Ghrelin’s role in regulating food intake among inpatients at nutritional risk: A secondary analysis of the randomized clinical trial EFFORT

Background: Ghrelin is an orexigenic hormone that stimulates food intake by hypothalamic actions. There is limited data on its circulating levels, pathophysiological role, and prognostic and therapeutic potential in dis ease-related malnutrition. Methods: We investigated via this secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) the association of admission ghrelin levels in terms of malnutrition phenotype, nutritional target achievement, and treatment response. The primary outcome was 30-day all-cause mortality. Results: A total of 997 patients with available ghrelin measurements were included. We found an association between high ghrelin levels upon admission and malnutrition severity according to the Nutritional Risk Screening 2002 (NRS) and an inverse association between high ghrelin levels and nutritional intake. Patients with high ghrelin levels had a 1.4-fold greater chance of reaching nutritional targets during hospitalization compared to those with lower levels (adjusted OR 1.40 [95% CI 1.01 1.93], P = 0.045). High ghrelin levels were not associated with mortality, complications, or adverse events, and both high and low ghrelin groups showed a similar response to nutritional therapy. Conclusion: We observed an association between high ghrelin levels upon admission in patients with more severe malnutrition according to the NRS and its components. A hypothesis may be generated that the hor mone’s orexigenic effect is impaired due to ghrelin resistance. However, under nutritional therapy, patients with high ghrelin levels were more likely to achieve nutritional targets. Ghrelin analogs during hospitaliza tion may help facilitate beneficial nutritional intake in this vulnerable patient population. Nevertheless, future research should investigate where this resistance stems from and differentiate between active and total ghrelin, as this could influence efficacy.