Exogenous Ketones Mitigate Hyperglycemia-Induced Microvascular Impairment in Females with Polycystic Ovary Syndrome

BACKGROUND: Females with polycystic ovary syndrome (PCOS) frequently exhibit vascular dysfunction and impaired glucose tolerance, both of which likely contribute to their elevated cardiovascular disease risk. Importantly, microvascular dysfunction often precedes macrovascular dysfunction and is considered an early marker of cardiovascular impairment. Postprandial hyperglycemia is known to transiently impair macrovascular (i.e., endothelial) function, and this impairment is prolonged in individuals with glucose intolerance. We recently demonstrated that acute exogenous ketone monoester (KME) supplementation can reduce postprandial hyperglycemia and improve endothelial function in females with PCOS. However, its effects on microvascular function remain unknown. To address this gap, we tested the hypothesis that acute KME improves microvascular function during an oral glucose tolerance test (OGTT) in females with PCOS. METHODS: Ten females with PCOS (age: 27 ± 5yr, body mass index: 23.8 ± 2.7kg/m 2 ) completed two experimental sessions. In a randomized, double-blind, crossover study, placebo-controlled, participants consumed either KME (482mg/kg) or a taste-matched placebo 30-min before completing a 2-hour 75g OGTT. Microvascular reactivity was assessed during brachial artery flow mediated dilation (FMD, via duplex vascular ultrasound), with peak forearm vascular conductance (FVC = forearm blood flow [FBF] / mean arterial pressure [MAP]) as the primary outcome. Measurements were obtained pre-OGTT, and at 0-, 60-, and 120-min post-OGTT. Peak FBF (peak mean velocity x πr2 x 60) was calculated as the highest value recorded during the 3-min post-occlusion reactive hyperemia period of the FMD protocol. MAP was measured via finger photoplethysmography calibrated to manual sphygmomanometry before each FMD. RESULTS: Peak FVC did not differ between conditions at baseline (P=0.799). In the placebo condition, peak FVC remained unchanged across the OGTT, whereas KME enhanced FVC across all OGTT timepoints, indicated by main effects of time (P=0.047) and KME (P=0.039), and a significant time × KME interaction (P< 0.001). The largest increase from baseline during KME occurred at 60min (+1.53 ml/min/mmHg [0.62; 2.44], P=0.004). This improvement was driven primarily by increases in FBF, as indicated by main effects of time (P= 0.036) and KME (P=0.016), and a time × KME interaction (P< 0.001). Similarly, FBF peaked during KME at 60min (132.2 ml/min [+53.7; +210.7], P=0.003), while MAP remain unchanged (60min: -1mmHg [-6; +4], P=0.936). CONCLUSION: These data indicate that acute KME supplementation improves forearm microvascular reactivity, quantified as peak FVC during postprandial hyperglycemia, and support its potential as a novel strategy to mitigate cardiovascular risk in females with PCOS. FUNDING: Canadian Institutes of Health Research This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.