Refeeding syndrome (RS) is a rare but potentially fatal condition that can occur during refeeding of severely malnourished individuals (such as anorexia nervosa patients). After prolonged starvation, the body begins to use fat and protein to produce energy because there are not enough carbohydrates. Upon refeeding, there’s a surge of insulin (because of the ingested carbohydrates) and a sudden shift from fat to carbohydrate metabolism. This sudden shift can lead to a whole set of problems that characterize the refeeding syndrome.
For example, one of the key features of RS is hypophosphotemia: abnormally low levels of phosphate in the blood. This occurs primarily because the insulin surge during food ingestion leads to a cellular uptake of phosphate. Phosphate is a very important molecule and its dysregulation affects almost every system in the body and can lead to “rhabdomyolysis, leucocyte dysfunction, respiratory failure, cardiac failure, hypotension, arrhythmias, seizures, coma, and sudden death.”
I’m not, however, going to go into too much detail on RS as there are pretty good sources available here, here, and here. Instead, I want to discuss some practical guidelines that have been recently proposed on how to avoid RS. These new suggestions have come about as a result of recent publications suggesting that current and commonly used refeeding guidelines might actually do more harm.
These new guidelines take into account clinical findings and pathophysiology of RS. Yay for evidence-based treatment!
What are the current clinical guidelines?
The National Institute for Clinical Excellence (NICE) recommends a gradual increase in calorie intake, regular physical monitoring and adjunctive oral supplements (such as phosphate). NICE guidelines also recommend a weekly weight gain of 0.5-1kg. The Society for Adolescent Health and Medicine, as well as the American Psychiatric Association echo these guidelines.
In all of these guidelines, initial caloric intake is below daily requirements, with slow increases recommended. It is important to emphasize that there is no evidence-based research behind recommendations in the current refeeding guidelines, which range from an initial rate of 10 to 60 kcal/kg per day.
(Just a note: 1 kcal = 1000 calories, but when we talk about food calories, we are actually talking about kilocalories or capital “C” calories, so 60 kcal/kg per day is the same as 60 calories/kg per day in normal speak. See this handy Wikipedia entry. Thanks Alison for pointing this out!)
In a short review of published studies on the occurrence of RS in anorexia nervosa patients, O’Connor and Goldin found that in all of the cases, the patients were following the currently published guidelines. “The refeeding syndrome presented itself with hypophophataemia, hypotension, and cardiac abnormalities while refeeding at an average rate of 27 kcal/kg per day.”
O’Connor and Goldin found that regardless of whether refeeding starts with 10 kcal/kg a day or 60 kcal/kg a day, there still seems to be a high risk of refeeding. So, simply starting low and increasing caloric intake doesn’t seem to prevent RS.
How can the current guidelines be improved?
Kohn et al. suggest the following modifications to the current guidelines:
So why these recommendations?
Let’s go in order.
Number 1. A previous study by Gniuli (2001) found delayed insulin release and resulting hypoglycemia after ingesting a test meal in anorexia nervosa patients compared to controls.
“These metabolic alterations may represent a way to preserve calories by enhancing energy storage; however, they potentiate the risk of developing recurrent hypoglycemia [low blood sugar] with intermittent oral feeding, and are more pronounced with calories in the form of carbohydrate, as compared with protein or fat.”
Using nasogastric feeding–which results in a constant supply of calories–can help avoid low blood sugar levels which result from the delayed insulin response to food intake in AN patients.
Number 2. Limiting carbohydrate intake can help reduce the insulin surge that can lead to RS. O’Connor and Golding write that reducing the calories coming from carbohydrates (ie, glucose) would limit the “shift in fluid and electrolytes and therefore possibly avert the refeeding syndrome.”
Number 3 & 4. The rationale for the relatively high initial daily energy intake (50 kcal/kg for a patient of 40kg, for example) is to avoid the the weight loss that occurs during the initial stages of refeeding (because the initial recommendations are still well below the daily metabolic requirements of the patients). Moreover, the authors report using these calorie guidelines in refeeding patients with good outcomes and no episodes of RS (Kohn & Madden, 2007; Whitelaw et al., 2010).
Number 5. Phosphate supplementation is crucial to avoid low phosphate levels. These recommendations are not new, but they are more specific (in terms of the actual amount to supplement) based on the authors’ clinical experience. Though, of course, the supplementation amount will vary from patient to patient and phosphate (and other electrolyte levels) must be measured regularly.
Number 6. This one is pretty straight forward: reintroduction of normal eating and the removal of the nasogastric tube.
So there you have it: a move toward evidence-based treatment guidelines, isn’t that great? I hope that the integration of these guidelines into mainstream medical practice prevents adverse outcomes and saves lives.
The authors conclude by summarizing their recommendations:
These studies highlight the importance of the maintenance of blood glucose and phosphate levels, and provision of adequate calories at the outset of refeeding, to establish early weight gain. The avoidance of low blood sugar from the effects of delayed insulin phase and metabolic changes with regard to glycogen storage and fatty oxidation support the use of continuous feeding strategies, such as nasogastric tube feeding at the outset of refeeding as well as limiting the proportion of daily calories from carbohydrates to less than 40%. Oral phosphate supplementation should be routine and blood phosphate levels should be maintained above 1.0 mg/dl.
O’Connor G, & Goldin J (2011). The refeeding syndrome and glucose load. The International Journal of Eating Disorders, 44 (2), 182-5 PMID: 20127933
Kohn, M., Madden, S., & Clarke, S. (2011). Refeeding in anorexia nervosa Current Opinion in Pediatrics, 23 (4), 390-394 DOI: 10.1097/MOP.0b013e3283487591