Nutritional Ketosis as a Therapeutic Approach in Critical Illness: A Systematic Review.

Critical illness encompasses the dysfunction of vital organs, the risk of death, and potential reversibility; it is a major cause of morbidity and mortality globally. The pathophysiology underlying many critical illnesses includes bioenergetic failure, inflammation, and oxidative stress. This systematic review aims to explore the use of nutritional ketosis (ketogenic feeds and exogenous ketone body administration) as a potential therapy, affecting the aforementioned pathways in patients with critical illnesses. This study was conducted, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search was conducted, systematically using PubMed, PubMed Central (PMC), Google Scholar, and the ScienceDirect databases in February 2024. The inclusion criteria were set to free full-text articles published within the past five years: human and animal studies, literature reviews, systematic reviews, meta-analyses, observational studies, randomized controlled trials, case reports, book chapters, gray literature, studies investigating adult samples, and articles in the English language. Exclusion criteria included pediatric studies as the topic has been studied more extensively in children, and this review aims to explore potential benefits in adult patients. The search was conducted through four databases; after the screening process, the remaining studies were assessed through quality appraisal tools appropriate to each study type. In the end, 11 studies were selected, including eight narrative reviews, one cohort study, one animal study, and one randomized controlled trial. The results of this review demonstrated that nutritional ketosis has potential safe and effective benefits for humans and animals. Nutritional ketosis shows therapeutic benefits for a vast variety of complications commonly associated with critical illness, status epilepticus, sepsis, viral infections, and glycemic control. In the end, both randomized and nonrandomized clinical trials are necessary for more conclusive findings.