Metabolic and hormonal changes during the refeeding period of prolonged fasting.

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, alpha-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.

Macro- and micronutrient losses and nutritional status resulting from 44 days of total fasting in a non-obese man.

OBJECTIVE: We wanted to establish and understand how the fractional losses of fat, fat-free tissues, and selected nutrients compare with that of body mass during a 44-d voluntary starvation (water only) and measurements of nutrient status. METHODS: We used anthropometry, sequential measurements of urinary substances during the fast, and blood analytes at the end of the fast. RESULTS: At the start of the fast, body weight was 96.0 kg (20% fat) and body mass index was 28.36 kg/m(2). The changes in body mass and arm anthropometry and in the pattern of urinary excretion of creatinine, ammonia, sodium, and ketone bodies during the study were consistent with starvation. At the end of the fast, body mass had decreased by 25.5%, of which a quarter to a third was due to loss of fat and the remainder to fat-free mass, predominantly muscle. There was an estimated loss of 20% of total body protein, 20-25% of fat-free mass, and a greater fractional loss of fat. Total energy expenditure was estimated to be 1638-2155 kcal/d of which 13.0-17.1% was from protein oxidation. Differential losses of minerals in urine ranged from 1.2% of estimated initial body content for manganese to 17.3% for selenium and 40.5% for zinc. At the end of the study, plasma concentrations of zinc and vitamin B12 were increased, those of copper, selenium, and manganese were normal, and there was biochemical evidence of deficiency in thiamine, riboflavin, and vitamin K (prothrombin time). CONCLUSION: The data confirm and extend the available information on prolonged fasting in lean individuals and have relevance to the understanding of the physiologic responses to starvation and the associated homeostatic mechanisms.