During World War II, many people suffered from hunger and starvation. Under these circumstances, Ancel Keys investigated the physical and mental effects of prolonged dietary restriction and the subsequent refeeding of 36 conscientious objectors in the Minnesota Starvation Experiment. Most of the subjects experienced periods of severe emotional distress, depression, social withdrawal, isolation, decline in concentration, and decreases in metabolic rate, respiration, and heart rate. Several of the participants developed edema in their extremities. Later, at the end of World War II, further observations were made by Schnitker and Burger. Numerous starving detainees developed severe symptoms such as heart failure, peripheral edema, and neurological disorders after a normal diet was reintroduced, and one of five died within the next few days. Those observations led to the first description of the refeeding syndrome (RFS), almost 75 years ago.
To date, there is still no commonly accepted definition of RFS, and its detailed pathophysiology remains largely unclear. This is primarily due to the fact that the clinical manifestations of RFS are nonspecific, leading to RFS frequently being overlooked, underdiagnosed, and subsequently untreated. In the study of Hernandez-Aranda, up to 48% of malnourished inpatients developed RFS. A sub-analysis of the 2019 study by Schuetz demonstrates that medical patients with confirmed RFS have significant mortality rates and increased non-elective hospital readmission, thus confirming the negative effect of RFS on clinical outcome.
Underlying causative factor of refeeding syndrome is the metabolic and hormonal changes caused by rapid refeeding, whether enteral or parenteral. In starvation the secretion of insulin is decreased in response to a reduced intake of carbohydrates. Instead fat and protein stores are catabolised to produce energy. This results in an intracellular loss of electrolytes, in particular phosphate. Malnourished patients’ intracellular phosphate stores can be depleted despite normal serum phosphate concentrations. When they start to feed a sudden shift from fat to carbohydrate metabolism occurs and secretion of insulin increases. This stimulates cellular uptake of phosphate, which can lead to profound hypophosphataemia. This phenomenon usually occurs within four days of starting to feed again.
- Hypophosphataemia: HALLMARK biochemical feature (Phosphate is necessary for the generation of ATO from ADP & AMP and other crucial phosphorylation reactions)
- Thiamine deficiency
- Disorder of sodium and fluid balance
- Changes in glucose, protein and fat metabolism
Serum phosphate concentrations < 0.50 mmol/l (normal range 0.85-1.40 mmol/l) can produce the clinical features of refeeding syndrome. However, early clinical features of refeeding syndrome are non-specific and may go unrecognised.
- Leucocyte dysfunction
- Respiratory failure
- Cardiac failure
- Seizures, coma
- Sudden death