Low-Calorie, High-Protein Ketogenic Diet Versus Low-Calorie, Low-Sodium, and High-Potassium Mediterranean Diet in Overweight Patients and Patients with Obesity with High-Normal Blood Pressure or Grade I Hypertension: The Keto–Salt Pilot Study

MDPI ^ | May 20, 2025 | Matteo Landolfo, Lucia Stella, et al

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Abstract

Dietary interventions are the first-line treatment for overweight individuals (OW) and individuals with obesity (OB) who have high-normal blood pressure (BP) or grade I hypertension, particularly when they are at low-to-moderate cardiovascular risk (CVR). However, current guidelines do not specify the most effective dietary approach for optimising cardiovascular and metabolic outcomes in this population.

This study aimed to compare the effects of a low-calorie, high-protein ketogenic diet (KD) versus a low-calorie, low-sodium, and high-potassium Mediterranean diet (MD) on BP profiles assessed via ambulatory BP monitoring (ABPM). It also evaluated changes in anthropometric measures, metabolic biomarkers, and body composition measured by bioelectrical impedance analysis (BIA).

Methods: This prospective observational bicentric pilot study included 26 non-diabetic adult outpatients with central OW or OB (body mass index, BMI > 27 kg/m²) and high-normal BP (≥130/85 mmHg) or grade I hypertension (140–160/90–100 mmHg), based on office BP measurements. All participants had low-to-moderate CVR according to the SCORE2 risk estimation tool. They were assigned to either the KD group (n = 15) or the MD group (n = 11). Comprehensive blood analysis, BIA, and ABPM were performed at baseline and after three months of intervention.

Results: At baseline, no significant differences were observed between the two groups. After three months, both diets led to substantial reductions in body weight (KD: 98.6 ± 13.0 to 87.3 ± 13.4 kg; MD: 93.8 ± 17.7 to 86.1 ± 19.3 kg, p < 0.001) and waist circumference. Mean 24-hour systolic BP (SBP) and diastolic BP (DBP) declined significantly in both groups (24 h SBP: 125.0 ± 11.3 to 116.1 ± 8.5 mmHg, p = 0.003; 24 h DBP: 79.0 ± 8.4 to 73.7 ± 6.4 mmHg, p < 0.001). Fat-free mass (FFM) increased, while fat mass (FM), blood lipid levels, and insulin concentrations decreased significantly. Improvements in ambulatory BP were correlated with the change in FM relative to FFM (ΔFM/ΔFFM). No significant between-group differences were detected at follow-up.

Conclusions: Both the KD and the MD effectively promoted weight loss, improved body composition, and enhanced bio-anthropometric and cardiovascular parameters in individuals with overweight or obesity and elevated BP. Although larger studies are needed to explore potential long-term differences, these findings indicate that the two popular dietary approaches confer comparable metabolic and cardiovascular benefits. The results highlight the central importance of weight loss and fat mass reduction, regardless of the specific dietary pattern chosen.

NOTE: A "bicentric pilot study" is a small, early-stage research project testing an idea at two different centers to see if it’s promising and practical enough to justify a bigger study later.

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