Refeeding syndrome is a serious medical complication that can occur during the early stages of eating disorder recovery when individuals who are malnourished begin eating normally again. Refeeding syndrome is especially common in patients recovering from anorexia nervosa, but can occur in anyone who has been starved for an extended period of time.
One of the earliest reported incidences of refeeding syndrome dates back to World War 2 when Far East prisoners of war started to eat again after a prolonged period of starvation. After being appropriately refed, the prisoners developed edema and cardiac issues that eventually led to death. During this time, a professor and physiologist at the University of Minnesota named Ancel Keys led the first experiment of its kind examining the physiological and psychological effects of famine and starvation. The experiment was named the Minnesota Starvation Study and it continues to provide clinicians today with vital information regarding how the body and mind react to starvation and refeeding.
Although the origins of refeeding syndrome date back many decades, is it often still overlooked and undiagnosed due to its complex presentation. Let’s take a closer look at the pathophysiology of refeeding syndrome.
What is Refeeding Syndrome?
Refeeding syndrome is defined as potentially fatal shifts in fluids and electrolytes that can occur in malnourished patients being refed due to hormonal and metabolic changes. The primary diagnostic marker of refeeding syndrome is hypophosphatemia (low phosphorus levels), but often includes additional micronutrient imbalances including hypokalemia (low potassium levels), hypomagnesaemia (low magnesium levels), low thiamine levels, and fluid retention.
What causes Refeeding Syndrome?
Under normal circumstances, the body breaks down carbohydrates into glucose to use as its primary fuel source. In the absence of adequate carbohydrates during times of starvation, the body switches to using fats and proteins for energy. This switch happens rather quickly in the absence of adequate food intake because the body is unable to store large amounts of carbohydrates at any given time.
Once an individual begins eating again and adequate carbohydrates are being consumed, the body begins using glucose for energy again. The increase in blood glucose causes insulin levels to rise. This rise in insulin leads to insufficient levels of phosphorus, potassium, and magnesium in the blood because they are quickly shuttled into the cell to assist with glucose metabolism.
How Common is Refeeding Syndrome?
The exact incidence of refeeding syndrome is difficult to identify because there is still no universally accepted definition. According to a meta-analyses, the prevalence of refeeding syndrome varied greatly between 0 – 62% depending on the definition and population used in various studies.
Risk Factors for Refeeding Syndrome:
Like mentioned previously, there is no universally accepted definition of refeeding syndrome in the literature. This makes it difficult to effectively diagnose and treat because lab work often comes back showing normal ranges for phosphorus, potassium, and magnesium. It is not until a patient is being refed that lab values will identify inadequate stores of these nutrients. Thankfully, the National Institute for Health and Clinical Excellence (NICE) developed guidelines for identifying individuals at high risk for developing refeeding syndrome.
Either the patient has one or more of the following:
- Body mass index (kg/m2) <16
- Unintentional weight loss >15% in the past three to six months
- Little or no nutritional intake for >10 days
- Low levels of potassium, phosphate, or magnesium before feeding
Or the patient has two or more of the following:
- Body mass index <18.5
- Unintentional weight loss >10% in the past three to six months
- Little or no nutritional intake for >5 days
- History of alcohol misuse or drugs, including insulin, chemotherapy, antacids, or diuretics
The American Society for Parenteral and Enteral Nutrition (ASPEN) has also proposed guidelines for assessing risk severity. According to their proposed diagnostic criteria, patients can be categorized on 3 levels of severity including mild, moderate, and severe. As always, it is important to get assessed by a trained clinician so they can help determine the best course of treatment.
- Mild – a decrease in any 1, 2, or 3 of serum phosphorus, potassium, and/or magnesium levels by 10% to 20%
- Moderate – a decrease in any 1, 2, or 3 of serum phosphorus, potassium, and/or magnesium levels by 20% to 30%
- Severe – a decrease in any 1, 2, or 3 of serum phosphorus, potassium, and/or magnesium levels by >30% and/or organ dysfunction resulting from a decrease in any of these and/or due to thiamine deficiency (severe), occurring within 5 days of a reintroduction of calories
Presentation of Refeeding Syndrome:
Hypophosphatemia
- Low phosphorus in the blood
- Considered the hallmark feature of refeeding syndrome
- Occurs within 1-3 days following increased food intake
- Signs/Symptoms: Irregular heartbeat, muscle weakness, seizures, delirium, heart failure, coma, death
Hypokalemia:
- Low potassium in the blood
- Important for muscle contraction, transmitting nerve signals, maintaining fluid balance, maintaining blood pressure
- Signs/Symptoms: Heart palpitations, muscles weakness and spasms, tingling and numbness, extreme fatigue, low blood pressure
Hypomagnesaemia:
- Low magnesium in blood
- Required for over 300 biochemical reactions
- Assists with blood glucose control, protein synthesis, blood pressure regulation, muscle and nerve function
- Signs/Symptoms: Irregular heartbeat, tremors, seizures, muscle cramps, tingling and numbness, coma, reduced oxygenation
Low Thiamine:
- Essential vitamin needed for carbohydrate metabolism
- Signs/Symptoms: Confusion, irritability, mood changes, memory loss, psychosis, coma, heart failure, edema
Fluid Retention:
- Reintroduction of carbohydrates during nutritional rehabilitation leads to increased secretion of insulin
- Rise in insulin levels causes kidneys to retain sodium and fluids
- Signs/Symptoms: Swelling in the body, especially the legs and feet
Treatment for Refeeding Syndrome:
Due to a lack of objective data from scientific studies, much confusion still exists regarding appropriate management recommendations for refeeding syndrome. Traditionally, clinical practice recommended a “start low and go slow” method of nutritional rehabilitation, but we now understand that starting calories too low can cause more harm than good. Most clinicians are comfortable starting patients at a higher than previously recommended calorie level as long as they are being overseen in a clinical setting so that fluid and electrolytes can be appropriately managed.
Going into detail on the specific nutrition recommendations is beyond the scope of this particular blog. The most important piece of information to take away is that if you or someone you know is struggling with an eating disorder, it is absolutely imperative you meet with a physician and get set up with an eating disorder treatment team so that all medical, psychological, and psychiatric concerns can be appropriately managed.
As always, please feel free to reach out with any questions or concerns.
Kelly Melanson, RD
