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

72 Participants Needed

Trial Summary

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.

What data supports the idea that DHA for Healthy Nutrition is an effective treatment?

The available research shows that DHA is effective in improving mental development and visual function in infants when added to their diet. It also suggests that low levels of DHA are linked to increased risks of depression and Alzheimer's disease in older people. Additionally, DHA has been shown to improve brain function in animal studies after brain injury. Compared to other treatments, DHA is particularly noted for its role in brain health and development. ^{1 2 3 4 5}

What safety data is available for DHA treatment?

The provided research abstracts do not directly address safety data for DHA treatment. They focus on the development and characterization of DHA delivery systems, its health benefits, and its role in development and metabolism. For specific safety data, further investigation into clinical trials or safety studies would be necessary. ^{4 6 7 8 9}

Is DHA a promising treatment for healthy nutrition?

Yes, DHA is a promising treatment for healthy nutrition. It is an essential omega-3 fatty acid found in fish and supplements, known for its benefits in brain development, body composition, and overall health. It supports neurological functions, enhances lean body mass, and has anti-inflammatory properties. ^{7 8 10 11 12}

What is the purpose of this trial?

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.

Research Team

Richard P Bazinet, PhD

Principal Investigator

University of Toronto

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment with docosahexaenoic acid after hypoxia-ischemia improves forepaw placing in a rat model of perinatal hypoxia-ischemia. [2021]

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Protocol for assessing whether cognition of preterm infants [2021]

5. France pubmed.ncbi.nlm.nih.gov

The n-3 docosapentaenoic acid (DPA): A new player in the n-3 long chain polyunsaturated fatty acid family. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Phospholipid Species in Newborn and 4 Month Old Infants after Consumption of Different Formulas or Breast Milk. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Docosahexaenoic Acid Inhibits PTP1B Phosphatase and the Viability of MCF-7 Breast Cancer Cells. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Self-nanoemulsifying drug delivery system of docosahexanoic acid: development, in vitro, in vivo characterization. [2022]

9. India pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Oxidation Parameters in Volunteers Supplemented with Microencapsulated Docosahexaenoic Acid. [2022]

10. Spain pubmed.ncbi.nlm.nih.gov

[Importance of docosahexaenoic acid (DHA): Functions and recommendations for its ingestion in infants]. [2010]

11. United States 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. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Docosahexaenoic Acid at 0.4% of Dietary Weight Enhances Lean Mass in Young Female Sprague-Dawley Rats. [2023]