Monounsaturated Fatty Acid Supplementation for Prediabetes

Overseen By Lindsey Porter

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Must not be taking: OTC supplements

Disqualifiers: Diabetes, Major cardiovascular disease, others

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a supplement called Palmitoleic acid on overweight and obese adults with pre-diabetes. The supplement aims to improve how the body handles sugar and reduce liver fat. It works by helping the liver, muscles, and fat tissue function better.

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

Yes, you must stop taking most medications, except for thyroid hormone (if TSH is normal), anti-hypertensives (if blood pressure is <150/90), and non-steroidal rescue inhalers for asthma. You also cannot use over-the-counter supplements, except for vitamin D, and must avoid supplements like fish oil for 3 months before the study.

Will I have to stop taking my current medications?

Yes, you will need to stop taking most medications, except for thyroid hormone (if your thyroid levels are normal), blood pressure medications (if your blood pressure is below 150/90), and non-steroidal rescue inhalers for asthma. You also cannot use over-the-counter supplements, except for vitamin D, and must avoid supplements like fish oil and other lipid supplements for 3 months before the study.

What data supports the idea that Monounsaturated Fatty Acid Supplementation for Prediabetes is an effective treatment?

The available research shows that Monounsaturated Fatty Acid Supplementation, specifically with palmitoleic acid, can help improve insulin sensitivity and reduce inflammation in a prediabetes model. This means it can help the body use insulin more effectively and lower inflammation, which are important for managing prediabetes. Compared to other treatments like omega-3 fatty acids, which are more focused on heart health and do not significantly affect glucose control, Monounsaturated Fatty Acid Supplementation seems to have a more direct impact on managing prediabetes. ^{1 2 3 4 5}

What evidence supports the effectiveness of the treatment Palmitoleic acid for prediabetes?

Research suggests that palmitoleic acid, a type of monounsaturated fatty acid, may help regulate blood sugar and improve metabolic health, which could be beneficial for people with prediabetes. Additionally, diets rich in monounsaturated fats have been associated with better blood sugar control and lower blood pressure in diabetic patients. ^{1 2 3 4 5}

What safety data exists for monounsaturated fatty acid supplementation in prediabetes?

The available research indicates that palmitoleic acid (POA), a monounsaturated fatty acid, has been studied for its effects on glucose and lipid metabolism, insulin sensitivity, and inflammation in prediabetic models. While the specific safety data is not detailed in the provided abstracts, POA is generally reported as beneficial in terms of insulin sensitivity and glucose tolerance in both human and animal studies. However, one study mentioning POA was withdrawn, which may suggest some concerns or issues that were not specified. Overall, the studies suggest potential therapeutic benefits, but specific safety data is not explicitly provided in the abstracts. ^{1 6 7 8 9}

Is palmitoleic acid safe for humans?

Palmitoleic acid, a type of monounsaturated fatty acid, has been studied for its effects on insulin sensitivity and glucose tolerance, and is generally considered beneficial in human and animal studies. However, specific safety data for humans is limited, and more research is needed to fully understand its safety profile. ^{1 6 7 8 9}

Is Palmitoleic acid a promising treatment for prediabetes?

Palmitoleic acid, a type of monounsaturated fatty acid, shows promise as a treatment for prediabetes. It can help regulate blood sugar levels, improve how the body uses insulin, and reduce inflammation, which are all important for managing prediabetes. ^{1 2 8 10 11}

How does the treatment with palmitoleic acid differ from other treatments for prediabetes?

Palmitoleic acid is unique because it is a monounsaturated fatty acid that can help regulate glucose levels, improve lipid metabolism, and reduce inflammation, which are key factors in managing prediabetes. Unlike some other treatments, it specifically targets these metabolic processes, potentially offering a novel approach to improving insulin sensitivity and reducing the risk of developing type 2 diabetes. ^{1 2 8 10 11}

Research Team

Mehmet Furkan Burak, MD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

Adults aged 18-70 with a BMI of 25-40, prediabetes (HbA1c between 5.6 - 6.5), and no major chronic diseases can join this trial. They should not be pregnant, breastfeeding, or have recently lost significant weight. Participants must not be on certain medications or have had more than three servings/day of high-fat dairy for the last three months.

Inclusion Criteria

My blood sugar and insulin resistance levels indicate I am pre-diabetic.

BMI 25-40 kg/m2

ALT, AST <300

Exclusion Criteria

I only use thyroid medication, blood pressure medication (with BP <150/90), or asthma inhalers.

I have diabetes or take medication to lower my blood sugar.

Pregnancy or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Dietary Adjustment

Participants consume a palmitoleic acid minimized diet

2 weeks

Treatment

Participants receive either POA or placebo capsules daily

8 weeks

2 overnight visits (in-person), 1 blood draw visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Palmitoleic acid
• Placebo

Trial Overview The study is testing if Palmitoleic acid (POA), an omega-7 fat found in diet, can improve insulin sensitivity and reduce liver fat in overweight individuals with prediabetes. This double-blind placebo-controlled trial compares POA against a placebo to see which is more effective.

Participant Groups

Group I: Palmitoleic acid Active Control 1 Intervention

The treatment arm will receive Palmitoleic acid (POA) supplement as Provinal® 420 mg capsules with at least 90% pure POA Ethyl Ester (less than 1% palmitic acid). Participants will be asked to consume 2 Provinal® 420 mg capsules twice a day for 8 weeks.

Group II: Placebo Placebo Group 1 Intervention

The placebo is a medium chain fatty acid in triglyceride form. The placebo has no shown health effects, neither beneficial or detrimental. Participants will be asked to consume 2 placebo capsules daily twice a day for 8 weeks.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Tersus Life Sciences LLC

Industry Sponsor

Trials

1

Recruited

40+

Findings from Research

Palmitoleic acid (POA) supplementation significantly improved insulin sensitivity and reduced nonfasting glucose levels in prediabetic rats, indicating its potential as a therapeutic agent for metabolic disorders.

Oleic acid (OA) also showed benefits by improving lipid metabolism and reducing inflammation, but its effects were less pronounced compared to POA, highlighting the distinct metabolic roles of different monounsaturated fatty acids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Different Insulin-Sensitising and Anti-Inflammatory Effects of Palmitoleic Acid and Oleic Acid in a Prediabetes Model. Miklankova, D., Markova, I., Hüttl, M., et al.[2022]

A diet rich in monounsaturated fatty acids (MUFA) can lead to lower glucose concentrations and blood pressure in diabetic patients, with potential increases in HDL-cholesterol levels, suggesting it may be beneficial for metabolic health.

Comparative studies indicate that while MUFA diets may not significantly alter overall lipid levels, they can improve vascular function, and fish oil has a notable triglyceride-lowering effect, although its impact on glucose control remains inconsistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fat modification in the diabetes diet. Julius, U.[2015]

Consumption of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), primarily from fish, is associated with a lower risk of type 2 diabetes and offers cardioprotective benefits for individuals with diabetes, including reduced cardiovascular mortality and improved lipid profiles.

Increasing n-3 LC-PUFA intake while reducing saturated fat may help prevent the progression from impaired glucose tolerance to type 2 diabetes, suggesting a potential dietary strategy for managing insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. Nettleton, JA., Katz, R.[2022]

Omega-3 fatty acids can improve lipid profiles in type 2 diabetic patients by lowering triglycerides and VLDL-cholesterol, but they may also increase LDL-cholesterol without affecting mortality or cardiovascular disease risk.

Current research primarily focuses on type 2 diabetes, indicating a need for more studies on type 1 diabetes and the unclear role of omega-6 fatty acids in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 and omega-6 fatty acids and type 2 diabetes. Jeppesen, C., Schiller, K., Schulze, MB.[2021]

Omega-3 fatty acids, particularly eicosapentaenoic and docosahexaenoic acid, can positively affect cardiovascular risk factors in diabetic patients, such as lipid metabolism and blood pressure.

In insulin-dependent diabetics, omega-3 fatty acids do not significantly interfere with blood glucose levels, making them a safe option for managing cardiovascular risks in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of omega-3 in diabetic patients]. Nosari, I., Cortinovis, F., Lepore, G., et al.[2015]

In a study involving KKAy mice (a model of type 2 diabetes), palmitoleic acid (POA) administration led to decreased plasma glucose levels, indicating a potential benefit for glucose management in diabetes.

However, POA intake was found to enhance vasoconstriction under hyperglycemic and hyperinsulinemic conditions, suggesting that while it may help with glucose levels, it could also contribute to increased vascular complications associated with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dietary palmitoleic acid on vascular function in aorta of diabetic mice. Takenouchi, Y., Seki, Y., Shiba, S., et al.[2022]

In a randomized controlled trial involving 60 adults with dyslipidemia, supplementation with 220.5 mg of purified palmitoleic acid for 30 days led to significant reductions in inflammatory markers and harmful lipids, including a 44% decrease in C-reactive protein (CRP) and a 15% reduction in triglycerides.

The study also found that palmitoleic acid supplementation increased beneficial high-density lipoprotein (HDL) levels by 5% and decreased low-density lipoprotein (LDL) levels by 8%, suggesting its potential as a treatment for hypertriglyceridemia and related lipid disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WITHDRWAN: Purified palmitoleic acid for the reduction of high-sensitivity C-reactive protein and serum lipids: a double-blinded, randomized, placebo controlled study. Bernstein, AM., Roizen, MF., Martinez, L.[2022]

Oleic acid, a monounsaturated fatty acid, has beneficial effects on insulin sensitivity and may help prevent insulin resistance and type 2 diabetes mellitus (T2DM), unlike palmitic acid, a saturated fatty acid.

The review highlights that oleic acid can reduce inflammation, inhibit endoplasmic reticulum stress, and improve insulin signaling and β cell survival, suggesting its potential role in delaying or preventing T2DM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palmitic and Oleic Acid: The Yin and Yang of Fatty Acids in Type 2 Diabetes Mellitus. Palomer, X., Pizarro-Delgado, J., Barroso, E., et al.[2022]

A new HPLC method was developed to accurately and quickly distinguish between cis- and trans-palmitoleic acids, which are important for assessing risks related to type II diabetes and coronary heart disease, allowing for analysis in just 10 minutes.

The HPLC method showed good sensitivity and precision, with limits of detection as low as 0.05 μg/mL for trans-POA, making it a more efficient alternative to the traditional GC method for analyzing these fatty acids in fish oil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the simultaneous determination of cis- and trans-palmitoleic acid in fish oil using HPLC and GC. Huang, WW., Hong, BH., Sun, JP., et al.[2020]

Dietary recommendations for fatty acids in patients with diabetes should be tailored differently than for the general population, as n-3 fatty acids can improve insulin resistance and lower blood pressure, while n-6 fatty acids may have mixed effects on cholesterol and lipoprotein oxidation.

High-carbohydrate, low-fat diets are less effective for managing diabetes compared to diets rich in monounsaturated fatty acids (MUFAs), which improve lipid profiles and may have antioxidant benefits, suggesting that a balanced approach to fat intake is crucial for optimizing blood glucose and lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fatty acids in the management of diabetes mellitus. Berry, EM.[2018]

Oleic acid may provide better outcomes than linoleic acid for individuals with type 2 diabetes by lowering plasma glucose, insulin levels, and cholesterol, but it could also have potential atherogenic effects.

Omega-3 fatty acids are beneficial for reducing triglycerides and do not negatively impact glycemic control at doses up to 3 g/d, making them a safe option for managing heart health in diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fats and diabetes mellitus: is there a good fat? Segal-Isaacson, CJ., Carello, E., Wylie-Rosett, J.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

The Different Insulin-Sensitising and Anti-Inflammatory Effects of Palmitoleic Acid and Oleic Acid in a Prediabetes Model. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Fat modification in the diabetes diet. [2015]

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

n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. [2022]

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

Omega-3 and omega-6 fatty acids and type 2 diabetes. [2021]

5. Italy pubmed.ncbi.nlm.nih.gov

[Use of omega-3 in diabetic patients]. [2015]

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

Effects of dietary palmitoleic acid on vascular function in aorta of diabetic mice. [2022]

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

WITHDRWAN: Purified palmitoleic acid for the reduction of high-sensitivity C-reactive protein and serum lipids: a double-blinded, randomized, placebo controlled study. [2022]

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

Palmitic and Oleic Acid: The Yin and Yang of Fatty Acids in Type 2 Diabetes Mellitus. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Comparing the simultaneous determination of cis- and trans-palmitoleic acid in fish oil using HPLC and GC. [2020]

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

Dietary fatty acids in the management of diabetes mellitus. [2018]

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

Dietary fats and diabetes mellitus: is there a good fat? [2019]