Most guidelines have been based on studies of female patients.
One of the earliest descriptions of the refeeding syndrome was made at the end of World War II, when one-fifth of starved Japanese prisoners of war died after they were refed with an aggressive program of nutrition and vitamins.
Refeeding syndrome commonly occurs in populations at high risk for malnutrition, from patients with eating disorders to those with renal failure who are on hemodialysis. Despite the longstanding recognition that refeeding syndrome is a serious clinical complication with a high mortality rate and the need for immediate medical intervention, high-quality scientific evidence on the etiology and management of refeeding syndrome is limited, and has largely been based on studies of female populations. Lack of a universally accepted definition has hampered the comparison of refeeding syndrome risk across studies and refeeding protocols.
While the impact of refeeding strategies in adolescents and young adults is an area of rigorous study, only one study to date has examined gender differences in refeeding outcomes and lengths of stay (Int J Eat Disord. 2022;55:247). In one of the few recent studies of males undergoing refeeding, a team from the University of California, San Francisco, did not find differences in the risk of developing electrolyte abnormalities among males versus females (J Eat Disord. 2024. 12:67).
Dr. Jason M. Nagata and colleagues from the Department of Psychiatry and Behavioral Sciences at UC San Francisco recently reviewed the electronic medical records of 601 adolescents and young adults admitted for medical instability to an inpatient eating disorder service located at a tertiary care hospital in Northern California between May 22, 2012 and August 31, 2020.
Patients ranged from 9 to 25 years of age when admitted. The patients fit a number of criteria for admission, including a low median body mass index, or BMI (≤ 75% for age and gender), severe bradycardia (< 50 beats/minute during the daytime, or < 45 beats/minute at night), hypotension (< 90/45 mmHg), and hypothermia
(< 96.0 °F, or < 35.6 °C). Other criteria included a sustained increase in heart rate (> 30 beats per minute in those older than 19 years of age), or sustained decreased blood pressure levels (>20 mmHg or >10 mmHg diastolic).
Refeeding syndrome risk was defined as hypophosphatemia (<3.0 mg/dL), hypokalemia (<3.5 mEq/L), and hypomagnesemia (<1.8 mg/dL). Logistic regression was used to assess factors associated with electrolyte abnormalities indicating refeeding syndrome risk.
A refeeding protocol
The authors reported that serum was drawn between 5am and 7am each day. The refeeding protocol began with 1000 kcal/day, and was increased by 200 kcal/day. Electrolytes were checked in the morning for at least seven days, to evaluate the risk of developing refeeding syndrome (unless the patient was discharged before seven days had lapsed). Refeeding hypophosphatemia, hypokalemia, or hypomagnesemia was defined as phosphorus (<3 mg/dL), potassium (<3.5 mEq/L), or magnesium (<1.8 mg/dL). The risk of the refeeding syndrome was indicated by electrolyte abnormalities beginning on the second day in the hospital, after one full day of refeeding. (Low potassium, magnesium, or phosphorus levels present at admission prior to the onset of the refeeding protocol were not included in the classification of electrolyte abnormalities indicating refeeding syndrome risk, but the patients were still included in the study to evaluate for subsequent laboratory abnormalities.)
To minimize electrolyte abnormalities due to purging, several protocols and precautions were implemented for any patient with a history of purging, including the presence of a patient care attendant who observed the patient during all meals/snacks and for a period following the completion of the meal/snack. Other precautions included taping or sealing sinks in the room, and limiting showers to early mornings before meals.
No differences were found between males and females, but older age mattered
The authors found no differences between males and females in development of the refeeding syndrome. They did find, however, that older age was associated with a higher risk of developing low phosphorus and magnesium levels. (In the current study, the authors focused on the electrolyte abnormalities indicating refeeding syndrome risk rather than direct measures of organ dysfunction.)
The incidence of electrolyte abnormalities indicating refeeding syndrome risk is of particular interest in male patients because males generally have higher refeeding goals and longer hospital stays than females, and therefore may be at added risk of developing refeeding syndrome. Older age and greater weight suppression at admission were associated with higher odds of refeeding hypophosphatemia and refeeding hypomagnesemia. None of the investigated factors was associated with refeeding hypokalemia.
Among this group of young adults, the authors did not find significant electrolyte differences between males and females that would lead to electrolyte abnormalities, and thus indicate the risk of developing the refeeding syndrome. They surmised that higher rates of electrolyte abnormalities in prior studies were due to overestimation by counting patients who received prophylactic electrolyte supplementation or those treated because of declining (but not low) serum levels as having had an electrolyte abnormality.
In 2018, Whitelaw et al. did not find associations of electrolyte abnormalities with duration of or recent weight loss (J Adolesc Health. 2018. 63:717). Thus, although it is plausible that total body mineral stores become increasingly depleted as illness continues, more studies are needed to determine whether this contributes to more frequent electrolyte abnormalities during renourishment. Perhaps the most important implication is that patients with delayed or missed diagnoses will be at higher risk due to longer durations of illness.
In Nagata’s study, the lack of gender differences in both individual and compound variables of electrolyte abnormalities indicating refeeding syndrome risk show great promise towards tailoring current refeeding protocols towards more aggressive treatment and advancement of diets in adolescent male populations with eating disorders. Dr. Nagata pointed out that males continue to be underrepresented in eating disorder research, despite their higher caloric requirements and longer hospitalizations. Higher initial caloric diets and rapid advancement of diet are associated with faster restoration of medical stability and shorter hospital stays, but such studies are not sex-stratified, he added.
The authors’ findings that males and females with eating disorders do not have statistically significant electrolyte abnormalities indicating the risk of refeeding syndrome suggest that higher or more aggressive refeeding protocols in male populations may be warranted, and that future studies are needed to better define this.
