The SPARK- Pilot study (Symptoms of PCOS Ameliorated by Responses to Keto-adaptation) is a 12-week clinical trial at The Ohio State University designed to explore how different ways of achieving ketosis may improve reproductive and metabolic health in women with Polycystic Ovary Syndrome (PCOS).

Participants will be randomly assigned to one of two groups:

• A ketogenic diet group, following a low-carbohydrate, nutrient-dense meal plan.
• A mixed diet plus ketone supplement group, following general dietary guidelines while taking an exogenous ketone supplement.

The study will measure whether these approaches help restore regular ovulation and improve hormone balance, metabolism, and overall well-being. Optional imaging using MRI will also examine heart and ovarian health.

This pilot study will help researchers understand if ketogenic nutrition strategies are a safe, effective way to support menstrual regularity and reduce PCOS-related symptoms, providing groundwork for larger clinical trials.

The SPARK study (Symptoms of PCOS Ameliorated by Responses to Keto-adaptation) is a 12-week randomized, two-arm intervention examining how nutritional ketosis influences ovulatory and metabolic outcomes in women with Polycystic Ovary Syndrome (PCOS).

PCOS is a common endocrine disorder that affects hormone balance, menstrual function, and metabolism. Current treatments often address single symptoms but rarely provide comprehensive improvement. Ketogenic dietary interventions have shown promise for improving insulin sensitivity, hormone profiles, and body composition; however, few studies have evaluated their direct impact on ovulation.

In this pilot trial, 40 women aged 18-40 years with diagnosed PCOS will be randomized to one of two groups:

Ketogenic Diet (KD): Participants will follow a low-carbohydrate, high-fat, moderate-protein diet designed to achieve and maintain nutritional ketosis (β-hydroxybutyrate ≥0.5 mmol/L).

Mixed Diet + Exogenous Ketone Supplement: Participants will consume a balanced diet aligned with USDA macronutrient recommendations and receive a ketone ester supplement.

Primary outcomes include changes in ovulatory status, assessed through hormonal markers, ovulation prediction tests, and continuous basal body temperature monitoring (OvuSense). Secondary outcomes include changes in reproductive hormones (progesterone, estrogen, LH, FSH), metabolic and lipid markers, and exploratory imaging of cardiovascular function and ovarian morphology via MRI.

This study will provide feasibility and preliminary efficacy data to inform a future large-scale clinical trial evaluating ketogenic strategies for improving menstrual regularity and overall health in women with PCOS.

Inclusion Criteria:

• Female participants aged 18-40 years.
• Clinical diagnosis of Polycystic Ovary Syndrome (PCOS) according to Rotterdam criteria (presence of at least two of the following: oligo- or anovulation, clinical or biochemical signs of hyperandrogenism, and/or polycystic ovaries on ultrasound).
• Willingness and ability to comply with all study procedures, including fasting (>10 hours; water only), avoidance of alcohol (>24 hours), and abstaining from exercise (>24 hours) prior to each test visit.
• Willing to maintain current diet, exercise, medication, and supplement habits throughout the study.
• Body mass index (BMI) ≥18 kg/m².
• Access to a smartphone, computer, or tablet for digital tracking and study communication.

Exclusion Criteria:

• Current adherence to a low-carbohydrate diet (<30% of total energy from carbohydrates).
• Non-PCOS etiologies of anovulation (e.g., menopause, oophorectomy, or other reproductive disorders).
• History of type 1 diabetes or uncontrolled type 2 diabetes.
• Weight loss ≥10% of body weight within the previous 6 months.
• Pregnancy or breastfeeding.
• Use of hormonal contraception or medications known to alter reproductive hormones within 3 months prior to enrollment.
• Active eating disorder or medical condition that could interfere with dietary intervention.
• Any condition that, in the opinion of the Investigator, could interfere with participation, data integrity, or safety.

This study enrolls biological females aged 18-40 years who have been clinically diagnosed with PCOS. Because the primary outcomes involve menstrual cyclicity, ovulatory function, and reproductive hormone regulation, eligibility is limited to individuals assigned female at birth. Self-identified women meeting these criteria are eligible to participate, regardless of gender identity, provided they have intact ovarian function and are not pregnant or breastfeeding.

This is an early-stage pilot study focused on feasibility and exploratory outcomes. At this stage, individual participant data (IPD) will not be publicly shared until all analyses are complete and findings are published. De-identified aggregate data may be shared upon reasonable request following publication, in accordance with institutional and IRB policies. If a larger, follow-up trial is initiated, a formal data-sharing plan will be developed to align with NIH and ICMJE requirements.

This is a pilot feasibility study; therefore, no masking will be implemented. Participants and investigators will be aware of group assignments due to the distinct nature of the dietary and supplement interventions. The study is designed as an open-label trial to evaluate adherence, feasibility, and physiological responses to each intervention before planning a larger randomized, controlled study.