Ketogenic Dietary Intervention in Men With Mild-to-Moderate COPD (COPDKETO)

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation, chronic inflammation, exercise intolerance, and alterations in body composition. In addition to pulmonary impairment, systemic manifestations such as increased inflammatory burden, skeletal muscle dysfunction, and adverse metabolic changes contribute substantially to morbidity and reduced quality of life. Nutritional interventions have therefore emerged as potential adjunctive strategies in COPD management.

Ketogenic diets are characterized by marked carbohydrate restriction, moderate protein intake, and increased dietary fat consumption, resulting in nutritional ketosis. Potential mechanisms relevant to COPD include reductions in systemic inflammation, changes in substrate utilization, reductions in adiposity, and alterations in respiratory gas exchange. However, randomized controlled studies investigating ketogenic dietary interventions in COPD remain limited.

This study is an 8-week, single-center, parallel-group pilot randomized controlled trial conducted in clinically stable men with GOLD stage I-II COPD. Participants are randomly allocated in a 1:1 ratio to either a ketogenic dietary intervention or a control group receiving standard dietary advice. The ketogenic diet is individually prescribed by a dietitian and aims to provide approximately 60-70% of total energy from fat, 15-20% from protein, and 5-10% from carbohydrates, with carbohydrate intake restricted to less than 50 g/day.

Nutritional ketosis is monitored using capillary beta-hydroxybutyrate measurements obtained throughout the intervention period. Pulmonary function is assessed using spirometry. Body composition and phase angle are measured using multifrequency bioelectrical impedance analysis. Functional exercise capacity is evaluated using the 6-minute walk test, and estimated aerobic capacity is derived from walking performance. Blood samples are collected to assess inflammatory and safety-related biomarkers, including C-reactive protein, lipid parameters, alanine aminotransferase, and creatinine.

The primary objective is to determine whether an 8-week ketogenic dietary intervention improves FEV1/FVC compared with standard dietary advice. Secondary objectives are to evaluate effects on systemic inflammation, phase angle, exercise capacity, body composition, and biochemical safety outcomes. As a pilot trial, the study is designed to generate effect-size estimates, assess feasibility and adherence, and inform the design of future larger multicenter randomized controlled trials.