Ketone Supplementation for Polycystic Ovary Syndrome

Recruiting at 1 trial location

Overseen By Charlotte Usselman, Ph.D

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: McGill University

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

Disqualifiers: Smoking, Cardiometabolic disease, Pregnancy, others

Compensation: Varies

Number of Visits: 2

Duration: 2 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ketone supplements (exogenous ketone supplementation) can improve heart health in women with polycystic ovary syndrome (PCOS), a condition often associated with insulin resistance and high blood pressure. Participants will consume both a ketone drink and a placebo on different days to determine which has better effects on blood sugar control and blood pressure. Women diagnosed with PCOS who do not smoke or have heart disease may be suitable for this study. As an unphased trial, it offers participants the chance to contribute to valuable research that could lead to improved heart health strategies for women with PCOS.

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.

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

Research has shown that ketone supplements are safe and generally well-tolerated. One study found that a specific type of ketone supplement, called a ketone monoester, was safe for healthy adults. Another study confirmed this, demonstrating that it can induce ketosis without causing issues.

These findings suggest that ketone supplements are generally safe. They have been used to help lower blood sugar and certain hormone levels in women with PCOS, showing potential benefits without serious side effects. This is encouraging, but effects can differ from person to person.

These studies provide strong evidence for the safety of ketone supplements. However, consulting a healthcare provider about whether joining the trial is a good choice is always wise. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ketone supplementation for Polycystic Ovary Syndrome (PCOS) because it offers a fresh approach to managing the condition. Unlike standard treatments like hormonal therapies and insulin sensitizers, ketone supplementation uses a unique active ingredient, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, to potentially impact metabolic pathways directly. This could provide a novel way to address insulin resistance, a common issue in PCOS, without relying on traditional medications. Moreover, by providing energy through an alternative metabolic pathway, ketone supplementation might offer benefits in managing symptoms more efficiently and with fewer side effects.

What evidence suggests that ketone supplementation might be an effective treatment for PCOS?

Research has shown that ketone supplements, which participants in this trial may receive, can help lower blood sugar levels in women with polycystic ovary syndrome (PCOS). Lowering blood sugar is important because it can help with insulin resistance, a common issue in PCOS. Other studies suggest that ketone supplements might also improve blood flow and reduce blood pressure. These benefits indicate that ketone supplements could support heart health in women with PCOS. Although more research is needed, early results are promising for those seeking to improve heart health with PCOS. ^{1 6 7 8 9}

Who Is on the Research Team?

Charlotte Usselman, Ph.D

Principal Investigator

McGill University

Are You a Good Fit for This Trial?

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 have been diagnosed with PCOS.

I was assigned female at birth.

Exclusion Criteria

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

Current pregnancy or currently breastfeeding

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Exogenous Ketone Supplementation

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

The ketogenic diet (KD) significantly improved metabolic parameters in DHEA-induced PCOS mice, including reduced body weight and lower blood glucose levels, while also increasing blood ketone levels after 1 to 3 weeks of treatment.

KD treatment enhanced ovarian function and reduced inflammation and cell apoptosis in the ovaries of PCOS mice, suggesting that the ketone body β-hydroxybutyrate may play a key role in these therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a ketogenic diet on reproductive and metabolic phenotypes in mice with polycystic ovary syndrome†. Liu, S., Yao, Q., Li, X., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40393075/

Ketone supplementation acutely lowers androgen and ... This study aimed to determine whether BHB supplementation acutely lowers circulating androgen and glucose levels in women with PCOS.

2. withpower.com withpower.com/trial/phase-polycystic-ovary-syndrome-2024-318fb

Ketone Supplementation for Polycystic Ovary Syndrome The objectives are to compare responses between KME and placebo ingestion, and examine all outcomes related to cardiovascular health in females with PCOS in ...

3. researchgate.net researchgate.net/publication/391642493_Ketone_supplementation_acutely_lowers_androgen_and_glucose_levels_in_women_with_polycystic_ovary_syndrome_PCOS

Ketone supplementation acutely lowers androgen and ... Ketone supplementation acutely lowers androgen and glucose levels in women with polycystic ovary syndrome (PCOS)

4. ecss2006.com ecss2006.com/ASP/CONGRESS/TOOLS/Scientific_Programme/Sessions_Abstract_Read.asp?mySessionID=CP-MH30&myAbstractID=1887

ECSS Congress Exogenous ketone supplementation can decrease blood glucose concentration and has been suggested to improve vascular function via improvements in blood flow in ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06155708/exogenous-ketone-supplementation-in-females-with-polycystic-ovary-syndrome

Exogenous Ketone Supplementation in Females with ... The objectives are to compare responses between KME and placebo ingestion, and examine all outcomes related to cardiovascular health in females ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03461068

NCT03461068 | Exogenous Ketones and Glucose Tolerance The purpose of this study is to determine whether supplementing with an acute dose of ketone monoester can improve the glycemic response to an oral glucose ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31655093/

Safety and tolerability of sustained exogenous ketosis ... We conclude that sustained exogenous ketosis using a ketone monoester is safe and well-tolerated by healthy adults.

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05762822/exogenous-ketone-ester-in-women-with-polycystic-ovary-syndrome

Exogenous Ketone Ester in Women with Polycystic Ovary ... Clinical studies suggest that ketogenic diets lower the levels of androgens. The ketone 3-hydroxybutyrate (3-OHB) may play an important role in ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724003613

Ketone Ester Effects on Biomarkers of Brain Metabolism ... This is the first study to investigate the AD-biomarker and cognitive effects of KME in humans. Ketone monoester is safe, tolerable, induces robust ketosis.