DHA for Healthy Nutrition

(DRI-DHA Trial)

Overseen By Amy M Symington, PhD student

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Toronto

Must not be taking: Anti-inflammatories, Lipid-controllers

Disqualifiers: Chronic diseases, Infections, Smoking, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different doses of DHA, an omega-3 fatty acid from fish, affect blood levels of another fatty acid called EPA. The goal is to determine a recommended intake for DHA, potentially leading to more sustainable fish farming. The trial seeks healthy vegans or vegetarians who have not recently used DHA or EPA supplements. Participants will take various doses of DHA, and researchers will track changes in their blood over eight weeks. This research could help establish dietary guidelines and improve omega-3 sustainability. As a Phase 1 trial, the focus is on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking nutritional science.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you use chronic anti-inflammatory or lipid-controlling medications, you may be excluded from participating.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that DHA, a type of omega-3 fatty acid, is generally safe for people. Studies have found that DHA rarely causes side effects in both babies and adults. The safety of DHA is often compared to the amount found in breast milk, which is considered safe for infants. However, taking more than 3 grams per day of DHA and other omega-3s might be risky because it can slow blood clotting.

The trial under consideration involves much lower doses, between 100 mg and 1000 mg per day. These amounts fall well within safe limits according to current research, suggesting DHA is likely to be well-tolerated at these levels. Remember, individual reactions can differ, so report any unusual symptoms to the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about these treatments because Docosahexaenoic Acid (DHA) is a key omega-3 fatty acid that plays a vital role in brain and eye health. Unlike many standard nutritional supplements that might focus on general multivitamin formulations, DHA specifically targets neural and visual functions, potentially offering more precise benefits. This trial explores varying doses, from 100mg to 1000mg per day, allowing researchers to pinpoint the most effective amount of DHA for optimal health benefits. By understanding the specific impact of DHA, there is potential to improve dietary recommendations for maintaining cognitive and eye health.

What evidence suggests that this trial's treatments could be effective for increasing blood EPA levels?

Research shows that DHA, a type of omega-3 fatty acid, benefits health. Studies have found that increasing DHA intake can lower triglyceride levels, which are blood fats affecting heart health. DHA also supports brain and eye health, aiding thinking and vision. While specific information on DHA alone is still under study, it is often combined with EPA, another omega-3, for additional health benefits, including potential heart health improvements. Current research, including this trial, examines how different DHA dosages affect EPA levels in the blood, which could inform dietary advice. ^{2 6 7 8 9}

Who Is on the Research Team?

Richard P Bazinet, PhD

Principal Investigator

University of Toronto

Are You a Good Fit for This Trial?

This trial is for healthy vegans or vegetarians aged 18-50 who don't eat meat or fish. It's designed to understand how different doses of DHA, an omega-3 fatty acid from algae oil, affect blood levels of another omega-3 called EPA.

Inclusion Criteria

Healthy vegans or vegetarians who do not consume meat or fish

Exclusion Criteria

BMI <18 kg/m2 or >30 kg/m2

Is or has participated in an intervention trial in the last six months

Having 3% or higher of DHA in their total plasma lipids

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Run-in

Participants undergo a run-in phase to gather questionnaire data before randomization

2 weeks

Treatment

Participants receive DHA supplementation at varying doses for 8 weeks

8 weeks

6 visits (in-person) for blood collection

Follow-up

Participants are monitored for changes in blood EPA levels and other biomarkers

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docosahexaenoic Acid (DHA)

Trial Overview

Participants will take one of six different daily doses of DHA (0, 100, 200, 400, 800 or 1000 mg) over eight weeks. The study aims to see at what dose and time frame the body's EPA levels change and how quickly DHA is processed in the body.

How Is the Trial Designed?

Group I: DHA1 - 100mg of DHA/d Active Control 1 Intervention

DHA1 participants will take 100mg/d of DHA. As the DHA supplements are 200mg of DHA per capsule the participants here will take one 200mg capsule every other day and the rest of the capsules will be placebos.

Group II: DHA5 - 1000mg of DHA/d Active Control 1 Intervention

DHA5 participants will take five 200mg capsules of DHA and no placebos per day.

Group III: DHA2 - 200mg of DHA/d Active Control 1 Intervention

DHA2 participants will take one 200mg capsule of DHA and 4 placebos per day.

Group IV: DHA3 - 400mg of DHA/d Active Control 1 Intervention

DHA3 participants will take two 200mg capsules of DHA and 3 placebos per day.

Group V: DHA4 - 800mg of DHA/d Active Control 1 Intervention

DHA4 participants will take four 200mg capsules of DHA and 1 placebo per day.

Group VI: DHA0 - 0mg of DHA/d Placebo Group 1 Intervention

DHA0 participants are in the placebo group and will take 5 soybean oil based capsules per day and will not receive any DHA. Every group takes 5 capsules per day to maintain blinding.

Docosahexaenoic Acid (DHA) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as DHA for:

• Infant formula supplementation
• Heart health support
• Brain function support

Approved in European Union as DHA for:

• Infant formula supplementation
• Heart health support
• Brain function support

Approved in Canada as DHA for:

• Infant formula supplementation
• Heart health support
• Brain function support

Approved in Japan as DHA for:

• Infant formula supplementation
• Heart health support
• Brain function support

Who Is Running the Clinical Trial?

University of Toronto

Lead Sponsor

Trials

739

Recruited

1,125,000+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Published Research Related to This Trial

A follow-up study of the N3RO trial, involving 1273 infants born before 29 weeks' gestation, aims to assess the long-term cognitive effects of DHA supplementation, which was given at 60 mg/kg/day during the first months of life.

While DHA supplementation did not reduce the risk of bronchopulmonary dysplasia (BPD) and may have increased the risk, the study will evaluate its impact on cognitive development at 5 years of age, focusing on full-scale IQ and other cognitive measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for assessing whether cognition of preterm infants Gould, JF., Makrides, M., Sullivan, TR., et al.[2021]

Supplementing infant formulas with docosahexaenoic acid (DHA) and arachidonic acid (AA) can significantly enhance mental development and visual function, bringing blood lipid levels in infants closer to those of breast-fed babies.

In older individuals, low levels of n-3 polyunsaturated fatty acids (PUFAs) are linked to increased risks of depression and Alzheimer's disease, and n-3 PUFAs, particularly eicosapentaenoic acid (EPA), have shown effectiveness in treating various psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life. Alessandri, JM., Guesnet, P., Vancassel, S., et al.[2019]

The newly developed lycosomal formulation of DHA (LF-DHA) significantly enhances DHA bioavailability, increasing serum concentrations by 34.6% and 94.1% after 2 and 4 weeks, respectively, compared to regular DHA.

LF-DHA not only reduces oxidative stress markers more effectively than other formulations but also improves plasma and tissue oxygen saturation, suggesting it may be a superior option for individuals with oxidative stress and subclinical hypoxia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Oxidation Parameters in Volunteers Supplemented with Microencapsulated Docosahexaenoic Acid. Petyaev, IM., Chalyk, NE., Klochkov, VA., et al.[2022]

In a study involving 84 seven-day-old Wistar rat pups, treatment with docosahexaenoic acid (DHA) after hypoxia-ischemia significantly improved functional outcomes, as measured by forepaw placing tests.

However, DHA treatment did not reduce brain volume loss in any brain region, indicating that while it may enhance function, it does not prevent structural damage following hypoxia-ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with docosahexaenoic acid after hypoxia-ischemia improves forepaw placing in a rat model of perinatal hypoxia-ischemia. Berman, DR., Liu, Y., Barks, J., et al.[2021]

n-3 docosapentaenoic acid (n-3 DPA) is a lesser-known omega-3 fatty acid that can enhance the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the body, potentially improving cardiovascular and metabolic health markers.

Recent studies suggest that n-3 DPA may play a crucial role in neuroprotection for the elderly and support early-life development, leading to the creation of two drugs specifically formulated with n-3 DPA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The n-3 docosapentaenoic acid (DPA): A new player in the n-3 long chain polyunsaturated fatty acid family. Drouin, G., Rioux, V., Legrand, P.[2019]

The study developed a self-nanoemulsifying drug delivery system (SNEDDS) for docosahexaenoic acid (DHA), which significantly improved its absorption in the intestines, achieving up to 98.7% absorption compared to 46.1% with traditional oil-based formulations.

The optimized SNEDDS formulation resulted in a 2.6-fold increase in DHA concentration in the brain, indicating enhanced bioavailability and potential benefits for brain development and function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-nanoemulsifying drug delivery system of docosahexanoic acid: development, in vitro, in vivo characterization. Puri, R., Mahajan, M., Sahajpal, NS., et al.[2022]

Supplementation of infant formula with arachidonic acid (AA) and docosahexaenoic acid (DHA) significantly alters the plasma phospholipid profile in infants, indicating that these fatty acids play a crucial role in lipid metabolism during early development.

Infants receiving the supplemented formula showed phospholipid levels of DHA comparable to breast milk-fed infants, although AA levels remained lower, suggesting that while DHA supplementation is effective, additional AA may be needed to match breast milk levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phospholipid Species in Newborn and 4 Month Old Infants after Consumption of Different Formulas or Breast Milk. Uhl, O., Fleddermann, M., Hellmuth, C., et al.[2022]

Docosahexaenoic acid (DHA) significantly reduces the viability of MCF-7 breast cancer cells and inhibits the activity of the pro-oncogenic enzyme protein tyrosine phosphatase 1B (PTP1B), suggesting its potential as a breast cancer preventive agent.

DHA shows greater inhibitory activity against PTP1B compared to other similar fatty acids and binds to an allosteric site on the enzyme, indicating a specific mechanism of action that could be leveraged for therapeutic purposes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docosahexaenoic Acid Inhibits PTP1B Phosphatase and the Viability of MCF-7 Breast Cancer Cells. Kuban-Jankowska, A., Gorska-Ponikowska, M., Sahu, KK., et al.[2020]

Docosahexaenoic acid (DHA) is crucial for developing visual and neurological functions in premature infants and neonates, highlighting its importance during early life stages.

DHA intake recommendations should be tailored based on breastfeeding patterns and dietary needs, especially for older children, pregnant, and lactating women, with an emphasis on oily fish consumption to prevent deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Importance of docosahexaenoic acid (DHA): Functions and recommendations for its ingestion in infants]. Gil-Campos, M., Dalmau Serra, J.[2010]

Rats fed an adequate amount of α-linolenic acid (ALA) showed a significantly higher capacity to synthesize docosahexaenoic acid (DHA) compared to those on ALA-deficient or high-ALA diets, indicating that a balanced ALA intake is crucial for optimal DHA production.

Increasing dietary ALA beyond a certain point (from 3% to 10%) did not enhance DHA synthesis rates, suggesting that there is a limit to how much ALA can be converted to DHA, and that excessive ALA may actually reduce the synthesis capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-Body Docosahexaenoic Acid Synthesis-Secretion Rates in Rats Are Constant across a Large Range of Dietary α-Linolenic Acid Intakes. Domenichiello, AF., Kitson, AP., Metherel, AH., et al.[2023]

A diet containing 0.4% docosahexaenoic acid (DHA) significantly increased lean mass by 6% in healthy female rats compared to a control diet, indicating its potential efficacy in improving body composition.

Higher DHA levels (1.2%) were associated with increased fat mass, suggesting that there is an optimal dose of DHA (0.4%) for enhancing lean mass while reducing fat mass, as evidenced by a 31.4% reduction in abdominal visceral fat compared to the higher DHA group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docosahexaenoic Acid at 0.4% of Dietary Weight Enhances Lean Mass in Young Female Sprague-Dawley Rats. Farahnak, Z., Lévy-Ndejuru, J., Lavery, P., et al.[2023]

Prenatal supplementation with 600 mg/d of DHA significantly reduced early preterm births and improved visual attention in infants during their first year, based on a randomized double-blind clinical trial involving approximately 200 infants.

However, the long-term follow-up revealed no consistent benefits in cognitive and behavioral development into childhood, with any observed increases in IQ scores being confounded by socioeconomic status (SES) factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Kansas University DHA Outcomes Study (KUDOS) clinical trial: long-term behavioral follow-up of the effects of prenatal DHA supplementation. Colombo, J., Shaddy, DJ., Gustafson, K., et al.[2023]

Citations

1.

fjps.springeropen.com

fjps.springeropen.com/articles/10.1186/s43094-024-00667-5

Omega-3 Fatty Acids: Sources, Functions, Health Benefits

A thorough analysis of omega-3 polyunsaturated fatty acids reveals both their remarkable therapeutic potential against a variety of diseases and their ...

2.

ods.od.nih.gov

ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/

Omega-3 Fatty Acids - Health Professional Fact Sheet

Each increase of 1 g/day of LC omega-3 reduced triglyceride levels by 5.9 mg/dL, and the effect was stronger in people with higher baseline triglyceride levels.

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2161831322009620

Omega-3 Fatty Acids EPA and DHA: Health Benefits ...

In a study using EPA+DHA supplementation, patients' weight significantly increased by 0.7 kg in the EPA+DHA treatment group at 6 mo (P = 0.02) and by 1.4 kg at ...

4.

thelancet.com

thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00277-7/fulltext

Effect of omega-3 fatty acids on cardiovascular outcomes

Omega-3 FAs reduced cardiovascular mortality and improved cardiovascular outcomes. The cardiovascular risk reduction was more prominent with EPA monotherapy ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10776907/

Docosahexaenoic acid - PMC

In adults, whereas n-3 LCPUFAs supplementation has led to some improvement in individuals with mild cognitive impairment, data are inconsistent ...

6.

redox.com

redox.com/wp-content/sds/1494.pdf

Safety Data Sheet Omega-3 Fatty Acids

Fire and Explosion Hazard. Containers may explode when heated. Fire may produce irritating and/or toxic fumes/vapours. SAFETY DATA SHEET OMEGA-3 ...

7.

fda.gov

fda.gov/media/182149/download

GRAS Notice (GRN) 1185, Docosahexaenoic Acid (DHA)

The enclosed document provides the notice of a claim that a food ingredient, the DHA-rich oil, described in the enclosed notification is exempt ...

8.

webmd.com

webmd.com/vitamins/ai/ingredientmono-864/docosahexaenoic-acid-dha

Docosahexaenoic Acid (Dha) - Uses, Side Effects, and More

Taking more than 3 grams daily of DHA and other omega-3 fatty acids is possibly unsafe. Doing so might slow blood clotting and increase the ...

9.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0952327809000945

Toxicology and safety of DHA

DHA consumption does not result in consistent adverse events in infants or adults. Safe intake levels may be modeled on DHA intake from human milk in infants.