University of Virginia Health System
Nutrition Support E-Journal Club
We enjoyed a hiatus from our journal club in December so that everyone had time for the holidays, and I think that most of us successfully achieved a positive calorie and nitrogen balance for a few days. Currently our facility seems to be experiencing a surge in inpatient admissions, so we have started the New Year "on roller skates!" This month's article addresses the resting calorie expenditure of patients with amyotrophic lateral sclerosis (ALS).
Desport J-C, Torny F, Lacoste M, et al. Hypermetabolism in ALS: correlations with clinical and paraclinical parameters. Neurodegenerative Dis 2005;2:202-207.
This is a prospective descriptive study of 168 patients (86 males; 81 females) with "probable or definite ALS" that compared resting energy expenditure (REE) as estimated by Harris-Benedict equation (cREE) with REE measured with indirect calorimetry (mREE). Recorded data included BMI, whole body impedance analysis for fat-free mass (FFM) and fat mass, indirect calorimetry, date of disease onset, type of ALS (bulbar vs spinal), start of Rilutek and vital capacity.
The study also reported changes in mREE over time in 44 patients that had more than one indirect calorimetry measurement, and factors that correlated with survival.
Inclusion and Exclusion Criteria were:
The study included patients with probable or definite ALS according to El Escorial criteria (World Federation of Neurology criteria @ http://www.wfnals.org/guidelines/1998elescorial/elescorial1998criteria.htm). Patients were excluded if they had uncontrolled diabetes, renal insufficiency, ketosis (ketones in urine), acute infection, or clinically apparent hyperventilation.
Major Results reported by authors:
The mean duration of illness at time of indirect calorimetry was 1.5 years.
The investigators reported that 62 % (104 out of 168) of the ALS patients had a mREE that was greater than 10% above the cREE. The mean mREE was 14% above the cREE number.
The mean BMI of the 168 patients was 24.4 +/- 4.4 and 16.1% of the patients were considered malnourished, with a BMI < 20. In the univariate analysis a number of factors were associated with mREE including age, sex, malnutrition, weight, BMI and fat-free mass (FFM). However in the multivariate analysis only age (decreased mREE with increasing age) and fat-free mass (increased mREE with increased FFM) remained significant.
In the 44 patients that had more than one indirect calorimetry measurement, 56.8% of the patients were hypermetabolic (compared to Harris-Benedict) at the first measurement, and 47.7% were hypermetabolic at the second measurement (332 +/-272 days later-2-20 months later).
The authors concluded that there was a hypermetabolic state in ALS that was stable over time, and was affected primarily by age, sex and fat-free mass. The abstract also states that REE was a prognostic factor for survival in the univariate analysis.
This is an important study because there is limited research into the nutrition requirements of patients with ALS. Previous studies had suggested that patients with ALS were hypermetabolic and that the hypermetabolism intensified in end-stage ALS.
Although the degree of hypermetabolism is relatively modest (114% of calculated), what is notable is that there would be hypermetabolism of any degree in a population that has been documented (1,2) to have decreased fat-free mass.
There are limitations to this study however. One major limitation is that Harris-Benedict equation does not accurately predict resting metabolic rate in healthy people 20-55% of the time according to validation studies (3). However, we do note that in these validation studies Harris-Benedict resulted in overestimates of REE more frequently than underestimates.
It would have strengthened this study considerable if age-matched healthy volunteers had completed the protocol and then resting metabolic rate, controlled for fat-free mass was compared between healthy and ALS patients. What is also interesting to note is that the average wt was 64.5 kg (142#) that included 86 men and 81 women-not typical of average weights in the US (this study was done in France).
The other issue that we discussed during the journal club is the issue of the clinical significance of REE in the ALS population. If ALS patients do have elevated REE after adjustment for fat-free mass, this certainly holds interest for those studying the causes and underlying pathophysiology of ALS. However, given the limited physical activity of these patients, our experience has been that total calorie requirements are relatively modest. Our clinical concern is that if we attempt to maintain body weight while muscle mass decreases we will end up adding extra weight as abdominal fat that will make ambulation and transferring more difficult. A positive energy balance in an ALS mouse model did extend survival by 20%, but there are no studies to let us know if maintaining a positive energy balance in humans is helpful or detrimental in these patients (4).
Our Take home message:
Patients with ALS may have an elevation in mREE, however studies with more rigorous methods that control for fat-free mass, age and sex are needed to confirm this theory. There is a need for intervention studies to determine if hypercaloric feeding (regardless of start weight) in humans with ALS has clinical benefits.
Kasarskis EJ, Berryman S, Vanderleest JG, et al. Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death. Am J Clin Nutr. 1996;63:130-137.
Slowie LA, Paige MS, Antel JP. Nutritional considerations in the management of patients with amyotrophic lateral sclerosis (ALS). J Am Diet Assoc 1983;83:44-7.
Frankenfield D, Roth-Yousey L, Compher C. Comparison of predictive equations for resting metabolic rate in healthy nonobese and obese adults: a systematic review. J Am Diet Assoc. 2005;105(5):775-89.
Dupuis L, Oudart H, Rene F, et al. Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: Benefit of a high-energy diet in a transgenic mouse model. PNAS 2004;101(30):11159-11164.
Check out the latest Practical Gastroenterology articles/info at:
Scroll down to GI Nutrition to the pull down menu with links within the GI nutrition site and look for "Nutrition Articles in Practical Gastroenterology."
The January 2008 article is:
Hamilton C, Seidner D. Metabolic bone disease in the patient on long term parenteral nutrition. Practical Gastro 2008;XXXII(1):18.
Joe Krenitsky MS, RD
Carol Parrish RD, MS
PS - Please feel free to forward this on to friends and colleagues.