Modified fasting therapy reduces blood pressure independent of weight loss, moderated by age, sex, and HbA1c: a retrospective mediation analysis in dysglycemic patients

Objective To evaluate the effect of modified fasting therapy on blood pressure in dysglycemic adults and to examine the mediating role of weight loss and modifying effects of age, sex, and baseline glycemic status. Methods This retrospective cohort study included 833 dysglycemic adults who underwent modified fasting therapy. Blood pressure, body weight, and laboratory parameters were measured before and after the intervention. Linear mixed models were used to estimate the effect of fasting on systolic blood pressure (SBP) and diastolic blood pressure (DBP), with adjustment for age, sex, baseline body mass index (BMI), glycosylated hemoglobin (HbA1c), and baseline blood pressure. Mediation analyses were performed using “MEMORE macro” and “wsMed” package to examine the mediating role of weight loss. Interaction terms were included to test effect modification by age, sex, and baseline HbA1c. Results Fasting therapy significantly reduced SBP (−7.73 mmHg, 95% CI: −8.64 to −6.82, p < 0.001) and DBP (−4.76 mmHg, 95% CI: −5.39 to −4.12, p < 0.001). Mediation analyses revealed that weight loss did not significantly mediate the blood pressure-lowering effect for either SBP (indirect effect: −0.22, p = 0.588) or DBP (indirect effect: 0.09, p = 0.636). The fasting effect was significantly modified by age, sex, and baseline HbA1c, with greater reductions observed in younger patients, males, and those with higher HbA1c levels. Conclusions Modified fasting therapy significantly reduces blood pressure in dysglycemic adults independent of weight loss. Age, sex, and baseline HbA1c modify the response, suggesting that personalized approaches may optimize the benefits of fasting-based interventions.