How to Use Labs to Detect and Treat Refeeding Syndrome

Preventing refeeding syndrome is essential. Refeeding syndrome can lead to life-threatening complications such as electrolyte imbalances, heart failure and respiratory issues, particularly in individuals who are malnourished. Careful monitoring of refeeding labs and electrolyte abnormalities, particularly hypokalemia, ensures a safe recovery and nutritional rehabilitation for individuals with eating disorders.

The Importance of Refeeding Labs

Refeeding syndromeis a potentially deadly imbalance of fluids and electrolytes caused by hormonal and metabolic changes that happen when nutrition is initiated in a malnourished person.

Many of the symptoms and warning signs of refeeding syndrome can present as early as five days after initiating refeeding.¹

Using labs to identify and treat refeeding syndrome helps determine which electrolytes and metabolic markers are abnormal and how deficiencies should be corrected.

The Risks of Refeeding Syndrome

Refeeding syndrome can cause a variety of serious medical complications in patients with eating disorders and severe malnutrition, including:¹

• Heart failure
• Cardiac arrythmias and/or cardiac arrest
• Respiratory depression, failure, and/or arrest
• Seizures
• Altered mental status

The high risk and mortality of refeeding syndrome highlights the importance of closely monitoring of electrolytes to prevent refeeding syndrome and organ dysfunction.

Avoiding Refeeding Syndrome: Labs to Monitor

Close monitoring of labs helps prevent and identify refeeding syndrome early and safely.

Phosphorus

Phosphorus plays a vital role in intracellular processes, the structural integrity of cells, enzyme and second messenger activation, and oxygen delivery.¹

Hypophosphatemia (low phosphorus) is the hallmark of refeeding syndrome and a significant cause for its development.^1,2

Hypophosphatemia can cause:¹

• Respiratory muscle dysfunction
• Respiratory failure
• Cardiac arrhythmias and cardiac arrest
• Reduced oxygen release to tissues
• Tissue hypoxia (inadequate oxygen in tissue)

Refeeding hypophosphatemia develops when patients begin refeeding and the glucose load of the ingested food triggers insulin release, increasing phosphate uptake and use in cells. This leads to a deficit of intracellular and extracellular phosphate.

Serum phosphorus levels should be monitored daily, at minimum, for at least the first week of refeeding.² Phosphorus should be administered orally or intravenously (IV), depending on the severity of the deficit.

When timing therapies, please note that oral phosphorus formulations will bind with oral magnesium formulations as well as calcium carbonate, inhibiting the absorption of both.

Potassium

Potassium is essential for nerve and muscle function, as well as for maintaining normal fluid levels within the body cells.³

Like phosphorus, potassium is absorbed into cells, and this process is directly stimulated by insulin secretion, which can lead to hypokalemia (low potassium).³

Hypokalemia (low potassium) can cause a wide variety of complications across multiple organ systems:

• Cardiac arrhythmias
• Hypotension
• Cardiac arrest
• Ileus
• Constipation
• Weakness
• Paralysis
• Respiratory depression
• Rhabdomyolysis

Serum potassium levels should be checked daily, at a minimum, during the first week of refeeding.

Magnesium

Hypomagnesemia (low magnesium) is another indicator of refeeding syndrome.¹ Magnesium is an essential cofactor for most enzyme systems, necessary for the structural integrity of DNA, RNA and ribosomes, and it influences membrane potential.

Like both phosphorus and potassium, magnesium is stimulated by insulin secretion and absorbed into cells to metabolize glucose, causing hypomagnesemia.⁴

Severe hypomagnesemia can result in:¹

• Cardiac arrhythmias and arrest
• Abdominal discomfort
• Tremors
• Paresthesia
• Tetany
• Seizures
• Weakness
• Ataxia

Serum magnesium levels should be monitored regularly during refeeding.² Magnesium can also be given either orally or through an IV, depending on the severity of the deficiency.

When timing therapies, please note that oral magnesium formulations will bind with oral phosphorus formulations, inhibiting the absorption of both.

Thiamin (vitamin B1)

Thiamin deficiency is a risk factor of refeeding syndrome.¹ Thiamin is an essential coenzyme in carbohydrate metabolism. It is thought that carbohydrates introduced during the refeeding process increase cellular thiamin utilization, leading to vitamin B1 deficiency.¹

Thiamin deficiency can cause:¹

• Hypothermia
• Heart failure
• Wernicke’s encephalopathy
• Korsakoff’s syndrome
• Coma

There should be a low threshold to provide high-dose IV thiamine to patients with any findings of thiamine deficiency during refeeding. Otherwise, oral thiamine should be initiated with nutritional rehabilitation.

Glucose

Glucose ingestion after a period of chronic malnutrition can suppress gluconeogenesis (glucose production from other substrates) through the release of insulin.³

This surge in insulin can cause hypoglycemia early in refeeding because of depleted glycogen stores.³ On the contrary, overly aggressive initiation of nutrition at the beginning of refeeding may result in the development of hyperglycemia and may contribute to:

• Osmotic diuresis
• Dehydration
• Metabolic acidosis
• Ketoacidosis

Excess glucose can also cause lipogenesis, which may cause:³

• Hepatic steatosis
• Increased carbon dioxide production
• Hypercapnia
• Respiratory distress

Hemolytic anemia

Hemolysis can occur due to refeeding syndrome. Without sufficient adenosine triphosphate (ATP), red blood cells may struggle to keep potassium levels inside the cells while releasing sodium outside. This imbalance can lead to water entering the cells (osmosis), increasing internal pressure and raising the likelihood that the red blood cells will lyse as they circulate in the bloodstream.

Labs indicative of hemolysis may show:

• Increased lactate dehydrogenase (LDH)
• Low haptoglobin
• Elevated unconjugated bilirubin
• Increased reticulocytes

Creatinine phosphokinase

Creatinine phosphokinase (CPK) is an enzyme found in several organs, mainly in the muscles of the body.

An increase in serum CPK levels can indicate rhabdomyolysis (muscle breakdown), although interpreting these values can be challenging in individuals with malnutrition due to significant muscle loss caused by the catabolic state malnutrition.⁵

Preventing Refeeding Syndrome

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

Electrolyte repletion

Electrolyte deficiencies before refeeding significantly increase the risk of developing refeeding syndrome once nutritional repletion begins and should be corrected as much as possible beforehand.

Normal concentrations of key electrolytes include:

• Phosphorus: > 2.7 mg/dL for adults
• Magnesium: > 1.4 mg/dL for adults
• Potassium: between 3.6 - 5.2 mmol/L
• Sodium: between 138 – 145 mmol/L

Nutritional rehabilitation

In addition to correcting electrolyte deficiencies, caloric intake should be gradually increased during refeeding, and patients should be closely monitored for physical signs of refeeding syndrome.

Increasing caloric intake should be guided by the expert guidance of a registered dietitian and other clinical team members with specialized knowledge of malnutrition and eating disorders.

Caloric needs can be estimated using the Harris-Benedict equation for basal energy expenditure (BEE), but a starting intake of 1,400-1,800 kcal per day is appropriate for most patients and can be increased by 300-400 kcal every 3-4 days.²

Intake can be adjusted according to the rate of weight gain, and liquid supplementation can be used during early refeeding to achieve caloric intake and weight restoration goals.²

Addressing eating disorder behaviors

For patients with eating disorders, you may see little or no weight gain during the first few weeks. In such cases, aggressively increasing calories is not recommended. Patients with eating disorders may have difficulty gaining weight early in refeeding, or they could still be engaging in disordered eating behaviors, such as covert exercise.²

For these patients, you should adjust caloric requirements based on each individual’s rate of weight gain and determine if disordered eating behaviors are still present.²

Treating refeeding syndrome

When refeeding syndrome is suspected, a patient should be hospitalized. Aggressive correction of electrolytes must be performed, either orally or via the intravenous route, depending on serum values.

Patients will also need very close cardiorespiratory monitoring due to the increased risk of cardiac complications and careful monitoring of:

• Lab values
• Vitamin supplementation
• Nutritional intake
• Daily weight measurements

Get Help to Avoid Refeeding Syndrome

Refeeding syndrome is a serious condition that requires careful monitoring and nutrition support. This critical first step in recovery from severe eating disorders and malnutrition requires medical expertise and experience. If you or a loved one may be at risk, specialized support is available to guide you safely through recovery.

Start now with a free assessment.

References

1. Da Silva, J. S. V., Seres, D. S., Sabino, K., Adams, S. C., Berdahl, G. J., Citty, S. W., Cober, M. P., Evans, D. C., Greaves, J. R., Gura, K. M., Michalski, A., Plogsted, S., Sacks, G. S., Tucker, A. M., Worthington, P., Walker, R. N., & Ayers, P. (2020). ASPEN Consensus Recommendations for Refeeding Syndrome. Nutrition in Clinical Practice, 35(2), 178–195. https://doi.org/10.1002/ncp.10474
2. Mehler, P. S., & Andersen, A. E. (2022, May 10). Eating Disorders: A Guide to Medical Care and Complications (fourth edition). Johns Hopkins University Press.
3. 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
4. Cederholm, T., & Bosaeus, I. (2024). Malnutrition in adults. New England Journal of Medicine, 391(2), 155–165. https://doi.org/10.1056/nejmra2212159
5. 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://www.acute.org/publications/nutritional-rehabilitation-practical-guidelines-refeeding-anorectic-patient