Ketogenic Approach to Restore Muscle in older patients with community-Acquired Pneumonia - KARMA-P Trial - Abstract Bacterial community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in older adults, often resulting in significant muscle wasting, systemic inflammation, and gut microbiome dysbiosis. Muscle loss, driven by bedrest, acute illness, and antibiotic-induced dysbiosis, all contribute to prolonged hospital stay, delayed recovery, and long-term physical decline. Current interventions such as physical rehabilitation and increased protein intake are largely ineffective in mitigating the acute illness-induced muscle wasting due to metabolic dysfunction such as impaired glucose control. Preliminary evidence suggests that ketogenic enteral feeding is safe, reduces inflammation, stabilizes metabolism and preserves functional outcomes in hospitalized patients. Because most of older hospitalized CAP patients are able to ingest food orally, our study aims to test the safety, feasibility and determine effect sizes for preliminary evidence of a 10-day oral ketogenic diet (low carbohydrate, high fat) in older CAP patients. We will conduct a double-blind pilot randomized clinical trial in 30 hospitalized older adults (>65 years) with bacterial CAP, randomizing participants to a ketogenic feeding (n=15) or standard hospital feeding (n=15). Muscle mass will be assessed using ultrasound, inflammatory and metabolic biomarkers from blood, and gut microbiome composition from rectal swabs collected at baseline, post-intervention, hospital discharge and 1- month follow-up. Physical function (short physical performance battery), handgrip strength, and activity levels (accelerometry) will be measured at discharge and follow-up. Daily blood ketone levels measurements will guide feeding adjustments to maintain ketosis, and dietary habits will be assessed weekly post-intervention until 1- month follow-up. Meals for the 10-day intervention will be prepared in a metabolic kitchen by a clinical nutritionist. Specific aims include: (1) assess the safety and feasibility of oral ketogenic feeding in older adults hospitalized with CAP, (2) determine an effect on in-hospital and post-discharge muscle mass compared to standard care hospital feeding, (3) determine an effect on physical function and activity status at discharge and 1-month post- discharge compared to control, and (4) determine an effect on gut microbiome composition and circulating biomarker levels of metabolic status (fasting glucose and insulin) inflammation and oxidative stress compared to standard feeding. If successful, this study will provide evidence for oral ketogenic feeding as an innovative intervention to prevent muscle wasting and functional decline, supporting a future phase III trial targeting older adults hospitalized with CAP. Keywords: high-fat, low-carbohydrate, aging, respiratory infection, muscle loss.
