Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals with Acute Spinal Cord Injury: study protocol for a randomized controlled trial
Abstract Background: Therapies that significantly improve the neurological and functional recovery of individuals with spinal cord injury (SCI) are still urgently needed. The ketogenic diet (KD) has been shown to improve forelimb motor function in a rat model of SCI, likely by reducing inflammation and cell death in the spinal cord. Furthermore, our recent pilot study in patients with SCI showed that, compared with a standard hospital diet (SD), 5 weeks of KD, started during acute care, improved upper extremity motor function and reduced serum levels of a neuroinflammatory blood protein. The primary goals of our proposed study are to 1) show the safety and feasibility of administering a KD during acute care for SCI; 2) determine if consuming 5 weeks of a KD significantly improves motor and sensory function, functional independence, and glycemic control; and 3) quantify serum biomarkers that are linked to improvements in neurological recovery and functional independence via targeted proteomics.Methods/Design: In a single-masked, longitudinal, randomized parallel controlled study design, 60 participants with acute SCI will be randomly assigned to KD or SD in a 1:1 ratio. We intend to recruit 24 participants for each group with traumatic SCI (C5–T12, American Spinal Injury Association impairment scale A–C, and aged 18–60 years). Patients will be taken to acute care after their injury. Neurological and functional examinations, resting energy expenditure, blood, urine, stool collection and protein analyses related to neuro recovery will be done within 72 h of injury, as baseline measures. Patients received five weeks of KD or SD according to their allocation. The KD is a high-fat, low-carbohydrate diet (3:1 ratio of fat: carbohydrate + protein) that includes ~75% total energy as fat, ~20% as protein, and ~5% as carbohydrate and fiber. The SD includes ~45-50% total energy as carbohydrate and fiber, ~30% total energy as fat, and ~20% total energy as protein. All baseline examinations will be repeated at discharge from the hospital at week 5 (discharge measure). Discussion: The proposed diet intervention is practical and safe and is expected to translate into efficacious early nutritional interventions. Intervention with a more neuroprotective diet during acute care of SCI can be implemented anywhere in the world at low cost and without major regulatory hurdles. Better functional recovery will lead to a better quality of life and long-term health outcomes in individuals with SCI. While this study targets SCI, if successful it has the potential to improve neurological outcomes for individuals with various traumatic injuries such as traumatic brain injury and stroke.