Omega-3 Fatty Acids for Type 2 Diabetes Risk Factors

Overseen By Riane Mahiout, BSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Institut de Recherches Cliniques de Montreal

Must not be taking: Hormone therapy, Corticosteroids, Antipsychotics, others

Disqualifiers: Cardiovascular disease, Diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

Every 3 minutes a new case of diabetes is diagnosed in Canada, mostly type 2 diabetes (T2D) increasing the risk for heart disease. T2D and heart disease share many common risk factors such as aging, obesity and unhealthy lifestyle. Paradoxically however, while lowering blood LDL, commonly known as "bad cholesterol", is protective against heart disease, research over the past 10 years have shown that the lower is blood LDL, the higher is the chance of developing T2D. This phenomena is happening whether blood LDL is lowered by a common drug against heart disease called Statins, or by being born with certain variations in genes, some of which are very common (\~80% of people have them). To date, it is unclear why lowering blood LDL is associated with higher risk for diabetes, and whether this can be treated naturally with certain nutrients. Investigators believe that lowering blood LDL by forcing LDL entry into the body tissue through their receptors promotes T2D. This is because investigators have shown that LDL entry into human fat tissue induces fat tissue dysfunction, which would promote T2D especially in subjects with excess weight. On the other hand, investigators have shown that omega-3 fatty acids (omega-3) can directly treat the same defects induced by LDL entry into fat tissue. Omega-3 is a unique type of fat that is found mostly in fish oil. Thus the objectives of this clinical trial to be conducted in 48 subjects with normal blood LDL are to explore if: 1. Subjects with higher LDL receptors and LDL entry into fat tissue have higher risk factors for T2D compared to subjects with lower LDL receptors and LDL entry into fat tissue 2. 6-month supplementation of omega-3 from fish oil can treat subjects with higher LDL receptors and LDL entry into fat tissue reducing their risk for T2D. This study will thus explore and attempt to treat a new risk factor for T2D using an inexpensive and widely accessible nutraceutical, which would aid in preventing T2D in humans.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants on hormone replacement therapy (except stable thyroid hormone), systemic corticosteroids, anti-psychotic medications, psycho-active medication, anticoagulant or anti-aggregates treatment, adrenergic agonist, anti-hypertensive drugs, weight-loss medication, and lipid-lowering medication.

What data supports the effectiveness of the treatment Omega-3 fatty acids for type 2 diabetes risk factors?

Research shows that omega-3 fatty acids can lower triglycerides (a type of fat in the blood) and may improve blood flow, which could be beneficial for heart health in people with type 2 diabetes. However, their direct effect on blood sugar levels and diabetes risk is still unclear. ^{1 2 3 4 5}

Is it safe to take omega-3 fatty acids for type 2 diabetes risk factors?

Omega-3 fatty acids, found in supplements like fish oil and krill oil, are generally considered safe for most people and have been shown to have heart health benefits. However, high doses can sometimes cause side effects like upset stomach or bleeding, so it's important to follow recommended dosages and consult with a healthcare provider. ^{1 2 4 6 7}

How does the treatment of omega-3 fatty acids differ from other treatments for type 2 diabetes?

Omega-3 fatty acids, such as EPA and DHA, are unique because they are natural compounds found in fish oil and are being studied for their potential to lower the risk of type 2 diabetes by affecting lipid (fat) levels in the blood. Unlike standard diabetes medications that directly lower blood sugar, omega-3s may offer cardiovascular benefits, although their exact role in diabetes prevention is still being researched. ^{1 2 5 8 9}

Research Team

May Faraj, PDt, PhD

Principal Investigator

Montreal Clinical Research Institute/ University of Montreal

Eligibility Criteria

This trial is for sedentary adults aged 45-74 with a BMI of 25-40 who are non-smokers, drink little alcohol, and have normal blood LDL cholesterol. It's not for those allergic to seafood or fish, with recent cancer history, high cardiovascular risk needing immediate treatment, diabetes, severe hypertension, renal or liver dysfunction, certain medication use or other medical conditions that the physician finds unsuitable.

Inclusion Criteria

You do not exercise regularly (less than 2 hours of structured physical activity per week).

I am a man or post-menopausal woman with a BMI between 25-40.

You are confirmed to have reached menopause based on a hormone test result.

Exclusion Criteria

You are allergic to seafood or fish.

I have diabetes or my fasting blood sugar is high.

I have a condition that makes me bleed easily.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Weight Stabilization

Participants undergo weight stabilization with a +/- 2 kg change over 4 weeks and confirmation of eligibility after a medical examination

4 weeks

1 visit (in-person)

Baseline Testing

Baseline testing to assess participants' risk factors for T2D, including white adipose tissue NLRP3 inflammasome activity, systemic inflammation, and insulin secretion and sensitivity

1-4 weeks

2 visits (in-person)

Treatment

24-week intervention with omega-3 fatty acid supplementation (3.6 g EPA and DHA, 2:1 ratio)

24 weeks

Regular check-ins (frequency not specified)

Post Intervention Testing

Post intervention testing to assess risk factors for T2D that were measured at baseline

1-4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Omega-3 fatty acids

Trial Overview The study tests if omega-3 fatty acids from fish oil can reduce the risk of type 2 diabetes in people with higher LDL receptors and fat tissue entry. Participants will take omega-3 supplements for six months to see if it treats defects caused by LDL entering fat tissue.

Participant Groups

Group I: Omega-3 fatty acids Experimental Treatment 1 Intervention

3.6 g EPA:DHA / day (2:1)

Omega-3 fatty acids is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Omega-3 fatty acids for:

• Hypertriglyceridemia
• Cardiovascular health

Approved in European Union as Omega-3 fatty acids for:

• Hypertriglyceridemia
• Cardiovascular health

Approved in Canada as Omega-3 fatty acids for:

• Hypertriglyceridemia
• Cardiovascular health

Who Is Running the Clinical Trial?

Institut de Recherches Cliniques de Montreal

Lead Sponsor

Trials

72

Recruited

10,300+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

A systematic review of 46 randomized clinical trials involving 4991 patients with type 2 diabetes found that omega-3 polyunsaturated fatty acids (n-3 PUFAs) significantly improved several cardiovascular risk factors, including total cholesterol, triglycerides, and hemoglobin A1c levels.

The study indicates that while n-3 PUFAs positively affect cardiovascular risk markers, they do not significantly impact renal function or insulin resistance, suggesting a targeted benefit for lipid profiles in type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of omega-3 fatty acids in type 2 diabetes: A systematic review and meta-analysis. Xiao, Y., Zhang, Q., Liao, X., et al.[2022]

In a study of 43,176 Chinese men and women aged 45-74, higher intakes of total omega-3 fatty acids were linked to a lower risk of developing type 2 diabetes, suggesting a protective effect.

Specifically, nonmarine omega-3 fatty acids (like ALA) were associated with a significant reduction in diabetes risk, while marine omega-3s (EPA and DHA) did not show a similar association.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids and incident type 2 diabetes: the Singapore Chinese Health Study. Brostow, DP., Odegaard, AO., Koh, WP., et al.[2023]

A review of 11 clinical trials involving (n-3) fatty acids in participants with type 2 diabetes showed no significant changes in fasting glucose or insulin levels, indicating that these fatty acids may not directly improve blood sugar control.

However, (n-3) fatty acids were found to lower serum triglycerides and potentially improve arterial blood flow, suggesting they could have cardiovascular benefits for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(n-3) Fatty Acids: Clinical Trials in People with Type 2 Diabetes. Hendrich, S.[2023]

Polyunsaturated fatty acids (PUFA) of the n-3 series are crucial for health, offering benefits like reducing cardiovascular risk and improving insulin sensitivity, which can help protect against obesity and type 2 diabetes.

Despite their benefits, there is some controversy regarding the effects of n-3 versus n-6 fatty acids, and high doses of n-3 fatty acid supplements may have adverse effects, highlighting the need for careful dietary management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-3 fatty acids in glucose metabolism and insulin sensitivity. Martín de Santa Olalla, L., Sánchez Muniz, FJ., Vaquero, MP.[2022]

A systematic review of 16 studies involving over 540,000 individuals found no significant association between the consumption of fish or seafood and the risk of developing type 2 diabetes, nor between EPA and DHA intake and diabetes risk.

While dietary alpha-linolenic acid (ALA) showed a non-significant trend towards a lower risk of diabetes, the overall findings suggest that neither fish/seafood nor EPA/DHA consumption poses major benefits or harms regarding diabetes development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis. Wu, JH., Micha, R., Imamura, F., et al.[2022]

In a randomized, double-blind trial with 47 participants, krill oil supplementation for 4 weeks improved endothelial function and reduced blood C peptide levels and insulin resistance compared to olive oil.

After an additional 17 weeks of krill oil supplementation, participants showed significant improvements in endothelial function and increased levels of high-density lipoprotein (HDL), indicating potential cardiovascular benefits for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of krill oil on endothelial function and other cardiovascular risk factors in participants with type 2 diabetes, a randomized controlled trial. Lobraico, JM., DiLello, LC., Butler, AD., et al.[2019]

In a study with male C57BL/6N mice fed a high-fat diet, omega-3 phospholipids (ω3PL) preserved insulin sensitivity and improved glucose metabolism, unlike omega-3 triacylglycerols (ω3TG), which worsened insulin sensitivity.

The research suggests that omega-3 PUFA from phospholipids, particularly from Krill oil, may enhance glucose homeostasis and could be beneficial as nutritional supplements for improving insulin sensitivity in obese type 2 diabetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased plasma levels of palmitoleic acid may contribute to beneficial effects of Krill oil on glucose homeostasis in dietary obese mice. Rossmeisl, M., Pavlisova, J., Bardova, K., et al.[2020]

In a study of 2,212 middle-aged and older Finnish men, higher levels of serum long-chain omega-3 polyunsaturated fatty acids (PUFAs) like EPA, DPA, and DHA were linked to a 33% lower risk of developing type 2 diabetes over an average follow-up of 19.3 years.

No significant associations were found between type 2 diabetes risk and other factors such as dietary ALA, dietary fish intake, or hair mercury levels, suggesting that the protective effect is specifically related to serum long-chain omega-3 PUFAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum omega-3 polyunsaturated fatty acids and risk of incident type 2 diabetes in men: the Kuopio Ischemic Heart Disease Risk Factor study. Virtanen, JK., Mursu, J., Voutilainen, S., et al.[2018]

In a pooled analysis of 65,147 participants from 20 studies, higher levels of seafood-derived n-3 fatty acids (EPA, DPA, DHA) were linked to a significantly lower risk of developing type 2 diabetes (T2D), with hazard ratios indicating a protective effect.

In contrast, the plant-derived n-3 fatty acid ALA showed no significant association with T2D risk, suggesting that the source of n-3 fatty acids may influence their impact on diabetes prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies. Qian, F., Ardisson Korat, AV., Imamura, F., et al.[2022]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

The effects of omega-3 fatty acids in type 2 diabetes: A systematic review and meta-analysis. [2022]

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

Omega-3 fatty acids and incident type 2 diabetes: the Singapore Chinese Health Study. [2023]

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

(n-3) Fatty Acids: Clinical Trials in People with Type 2 Diabetes. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

N-3 fatty acids in glucose metabolism and insulin sensitivity. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Effects of krill oil on endothelial function and other cardiovascular risk factors in participants with type 2 diabetes, a randomized controlled trial. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Increased plasma levels of palmitoleic acid may contribute to beneficial effects of Krill oil on glucose homeostasis in dietary obese mice. [2020]

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

Serum omega-3 polyunsaturated fatty acids and risk of incident type 2 diabetes in men: the Kuopio Ischemic Heart Disease Risk Factor study. [2018]

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

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies. [2022]