Case Report

Diagnosis and Management of Refeeding Syndrome in Older Adults

Naseem Sunnoqrot, MD1,2 • Ravi Kant, MBBS1,2 • Conrad May, MD1,2 • Steven R. Gambert, MD, AGSF, MACP1,2,3 1Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 2Gerontology Research, Education and Clinical Center (GRECC), Baltimore VA Medical Center, Baltimore, MD 3R Adams Cowley Shock Trauma Center, University of Maryland Medical Center, Baltimore, MD

Key words: Refeeding syndrome, malnutrition, hypophosphatemia, parenteral nutrition.

Refeeding syndrome was first recognized after World War II, when prisoners were released to American military bases in the Philippines. It was also noted following the large-scale famine that spread across Europe and Asia during the final years of the war, leaving millions of starving victims in addition to survivors of concentration camps, where malnutrition was ubiquitous. An increased death rate was noted shortly after these vulnerable individuals were provided with nutrition. Although there is no universally accepted definition, refeeding syndrome is typically characterized by potentially fatal hypophosphatemia and other metabolic disorders when resuming feeding, either enterally or parenterally, in malnourished or starved patients.

The definition of refeeding syndrome, an understanding of its pathophysiology, and guidelines for its prevention and treatment have developed over the years. The Minnesota Starvation Experiment, a clinical study performed at the University of Minnesota between November 19, 1944, and December 20, 1945,1,2 was instrumental in investigating the effects of resumed feeding for previously starved persons. The investigation was designed to determine the physiological and psychological effects of severe and prolonged dietary restriction and the efficacy of various dietary rehabilitation methods.1,2 Although the final results were published in 1950 in a text titled The Biology of Human Starvation, the preliminary data were used by relief workers early after World War II.1 

Although our understanding of the pathophysiology of refeeding syndrome has evolved, it may be underrecognized in older persons, as the initial symptoms are nonspecific. Symptoms of malnutrition are frequently seen in older adults, but if patients with refeeding syndrome are inappropriately treated, the consequences can be fatal. Our case presentation demonstrates how an understanding of the complex pathophysiology of refeeding syndrome and a thorough work-up to identify and monitor biochemical abnormalities enabled us to treat the patient quickly and successfully. A discussion of the pathophysiology is provided, broken down according to the key electrolytes involved, and followed by our recommendations for prevention and management of this phenomenon.

Case Presentation 

An 85-year-old man with a history of diabetes mellitus, congestive heart failure, peripheral vascular disease, and hypertension was admitted to the hospital for progressively worsening nausea, vomiting, and poor oral intake. He had been discharged 2 weeks earlier after hospitalization for lower extremity cellulitis, for which he was treated with trimethoprim/sulfamethoxazole and ciprofloxacin. At the time of admission, the physical examination revealed an emaciated man who was not in acute distress. His vital signs were as follows: blood pressure, 124/44 mm Hg; pulse, 61 beats per minute; and temperature, 96.8°F. He weighed 125 lb, with a body mass index (BMI) of 17 kg/m2. The patient’s weight was noted to be 151 lb just 1 month prior to this admission. Notable laboratory test results on admission were as follows: blood urea nitrogen (BUN) level, 103 mg/dL (normal, 8-23 mg/dL); creatinine level, 5.2 mg/dL (normal, 0.6-1.2 mg/dL); and phosphate level, 8.6 mg/dL (normal, 2.7-4.5 mg/dL). At baseline, his BUN level was 18 mg/dL and his creatinine level was 0.9 mg/dL. On admission, the patient’s medications included aspirin 325 mg daily, furosemide 20 mg daily, hydrochlorothiazide 25 mg daily, lisinopril 20 mg daily, metoprolol 12.5 mg twice daily, simvastatin 80 mg daily, and metformin 500 mg daily. 

A presumptive diagnosis of acute renal failure secondary to medications (trimethoprim/sulfamethoxazole, metformin, lisinopril) and/or dehydration was made. The hyperphosphatemia was presumed to be secondary to acute renal failure. The patient was treated with intravenous hydration; no phosphate binders were administered. His renal failure, nausea, and vomiting resolved rapidly, after which his appetite improved and he started to eat orally. On hospital day 5, he was noted to be confused. At that time, his laboratory tests revealed a BUN level of 39 mg/dL, a creatinine level of 1.3 mg/dL, and a phosphate level of 1.4 mg/dL. While in the bathroom on hospital day 7, he suddenly became unresponsive. His electrolyte panel revealed worsening hypophosphatemia with the level down to 0.7 mg/dL, along with hypokalemia, hypomagnesemia, and hypocalcemia. The patient was treated aggressively with both oral and intravenous phosphate, as well as calcium, magnesium, and potassium. After 3 days of supplementation, his electrolyte levels returned to normal and the patient regained his baseline mental status. 

Pathophysiology of Starvation and Refeeding Syndrome 

During the first few days of starvation, the body goes through the process of glycogenolysis in the liver to free up glucose. When glycogen stores are depleted, insulin levels decrease, resulting in increased lipolysis and muscle breakdown, which fuels gluconeogenesis with amino acids and fatty acids as substrates. Further muscle loss is prevented through the suppression of gluconeogenesis and the use of ketones for energy generation. In other words, the main energy source shifts from carbohydrate to fat, leading to a major consumption of minerals and vitamins in the body and predisposing it to deficiencies in total body amounts of phosphorus, potassium, magnesium, and B vitamins, especially thiamine. These deficiencies might not be obvious because of the deceptively normal serum levels that occur with shifts between the intra- and extracellular compartments. When feeding is restarted, the reverse occurs. Elevated levels of insulin lead to an anabolic state to rebuild muscle protein and fatty tissues. This process involves different substances being transported into the cell, resulting in various deficiencies and biochemical derangements. Glucose metabolism causes an increase in the use of phosphorus to produce adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG).3 The hallmarks of refeeding syndrome are hypophosphatemia, hypomagnesemia, hypokalemia, and thiamine deficiency. In addition, sodium and water retention might also ensue so that the body can maintain osmotic neutrality. Vulnerable patients are usually cachectic and catabolic, but they often have relatively preserved levels of serum protein. This is in contrast to patients with pure protein-calorie malnutrition (Kwashiorkor type), who appear less malnourished, have marked hypoalbuminemia, and have an increased susceptibility to infections.4,5

Normal values for phosphorus are 2.7 to 4.5 mg/dL. Its most common inorganic form, phosphate, occurs mainly intracellularly (99%). Although clinical manifestations can occur when levels are less than 2 mg/dL, a full-blown clinical picture is rarely seen until levels are less than 1 mg/dL. Phosphorus is used for the phosphorylation of adenosine diphosphate and adenosine monophosphate to produce ATP. ATP is the so-called molecular unit of currency of intracellular energy transfer because of its essential role in transporting chemical energy for metabolism inside the cell.4 It is also necessary for the production of 2,3-DPG, which is responsible for efficient oxygen transfer in tissues. Upon refeeding, the resulting surge in insulin leads to a profound decrease in serum levels with the potential for cardiac failure and fatal arrhythmias, confusion, coma, respiratory failure, neuromuscular weakness, thrombocytopenia, hemolysis, and leukocyte and platelet dysfunction. Studies have shown that the incidence of hypophosphatemia is high, approaching 42%, in the hospital setting.3 It is therefore important to recognize other common causes of a low phosphorus level, especially in the critical care setting; these include sepsis, rehydration, diabetic ketoacidosis, malabsorption, and medications.3 Profound hypophosphatemia may lead to sodium and water retention that additionally may contribute to congestive heart failure.6

Potassium is predominantly an intracellular electrolyte with 98% of the total body amount being within cells. Insulin plays a key role in the regulation of potassium, and upon refeeding, rising levels of insulin help glucose enter cells via the Na+/K+-ATPase (sodium-potassium adenosine triphosphatase) transport mechanism. The net result is an intracellular shift with resultant hypokalemia, potentially leading to different types of cardiac arrhythmias, neuromuscular weakness and irritability, respiratory failure, rhabdomyolysis, and, in extreme cases, ileus. More than 20% of hospitalized patients develop hypokalemia sometime during their hospitalization, with the most common causes being diuresis, diarrhea, vomiting, and alkalosis.3 Magnesium is essential for potassium uptake and maintenance of intracellular levels of potassium. Magnesium depletion should always be considered in patients with difficult-to-treat hypokalemia.3 

Magnesium must also be considered while refeeding a person previously calorically deprived. Only 1% of magnesium is in the extracellular compartment and serum levels are usually unreliable.3 Magnesium plays an important role in ATP phosphorylation and maintains neuromuscular stability by inhibiting the release of acetylcholine. Low potassium levels may lead to cardiac arrhythmias, neuromuscular weakness, seizures, confusion, abdominal pain, diarrhea, and constipation, and may also complicate the management of hypokalemia.7 Hypomagnesemia may additionally be encountered as a complication of chronic alcoholism, malnutrition, or diuretic and other medication use.

Vitamin deficiencies will usually occur with starvation, the most significant of which is thiamin (vitamin B1), an essential coenzyme in carbohydrate metabolism. Thiamine is a water-soluble vitamin that works as a cofactor in converting pyruvate to acetyl-coenzyme A via its active metabolite, thiamine pyrophosphate.8 The latter is important for several reactions in glucose utilization. A severe deficiency of thiamine leads to an accumulation of pyruvate, which may result in lactic acidosis when it converts to lactate.3 The biological half-life of thiamine is 9.5 to 18.5 days.8 An acute insulin rise leads to a rapid intracellular shift. It is essential and a standard practice to administer thiamine before glucose in comatose patients to prevent an acute drop in thiamine levels, especially in persons who may already be deficient, such as those with chronic alcoholism. Low thiamine levels can lead to neuropsychiatric and other complications. Low stores are prevalent in patients being treated with dialysis; those with diarrhea, alcoholism, and malabsorption; and those who have undergone bariatric surgery.8 Acute heart failure may also be noted in addition to confusion.6 Thiamine deficiency can result in Wernicke’s encephalopathy, a well-described syndrome characterized by ataxia, ophthalmoplegia, nystagmus, confusion, and impairment of short-term memory.9 

Prevention and Management 

The incidence of refeeding syndrome is unknown, partly due to the lack of a universally accepted definition. While the incidence of hypophosphatemia is reported to be 30% to 38% in patients receiving parenteral nutrition, it may increase to 100% if parenteral nutrition is not supplemented with phosphate.10 Refeeding syndrome often goes unrecognized in elderly malnourished patients.11 Elders are at particular risk because of the high prevalence of malnutrition and the decreased physiologic reserve that is unmasked during periods of stress. Elderly patients can be malnourished from decreased intake, poor absorption, high nutrient losses, or increased metabolic demand. The multidisciplinary team, including a physician trained in nutritional support, a dietician, a nutrition nurse, and other allied healthcare professionals, should be involved in the care of severely malnourished elderly patients. Prevention is the key to successful management. Identification of at-risk patients, appropriate initiation of a feeding regimen, careful monitoring during feeding, and early recognition of signs and symptoms of complications are crucial. The Table outlines the risk factors for refeeding, as established by the United-Kingdom—based National Institute for Health and Clinical Excellence (NICE).13-15 Additional risk factors for refeeding problems are also outlined in the table.  

risk factors for refeeding syndromeEvery elderly malnourished patient or at high risk for malnourishment should be screened for the risk of developing refeeding syndrome, and a formal nutritional assessment should be done for those deemed at risk. An initial evaluation should involve a thorough history and physical examination targeted at identifying risk factors and characteristics of malnutrition. Laboratory assessment should involve baseline measurements of electrolytes (phosphorus, magnesium, calcium, sodium), prealbumin, glucose, renal function, liver function, serum vitamin B12, and serum folate levels. Serum albumin is of virtually no value in the assessment or monitoring of nutritional status.15 Prealbumin has a short half-life of approximately 2 days compared with that of albumin (half-life of 2-3 weeks).15 Prealbumin is therefore more sensitive than albumin to changes in protein-energy status and its concentration closely reflects recent dietary intake rather than overall nutritional status.15 Because of this short half-life, however, the concentration of prealbumin falls rapidly during critical illness, systemic inflammation, or exacerbation of chronic conditions. Hence, serial measurements of prealbumin may be more accurate for assessing the adequacy of nutritional intake.

Nutrition support should be provided to patients who are malnourished or at risk of malnourishment by oral, parenteral, or enteral routes. Oral and enteral routes are preferred over parenteral. There are numerous published regimens for feeding patients at risk of refeeding syndrome. The minimum glucose requirement for a 155-lb adult to suppress gluconeogenesis, spare proteins, and supply fuel to the central nervous system is approximately 100 g to 150 g daily.12 In patients at high risk of developing refeeding problems, guidelines from the NICE in the United Kingdom13 recommend starting nutrition support at a maximum of 10 kcal/kg per day and increasing levels slowly to meet or exceed full needs within 4 to 7 days. Even lower calorie supplementation, only 5 kcal/kg per day, is appropriate in extreme cases (eg, for persons with a BMI <14 kg/m2 or negligible intake for more than 15 days).13 Patients should be closely monitored, with clinical, biochemical, and electrocardiogram assessment if needed. If refeeding syndrome is suspected, the intake of energy should be reduced or stopped. The feeding rate should be gradually increased over the course of 3 to 5 days12 to meet full requirements for fluid, electrolytes, vitamins, and minerals if the patient is clinically and biochemically stable.

Any electrolyte abnormalities (especially hypophosphatemia, hypokalemia, and hypomagnesemia) should be corrected before nutrition support is initiated.12 NICE guidelines13 recommend providing oral, enteral, or intravenous supplements of potassium (likely requirement, 2-4 mmol/kg daily), phosphate (likely requirement, 0.3-0.6 mmol/kg daily), and magnesium (likely requirement, 0.2 mmol/kg daily intravenous; 0.4 mmol/kg daily oral), unless prefeeding plasma levels are elevated. Patients should be closely monitored for the development of electrolyte abnormalities during feeding and any deficiency should be corrected as necessary. While vitamin D deficiency is usually not considered a part of refeeding syndrome, the concomitant presence of this vitamin deficiency will inhibit the ability to absorb dietary phosphate and possibly prolong the duration of hypophosphatemia. Therefore, a 25-hydroxy vitamin D test should be given, and any vitamin D deficiency corrected. 

Fluid and sodium should be minimized during the first few days of nutritional support12 and fluid balance should be monitored closely along with overall clinical status. Thiamine and multivitamins are important supplements when beginning nutritional support and are included in most standard formulas.3 Supplemental thiamine at 50 mg or 100 mg daily administered intravenously, or 100 mg given orally for 5 to 7 days should be provided to patients at risk for thiamine deficiency or refeeding syndrome.12 Balanced supplementation with multivitamins and trace elements is reasonable, but their role is less defined than that of thiamine in the pathophysiology of refeeding syndrome.


The initial clinical features of refeeding syndrome are nonspecific and may go unrecognized, with potentially fatal outcomes. Further study of this condition is warranted. As demonstrated by our case patient, increased awareness, early identification of individuals at risk, and timely correction of the biochemical abnormalities can prevent or mitigate the adverse consequences of this potentially fatal condition. 


  1. Keys A, Brožek J, Henschel A, Mickelsen O, Taylor H. L. The Biology of Human Starvation. St. Paul, MN: University of Minnesota Press, 1950.
  2. Tucker T. The Great Starvation Experiment: Ancel Keys and the Men Who Starved for Science. New York, NY: Free Press, 2006.
  3. Adkins SM. Recognizing and preventing refeeding syndrome. Dimens Crit Care Nurs. 2009;28(2):53-58.
  4. Knowles JR. Enzyme-catalyzed phosphoryl transfer reactions. Annu Rev Biochem. 1980;49:877-919.
  5. Weinsier RL, Krumdieck CL. Death resulting from overzealous total parenteral nutrition: the refeeding syndrome revisited. Am J Clin Nutr. 1981;34(3):393-399.
  6. Mallet M. Refeeding syndrome. Age Ageing. 2002;31(1):65-66.
  7. Lucy Jones L, BSC, Hons, R. Overweight but undernourished: refeeding syndrome after bariatric surgery. Bariatric Times. 2010;7(3):18-21.
  8. McCray S, Walker S, Parish CR. Much ado about refeeding. Pract Gastroenterol. 2005.
  9. Aminoff MJ, Greenberg DA, Simon RP. Clinical Neurology. 6th ed. New York, NY: McGraw-Hill, 2005:113.
  10. Lin KK, Lee JJ, Chen HC. Severe refeeding hypophosphatemia in a CAPD patient: a case report. Ren Fail. 2006;28(6):515-517.
  11. Vaszar LT, Culpepper-Morgan JA, Winter SM. Refeeding syndrome induced by cautious enteral alimentation of a moderately malnourished patient. Gastroenterologist. 1998;6(1):79-81.
  12. Shenkin A. Serum prealbumin: Is it a marker of nutritional status or of risk of malnutrition? Clin Chem. 2006;52(12):2177-2179.
  13. Kraft MD, Btaiche IF, Sacks GS. Review of the refeeding syndrome. Nutr Clin Pract. 2005;20(6):625-633.
  14. National Institute for Health and Clinical Excellence. Nutrition support in adults: oral nutrition support, enteral tube feeding and parenteral nutrition. NICE Clinical Guidelines, CG32. Published 2006. Accessed November 12, 2012.
  15. Yantis MA, Velander R. How to recognize and respond to refeeding syndrome. Nursing. 2008;38(5):34-39.


The authors report no relevant financial relationships.


Address correspondence to:

Steven R. Gambert, MD, AGSF, MACP

University of Maryland Medical Center

N3E09, 22. S. Greene Street

Baltimore, MD 21201