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Refeeding Syndrome - Causes, Prevalence, Complications, and Treatment

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Refeeding syndrome is associated with hypophosphatemia, hypokalemia, and hypomagnesemia. The article reviews the genesis and management of the syndrome.

Written by

Dr. Parul Anand

Medically reviewed by

Dr. Achanta Krishna Swaroop

Published At September 30, 2022
Reviewed AtMay 6, 2024

What Is Refeeding Syndrome?

Refeeding syndrome is a clinical complication when a patient is given nutrition after prolonged starvation. It is a medical complication associated with nutrition replenishment seen in malnourished persons, those having eating disorders like anorexia nervosa (a condition characterized by low body weight), and on hemodialysis (as seen in renal failure patients). As soon as the patients start eating, fluids and electrolytes balance shift, metabolic activities get disturbed, and cardiopulmonary, neurological, and renal dysfunctions occur.

The characteristics of refeeding syndrome are hypophosphatemia (when the serum phosphate level is less than 2.5 mg/dL), hypokalemia (serum potassium level less than 3.5mEq/L), hypomagnesemia (serum magnesium level less than 1.8 mg/dL) abnormal blood glucose levels, and thiamine deficiency, making this syndrome a highly morbid and mortal condition requiring immediate medical treatment. Evidence proves that more prolonged periods of starvation lead to death following nutritional and vitamin replenishment.

What Is the Etiology of the Refeeding Syndrome?

The genesis of refeeding syndrome is considered to be multifactorial. Usually, the malnourished patients, when suddenly fed after a long period of starvation, are the primary sufferers of the syndrome. The leading causes of refeeding syndrome include:

  • Chronic alcoholism.

  • Poorly controlled diabetes.

  • Chronic malnutrition.

  • Inflammatory bowel disease.

  • Oncological conditions.

  • Post-operative state.

What Is the Prevalence of the Syndrome?

As per the National Institute for Healthcare and Excellence guidelines, the following risk factors are accountable for refeeding syndrome - low body mass index (BMI), unintentional weight loss, low initial electrolyte concentrations, alcohol abuse history, and starvation. Hypophosphatemia is a clinical sign of refeeding syndrome. The prevalence of refeeding syndrome is still undefined as there is no uniform study methodology. In a study conducted on ICU patients, it has been seen that 34% of the patients show nutritional replenishment following feeding after days of starvation. In critical care units, the patients suffering from refeeding syndrome show hyperglycemia and increased insulin levels associated with TPN (total parenteral nutrition), thus leading to electrolyte imbalance.

How Does It Occur?

When a patient is starving for a more extended period, gluconeogenesis and proteolysis increase. Also, there is a depletion of vitamins and intracellular electrolytes. As the sequence continues, there is an increase in glucose levels in the bloodstream, due to which a rise in insulin levels occurs.

Hypokalemia: There is an intracellular movement of phosphorus and potassium, resulting in a decrease in extracellular levels of potassium. An increase in insulin and intracellular migration of electrolytes causes an electrolyte imbalance. Hypokalemia is responsible for causing severe diseases like cardiac arrhythmias, generalized weakness, respiratory distress, fatigue, paralysis, hypoventilation, etc.

Hypophosphatemia: It follows the exact pathophysiology of hypokalemia. If the starvation continues, the phosphorus reserves start depleting as phosphorus is a critical component required for forming ATP (adenosine triphosphate) and plays a significant role in the heart's conduction. Decreased levels of phosphorus, called hypophosphatemia, cause fatal conditions like cardiac arrhythmias and contractility. Also, these decreased levels are accountable for a decrease in 2, 3 diphosphoglycerate (2,3 DPG), leading to a high affinity of hemoglobin for oxygen. Thus, the release of oxygen to tissues is diminished. This causes secondary organ failure due to a poor prognosis. Hypophosphatemia also causes acute respiratory failure.

Hypomagnesemia: It is associated with refeeding syndrome; however, it worsens hypokalemia. Enzymes involved in the process of formation of ATP are seen to be dependent on the levels of manganese, too, therefore, decreased levels of manganese are associated with many neuromuscular disorders like ataxia convulsions, vomiting, vertigo, paresthesia, etc. in the patients suffering from refeeding syndrome.

What Is the Relation Between Refeeding Syndrome And Thiamine?

Refeeding syndrome is usually seen to be associated with thiamine. For the metabolism of glucose, thiamine is required. Thiamine levels increase in patients suffering from starvation as there is a replenishment of nutrients, but lactate levels are stored up. Due to insufficient amounts of thiamine, cardiac dysfunction occurs. Karsakoff’s encephalopathy and Wernick’s diseases occur due to deficiency of thiamine; the classical triad of this disease is ophthalmoplegia, gait disturbances, and mental status changes like hallucinations and confabulations. A shortage of thiamine also causes alcohol abuse.

What Are the Complications?

Refeeding syndrome affects different organ systems in humans. Following are the complications associated with this syndrome:

  • Cardiac arrest.

  • Fluid retention.

  • Paralysis.

  • Seizures.

  • Confusion.

  • Respiratory distress.

  • Bowel changes.

  • Cardiac arrhythmia - Irregular heartbeat, either tachycardia (fast heartbeat) or bradycardia (slow heartbeat).

How Does It Get Treated?

  • To the patients who are in hospital for a prolonged duration or are being metabolically starved, enteral feeding is given initially.

  • The focus is to be given to carefully depleting nutrients and conserving calories. Patients suffering from critical burns are also given enteral feeding rather than parenteral, depending upon the parent’s tolerance level.

  • Gut flora preservation, immunity development, and systemic bacteria reduction are crucial factors for treating the refeeding syndrome.

  • L-arginine and glutamine supplements are required for maintaining these factors.

  • Potassium, phosphorus, and manganese levels should be monitored before nutritional replenishment. The nutritional replenishment should be delayed in case any of these minerals are decreased.

  • Electrolyte monitoring should also be done after 12 hours for the first three days in high-risk patients.

What Do the Studies Suggest for Management?

As per the ASPEN’S guidelines, before the initiation of dextrose supplement intake in the patients, 100 mg thiamine is to be administered. Thiamine levels are to be checked regularly. There must be protein restriction, no use of fluids, sodium intake, and vitals should be monitored every four hours in high-risk patients.

According to the National Institute for Health and Clinical Excellence (NICE), high-risk patients need to undergo- weight fluctuations check, screening for previous alcohol use, and nutritional assessment. There must be an evaluation of all potassium, phosphorus, and magnesium levels as the nutritional replenishment is associated with specific electrolytes such as potassium- 2 to 4 mmol/kg/day, phosphate - 0.3 to 0.6 mmol/kg/day, magnesium- 0.2 mmol/kg/day to be given. 100 mg thiamine should be issued 30 minutes before the nutritional replenishment, which is to be continued for seven to ten days to prevent neurological complications.

What Is the Differential Diagnosis of the Syndrome?

In the case of refeeding syndrome, the differential diagnosis is difficult as other medical conditions need to be ruled out as well. There can be fluid overload resulting in the depletion of many electrolytes like sodium, potassium, magnesium, and phosphorus. Due to this electrolyte imbalance, high-risk patients suffering from cardiac arrhythmias show long QT segments.

How Does the Prognosis Go?

In mild electrolyte imbalance, the patients may not show apparent symptoms, and the refeeding syndrome remains unpredicted. The prognosis is based on biochemical and electrolyte changes. The patients show comorbidities in cases where symptoms do not subside but are exaggerated by alcohol abuse; thus, the prognosis worsens.


Refeeding syndrome is a metabolic condition that mainly affects individuals undergoing prolonged starvation or those hospitalized for a longer duration. As soon as the nutritional replenishment begins, three primary disorders- hypokalemia, hypophosphatemia, and hypomagnesemia thus decrease the levels of nutrition. The management requires the proper monitoring and care of the patient as he starts getting fed. Many studies provide guidelines regarding the control of the syndrome.

Frequently Asked Questions


What Are the Clinical Manifestations of Refeeding Syndrome?

Clinical features of the refeeding syndrome include electrolyte imbalances such as low levels of magnesium, potassium, and phosphorus, leading to symptoms like muscle weakness, cardiac arrhythmias, and respiratory failure. Other manifestations may include fluid retention, swelling, confusion, and, in severe cases, seizures or coma.


What Is the Common Cause of Refeeding Syndrome?

The most common cause of refeeding syndrome is the rapid reintroduction of nutrition, particularly carbohydrates, in individuals who are severely malnourished or have experienced prolonged fasting.


What Is Refeeding Syndrome?

Refeeding syndrome is a very serious condition that can be life-threatening. It happens when someone who is malnourished, like someone with anorexia or severe malnutrition, starts eating again too quickly. It is characterized by a shift in which the body switches from using the energy it has stored to making and saving energy. This shift may lead to electrolyte imbalances and other clinical manifestations.


What Is Considered to Be the Hallmark of Refeeding Syndrome?

The main sign of refeeding syndrome is a quick and big change in electrolyte levels, especially low levels of phosphate in the blood (hypophosphatemia). When someone who has not been eating enough food gets proper nutrition, especially carbohydrates, the body's insulin levels go up, causing the cells to take in more phosphate, potassium, and magnesium. This sudden increase can use up the body's supplies of these important electrolytes, which can lead to a series of problems with the body's metabolism and possibly dangerous complications.


How Is Refeeding Syndrome Diagnosed?

Doctors identify refeeding syndrome by examining a patient, doing tests on their blood, and checking their electrolyte levels (such as phosphorus, potassium, and magnesium), glucose levels, liver function, and kidney function.


Which IV Is Used in Case Refeeding Syndrome?

In severe cases of refeeding syndrome, it is usually necessary to give essential electrolytes and nutrients through a needle in the vein (IV). Some common IV solutions used have things like phosphorus, potassium, magnesium, glucose, thiamine (vitamin B1), and multivitamins. These are used to fix nutritional problems and stop things from getting worse.


What Vitamin Is Deficient in Refeeding Syndrome?

Refeeding syndrome can lead to a deficiency of thiamine (vitamin B1). Thiamine supplementation is an essential component of refeeding protocols to prevent or treat this deficiency and its associated complications.


What Are the High-Risk Factors Associated With Refeeding Syndrome?

- Prolonged starvation or severe malnourishment.

- Low body weight and low BMI (body mass index).

- Previous history of refeeding syndrome.


What Are Some Good Foods for Refeeding?

During refeeding, it is essential to introduce nutrient-rich foods gradually to support the body's recovery without overwhelming it. Good foods for refeeding include:

- Easily digestible protein sources like lean meats, fish, tofu, or eggs.

- Complex carbohydrates such as brown rice, quinoa, and whole wheat bread.

- Nutrient-dense fruits and vegetables.


How Long Does Refeeding Syndrome Last?

The time it takes to recover from refeeding syndrome can differ for each person. It depends on how bad the case is and how quickly it is noticed and treated. With the right and timely interventions, the initial stage of refeeding syndrome, which comes with big changes in the body's metabolism, imbalanced electrolytes, and problems, can go on for a few days to a couple of weeks. However, it can take several weeks to months for someone to fully recover and stabilize from refeeding syndrome.


How Is Refeeding Edema Treated?

Refeeding edema, a common complication of refeeding syndrome, is treated by managing the underlying electrolyte imbalances and fluid retention. The treatment involves a gradual and controlled reintroduction of nutrition to prevent sudden shifts in electrolyte levels. Doctors may also adjust fluid intake, monitor electrolyte levels closely, and use diuretics cautiously if necessary to address excessive fluid retention.


Why Is Phosphate Low in Individuals With Refeeding?

When someone who is very undernourished starts eating again, especially foods that have carbohydrates, the amount of insulin in their body increases. The increased insulin helps the cells in their body absorb more phosphate. This quick increase in phosphate, as well as other electrolytes like potassium and magnesium, reduces the body's supply, causing low levels of phosphate.


How Much Protein Is Required for Refeeding Syndrome?

Individuals with refeeding syndrome need to get enough protein when they start eating again to help their body repair and heal. Healthcare workers usually try to give patients who are at risk or recovering from refeeding syndrome about 1.2 to 15 grams of protein for every kilogram of their body weight each day.


How Is Refeeding Syndrome Treated?

Doctors help patients with refeeding syndrome by slowly and carefully reintroducing food under their supervision. They begin with diets with fewer calories and carbs and slowly increase the amount of calories and nutrients they eat over several days to weeks. Electrolyte levels, especially phosphorus, potassium, and magnesium, are closely monitored and supplemented as needed. Thiamine is often administered to prevent or treat thiamine deficiency.

Dr. Achanta Krishna Swaroop
Dr. Achanta Krishna Swaroop



refeeding syndrome
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