Effects of a Very Low Carbohydrate Ketogenic Diet or Mediterranean Diet on Markers of Musculoskeletal Health in Older Adults

Overview

Preclinical data indicate that very low carbohydrate ketogenic diets (KD) may prevent progression of age-related sarcopenia (skeletal muscle decline) but also may disturb bone metabolism. The investigators will pilot test a randomized trial comparing the effects of short-term adaptation to a well-formulated ketogenic diet and Mediterranean diet on markers of bone metabolism and muscle function in older adults. The expected results will help inform the benefit-risk assessment for older patients considering longer term use of KD therapy.

Eucaloric very low carbohydrate ketogenic diets (KD) are therapeutic diets that mimic fasting by generating ketones for metabolic fuel while meeting nutritional requirements (nutritional ketosis). Nutritional ketosis may broadly benefit healthspan through mechanisms such as suppression of inflammation or induction of autophagy, and preclinical and emerging clinical data indicate that KD therapy may help slow progression of age-related conditions including sarcopenia. However, questions remain about the benefits and risks of KD, especially relative to recommended therapeutic diets such as the Mediterranean Diet (MD) for which there is evidence of benefit for age-related conditions. For example, KD has shown efficacy for weight loss, which could reduce ectopic lipid accumulation that weakens muscle and bone. KD has been shown to increase skeletal muscle mitochondrial mass, mitochondrial activity, and strength in aged mice, possibly by increasing peroxisome proliferator-activated receptor activity and preserving fast-oxidative fibers that typically decline with age. However, long term use of KD may adversely impact bone. KD can cause deterioration of bone in juvenile mice without evidence of undernutrition and is associated with skeletal demineralization in children being treated for drug-resistant epilepsy. Given the burden of musculoskeletal disease in older Americans, it is vital to understand the effects of KD on the musculoskeletal system of older adults to inform the benefit-risk assessment for an older patient and to optimize the effectiveness of KD for age-related conditions. The investigators are conducting a pilot test of a randomized clinical trial comparing the effects of short-term adaptation to a well-formulated KD and MD on markers of bone health and muscle function in older adults. The investigators will supply fresh prepared meals to achieve high adherence to the dietary interventions and adequate contrast in metabolic state between treatment groups. Potential participants will complete a screening process so the investigators can determine whether potential participants are eligible to enroll in the study. At the first screening visit, the study team will measure blood pressure, height, and weight. Individuals will complete questionnaires that collect information about their health history, dietary intake, and physical activity habits. No more than 50 mL of blood will be collected from potential participants to run routine clinical lab tests to evaluate health status. If an individual remains eligible after the first screening visit, they will be invited to complete a 24-hour urine collection (at home) and to schedule a second screening visit. At the second screening visit, a physician will conduct a physical exam and assess their body composition with an x-ray technology called dual-energy x-ray absorptiometry (DEXA or DXA). If an individual remains eligible after the second screening visit, they will be invited to enroll in the dietary intervention study. Once enrolled, the participant will be assigned to either a very low carbohydrate ketogenic dietary pattern or a Mediterranean dietary pattern. The investigators will provide most of the food the participant will need each day in the form of a nutrition shake (breakfast) and two prepared meals (lunch and dinner). A study dietitian will be available to provide continuous support through a secure messaging app. While in the dietary intervention phase of the study, participants will come to the UF Clinical and Translational Science Building once a week for 6 weeks. The study team will measure participant blood pressure and weight at each visit. At the first, middle, and final visits, the study team will collect a blood sample and urine sample from participants for lab testing, and participants will complete a short series of tests that measure physical performance. Our ultimate research goal is to determine the effects of KD on body composition and clinically relevant measures of bone health and muscle function, as those data are needed to (1) inform the benefit-risk assessment for an older patient who is considering longer term adherence to KD therapy and (2) optimize the effectiveness of KD for age-related conditions.