Fasting mimicking diet cycles versus a Mediterranean diet and cardiometabolic risk in overweight and obese hypertensive subjects: a randomized clinical trial

Abnormalities in the vascular endothelium such as impaired vasodilation can contribute to atherosclerosis and hypertension. Here we have performed a single-center randomized clinical trial to evaluate the efficacy of 4 months of a continuous Mediterranean diet (MD) regimen as compared to 4 cycles of fasting mimicking diet (FMD) administered for only 5 days/month on endothelial function, measured as reactive hyperemia index (RHI) and large/small-resistance artery compliance (AC1/AC2), and on other cardiometabolic risk factors, in hypertensive patients with obesity/excess weight [both sexes, body mass index (BMI) ≥ 28, RHI ≤ 2.0, and/or small-resistance artery compliance (AC2) ≤ 5.0]. At the end of the intervention period, FMD but not MD decreased RHI (p = 0.0023) compared to baseline with no increase in the portion of patients with abnormal RHI. Both FMD and MD improved PULS cardiac test score; evaluating the risk of cardiovascular events. FMD and MD did not show any significant change in either AC1 or AC2 compared to baseline. Both FMD and MD led to comparable decreases in weight, waist circumference, BMI, body fat mass and % body fat, total cholesterol, and leptin. FMD decreased HbA1c (p = 0.0059) and IGF-1 (p = 0.0427), while MD decreased glucose (p = 0.0488), HOMA-IR (p = 0.0476), and HDL-C (p = 0.0419). None of the parameters were significantly different between the FMD vs. MD group at the end of the intervention period. During the 3-month follow-up period, the FMD and MD groups continued to display weight and BMI reduction; however, the MD group also lost fat free mass (FMD vs. MD, p = 0.0498). In summary, both MD and FMD reduced a range of cardiometabolic risk factors, but FMD also decreased RHI, a change associated with either impaired functional integrity of vascular endothelial cells but also with vascular rejuvenation, with the latter being more likely considering the improved cardiometabolic profile, reduced PULS cardiac score and calculated heart age, and unaltered arterial compliance in the FMD group. MD but not FMD cycles caused loss of lean body mass.