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

N Rittig; M C Arlien-Søborg; M V Svart; H H Thomsen; K Kirkegaard; V H Greve; M M Nielsen; K Stochholm; M J Ornstrup; C H Gravholt

doi:10.1093/ejendo/lvaf106

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

N Rittig^*
, M C Arlien-Søborg
, M V Svart
, H H Thomsen
, K Kirkegaard
, V H Greve
, M M Nielsen
, K Stochholm
, M J Ornstrup
, C H Gravholt

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

3 Citationer (Scopus)

Abstract

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).

Originalsprog	Engelsk
Tidsskrift	European Journal of Endocrinology
Vol/bind	192
Nummer	6
Sider (fra-til)	717–727
Antal sider	11
ISSN	0804-4643
DOI	https://doi.org/10.1093/ejendo/lvaf106
Status	Udgivet - 1 jun. 2025

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Rittig, N., Arlien-Søborg, M. C., Svart, M. V., Thomsen, H. H., Kirkegaard, K., Greve, V. H., Nielsen, M. M., Stochholm, K., Ornstrup, M. J., & Gravholt, C. H. (2025). Ketone supplementation acutely lowers androgen and glucose levels in women with polycystic ovary syndrome: a randomized clinical trial. European Journal of Endocrinology, 192(6), 717–727. https://doi.org/10.1093/ejendo/lvaf106

@article{bd02b34bde8146ba85e43280ccd1e01b,

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

abstract = "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).",

keywords = "3-hydroxybutyrate, PCOS, androgens, glucose, ketones, metabolism",

author = "N Rittig and Arlien-S{\o}borg, \{M C\} and Svart, \{M V\} and Thomsen, \{H H\} and K Kirkegaard and Greve, \{V H\} and Nielsen, \{M M\} and K Stochholm and Ornstrup, \{M J\} and Gravholt, \{C H\}",

year = "2025",

month = jun,

day = "1",

doi = "10.1093/ejendo/lvaf106",

language = "English",

volume = "192",

pages = "717–727",

journal = "European Journal of Endocrinology",

issn = "0804-4643",

publisher = "Oxford University Press",

number = "6",

}

Rittig, N , Arlien-Søborg, MC , Svart, MV , Thomsen, HH , Kirkegaard, K, Greve, VH, Nielsen, MM, Stochholm, K , Ornstrup, MJ & Gravholt, CH 2025, 'Ketone supplementation acutely lowers androgen and glucose levels in women with polycystic ovary syndrome: a randomized clinical trial', European Journal of Endocrinology, bind 192, nr. 6, s. 717–727. https://doi.org/10.1093/ejendo/lvaf106

Ketone supplementation acutely lowers androgen and glucose levels in women with polycystic ovary syndrome: a randomized clinical trial. / Rittig, N ; Arlien-Søborg, M C ; Svart, M V et al.
I: European Journal of Endocrinology, Bind 192, Nr. 6, 01.06.2025, s. 717–727.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Ketone supplementation acutely lowers androgen and glucose levels in women with polycystic ovary syndrome

T2 - a randomized clinical trial

AU - Rittig, N

AU - Arlien-Søborg, M C

AU - Svart, M V

AU - Thomsen, H H

AU - Kirkegaard, K

AU - Greve, V H

AU - Nielsen, M M

AU - Stochholm, K

AU - Ornstrup, M J

AU - Gravholt, C H

PY - 2025/6/1

Y1 - 2025/6/1

N2 - 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).

AB - 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).

KW - 3-hydroxybutyrate

KW - PCOS

KW - androgens

KW - glucose

KW - ketones

KW - metabolism

UR - https://www.scopus.com/pages/publications/105008088309

U2 - 10.1093/ejendo/lvaf106

DO - 10.1093/ejendo/lvaf106

M3 - Journal article

C2 - 40393075

SN - 0804-4643

VL - 192

SP - 717

EP - 727

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 6

ER -

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

Abstract

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