Ketone supplementation acutely lowers androgen and glucose levels in women with polycystic ovary syndrome: a randomized clinical trial

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BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder linked to insulin resistance and elevated androgens. While ketogenic diets reduce androgen and glucose levels in women with PCOS, the direct role of β-hydroxybutyrate (BHB) remains unclear. This study aimed to determine whether BHB supplementation acutely lowers circulating androgen and glucose levels in women with PCOS. METHODS: A randomized, placebo-controlled crossover trial was conducted involving 20 women diagnosed with PCOS. Participants underwent fasting blood sampling on 2 occasions. They were randomly assigned to receive either a ketone supplement or a taste-matched placebo. Each intervention was administered over 10 h, with 1 dose administered the evening before and another 2 h prior to blood collection. RESULTS: Following BHB supplementation, blood D-β-hydroxybutyrate levels reached 2.4 ± 1.2 mM, compared with 0.1 ± 0.1 mM in the control group (P < .001). Androgen concentrations were generally lower with BHB supplementation, with mean reductions in testosterone (-13%, 95% CI, -27 to 1, P = .067), free testosterone (-21%, 95% CI, -43% to 1%, P = .057), androstenedione (-14%, 95% CI, -29 to 0, P = .050), and 11-ketotestosterone (-21%, 95% CI, -38 to -4, P = .020) compared with control. Fasting plasma glucose levels were 4.6 ± 0.7 mM after BHB supplementation, versus 5.1 ± 0.4 mM in the placebo group (mean -10%, 95% CI, -5% to -15%, P < .001). CONCLUSION: Ketone supplementation acutely lowers androgen and glucose levels in women with PCOS. These findings highlight the potential for ketone-based therapies as a novel treatment for PCOS and suggest the need for long-term clinical trials to further explore these effects. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05762822).