Using Labs to Detect & Treat Refeeding Syndrome

Using labs to detect refeeding syndrome are crucial in the prevention of refeeding syndrome because they help monitor electrolyte imbalances and metabolic changes that can arise when reintroducing nutrition to individuals who are malnourished.

How to Use Labs to Detect and Treat Refeeding Syndrome

The use of labs in the identification and treatment of refeeding syndrome offers insight into what electrolytes and substances are abnormal and how deficiencies need to be addressed.

Refeeding syndrome is a potentially fatal shift in fluids and electrolytes, caused by hormonal and metabolic changes that occur in a malnourished individual when refeeding is initiated.

Many of the symptoms and warning signs of refeeding syndrome can present as early as five days after initiating refeeding.

Labs to monitor for refeeding syndrome

Refeeding syndrome can cause a variety of serious medical complications in patients with eating disorders and severe malnutrition, including irregular heartbeat, seizures, coma and heart failure, highlighting the importance of closely monitoring of electrolytes to prevent refeeding syndrome and organ dysfunction.

Phosphorous

Phosphorous plays a vital role in intracellular processes, the structural integrity of cells, enzyme and second messenger activation and oxygen delivery.

Hypophosphatemia (low phosphorous levels) is the hallmark of refeeding syndrome and a significant cause for development of refeeding syndrome.

This condition develops during the refeeding process when the glucose load of the ingested food increases insulin release, increasing uptake and use of phosphate in the cells. This leads to a deficit of intracellular and extracellular phosphate.

Hypophosphatemia complications

Hypophosphatemia can cause:

• Diaphragmatic muscle fatigue
• Respiratory failure
• Hemolysis
• Rhabdomyolysis
• Edema due to heart failure
• Seizures

Potassium

Potassium is essential to nerve and muscle function as well as maintaining normal fluid levels within cells. 

Like phosphorous, potassium is taken up into cells as they increase in volume and number and as a direct result of insulin secretion, resulting in hypokalemia (low potassium).

Hypokalemia complications

Hypokalemia can cause a wide variety of complications across multiple organ systems:

• Cardiac complications: cardiac arrhythmias, hypotension and cardiac arrest
• Gastrointestinal complications: ileus and constipation
• Renal complications: inability to concentrate urine and abnormalities in other important electrolytes
• Neuromuscular dysfunctions: weakness, paralysis, paresthesia, confusion, rhabdomyolysis and respiratory depression

Magnesium

Magnesium is a vital cofactor in most enzyme systems, necessary for the structural integrity of DNA, RNA and ribosomes and affects membrane potential.

Refeeding syndrome is associated with hypomagnesemia (low magnesium).

Unlike with potassium and phosphorous, the mechanism through which hypomagnesemia is caused by refeeding syndrome is unclear, possibly from intracellular movement of magnesium ions into cells during the refeeding process.

Hypomagnesemia complications

Severe hypomagnesemia can result in:

• Cardiac arrhythmias
• Abdominal discomfort
• Neuromuscular dysfunctions, like tremor, paresthesia, tetany, seizures, weakness and ataxia
• Irritability and confusion

Other valuable refeeding labs to monitor

Monitoring other substances, like glucose, vitamins and body fluid distribution, can also be associated with refeeding syndrome and offer valuable insight.

Glucose

Glucose ingestion after a period of chronic malnutrition can suppress gluconeogenesis (glucose production from other substrates) through the release of insulin.

This surge in insulin can cause hypoglycemia early in refeeding due to the lack of glycogen stores. On the contrary, overfeeding and the development of hyperglycemia may contribute to osmotic diuresis, dehydration, metabolic acidosis and ketoacidosis. 

Excess glucose can also cause lipogenesis, which may cause fatty liver, increased carbon dioxide production, hypercapnia and/or respiratory distress.

Thiamin (vitamin B1)

Thiamin is an essential coenzyme in carbohydrate metabolism. It is believed that carbohydrates introduced during the refeeding process cause an increase in cellular thiamin utilization, leading to Vitamin B1 deficiency. 

Thiamin deficiency can cause Wernicke’s encephalopathy or Korsakoff’s syndrome in severe cases.

Refeeding Edema

The reintroduction of carbohydrates during the refeeding process rapidly decreases the renal excretion of sodium and water, which is known as refeeding edema.

This can contribute to increased likelihood of edema formation, which can be distressing to patients.

Lab results indicating refeeding syndrome

Low serum levels of specific electrolytes, including phosphate, magnesium and potassium are the leading indicators of refeeding syndrome.

Other lab tests, like thiamin deficiency, elevated creatine phosphokinase (CPK) and acute worsening of anemia can suggest development of refeeding syndrome.

Low serum phosphate

Serum levels of phosphorous should be monitored daily for at least the first week of refeeding. Phosphorous should be administered either via the oral route or intravenously (IV), depending on the severity of the deficit.

A normal serum phosphorous is considered greater than 2.7 mg/dL for adults.

Low serum magnesium

Serum levels of magnesium should be monitored regularly during the refeeding process. Magnesium can also be administered either via the oral or intravenous route, depending on the severity of the deficit.

A normal serum magnesium level is considered greater than 1.4 mg/dL for adults.

Low serum potassium

Serum levels of potassium should be monitored daily for at least the first week of the refeeding process.

Normal concentrations of Potassium (K+) are 3.6-5.2 mmol/L.

Anemia

Hemolysis can develop due to refeeding syndrome. Without adequate adenosine triphosphate (ATP), it can be difficult for the red blood cells to maintain appropriate levels of potassium within the cells while exuding sodium outside the cells. This can cause increased water to move into the cells (osmosis), increasing the pressure within the cell and increasing the risk that the red blood cells will lyse as they circulate throughout the bloodstream.

Labs suggestive of hemolysis can include increased lactate dehydrogenase (LDH), low haptoglobin, increased unconjugated bilirubin and increased reticulocytes.

High creatinine phosphokinase (CPK)

CPK is an enzyme found in a few different organs but largely in the muscles of the body.

An increase in serum CPK levels can be indicative of rhabdomyolysis (muscle breakdown), although the serum values may be difficult to interpret in an individual with malnutrition given the significant muscle loss (atrophy) that results from catabolic state of malnutrition.

Low thiamin

Low vitamin B1 is an important enzyme involved in the metabolism of carbohydrates. Although low thiamin is not indicative of refeeding syndrome, it is a significant risk factor for the development of refeeding syndrome.

Using labs to prevent refeeding syndrome

Effective refeeding is a delicate process. Each patient requires individual care dependent on their weight, rate of weight gain, electrolyte abnormalities, medical complications and clinical presentation.

Close monitoring of electrolytes, glucose, liver function tests and blood cell counts are very important at baseline and during the refeeding process.

Electrolyte deficiencies prior to refeeding significantly increase the risk for development of the refeeding syndrome once nutritional repletion is begun and need to be corrected as much as possible before refeeding is initiated.

In addition to correcting electrolyte deficiencies, caloric intake should be slowly increased upon re-nutrition, and patients should be clinically monitored for the physical manifestations of refeeding syndrome.  

Last Updated: October 2024 by Dennis Gibson, MD, FACP, CEDS

References

• Mehler, P. S., & Andersen, A. E. (2017, November 29). Eating Disorders: A Guide to Medical Care and Complications (third edition). Johns Hopkins University Press.

• Mehanna, H. M., Moledina, J., & Travis, J. (2008, June 26). Refeeding syndrome: what it is, and how to prevent and treat it. BMJ, 336(7659), 1495–1498. https://doi.org/10.1136/bmj.a301

• Crook, M., Hally, V., & Panteli, J. (2001, July). The importance of the refeeding syndrome. Nutrition, 17(7–8), 632–637. https://doi.org/10.1016/s0899-9007(01)00542-1
• Mehler, P. S., Winkelman, A. B., Andersen, D. M., & Gaudiani, J. L. (2010). Nutritional Rehabilitation: Practical Guidelines for Refeeding the Anorectic Patient. Journal of Nutrition and Metabolism, 1–7. https://doi.org/10.1155/2010/625782
• da Silva, J.S.V., Seres, D.S., Sabino, K., et al. (2020). ASPEN consensus recommendations for refeeding syndrome. Nutrition in Clinical Practice, 35(2): 178-95.