Critical ill patients experience catabolic stress, which results in a systemic inflammatory response. The inflammatory response is associated with increased complications, including infection, multi-organ dysfunction, increased length of ICU stays, and mortality. l-Carnitine supplementation may play an important role in these patients by regulating inflammatory cell function. The purpose of the present study was to investigate the effect of l-Carnitine supplementation on clinical status, inflammatory markers, and mortality rate in critically ill patients admitted to the intensive care unit (ICU). This randomized, double-blind, placebo-controlled trial was performed on critically ill patients. Subjects were randomly assigned into placebo (n=27) and l-Carnitine (n=27) groups. l-Carnitine (3000mg/day) was administered via nasogastric tube for the intervention group for 7 days, while the other group received a placebo for the same duration. Serum levels of inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. Nutritional status and the acute physiology and chronic health evaluation (APACHE) score, sequential organ failure assessment (SOFA) score, and 28-day mortality were also recorded. Fifty-one critically ill patients completed the study. l-Carnitine supplementation significantly reduced the levels of CRP (mean change±SE:-34.9±6.5) and IL-6 (mean change±SE:-10.64±2.16) compared to the baseline, which is both statistically significant compared with the control group (p<0.05). The SOFA and APACHE scores were significantly reduced in the l-Carnitine group compared with the placebo group (p=0.02 and p<0.001, respectively). l-Carnitine supplementation showed beneficial effects on inflammatory and clinical outcomes of critically ill patients. Trial registration: IRCT, Registered 30 May 2018, https://www.irct.ir/trial/30748.

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