Hypermetabolism in ALS patients: an early and persistent phenomenon

Abstract

The malnutrition common among patients with ALS can be attributed in some cases to increased resting energy expenditure (REE). However, the origins and evolution of this hypermetabolism have yet to be fully elucidated. The aim of the present study was to monitor REE over time in patients with ALS and to identify factors that may explain any variation observed. ALS patients underwent nutritional, neurological and respiratory assessment every 6 months for 2 years (or until they died or became physically incapable of being examined). Sixty-one patients were studied. At inclusion, 47.5% exhibited hypermetabolism, with a mean measured REE (mREE) 19.7 +/- 6.4% higher than the mean calculated REE (cREE) (P < 0.0001). The hypermetabolism persisted when mREE was normalized for fat free mass (FFM): 35.1 +/- 4.2 versus 32.3 +/- 4.7 kcal/kg day(-1) (P = 0.02) in hypermetabolic and normometabolic patients, respectively. In univariate analysis, mREE was negatively correlated with age and positively correlated with BMI, FFM, energy and protein intakes, and albumin level. No correlation was found with neurological scores, disease characteristics, respiratory function and survival. Multivariate analysis revealed no significant factors. Only 10 of 45 patients in whom REE was measured at least twice changed their metabolic status. Neither mREE nor mREE/cREE varied significantly over time, despite deteriorating neurological, nutritional and respiratory parameters (P < 0.0001), and an increase in mREE/FFM (P = 0.01). This study confirms that about 50% of ALS patients are hypermetabolic, and 80% show no change in metabolic status over time. Thus, metabolic status (a clinically useful indicator of the need for nutritional support) can be determined early in the evolution of the disease. The origin of hypermetabolism in this context remains unknown, but growing evidence points to mitochondria as having an important role.

Nutritional care in motor neurone disease/ amyotrophic lateral sclerosis

“…During the course of ALS, nutritional status (NS) declines, and is often inadequately treated in clinical practice, Although various studies confirm the correlation between decrease in body weight and body mass index as negative predictors of survival [7][8][9] . Some factors are inherent to the amendments to the NS and the reduction of food intake in patients with it, such as: loss of appetite, dysphagia, dyspnea, depression and hypermetabolism [10][11][12] . Hypermetabolism origin and development in ALS have not been thoroughly elucidated; 50% of these patients, however, present in hypermetabolic state 11 causing the increased nutritional needs make the nutritional treatment even more complex.…”

“…Some factors are inherent to the amendments to the NS and the reduction of food intake in patients with it, such as: loss of appetite, dysphagia, dyspnea, depression and hypermetabolism [10][11][12] . Hypermetabolism origin and development in ALS have not been thoroughly elucidated; 50% of these patients, however, present in hypermetabolic state 11 causing the increased nutritional needs make the nutritional treatment even more complex.…”

“…Malnutrition, common with progression of disease, muscle strength and breathing capacity due to weakening as well as increase the relative risk of death 13,14,15 . Meet the energy requirements of macro and micronutrients, adjust degree of dysphagia brought and indicate enteral nutritional therapy at right time have been the subject 9,11,16 . Within this context, this present review aims to present nutritional treatment strategies for the maintenance of NS of ALS patients.…”

Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

“…Thus protein misfolding may not represent a distinct toxic molecular mode of interaction as generally assumed but perhaps rather the systemic loss of available cellular energy caused by increased protein turnover [101]. This would explain metabolic features of neurological diseases [111] such as the persistent hyper-metabolism of ALS patients [112] and the link between proteasome inhibition and toxicity of ALS-related SOD1 mutants [109], and it indicates why protein misfolding diseases are primarily neurological, since neurons need energy to maintain ion gradients for signaling [35].…”

Uso de simbiótico no tratamento de pacientes obstipados com esclerose lateral amiotrófica

“…O baixo consumo alimentar associado ao aumento do gasto energético e ao prejuízo na absorção intestinal de nutrientes contribuem para a desnutrição e para menor sobrevida [19][20][21][22][23][24][25] . A obstipação, por si só, já é um incômodo encontrado frequentemente na população idosa 26 e nos países ocidentais 27 .…”