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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a supplement called Palmitoleic acid (POA) can improve insulin sensitivity and reduce liver fat in people with prediabetes. POA is a special kind of fat that might help lower the risk of type-2 diabetes and heart disease. Participants will take either the POA supplement or a placebo (a substance with no health effects) for eight weeks. The trial seeks overweight or obese adults with prediabetes who struggle with blood sugar control. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new ways to manage prediabetes.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that palmitoleic acid (POA), a type of omega-7 fat, is generally safe for consumption. Studies have found that POA can help control blood sugar and reduce liver fat without causing serious side effects. In previous research, participants who took POA experienced better heart health, such as improved cholesterol levels, and did not report major negative effects. Although detailed studies on humans remain limited, animal research supports these benefits, showing improvements in liver and muscle health. This trial is in the "Not Applicable" phase, indicating that the treatment is expected to be safe based on current evidence. This makes POA an interesting option for those with prediabetes seeking a natural supplement. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about palmitoleic acid for prediabetes because it offers a novel approach compared to the usual lifestyle modifications and medications like metformin. Unlike these standard treatments, palmitoleic acid is a monounsaturated fatty acid that may improve insulin sensitivity by directly influencing fat metabolism. This unique mechanism could provide an additional or alternative option for managing prediabetes, particularly for individuals who may not respond well to existing treatments. The potential for palmitoleic acid to offer benefits with fewer side effects makes it an appealing candidate for further study.

What evidence suggests that Palmitoleic acid might be an effective treatment for prediabetes?

Research has shown that Palmitoleic acid (POA), a type of healthy fat, may improve insulin use and reduce liver fat. People with higher POA levels tend to have a lower risk of developing type-2 diabetes and heart disease. In animal studies, POA helped the liver and muscles process sugar more effectively. Research also suggests that POA might reduce inflammation and improve overall metabolism. While these findings are encouraging, this trial will compare the effects of POA supplementation with a placebo in people with prediabetes to better understand its impact. ^{1 2 3 6 7}

Who Is on the Research Team?

Mehmet Furkan Burak, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

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Protocol for a randomized placebo-controlled clinical trial ... This double-blind placebo-controlled clinical trial tests the hypothesis that POA increases insulin sensitivity and decreases hepatic lipogenesis in overweight ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10835623/

Protocol for a randomized placebo-controlled clinical trial ... This double-blind placebo-controlled clinical trial tests the hypothesis that POA increases insulin sensitivity and decreases hepatic lipogenesis in overweight ...

3. withpower.com withpower.com/trial/phase-insulin-resistance-10-2022-e55ac

Monounsaturated Fatty Acid Supplementation for ... 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 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000291652500320X

Effects of a palmitoleic acid concentrated oil on C-reactive ... Palmitoleic acid (POA) is an n–7 monounsaturated fatty acid. Preclinical studies suggest cis-POA lowers inflammation and improves metabolism.

5. academic.oup.com academic.oup.com/nutritionreviews/article/83/5/897/7895736

Effect of Fatty Acids on Glucose Metabolism and Type 2 ... This review will provide an update on the mechanisms of action of fatty acids on glucose metabolism and type 2 diabetes, as well as dietary recommendations

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S175646461930444X

A review of biological functions, health benefits, and ... Palmitoleic acid, also known as (9Z)-hexadec-9-enoic acid, is an omega-7 monounsaturated fatty acid that is known to exhibit multiple biological functions.

7. metabolon.com metabolon.com/metabolites/palmitoleic-acid/

Palmitoleic Acid Similarly, other studies demonstrated that palmitoleic acid supplementation in a mouse model of type 2 diabetes significantly reduced liver and hepatic ...