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Metabolic and hormonal changes during the refeeding period of prolonged fasting

¹ Department of Endocrinology and ² Centre for Adult and Paediatric Gastroenterology, Barts and the London Medical School, London EC1A 7BE, UK and ³ Institute of Human Nutrition, University of Southampton, Southampton SO16 6YD, UK

(Correspondence should be addressed to M Korbonits who is now at Department of Endocrinology, Barts and the London Medical School, John Vane Science Centre, Charterhouse Square, Room 114C, London EC1M 6BQ, UK; Email: m.korbonits{at}qmul.ac.uk)

Objective: The discovery of leptin, a hormone primarily involved in adaptation to fasting, led to an increased interest in appetite regulation and appetite-modulating hormones. Here, we present unique data from a case of extreme starvation and refeeding, showing changes in plasma concentrations of appetite-modulating and metabolic hormones as well as biochemical changes, and draw attention to the dangers of the refeeding syndrome.

Patients and methods: We studied the refeeding period of a 44-day voluntary fast uncomplicated by underlying disease. Biochemical and hormonal variables were compared with 16 matched subjects such that the BMI range of the controls covered the entire spectrum for the index subject’s recovering BMI.

Results: Lack of calorie intake with free access to water resulted in 25% loss of body weight. Haemoconcentration was observed and feeding was started with a low sodium, hypocaloric liquid formulation. During early refeeding, marked hypophosphataemia, haemodilution and slight oedema developed. Vitamins B1, B12 and B6 were depleted while serum free fatty acids, ketone bodies and zinc levels were abnormally high; abnormal liver function developed over the first week. The hormonal profile showed low IGF-I and insulin levels, and elevated IGF-binding protein-1 concentrations. Appetite-regulating hormones were either very low (leptin and ghrelin) or showed no marked difference from the control group (peptide YY, agouti-related peptide, -melanocyte-stimulating hormone, neuropeptide Y and pro-opiomelanocortin). Appetite was low at the beginning of refeeding and a transient increase in orexin and resistin was observed coincidently with an increase in subjective hunger.

Conclusions: Our study illustrates the potential dangers of refeeding and provides a comprehensive insight into the endocrinology of prolonged fasting and the refeeding process.