The Metabolic Responses to Starvation and Refeeding in Adolescents with Anorexia Nervosa

Abstract

Adaptive changes in metabolism result in decreased energy requirements in AN. A retrospective study of 21 hospitalized female AN patients demonstrated that indirect calorimetry (IC) measurement of resting energy expenditure (REE) was significantly lower than REE calculated by the Harris-Benedict equation (HBE). The HBE was adjusted by multiple-regression analysis to reflect the hypometabolic state of AN, and the adjusted equation was prospectively validated in 37 hospitalized female AN patients. Refeeding requires an understanding of both baseline requirements and metabolic changes that occur during nutritional rehabilitation. In our present study, we prospectively evaluated changes in fasting and postprandial REE in 50 hospitalized female patients meeting DSM-IV criteria for AN. Baseline IC measurements of fasting and postprandial REE were obtained within three days of admission, and every two weeks thereafter. Mean fasting REE increased significantly from 72 (+/-11.7) to 83.2 (+/-12.6) percent of predicted (p < 0.001) during the first two weeks of hospitalization. Likewise, postprandial REE also increased significantly from 17.5 (+/-18.2) to 27.9 (+/-15.9) percent above fasting REE during the same time period (p < 0.01). Significant increases in both REE and postprandial REE persisted in patients requiring longer hospitalizations. Despite the fact that prescribed energy intake and triiodothyronine (T3-RIA) levels increased during refeeding, there was no significant relationship between postprandial REE and energy intake or T3 levels after baseline. We conclude that energy metabolism in AN adapts to semistarvation by a reduction in fasting REE. With refeeding there is a reversal of this adaptive function, demonstrated by an increase in both fasting and postprandial energy expenditure. The increase in postprandial REE is not related to energy intake or thyroid function.

Coupling between Nutrient Availability and Thyroid Hormone Activation

“…Notably, thyroidal activity is restored promptly upon refeeding, as seen in patients recovering from anorexia nervosa (4). In such patients, weight gain and an increase in serum T 3 2 are closely associated with acceleration in energy expenditure (4). These observations indicate that the set point at which the hypothalamic-pituitary-thyroid activity is maintained is affected by nutrient availability, with the lowest (default) levels of activity seen during caloric restriction.…”

“…T 4 to T 3 Conversion in Intact Cells-The production of T 3 from outer ring-labeled T 4 in intact cells was analyzed by measuring 125 I in the medium as described elsewhere (31) except that the assay was stopped 12 h after the addition of […”

“…During fasting, the hormonal milieu is dominated by low levels of insulin and thyroid hormones, which has been proposed as an explanation for the slowdown in weight loss after a few days of caloric restriction (2,3). Notably, thyroidal activity is restored promptly upon refeeding, as seen in patients recovering from anorexia nervosa (4). In such patients, weight gain and an increase in serum T 3 2 are closely associated with acceleration in energy expenditure (4).…”

Nutritional Evaluation of Eating Disorders

“…It seems that this equation overestimates the energy requirements in undernourished people while it underestimates the energy requirements because eating disorder patients increase the energy requirements during re-nutrition (Cuerda et al, 2005;Krahn et al, 1993;Marra et al, 2002;Schebendach et al, 1997). It only appears to be appropriate when the weight normalization and stabilization in eating disorders (Forman-Hoffman et al, 2006).…”

“…Nutritional requirements are directly related to the basal metabolic rate, which is often diminished in anorexia nervosa and augmented in bulimia nervosa Nicholls et al, 2002;Russell et al, 2001;Scalfi et al, 2010;Schebendach et al, 1997;Sedlet et al, 1989). However, anorectic patients tend to present high respiratory coefficient and induced thermogenesis, which may explain the high weight reduction in emaciated patients and the difficulties to recovery and maintain a healthy weight (Russell et al, 2001).…”