Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: a pilot, randomized safety and feasibility trial

Abstract

Study design Longitudinal, randomized study. Objectives (1) Test the safety and feasibility of a ketogenic diet (KD) intervention in the acute stages of spinal cord injury (SCI), (2) assess the effects of a KD on neurological recovery, and (3) identify potential serum biomarkers associated with KD-induced changes in neurological recovery. Setting Acute care and rehabilitation facility. Methods The KD is a high-fat, low-carbohydrate diet that includes ≈70-80% total energy as fat. Seven participants with acute complete and incomplete SCI (AIS A-D) were randomly assigned to KD (n = 4) or standard diet (SD, n = 3). Neurological examinations, resting energy expenditure analysis, and collection of blood for evaluation of circulating ketone levels were performed within 72 h of injury and before discharge. Untargeted metabolomics analysis was performed on serum samples to identify potential serum biomarkers that may explain differential responses between groups.Results Our pilot findings primarily demonstrated that KD is safe and feasible to be administered in acute SCI. Furthermore, upper extremity motor scores were higher (p < 0.05) in the KD vs. SD group and an anti-inflammatory lysophospholipid, lysoPC 16:0, was present at higher levels, and an inflammatory blood protein, fibrinogen, was present at lower levels in the KD serum samples vs. SD serum samples. Conclusion Taken together, these preliminary results suggest that a KD may have anti-inflammatory effects that may promote neuroprotection, resulting in improved neurological recovery in SCI. Future studies with larger sample size are warranted for demonstrating efficacy of KD for improving neurological recovery.

Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals with Acute Spinal Cord Injury: study protocol for a randomized controlled trial

“…In addition, a study by Streijger et al (2013) showed the critical role of ketones in neuroprotection by starting a KD four hours after cervical hemi-contusion in rats with SCI (19). Consistent with the published effects of a KD in rat models of SCI and in humans with hyperglycemia, our randomized pilot feasibility trial (20) showed that, compared with a standard hospital diet (SD), five weeks of KD improved upper extremity motor scores (Fig 1).…”

“…Because glutamate excitotoxicity, inflammation, and induction of apoptotic pathways lead to progressive degeneration in the spinal cord shortly after the injury, inhibition ofthese processes by ketone bodies may enhance neurological recovery after an SCI. In support of these hypotheses, we recently showed, for the first time, that compared with an SD, five weeks of KD improved upper extremity motor function in patients with acute SCI (figure 1)(20). In addition, a neuroinflammatory blood protein, fibrinogen, was present at lower levels in the KD serum samples than in the SD serum samples.…”

The Effects of a Ketogenic Diet on Sensorimotor Function in a Thoracolumbar Mouse Spinal Cord Injury Model

“…While no studies that we are aware of have addressed the effects of KD on thoracic SCI or peripheral nerve injury, there have been reports of the beneficial effects of KD on the recovery of reaching behavior in high cervical injuries in both mouse studies (Streijger et al, 2013) and human studies (Yarar-Fisher et al, 2018). These effects on reaching behavior in mice were confined to supination and grasping, suggesting regional effects on the cervical motor circuit.…”

Ketogenic Diet-mediated Steroid Metabolism Reprogramming Improves the Immune Microenvironment and Myelin Growth of Spinal Cord Injury Rats Through Gene Analysis and Co-expression Network Analysis

“…Interestingly, recent studies have suggested that a KD might also be bene cial to humans with neurological disorders, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and traumatic brain injury [11][12][13]. Multiple reports have revealed that a KD may exert neuroprotective effects after SCI [14][15][16][17][18][19]. For example, Tetzlaff et al found that KD improves forelimb motor function after SCI [14].…”