Synergistic effects of a ketogenic diet and interval exercise on vascular function in obese female undergraduate students: a randomised controlled trial demonstrating accelerated improvement

Obesity in female undergraduate students heightens cardiovascular risk through endothelial dysfunction, yet the synergistic effects of ketogenic diets (KDs) and exercise remain underexplored in this demographic. Between September 2024 and January 2025, 110 obese female undergraduate students (body mass index ≥ 30 kg/m²) were randomly assigned to either a control group (KD only, n = 55) or an observation group (KD + exercise, n = 55). The 4-month exercise protocol alternated 10-minute aerobic with 5-minute resistance bouts (four times per week). The primary outcome was wall shear stress (WSS). Secondary outcomes included lipid profiles (total cholesterol, triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C]), endothelial markers (nitric oxide [NO], endothelin-1 [ET-1], vascular endothelial growth factor) measured at baseline and monthly and cardiac function indices (stroke volume, cardiac output, end-diastolic volume). Generalised estimating equations were applied to analyse time–group interactions. At 2 months, the observation group demonstrated substantially greater improvements in WSS (1.534 dynes/cm²), NO (4.916 µmol/L) and HDL-C (8.4%), along with reductions in ET-1 (− 3.327 ng/L) and LDL-C (− 12.3%) than the control group (all p < 0.05). Generalised estimating equations confirmed substantial time–group interactions for WSS (β₃ = 1.743) and endothelial function markers (β₃ = 1.345; 1.854; p < 0.001). Ketogenic diet–exercise synergy substantially improves vascular function within 2 months in obese female undergraduate students. However, long-term lipid monitoring remains essential due to heterogeneous LDL-C responses to KDs. This study uniquely addresses the research gap regarding the synergistic vascular effects of KDs combined with structured interval training, highlighting its novelty as the first trial in obese young women linking endothelial biomarkers with haemodynamic adaptations. 1. Accelerated vascular improvement: this is the first randomised controlled trial to demonstrate substantial enhancement in endothelial function and wall shear stress within 2 months – twice as fast as exercise-alone interventions – in obese female undergraduate students. 2. Novel exercise–ketogenic diet (KD) synergy: the interval aerobic–resistance protocol induces pulsatile shear stress, synergising with ketosis – a newly characterised mechanism for vascular protection in high-risk populations. 3. Clinical translation-ready: the protocol provides a university-implementable framework (dietitian-guided KD with supervised exercise), incorporating low-density lipoprotein cholesterol safety monitoring, offering a cost-effective model for reducing cardiovascular disease risk.