What Is Refeeding Syndrome? Warning Signs & Complications

Known as refeeding syndrome, when individuals who are malnourished begin to eat again, the sudden shift in metabolism can cause rapid and potentially fatal shifts in electrolytes, particularly phosphorus, potassium and magnesium, causing a variety of medical complications.

What is Refeeding Syndrome?

Refeeding syndrome is a serious and potentially fatal complication of nutritional rehabilitation. It occurs in significantly malnourished patients when a diet of increasing calories is initiated orally, enterally or parenterally. Refeeding syndrome can cause:

• Cardiovascular issues
• Respiratory failure
• Seizures
• Death

Refeeding syndrome definition

The most recent definition of refeeding syndrome proposed by the American Society for Parenteral and Enteral Nutrition (ASPEN) committee defines refeeding syndrome as a decrease in any 1, 2 or 3 of serum phosphorous, potassium and/or magnesium levels:

• Mild: decrease by 10-20%
• Moderate: decrease by 20-30%
• Severe: decrease by >30% and/or organ dysfunction resulting from a decrease in any of these and/or due to thiamin deficiency

These changes also occur within 5 days of reinitiating or substantially increasing energy provisions.

How refeeding syndrome occurs

Refeeding syndrome occurs when a patient who is malnourished begins the refeeding process. As the patient begins metabolizing nutrients, particularly carbohydrates, insulin is released. Insulin helps the body to build up some of these very unhealthy tissues (anabolism) as it causes cells in the body to uptake phosphorous and other electrolytes.

Phosphorous is also important in the production of adenosine triphosphate (ATP), which transports chemical energy within cells for metabolism. In a hypophosphatemic state, the body cannot produce enough ATP, which causes various organs to start to fail.

Nutritional rehabilitation and refeeding syndrome

For severely underweight patients with eating disorders, like anorexia nervosa or ARFID, or due to non-eating disorder malnutrition, nutritional rehabilitation is an essential intervention.

During the refeeding process, food is reintroduced based on metabolic need to address the serious medical complications of malnutrition. However, it is critical that patients be closely monitored by experienced medical professionals during initial refeeding to prevent refeeding syndrome.

Who is at risk for refeeding syndrome?

While there is no single marker to identify which patients will develop refeeding syndrome, the American Society for Parenteral and Enteral Nutrition (ASPEN) has published two sets of criteria for identifying patients at heightened risk for refeeding syndrome.

Highest risk

According to these guidelines, patients at the highest risk for refeeding syndrome meet one or more of the following criteria:

• Body mass index (BMI) under 16 kg/m²
• Weight loss of more than 7.5% in 3 months or >10% in 6 months
• None or negligible oral intake for >7 days or <50% of estimated energy requirement for >5 days during an acute illness or injury or <50% of estimated energy requirement for >1 month
• A blood test that reveals moderately/significantly low levels of phosphorous, potassium or magnesium or normal levels after recent low levels that required significant or multiple-dose supplementation
• Evidence of severe loss of subcutaneous fat
• Evidence of severe loss of muscle mass

Patients with eating disorders

Patients with eating disorders may also have significant risk for refeeding syndrome as well if they meet two or more of the following criteria:

• BMI of 16-18.5 kg/m²
• Weight loss of 5% in 1 month
• Little to no food for the past 5-6 days or <75% of estimated energy requirement for >7 days during an acute illness or injury or <75% of estimated energy requirement for >1 month
• Minimally low levels of potassium, phosphate, or magnesium or normal levels after recent low levels that required minimal or single-dose supplementation
• Evidence of moderate loss of subcutaneous fat
• Evidence of mild or moderate loss of muscle mass during the past 3-6 months
• Little to no food intake for the past 5 or more consecutive days
• A history of alcoholism or drug misuse, including insulin, chemotherapy drugs, diuretics and antacids

Chronic alcoholism, cancer, uncontrolled diabetes or recent surgery may also elevate the risk of developing refeeding syndrome in those with eating disorders.

Refeeding syndrome statistics

The prevalence of refeeding syndrome is unknown due to varying definitions across studies. While meta-analyses have been performed, the heterogeneity of the data has made it difficult to draw any conclusions on the rate of refeeding syndrome.

How refeeding syndrome occurs

Malnourished individuals, whether due to an eating disorder or other condition, are in a catabolic state (a breakdown of the tissues and organs) due to:

1. A lack of nutritional substrates, including:
   • Depleted energy reserves, such as fatty acids, glycogen and proteins
   • Vitamins
   • Intracellular electrolytes
2.  Hormonal changes that occur alongside starvation

Phosphorous is the most important intracellular electrolyte in the context of refeeding syndrome. Phosphorous is a vital component of adenosine triphosphate (ATP), which is needed by all cells to perform all their basic functions. 

When refeeding is initiated and the body suddenly starts to take in nutrition, it changes from a catabolic state to an anabolic state (build-up of the tissues and organs).

Carbohydrates make up most of the consumed macronutrients, causing the release of insulin. Insulin has anabolic properties and acts to push phosphorous, potassium and glucose into the cells of the body, further depleting any remaining phosphorous that is needed by more active cells and tissues.

The brain, muscles (including the heart and diaphragm) and blood cells are highly dependent on phosphorous and these tissues can quickly start to fail.

Refeeding syndrome symptoms

A sudden change in the balance of phosphorous and other electrolytes causes the heart to work harder to manage a higher blood volume, which can cause a variety of different symptoms, including:

• Fatigue
• Weakness
• Confusion
• Difficulty breathing
• Edema
• Hypophosphatemia (low phosphorous)
• Hypokalemia (low potassium)
• Rhabdomyolysis (muscle break down)
• Hemolysis (rupture of blood cells as they travel in the blood stream)
• Seizures
• Heart failure

Symptoms of refeeding syndrome can occur as early as four days after refeeding is initiated.

Refeeding edema

Another sign of refeeding syndrome is edema (swelling) of the lower extremities. During refeeding, the body secretes insulin. As a result, the kidneys retain salt and water, causing the legs to swell. Edema in refeeding syndrome can also be worsened by impaired cardiac function, which further increases the risk for edema formation. Upon observation, medical intervention is necessary.

How to avoid refeeding syndrome

Refeeding syndrome can be easily avoidable with the use of lab monitoring and when under the care of those who are experienced and specialized in the refeeding of malnourished patients.

Is refeeding syndrome fatal?

Yes, refeeding syndrome can be fatal if inappropriately managed in a timely manner. Organ function will be severely compromised in the setting of hypophosphatemia, and organ failure can increase the likelihood of poor outcomes, including death.

References

• The incidence of the refeeding syndrome. A systematic review and meta-analyses of literature - PubMed (nih.gov)
• da Silva, Joshua S. V et al. “ASPEN Consensus Recommendations for Refeeding Syndrome.” Nutrition in clinical practice 35.2 (2020): 178–195. Web.