**2. Methods**

In this perspective, we have reviewed the main current data referring to ketone bodies in correlation with nutrition and metabolic pathways as well as to signaling functions, and the potential impact on clinical conditions. Data were selected following eligibility criteria according to the reviewed topic. We used a set of electronic databases (Medline/PubMed, Scopus, Web of Sciences (WOS), Cochrane Library) for a systematic search until July 2022 using MeSH keywords/terms, such as "ketone bodies", "BHB", "acetoacetate", "inflammation", "anti-oxidant", "critical illness". We applied no date or language restrictions. We followed the Preferred Reporting Items for the Systematic Review and Meta-Analysis (PRISMA) statement [17]. Two independent reviewers performed title-abstract screening on all selected studies, then the full texts of the selected articles were reviewed. In cases of duplicate information, the data were checked and combined. Studies reporting ketone bodies as well as BHB and acetoacetate were selected. Publications were selected using specific keywords (i.e., ketone bodies, BHB, acetoacetate, inflammation, antioxidant, etc.) also according to the date of publication (not older than 1990) and for the fulfillment of the topic of this review. Studies that were just case reports and commentaries were excluded. The extraction of the data from included studies was performed by two reviewers separately, considering key characteristics including publication year, author, type of study, country, sample size, and laboratory findings. The funnel plot and Egger's regression test were used to assess publication bias [18].
