Association of leucine and other branched chain amino acids with clinical outcomes in malnourished inpatients: a secondary analysis of the randomized clinical trial EFFORT

The essential branched-chain amino acids leucine, isoleucine and valine are considered anabolic and stimulate protein synthesis in the muscles as well in the liver. They also promote muscle recovery and contribute to glucose homeostasis. Recent studies in critically ill patients have demonstrated that depletion of plasma leucine is associated with increased mortality, but data in the non-critical care setting is lacking. This secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT), investigated the impact of leucine, isoleucine, and valine metabolism on clinical outcomes. The primary endpoint was 180-day all-cause mortality. Among 238 polymorbid patients with available metabolite measurements, low serum leucin levels were associated with a doubled risk of 180-day all-cause mortality in a fully adjusted regression model (adjusted HR 2.20 [95% CI 1.46-3.30], p