measure: Changes in omega-3 polyunsaturated fatty acid (n-3 PUFA) blood levels, secondaryOutcomes measure: Changes in the delta carbon 13 (δ13C) n-3 PUFA signatures, secondaryOutcomes measure: Measure of n-3 LC PUFA turnover rates, secondaryOutcomes measure: Measure of n-3 LC PUFA half-lives, otherOutcomes measure: Increased intake of dietary α-Linolenic acid (ALA) and the inhibition of long chained omega-3 polyunsaturated fatty acids (LC n-3 PUFA) synthesis, otherOutcomes measure: Comparing the potential change in omega-3 long chained polyunsaturated fatty acids (n-3 LC PUFA) levels between male and female participants, otherOutcomes measure: Comparing the potential change in n-3 LC PUFA δ13C signatures between male and female participants, otherOutcomes measure: Comparing the potential change in n-3 LC PUFA levels between genetic variations, otherOutcomes measure: Comparing the potential change in n-3 LC PUFA δ13C signatures between genetic variations, otherOutcomes measure: Changes in cardiovascular disease (CVD) biomarkers (BMI in kg/m^2), otherOutcomes measure: Changes in cardiovascular disease (CVD) biomarkers (Waist circumference in cm/inch), otherOutcomes measure: Changes in cardiovascular disease (CVD) biomarkers (blood pressure in mmHg), otherOutcomes measure: Changes in cardiovascular disease (CVD) biomarkers (heart rate in beats per minute), otherOutcomes measure: Changes in cardiovascular disease (CVD) biomarkers (blood lipid profile changes in mmol/L), otherOutcomes measure: Changes in δ13C DHA signature levels to document adherence, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 50 Years, stdAges: ADULT, contactsLocationsModule locations facility: Clinical Nutrition and Risk Factor Modification Centre, status: RECRUITING, city: Toronto, state: Ontario, zip: M5C 2T2, country: Canada, contacts name: Amy Symington, PhD student, role: CONTACT, email: dhatrial@unityhealth.to, contacts name: John Sievenpiper, MD, PhD, FRCPC, role: CONTACT, email: john.sievenpiper@alumni.utoronto.ca, contacts name: Richard Bazinet, PhD, role: SUB_INVESTIGATOR, contacts name: John Sievenpiper, MD, PhD, FRCPC, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 43.70011, lon: -79.4163, hasResults: False