A Dose Response Investigation of Docosahexaenoic Acid (DHA)
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.
- EligibilityCriteria: Inclusion Criteria:  Healthy vegans or vegetarians who do not consume meat or fish.  Exclusion Criteria:  Has regularly consumed EPA and/or DHA supplements within the past six months Having 3% or higher of DHA in their total plasma lipids BMI <18 kg/m2 or >30 kg/m2 Menopausal or post-menopausal Pregnant or breastfeeding Currently taking contraceptives Has a chronic or communicable diseases (like multiple sclerosis, kidney and inflammatory bowel disease, Type 2 diabetes, cancer or heart disease) Suffers from acute or chronic infections, use of chronic anti-inflammatory medication, use of lipid-controlling medication, hypertriglyceridemia (>4 mmol/l) or hypercholesterolemia (LDL-C >5 mmol/l) Anticipates major changes in lifestyle Is a smoker Is a heavy alcohol user (>3 drinks/day) Has had a major surgery involving organs like open heart surgery or organ transplants in the last six months Is or has participated in an intervention trial in the last six months - HealthyVolunteers: Accepts Healthy Volunteers - Gender: All - MinimumAge: 18 Years - MaximumAge: 50 Years - StdAgeList: Adult