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.
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.
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.
Parallel
Ketogenic diet
Other interventionA well-formulated ketogenic diet designed to achieve nutritional ketosis (β-hydroxybutyrate ≥0.5 mmol/L). The diet emphasizes non-starchy vegetables as the primary carbohydrate source (20-50 g/day), moderate protein intake (1.2-1.6 g/kg/day), and sufficient dietary fat for energy and satiety. All meals and snacks will be provided during the initial two weeks, followed by a self-guided phase with ongoing dietitian support and education materials. Participants will monitor daily fasting ketones and glucose using a handheld analyzer (KetoMojo).
Exogenous Ketone Supplement
Dietary supplementA dietary supplement containing a ketone ester designed to elevate circulating β-hydroxybutyrate concentrations to nutritional ketosis levels without carbohydrate restriction. Participants will consume the supplement throughout the 12-week intervention while following a balanced, mixed diet consistent with USDA dietary guidelines.
Change in Ovulatory Status
To evaluate whether ketogenic dietary intervention or exogenous ketone supplementation restores ovulatory function in women with Polycystic Ovary Syndrome (PCOS). Ovulatory status will be assessed using a combination of validated measures, including basal body temperature monitoring via BBT, urinary luteinizing hormone (LH) surge detection using ovulation predictor kits, and serum progesterone levels. Participants will be classified as ovulatory or anovulatory based on hormonal and temperature cycle confirmation.
Change in Serum Progesterone Concentration (ng/mL)
To determine the effects of ketogenic diet and exogenous ketone supplementation on circulating reproductive hormone concentrations. Serum progesterone will be analyzed using standard immunoassay techniques (Quest Diagnostics panels and/or validated ELISA assays). Hormonal changes will be compared between baseline and post-intervention to assess improvements in reproductive axis regulation.
Change in Serum Estradiol Concentration (pg/mL)
To determine the effects of ketogenic diet and exogenous ketone supplementation on circulating reproductive hormone concentrations. Serum estradiol will be analyzed using commercially available immunoassay kits (Quest Diagnostics panels and/or validated ELISA assays). Hormonal changes will be compared between baseline and post-intervention to assess improvements in reproductive axis regulation.
Change in Serum Luteinizing Hormone Concentration (mIU/mL)
To determine the effects of ketogenic diet and exogenous ketone supplementation on circulating reproductive hormone concentrations. Serum luteinizing hormone (LH) will be analyzed using standard immunoassay techniques (Quest Diagnostics panels and/or validated ELISA assays). Hormonal changes will be compared between baseline and post-intervention to assess improvements in reproductive axis regulation.
Change in Serum Follicle Stimulating Hormone Concentrations (mIU/mL)
To determine the effects of ketogenic diet and exogenous ketone supplementation on circulating reproductive hormone concentrations. Serum follicle-stimulating hormone (FSH) will be analyzed using standard immunoassay techniques (Quest Diagnostics panels and/or validated ELISA assays). Hormonal changes will be compared between baseline and post-intervention to assess improvements in reproductive axis regulation.
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