Effects of the ketogenic diet compared to the mediterranean diet in patients with acromegaly

Background and Aim: The current study aims to evaluate the impact of a ketogenic diet followed by a Mediterranean diet on IGF-1 levels and metabolic parameters in patients with active acromegaly. Materials and Methods: We conducted a prospective study on 25 acromegalic patients followed at our endocrinology unit on medical treatment (17 were treated with somatostatin analogues alone, 5 were on combined pegvisomant and somatostatin analogues and 3 were on pegvisomant treatment alone). Participants underwent a structured dietary intervention: an initial ketogenic diet (70% fat, 25% protein, 5% carbohydrates) for 3 weeks, followed by a Mediterranean diet (40% carbohydrates, 30% fat, 30% protein) for further 3 weeks. Anthropometric parameters, fasting glucose, insulin, HOMA-IR, HbA1c, lipid profile, liver enzymes, IGF-1 levels, and inflammatory markers (neutrophil-to-lymphocyte ratio, lymphocyte-to-platelet ratio) were assessed at baseline, after the ketogenic phase, and at the end of the Mediterranean phase. In addition, a bioelectrical impedance analysis (BIA) was performed at baseline and after ketogenic diet to evaluate fat and lean masses. Pharmacological treatment for acromegaly was maintaned stable for the duration of the study. Results: All included patients completed the study. After 3 weeks of ketogenic diet, we observed a significant reduction in weight (P = 0. 001), BMI (P = 0. 009), waist circumference (P = 0. 011), hip circumference (P = 0. 003), lean mass (P = 0. 01), fat mass (P = 0. 01), IGF-1 (P = 0. 02), blood glucose (P = 0. 004), and AST (P = 0. 021), compared to baseline. After we compared the effects of the ketogenic diet vs Mediterranean diet and we found significant higher glucose (P = 0. 045), insulin (P = 0. 006) and HOMA-IR (P = 0. 003) values. At multivariate analysis, IGF-1 positively correlated with weight (P = 0. 014, beta = 1. 568). Discussion: Our findings suggest that a ketogenic diet may play a role in modulating IGF-1 levels and improving metabolic parameters in patients with active acromegaly. IGF-1 reduction may be partly mediated by the lower insulin levels induced by KD, as insulin is a known regulator of hepatic IGF-1 production. Furthermore, the significant weight loss observed during the KD phase may have contributed to the decrease in IGF-1, as demonstrated by the positive correlation between IGF-1 and body weight in our multivariate analysis. Our study provides preliminary evidence supporting the use of KD as a potential adjunctive strategy in the metabolic management of acromegalic patients. Further larger-scale, long-term studies are warranted to confirm these findings.