Investigation of Refeeding syndrome-related substances for development preventive and treatment strategies

Background and objectives: Refeeding syndrome (RFS) is the general term for a series of metabolic complications that develop when chronically malnourished patients are rapidly initiated on excessive nutritional therapy. Since details of the pathogenetic mechanisms of RFS are unknown, aggressive nutritional therapy should not be administered to malnourished individuals. Clarification of the metabolic status resulting from malnutrition prior to RFS might allow metabolic correction before nutritional therapy is initiated, and help to establish preventive and treatment strategies for metabolic correction before the onset of RFS. In this animal study, we investigated candidate preventive and treatment substances for RFS using blood metabolome analysis prior to RFS. Methods: We created a mild RFS animal model using rats that were fasted for 24-hours and refed with oral gavage using a 50% glucose solution and intraperitoneal administration of insulin. Identification of hypophosphatemia 24-hours after refeeding was used to confirm the development of mild RFS. 1. Metabolome analysis Blood samples were obtained from mild RFS model (fasted) and healthy rats (feed) for metabolome analysis to identify metabolic changes prior to the onset of RFS. Substances likely to have an association with the onset of RFS were evaluated, and candidate substances were extracted by %CV calculation and volcano plot analysis. 2.Prevention of hypophosphatemia by administration of candidate substances. In a separate experiment, mild RFS model rats were given the identified candidate substances prior to refeeding. Plasma phosphorus concentrations and other items related to RFS were measured and statistically analyzed before and after RFS. Results: Blood metabolome analysis evaluated 711 substances. Of these, 160 substances were found to be lower in the mild RFS group before RFS than in the normal group. Statistical analysis revealed substances A, B and C as being associated with the onset of RFS. We are currently investigating the preventive effects of the candidate substances by administering them before refeeding. Conclusions: These results suggest that any of the candidate substances prior to refeeding might prevent hypophosphatemia.