refeeding syndrome ( rfs ) represents a life threatening clinical disorder that happens to occur when restarting feeding in patients with malnutrition or after prolonged starvation . it was first reported among people released from concentration camps following the second world war . oral feeding of these severe malnourished individuals often ended in diarrhea , heart failure , neurological complications , and death [ 24 ] . although this condition has been extensively described in the medical literature , it is underdiagnosed and commonly missed in everyday practice . the following is the description of a young woman that was admitted to our internal medicine ward with a prolonged history of feeding problems and severe malnutrition . attempts to improve her condition resulted in severe electrolyte imbalance and neurological problems compatible with rfs . she complained of anorexia and considerable weight loss during the last year , sometimes accompanied by nausea and vomiting of unknown cause . her weight was 30  kg and the body mass index ( bmi ) was 12.5 ( normal range : 2025 ) . during the first days after admission she received oral intake . the patient , her family , and the staff were advised regarding the recommended pace of the feeding process , based on the principle food was given by the nursing personnel and the patient ate small quantities by herself . during feeding she was always accompanied by her family or a nurse . as the patient was free to eat by herself and was eager to be released , she succeeded in circumventing the recommendations around . two days after admission at night hours , when accompanied by a member of the family , she ingested large quantity of food , relative to her regular daily intake during the previous days , in a way that suggested a this meal included mainly carbohydrates ( simple sugars ) and fats with a total caloric intake of 670 calories ( 49% of calories from carbohydrate and 46% of calories from fat ) . the recommended daily caloric intake in her condition should be 20  kcal / kg / day , which in her case , weighing 30  kg , should be about 600  kcal per day . the meal she ingested that night increased the total amount of calories ingested by the patient that day to the double allowed on 24 hours . on the day after the binge meal she complained of weakness and loss of appetite that resulted in a decrease in food intake . she complained of headache and looked weakened and impassive , with great difficulty in understanding and in giving suitable answers to questions asked . on the same period of time routine blood tests showed liver function tests abnormalities , electrolytes imbalance , and normal protein ( total ) and albumin values ( table 1 ) . the chest xr was within normal limits and the ecg showed regular and normal rhythm . on the second and third day after the  binge eating , clinical findings at that moment included limb edema , psychomotor agitation , headache , weakness , gastrointestinal unrest , trembling , unstable gait , and ophthalmoplegia ( frozen gaze ) , suggesting thiamine deficiency and wernicke 's encephalopathy . the patient was started on thiamine ( vitamin b1 ) 100  mg orally and intravenously , based on her signs and symptoms and the laboratory results previously mentioned . thiamine ( vitamin b1 ) level prior to treatment was low ( 16  mg / ml ) , as later reported . isolated episodes of hallucinations , convulsions , and syncope occurred sporadically during the next days . two days after starting thiamine administration there was an increase in appetite and food ingestion and a marked improvement in blood electrolytes ( k , na ) and magnesium values . on the course of hospitalization nutritional guidance was given to the patient and her family and they were informed about the risks involved with uncontrolled eating . in an attempt to reach control of the quantity and quality of food intake by the patient , she was advised to drink a formula of  ensure plus  ( containing 237  cc/355  kcal/13  gm protein / day divided into small portions during the course of the day ) , in addition to her usual daily intake . the hours and quantities of food ingested and the daily weight were registered by the nursing staff . a multidisciplinary teamwork , including physicians , dietician , nursing staff , and social worker , was involved in the treatment of the patient . at the same time , her family was recruited for her support , companion , and backing and for updating and reporting on changes of behavior that could counterbalance nutritional recommendations . gradually she started gaining weight and after initial improvement she was transferred to the psychiatric ward . her nutritional condition , under further dietician supervision , progressively improved and on the first month after admission , she gained 4.2 kilograms of weight , representing about 12% of her body weight . on the second month of hospitalization ( including her psychiatric hospitalization ) she gained another 5.8  kg of weight . in total she regained about 10  kg of weight , representing about 25% of her body weight , and the syndrome usually occurs after initiating guided feeding by the caregiver , especially of carbohydrates , liquids , and salt in a quantity that the cardiovascular and metabolic systems can not hold . in the present case , , this is an unexpected outcome and , to our knowledge , has not been reported before . manzanares and hardy accentuated some of the main features of the rfs , including electrolyte imbalance such as hypophosphatemia , hypokalemia , and hypomagnesemia ; rfs increases phosphorylation of glucose and salt and water retention leading to edema and heart failure . the resultant hyperglycemia stimulates insulin secretion and triggers the intracellular process for energy production which requires phosphate . phosphate is necessary for the generation of adenosine triphosphate from adenosine diphosphate and adenosine monophosphate and other crucial phosphorylation reactions . there is activation of the na - k atpase transporter resulting in a shift of potassium and phosphate from the extracellular to the intracellular compartment with a consequent drop in serum electrolyte levels resulting in hypophosphatemia , hypokalemia , hypomagnesemia , and the following metabolic acidosis , ketoacidosis , and hyperosmolar states [ 7 , 8 ] . hypophosphatemia has been described in about 100% of the cases of rfs [ 6 , 911 ] . hypophosphatemia is almost universally present in cases of rfs and has been used as a surrogate or , perhaps , as the main marker for this syndrome . as previously mentioned , phosphorus is essential for atp formation and energy creation , especially from carbohydrate metabolism . phosphorus deficiency could result in myriad of complications , including hemolysis , rhabdomyolysis , neurological changes , edema , cardiac decompensation , congestive heart failure ( chf ) hypotension , arrhythmias pulmonary failure , and death [ 5 , 6 , 8 ] . nevertheless , in the usual clinical practice , this condition is overlooked and underdiagnosed . in the recent review previously cited , the authors described a large spectrum of disorders either asymptomatic or , on the contrary , presenting with severe malnutrition , that can result in rfs . the cutoff point for the diagnosis of this syndrome is arbitrary and the diagnosis is based on symptoms and signs . therefore it is very important to look and detect serum biochemical changes for the correct diagnosis and prevention of the syndrome [ 1 , 11 ] . there are great variations in the essential features of this condition , from asymptomatic cases to those presenting with severe malnutrition , which are at risk of overt and even life threatening symptoms . the typical presentation of this syndrome is therefore not clear cut . as pointed by stanga et al . , the full - blown syndrome should be defined by the presence of symptoms , but significant biochemical changes should be detected early in order to prevent the clinical features developing . they suggest adapting the terms  symptomatic rfs  and  potential or biochemical rfs  for the various presentations of this syndrome . in 2006 a guideline was published by the national institute for health and clinical excellence ( nice ) in england and wales that used best available evidence for managing nutrition disorders , including the present condition . despite publication of these guidelines , awareness of . surveyed medical personnel and found that only 44% of the physicians were aware of these guidelines and followed up them , in contrast to 70% of the dieticians . thirty - nine percent of the participants considered that the recommendations have to be followed up as guidance to treatment . thirty - six percent found the recommendations too strict , whereas other participants reported that they never met a condition such as rfs . the diversified point of view makes necessary further gathering of clinical data in order to set clear guidelines for treatment . in the paper previously mentioned , 48% of the cases of rfs had severe malnutrition , 34% were admitted to an intensive care unit , 25% were oncologic patients , and 9.5% had gastrointestinal fistula . because of the nonspecific presentation and rareness , the diagnosis of this disorder is difficult even by those familiar with these conditions . although not all the subjects at risk will experience rfs , prediction for the specific patient that will contract this disorder is difficult . there is great importance in identifying the groups at risk and the first symptoms and signs of this condition . not only are patients with extreme malnutrition , including anorexia nervosa , at high risk , but also other groups of subjects experiencing limited supply of food , psychiatric disorders , old age , or increased metabolic demands . rfs presents usually after oral or parenteral artificial feeding [ 1 , 11 , 14 ] . rfs after self - administered feeding , as in the present case , is rare . as pointed by manzanares and hardy , it is likely that thiamine may be one of the contributing factors leading to sudden death during rfs . thiamine deficiency in acute rfs can cause chf ( wet beriberi ) or wernicke 's encephalopathy ( we ) ( dry beriberi ) . we is an acute , neuropsychiatric syndrome characterized by acute confusional state , ataxia , hypothermia , and even coma . in one of the articles the authors described 27 cases in whom the syndrome developed on the first 5 days after feeding . the level of thiamine was determined and found to be very low , confirming the diagnosis of rfs . in the case we presented , thiamine level was low , and other features typical of we and rfs were also present . the vitamin reservoir could be depleted in 2 - 3 weeks if new supply is lacking . there are several populations with an increased risk for developing a deficit in vitamin b1 . conditions causing undernutrition are frequently related to thiamine deficiency : malabsorption secondary to surgery or gastrointestinal disease , increase in metabolic demands , and greater renal or gastrointestinal loss of nutrients , including magnesium . the most frequent cause of thiamine deficiency is alcoholism and , as frequently practiced , therapy of an alcoholic bout includes administration of vitamin b1 . symptoms of deficiency are not specific and include frequent headache , weakness , confusion , opthalmoplegia , ataxia , abdominal discomfort , and cardiovascular manifestations as congestive heart failure [ 14 , 15 ] . the most significant indication of thiamine deficiency is we . a deficit of this vitamin manifests usually after intravenous glucose administration together with increased oral carbohydrate consumption . this results in a metabolic shift from fats to carbohydrate use for energy production , a process requiring increased amounts of thiamine and leading to acute thiamine deficiency . conditions related to an increased risk for we are those causing vitamin b1 deficiency , including alcohol abuse , surgical procedures of the gastrointestinal tract , recurrent vomiting or chronic diarrhea , cancer and chemotherapeutic treatments , and systemic diseases   ( table 2 ) . therefore , it is mandatory that thiamine be given before or concomitantly with intravenous administration of glucose when risk for we is suspected . in the present case a dose of 100  mg of thiamine was given . although much higher doses are currently recommended by some organizations such as the european federation of neurological societies ( efns ) and the royal college of physicians [ 17 , 18 ] ( 200  mg intravenously 3 times daily and 500  mg three times daily , resp . ) , these recommendations have not been accepted universally . in addition , at the time the patient was given 100  mg of thiamine , his weight and bmi were very low ( 30 and 12 , resp . ) and we were not certain of a definitive diagnosis of we . furthermore , a rapid improvement and the disappearance of symptoms of we on the following days were noted , explaining why we did not increase the dose of thiamine . a late cochrane report commented that the 200  mg dose was superior to the mean result of all the other dosages , but concluded that there is insufficient evidence from randomized controlled clinical trials to guide clinicians in the dose , frequency , route , or duration of thiamine treatment for prophylaxis against , or treatment , of wernicke - korsakoff syndrome ( wks ) due to alcohol abuse . similarly , the efns guidelines , previously mentioned , reported that there is no consensus on the optimal dose of thiamine , its preparation form , duration of treatment , or the number of daily doses and that , according to many case reports , treatment with either 100 or 200  mg thiamine given intravenously has cured the disease in the nonalcoholic . they also added that since studies of sufficient quality to warrant a formal recommendation are lacking , there is no evidence to support conclusions as to dosage , route of administration , and treatment time of thiamine . as high levels of vitamin b1 are not toxic , it is recommended that the vitamin be taken uninterruptedly during several months . in the present case we identified thiamine deficiency during rfs development as a consequence of the  binge eating  that included , worsening of symptoms in our patient occurred 24 hours after the feeding bout and progressed during the following days . laboratory findings at that time included hypophosphatemia , hypercalcemia , hypokalemia , hypernatremia , and hypoglycemia . as the clinical presentation included features typical of we , we decided to administer thiamine , both intravenously and orally . current guidelines recommend the use of magnetic resonance imaging ( mri ) for the diagnosis of we . in the present case , the patient in this report presented with most of the classical clinical signs in use for the diagnosis of we . caine et al . studied clinical features of 28 autopsy - proven alcoholic patients with we that were well evaluated during life . they found that the sensitivity of the classic triad ( eye signs , cerebellar signs , and confusion ) for the diagnosis of we was 23% but rose to 85% if the patients had at least two of the four following features : dietary deficiencies , eye signs , cerebellar signs , and either mild memory impairment or an altered mental state . in addition , electrolyte imbalance was present and the patient responded rapidly to the treatment given . although mri can confirm the diagnosis , we believe that a reliable diagnosis can be done based on strong clinical features such as in the present patient . thiamine was administered and after a few days there was improvement in laboratory parameters and a partial recovery in cognition . keep in mind the following distinctive features of rfs.high risk groups such as extreme malnutrition.low levels of phosphorus , magnesium , potassium , and calcium.low levels of vitamin b1.hyperglycemia/hypoglycemia.danger for rfs being higher in the five first days of refeeding.keeping with the principle danger for rfs being higher in the five first days of refeeding . keeping with the principle when acute weight loss is more than 15% of the usual weight , the risk for rfs increases and feeding has to be completed under medical supervision , even if the patient is overweight . special attention should be given to the electrolyte disturbances , such as hypokalemia , hypophosphatemia , hypomagnesaemia , and their early identification . alertness and collaboration of a multidisciplinary professional team can prevent this disorder from happening in the population at risk . steps for prevention of this syndrome have to be taken , such as the routine determination of serum electrolytes and phosphorus , and feeding has to be done at a slow controlled pace with special attention to details of micronutrients , such as vitamin b1 , that can prevent worsening of the patient condition , forward recovery , and shorten the length of hospitalization . the question that emerges from this paper is if every patient admitted with extreme weight loss , cachexia , or drastic weight reduction should receive thiamine intravenously on the first three days of hospitalization or when starting nutrition . should thiamine be given prior to the occurrence of the rfs , as part of a protocol in patients with increased risk for this syndrome ? this question is of crucial importance and hopefully , an answer will be given in the near future .
rapid restoration of nutrients and electrolytes after prolonged starvation could result in a life threatening condition characterized by sensory and neurological dysfunction and severe metabolic imbalance that has been designated as refeeding syndrome . 
 its diagnosis is frequently missed resulting in severe complications and even death . 
 we describe a 25-years - old female patient with mental disorders and severe malnutrition who developed severe clinical manifestations and biochemical abnormalities characteristic of the refeeding syndrome , after restarting oral feeding on her own . 
 schizophrenia was later diagnosed . 
 increased awareness of this condition and its complications is necessary to prevent its detrimental complications .