Refeeding syndrome is a

metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

disturbance that occurs as a result of reinstitution of nutrition in people and animals who are

starved ''Starved'' is an American television sitcom that aired for one season on FX for seven episodes in 2005. The series was about four friends who each suffer from eating disorders, who met at a "shame-based" support group called Belt Tighteners. I ...

, severely

malnourished Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues a ...

, or metabolically stressed because of severe illness. When too much food or liquid nutrition supplement is eaten during the initial four to seven days following a

malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues a ...

event, the production of

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...

fat In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food. The term often refers spec ...

and

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

in cells may cause low serum concentrations of

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...

and

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

. Cardiac, pulmonary and neurological symptoms can be signs of refeeding syndrome. The low serum

minerals In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. (2 ...

, if severe enough, can be fatal.

Cause

Any individual who has had a negligible nutrient intake for many consecutive days and/or is metabolically stressed from a critical illness or major surgery is at risk of refeeding syndrome. Refeeding syndrome usually occurs within four days of starting to re-feed. Patients can develop fluid and

electrolyte imbalance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...

, especially

hypophosphatemia Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Symptoms may include weakness, trouble breathing, and loss of appetite. Complications may include seizures, coma, rhabdomyolysis, or softening ...

, along with neurologic, pulmonary, cardiac, neuromuscular, and hematologic complications. During

fasting Fasting is the abstention from eating and sometimes drinking. From a purely physiological context, "fasting" may refer to the metabolic status of a person who has not eaten overnight (see " Breakfast"), or to the metabolic state achieved after ...

, the body switches its main fuel source from carbohydrates to fat tissue

fatty acids In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...

and

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

as the main energy sources. The spleen decreases its rate of red blood cell breakdown thus conserving

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

s. Many intracellular minerals become severely depleted during this period, although serum levels remain normal. Importantly,

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

secretion is suppressed in this fasting state, and

glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...

secretion is increased. During refeeding, insulin secretion resumes in response to increased

blood sugar Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...

, resulting in increased glycogen, fat, and protein synthesis. Refeeding increases the

basal metabolic rate Basal metabolic rate (BMR) is the rate of food energy, energy expenditure per unit time by endotherm, endothermic animals at rest. It is reported in energy units per unit time ranging from watt (joule/second) to ml O2/min or joule per hour per kg b ...

. The process requires

and

which are already depleted, and the stores rapidly become used up. Formation of phosphorylated carbohydrate compounds in the liver and skeletal muscle depletes intracellular ATP and 2,3-diphosphoglycerate in

red blood cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...

, leading to cellular dysfunction and inadequate oxygen delivery to the body's organs. Intracellular movement of electrolytes occurs along with a fall in the serum electrolytes, including phosphate and magnesium. Levels of serum glucose may rise, and B₁ vitamin

thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...

may fall. Abnormal heart rhythms are the most common cause of death from refeeding syndrome, with other significant risks including confusion,

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...

and convulsions and

cardiac failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, an ...

Clinical situations

The syndrome can occur at the beginning of treatment for

anorexia nervosa Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gr ...

when patients have an increase in calorie intake and can be fatal. It can also occur after the onset of a severe illness or major surgery. The shifting of electrolytes and fluid balance increases cardiac workload and heart rate. This can lead to acute heart failure. Oxygen consumption is increased which strains the respiratory system and can make weaning from ventilation more difficult.

Diagnosis

Refeeding syndrome can be fatal if not recognized and treated properly. An awareness of the condition and a high index of suspicion are required in order to make the diagnosis. The electrolyte disturbances of the refeeding syndrome can occur within the first few days of refeeding. Close monitoring of blood biochemistry is therefore necessary in the early refeeding period.

Treatment

In critically ill patients admitted to an

intensive care unit 220px, Intensive care unit An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensiv ...

, if phosphate drops to below 0.65 mmol/L (2.0 mg/dL) from a previously normal level within three days of starting enteral or parenteral nutrition, caloric intake should be reduced to 480 kcals per day for at least two days while electrolytes are replaced. Daily doses of

vitamin B B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds that often coexist ...

complex (strong) and a multivitamin and mineral preparation are strongly recommended. Blood biochemistry should be monitored regularly until it is stable. Although clinical trials are lacking in patients other than those admitted to intensive care, it is commonly recommended that

energy intake In biology, energy homeostasis, or the homeostatic control of energy balance, is a biological process that involves the coordinated homeostatic regulation of food intake (energy inflow) and energy expenditure (energy outflow). The human brain, parti ...

should remain lower than that normally required for the first 3–5 days of treatment of refeeding syndrome for all patients.

History

In his 5th century BC work 'On Fleshes' (''De Carnibus''),

Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history of ...

writes, "if a person goes seven days without eating or drinking anything, in this period most die; but there are some who survive that time but still die, and others are persuaded not to starve themselves to death but to eat and drink: however, the cavity no longer admits anything because the

jejunum The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previous ...

(nêstis) has grown together in that many days, and these people too die." Though Hippocrates misidentifies the cause of death, this passage likely represents an early description of refeeding syndrome. The Roman Historian Flavius

Josephus Flavius Josephus (; grc-gre, Ἰώσηπος, ; 37 – 100) was a first-century Romano-Jewish historian and military leader, best known for ''The Jewish War'', who was born in Jerusalem—then part of Roman Judea—to a father of priestly d ...

writing in the first century described classic symptoms of the syndrome among survivors of the siege of Jerusalem. He described the death of those who overindulged in food after the famine, whereas those who ate at a more restrained pace survived. There were numerous cases of refeeding syndrome in the

Siege of Leningrad The siege of Leningrad (russian: links=no, translit=Blokada Leningrada, Блокада Ленинграда; german: links=no, Leningrader Blockade; ) was a prolonged military blockade undertaken by the Axis powers against the Soviet city of L ...

during

World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...

, with Soviet civilians trapped in the city having becoming malnourished due to the German blockade. (Machado). A common error, repeated in multiple papers, is that "The syndrome was first described after

in Americans who, held by the

Japanese Japanese may refer to: * Something from or related to Japan, an island country in East Asia * Japanese language, spoken mainly in Japan * Japanese people, the ethnic group that identifies with Japan through ancestry or culture ** Japanese diaspor ...

prisoners of war A prisoner of war (POW) is a person who is held Captivity, captive by a belligerent power during or immediately after an armed conflict. The earliest recorded usage of the phrase "prisoner of war" dates back to 1610. Belligerents hold priso ...

, had become malnourished during captivity and who were then released to the care of United States personnel in the Philippines." However, closer inspection of the 1951 paper by Schnitker reveals the prisoners under study were not American POWs but Japanese soldiers who, already malnourished, surrendered in the Philippines during 1945, after the war was over. Refeeding syndrome has also been documented among survivors of the

Ebensee concentration camp Ebensee was a subcamp of Mauthausen concentration camp established by the SS to build tunnels for armaments storage near the town of Ebensee, Austria, in 1943. The camp held a total of 27,278 male inmates from 1943 until 1945. Between 8,500 and ...

upon their liberation by the U.S. Army in May 1945. After liberation, the inmates were fed rich soup; the stomachs of a few presumably could not handle the sudden caloric intake and digestion, and they died. It is difficult to ascertain when the syndrome was first discovered and named, but it is likely the associated electrolyte disturbances were identified perhaps in

Holland Holland is a geographical regionG. Geerts & H. Heestermans, 1981, ''Groot Woordenboek der Nederlandse Taal. Deel I'', Van Dale Lexicografie, Utrecht, p 1105 and former province on the western coast of the Netherlands. From the 10th to the 16th c ...

, the Netherlands during the closing months of World War II.

References

Bibliography

* Shils, M.E., Shike, M., Ross, A.C., Caballero, B. & Cousins, R.J. (2006). Modern nutrition in health and disease, 10th ed. Lippincott, Williams & Wilkins. Baltimore, MD. * Mahan, L.K. & Escott-Stump, S.E. (2004) Krause's Food, Nutrition, & Diet Therapy, 11th ed. Saunders, Philadelphia, PA. * * * * * National Institute for Clinical Excellence (2008). CG32 Nutrition support in adults: full guideline. http://guidance.nice.org.uk/CG32/Guidance/pdf/English

External links

{{DEFAULTSORT:Refeeding Syndrome Nutrition Metabolic disorders Intensive care medicine Syndromes