Ketone Supplementation for Polycystic Ovary Syndrome

Overseen By Charlotte Usselman, Ph.D

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: McGill University

Must not be taking: Anti-hypertensives, Anti-androgens, Metformin

Disqualifiers: Smoking, Cardiometabolic disease, Pregnancy, others

Trial Summary

What is the purpose of this trial?

Polycystic ovary syndrome (PCOS) affects 1 in 5 females of reproductive age. Commonly characterized as a disorder of infertility, PCOS is often accompanied by 3 potent cardiovascular disease (CVD) risk factors: insulin resistance, endothelial dysfunction, and elevated blood pressure. Accordingly, PCOS is associated with the development of CVD, the second leading cause of death in females in Canada. However, effective treatments to improve cardiovascular health in PCOS are lacking. Exogenous ketone monoester (KME) ingestion has been shown to improves outcomes associated with insulin resistance, endothelial function, and blood pressure regulation in healthy individuals and individuals predisposed to CVD. Therefore, oral ketone supplements offer a practical and effective strategy for improving cardiovascular health; however, this treatment has yet to be evaluated in PCOS. Therefore, the overall goal of this project is to employ KME ingestion to improve markers of cardiovascular health in females with PCOS. On two different days, participants will consume either a beverage containing a ketone supplement or a beverage containing a placebo supplement. The objectives are to compare responses between KME and placebo ingestion, and examine all outcomes related to cardiovascular health in females with PCOS in comparison with female controls of similar age and body mass index. The effects of KME ingestion will be quantified on: 1) glycemic control during an oral glucose tolerance test; 2) endothelial function using the flow-mediated dilation test; 3) blood pressure and acute blood pressure regulation; and 4) hemodynamic responses to acute exercise.

Will I have to stop taking my current medications?

Yes, you will need to stop taking medications that could affect the study's outcomes, such as blood pressure medications, anti-androgens, and metformin.

What data supports the effectiveness of the treatment Exogenous Ketone Supplementation for Polycystic Ovary Syndrome?

Research on ketogenic diets, which increase ketone levels in the body, shows benefits for women with PCOS, such as weight loss, improved insulin sensitivity, and better reproductive health. These findings suggest that ketone supplementation might also help manage PCOS symptoms. ^{1 2 3 4 5}

How does exogenous ketone supplementation differ from other treatments for PCOS?

Exogenous ketone supplementation is unique because it provides an alternative energy source by increasing ketone levels in the body, which may help manage insulin resistance, a common issue in PCOS. Unlike other treatments that focus on hormone regulation or antioxidant effects, this approach targets metabolic pathways directly. ^{1 6 7 8 9}

Research Team

Charlotte Usselman, Ph.D

Principal Investigator

McGill University

Eligibility Criteria

This trial is for females aged 18 to 40 who have been diagnosed with Polycystic Ovary Syndrome (PCOS). Participants must not be current smokers or have a significant smoking history, and should not have any major heart, metabolic, neurological diseases, or other endocrine disorders besides PCOS. They also shouldn't be pregnant, breastfeeding, or on medications that could affect the study's outcomes.

Inclusion Criteria

I am between 18 and 40 years old.

I have been diagnosed with PCOS.

I was assigned female at birth.

Exclusion Criteria

I am currently smoking or have a long history of smoking.

I have or had serious heart, blood pressure, brain, hormone diseases except for PCOS.

Current pregnancy or currently breastfeeding

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants consume either a ketone supplement or a placebo on two different days to assess cardiovascular health markers

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Exogenous Ketone Supplementation (Other)

Trial Overview The trial is testing whether drinking a ketone supplement can improve cardiovascular health in women with PCOS. It compares the effects of this supplement to a placebo drink on blood sugar control after eating glucose, blood vessel function, blood pressure regulation during rest and exercise.

Participant Groups

Group I: Ketone Experimental Treatment 1 Intervention

- Ketone monoester supplement in the form of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.45ml/kg body weight) ingested with water and vanilla-flavored stevia in a total volume of 100 ml.

Group II: Placebo Placebo Group 1 Intervention

100 ml water combined with 10ml bitter flavor and vanilla-flavored stevia

Who Is Running the Clinical Trial?

McGill University

Lead Sponsor

Trials

421

Recruited

1,017,000+

Findings from Research

A ketogenic diet (KD) significantly improved liver function markers in obese women with polycystic ovary syndrome (PCOS) and liver dysfunction, with six out of seven participants showing resolution of fatty liver after 12 weeks, compared to only one out of ten in the control group.

The KD group also experienced notable reductions in body weight and blood glucose levels, alongside improvements in menstrual cycle regularity, demonstrating its potential as an effective alternative to conventional pharmacological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open-label, parallel-group, controlled pilot trial. Li, J., Bai, WP., Jiang, B., et al.[2021]

The ketogenic diet (KD) shows promise in managing polycystic ovary syndrome (PCOS) by improving insulin sensitivity, regulating weight, and enhancing metabolic health, particularly in adolescents with excessive body weight.

Despite its potential benefits, there is limited research specifically on the effects of a low-calorie ketogenic diet in adolescents with PCOS, highlighting the need for further studies to clarify its long-term impacts on fertility and metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Calorie Ketogenic Diet: Potential Application in the Treatment of Polycystic Ovary Syndrome in Adolescents. Calcaterra, V., Cena, H., Sottotetti, F., et al.[2023]

In a study of 28 overweight women with polycystic ovary syndrome (PCOS) over 16 weeks, both high protein and low protein diets led to significant weight loss (7.5%) and reductions in abdominal fat (12.5%), improving menstrual cyclicity and insulin resistance regardless of diet type.

While both diets were effective, the high protein diet showed minor advantages in endocrine and metabolic improvements, suggesting that weight loss itself is crucial for enhancing cardiovascular and reproductive health in women with PCOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. Moran, LJ., Noakes, M., Clifton, PM., et al.[2022]

In a study of 84 obese/overweight women with PCOS, a very-low-calorie ketogenic diet (VLCKD) led to significantly greater reductions in BMI and body circumference compared to a Mediterranean diet (MD) over 120 days.

The VLCKD also resulted in improved metabolic parameters, such as lower HOMA index values and reduced incidence of ovarian hyperstimulation syndrome (OHSS), making it a promising dietary approach for enhancing reproductive health and preparing for IVF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Nutritional Therapy in the Management of Overweight/Obese PCOS Patient Candidates for IVF. Meneghini, C., Bianco, C., Galanti, F., et al.[2023]

Antioxidant supplements significantly improve insulin resistance, fasting insulin levels, and fasting plasma glucose in women with polycystic ovary syndrome (PCOS), based on a systematic review of 18 trials involving 1113 participants.

While these supplements are effective for enhancing glucose metabolism, they do not significantly improve most lipid profile indices in women with PCOS, except for triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antioxidant supplements relieve insulin resistance but do not improve lipid metabolism in women with polycystic ovary syndrome: a meta-analysis of randomized clinical trials. Wang, R., Miao, C., Chen, Y., et al.[2023]

In a 12-week study involving 70 vitamin D-deficient women with phenotype B-PCOS, vitamin D supplementation significantly improved metabolic parameters, including reduced fasting plasma glucose and insulin levels compared to placebo.

Vitamin D supplementation also led to decreased inflammation markers, such as high-sensitivity C-reactive protein (hs-CRP) and malondialdehyde (MDA), indicating potential benefits for overall metabolic health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Vitamin D Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Maktabi, M., Chamani, M., Asemi, Z.[2018]

In a study of 60 vitamin D-deficient women with PCOS, co-supplementation of vitamin D, vitamin K, and calcium for 8 weeks significantly reduced levels of free testosterone and dehydroepiandrosterone sulfate (DHEAS), indicating potential hormonal benefits.

The supplementation also improved oxidative stress markers, showing a significant increase in plasma total antioxidant capacity and a decrease in malondialdehyde levels, suggesting enhanced antioxidant defense in these women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Vitamin D-K-Calcium Co-Supplementation on Endocrine, Inflammation, and Oxidative Stress Biomarkers in Vitamin D-Deficient Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Razavi, M., Jamilian, M., Karamali, M., et al.[2017]

Polycystic ovary syndrome (PCOS) affects up to 25% of women of reproductive age and is linked to serious long-term health issues like insulin resistance and cardiovascular risk.

Natural supplements such as inositols, resveratrol, and omega-3 fatty acids may help alleviate PCOS symptoms by addressing key issues like insulin resistance, hyperandrogenism, and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural Molecules in the Management of Polycystic Ovary Syndrome (PCOS): An Analytical Review. Iervolino, M., Lepore, E., Forte, G., et al.[2021]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open-label, parallel-group, controlled pilot trial. [2021]

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

Effects of a ketogenic diet on reproductive and metabolic phenotypes in mice with polycystic ovary syndrome†. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Low-Calorie Ketogenic Diet: Potential Application in the Treatment of Polycystic Ovary Syndrome in Adolescents. [2023]

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

Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Impact of Nutritional Therapy in the Management of Overweight/Obese PCOS Patient Candidates for IVF. [2023]

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

Antioxidant supplements relieve insulin resistance but do not improve lipid metabolism in women with polycystic ovary syndrome: a meta-analysis of randomized clinical trials. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

The Effects of Vitamin D Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

The Effects of Vitamin D-K-Calcium Co-Supplementation on Endocrine, Inflammation, and Oxidative Stress Biomarkers in Vitamin D-Deficient Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. [2017]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Natural Molecules in the Management of Polycystic Ovary Syndrome (PCOS): An Analytical Review. [2021]