Does Intermittent Fasting Improve Microvascular Endothelial Function in Healthy Middle-aged Subjects?

Background: Reduced endothelial nitric oxide bioavailability, a hallmark of endothelial dysfunction, is commonly encountered in cardiovascular diseases. Intermittent fasting reduces serum markers of oxidative stress, while nitric oxide levels may rise. Whether this translates into persistent improvements in endothelial function is unknown. The aim of the study was to address the effects of intermittent «Ramadan-type» fasting on endothelial function, nitric oxide bioavailability, biological parameters and blood pressure. Methods: We tested this hypothesis in fourteen healthy middle-aged male subjects, using a prospective casecontrolled study design. Microvascular endothelial function of skin vessels was evaluated with a laser Doppler imager, Before-fasting, after thirty days of fasting, and one month thereafter (Post-fasting). Endothelial dependent and independent dilatations were assessed by acetylcholine and sodium nitroprusside iontophoresis, respectively. The hyperemic response to heating after a specific nitric oxide-synthase inhibitor L-N-arginine-methyl-ester administration, versus a saline solution, allowed further characterization of nitric oxide-mediated vasodilation. Blood pressure, body mass index, metabolic parameters were determined in all subjects. Results: Blood pressure decreased, while blood glucose and LDL-cholesterol increased during fasting (all p<0.05 vs. Before-fasting). Body mass index did not change. Hyperemic skin reactions assessed by acetylcholine increased during Fasting and Post-fasting, while sodium nitroprusside-induced hyperemia and nitric oxide-related vasodilation in response to heating increased during Fasting only (all p<0.05 vs. Before-fasting). Rises in serum triglycerides and blood urea nitrogen during fasting blunted nitric oxide-related vasodilation improvement upon heating (r=-0.55 and -0.60 respectively, p<0.05). These parameters did not change over time in thirteen matched controls. Conclusion: Intermittent fasting improved endothelial and non-endothelial dependent vasodilations and decreased blood pressure. Increased nitric oxide bioavailability during this period was negatively related to rises in serum triglycerides and blood urea nitrogen.