Author(s): VERMAERKE, N., STALMANS, M., NARANG, B., ENGELBRECHT, L., LAURIKS, W., ROBBERECHTS, R., RAMAEKERS, M., KOPPO, K., DEBEVEC, T., POFFÉ, C., Institution: HASSELT UNIVERSITY, Country: BELGIUM, Abstract-ID: 2391

INTRODUCTION:
Regular physical activity improves vascular function, and promotes angiogenesis and erythropoiesis, which are further augmented by hypoxia. Early evidence suggests that long-term exogenous ketosis (EK) can enhance vascular function and angiogenesis. However, the acute responses and underlying mechanisms remain unknown. Moreover, acute and prolonged EK may increase blood erythropoietin (EPO) concentrations in normoxia. Nonetheless, whether this effect is additive to hypoxia is unclear, as an EK-mediated attenuation of blood deoxygenation may counteract the [EPO] increase.
METHODS:
In a randomized, placebo-controlled, crossover design, 13 male and 2 female participants completed four experimental sessions. Each included a high-intensity interval training session, followed by recovery either in normoxia or normobaric hypoxia (3,000m simulated altitude, FIO2: 14.5%), with placebo or Ketone-IQ (KIQ) supplementation. Macro- and microvascular function were assessed throughout a vascular occlusion protocol, using femoral artery blood flow and muscle oxygenation, respectively, after 2.5 and 5.5h recovery. Additionally, serum EPO and endothelin-1 (ET-1) concentrations, and skeletal muscle expression of pro-angiogenic and vascular integrity markers, were evaluated.
RESULTS:
In normoxia and hypoxia, KIQ increased post-occlusion blood velocity (+15%) and muscle reoxygenation rate (+9%). Furthermore, muscle expression of pro-angiogenic and vascular integrity markers (including vascular endothelial growth factor, peroxisome proliferator-activated receptor gamma coactivator 1α, and angiopoietin-1), as well as serum [EPO] (+15%) increased with KIQ, while serum [ET-1] was reduced (-13%).
CONCLUSION:
EK appears as a promising strategy to enhance vascular function and integrity, angiogenic signaling, and circulating [EPO] in response to exercise and hypoxia, thereby facilitating beneficial adaptive responses.