Estimating daily energy expenditure in individuals with amyotrophic
Edward J Kasarskis, Marta S Mendiondo, Dwight E Matthews, Hiroshi Mitsumoto, Rup Tandan, Zachary Simmons,
Mark B Bromberg, and Richard J Kryscio for the ALS Nutrition/NIPPV Study Group
Background: Patients with amyotrophic lateral sclerosis (ALS)
experience progressive limb weakness, muscle atrophy, and dyspha-
gia, making them vulnerable to insufficient energy intake. Methods
to estimate energy requirements have not been devised for this
Objective: The goal was to develop equations to estimate energy
requirements of ALS patients.
Design: We enrolled 80 ALS participants at varying stages of their
illness and studied them every 16 wk over 48 wk. At each time, we
determined total daily energy expenditure (TDEE) in the home
setting over a 10-d period by using the doubly labeled water
method. We then developed statistical models to estimate TDEE
by using factors easily obtained during a routine clinical visit.
Results: The most practical TDEE models used the Harris-Benedict,
Mifflin-St Jeor, or Owen equations to estimate resting metabolic
rate (RMR) and 6 questions from the revised ALS Functional Rat-
ing Scale (ALSFRS-R) that relate to physical activity. We de-
veloped a Web-based calculator to facilitate its use. In the
research setting, measuring body composition with bioelectrical
impedance spectroscopy enabled the estimation of RMR with the
Rosenbaum equation and the same 6 questions from the
ALSFRS-R to estimate TDEE. By using these models, the esti-
mate of TDEE for nutritional maintenance was 6500 kcal/d across
the spectrum of ALS progression.
Conclusions: Our results emphasize the importance of physical
function and body composition in estimating TDEE. Our predictive
equations can serve as a basis for recommending placement of
a feeding gastrostomy in ALS patients who fail to meet their energy
requirements by oral intake. This trial was registered at clinical-
trials.gov as NCT00116558. Am J Clin Nutr 2014;99:792–803.
Amyotrophic lateral sclerosis (ALS4; Lou Gehrig’s disease) is
a progressive disorder in which motor neurons in the cortex,
brainstem, and spinal cord degenerate and die (1, 2). The
functional consequences are progressive muscle atrophy and
profound weakness, with death typically occurring after 4 y
because of respiratory insufficiency (3). The majority of ALS
patients experience dysphagia as a result of progressive weak-
ness of the tongue and other oropharyngeal muscles (4–6). Al-
though dysphagia is a troublesome symptom in itself, it can be
a harbinger of nutritional insufficiency (7). Inadequate nutri-
tional intake is an evolving threat originating from at least 2
sources: oropharyngeal weakness that causes impaired chewing
and deglutition and upper extremity weakness that limits the
ability to manipulate food and bring it to the mouth (8–10).
Others may have anorexia from depression or early satiety.
The indication for a feeding gastrostomy is failure of oral
intake to meet total daily energy expenditure (TDEE) (11, 12).
TDEE can be measured directly by using doubly labeled water
(DLW) as the reference method (13, 14). In other populations,
TDEE can also be estimated by using equations for resting
metabolic rate (RMR) (15–18) with adjustments for physical
activity or metabolic stress. Currently there are no validated
equations to estimate TDEE in patients with ALS. The approach
in the American Academy of Neurology practice parameters
uses indirect indicators of insufficient energy intake (EI), such
as the presence of dysphagia or weight loss, to recommend
gastrostomy tube placement (9).
1Fromthe Department of Neurology (EJK), the Graduate Center for Nu-
trition (EJK), and the Graduate Center for Toxicology (EJK); the Department
of Biostatistics, College of Public Health (MSM); the Sanders Brown Center
on Aging (MSM and RJK); and the Department of Statistics, College of Arts
and Science (RJK), University of Kentucky, Lexington, KY; Neurology Ser-
vice, Lexington VA Medical Center, Lexington, KY (EJK); the Departments
of Chemistry and Medicine (DEM) and Neurology (RT), University of Ver-
mont, Burlington, VT; the Department of Neurology, Columbia University,
New York, NY (HM); the Department of Neurology, Pennsylvania State
University, Hershey, PA (ZS); and the Department of Neurology, University
of Utah, Salt Lake City, UT (MBB).
2Supportedby National Institute of Neurological Disorders and Stroke
grant RO1 NS045087; the General Clinical Research Centers at Columbia
(RR00645), Vermont (RR00109), Kentucky (RR02602), Utah (RR00064),
and Penn State (RR10732 and CO6-RR016499); the ALS Hope Foundation;
the Cynthia Shaw Crispen Endowment; and the Kevin Heidrich/Team 7
3Address reprintrequests and correspondence to EJ Kasarskis, Depart-
ment of Neurology, University of Kentucky, KY Clinic, Room L445, Lex-
ington, KY 40536-0284. E-mail: email@example.com.
4Abbreviationsused: ALS, amyotrophic lateral sclerosis; ALSFRS-R, re-
vised ALS functional rating scale; ALSFRS-6, sum of questions 1, 4, 6, 7, 8,
and 10 of the ALSFRS-R; BIS, bioimpedence spectroscopy; DLW, doubly
labeled water; EI, energy intake; LMM, linear mixed model; MMT, manual
muscle testing; NIPPV, noninvasive positive pressure ventilation; RMR, rest-
ing metabolic rate; TBW, total body water; TDEE, total daily energy expen-
diture; TSH, thyroid-stimulating hormone.
ReceivedJuly 1, 2013. Accepted for publication January 15, 2014.
Firstpublished online February 12, 2014; doi: 10.3945/ajcn.113.069997.
Am J Clin Nutr 2014;99:792–803. Printed in USA. ? 2014 American Society for Nutrition
In contrast to other medical conditions, weight is not a direct
index of energy balance in ALS (19). Weight change is multi-
factorial and originates from the following: 1) muscle atrophy as
a result of denervation after motor neuron degeneration, 2) lower
extremity edema from immobility, and 3) weight loss from
undernutrition because of reduced EI and increased TDEE
compared with matched controls (6, 13, 14). The reported in-
crease in TDEE has been attributed to the following: increased
energy utilization by weakened skeletal muscles when per-
forming functional tasks such as walking; nonfunctional mus-
cular activity such as spasticity, cramps, fasciculations, and/or
pseudobulbar motor activities (uncontrolled laughing or crying);
and the metabolic cost of increased protein catabolism (13, 14).
Chronic energy insufficiency leads to catabolism of functioning
innervated muscle fibers to compensate for inadequate EI with
accelerated loss of muscle power (20, 21). Protein malnutrition
does not appear to be a typical feature of ALS (22, 23).
To develop a method to estimate TDEE, we conducted a multi-
center study to develop ALS-specific predictive equations on the
basis of measures that are achievable in practice (14). In this way,
clinic to establish EI targets for the ALS patient. The inability to
meet TDEE with oral EI would then serve as the criterion for
recommending a feeding gastrostomy on the basis of the concept of
maintaining energy balance (11, 12), rather than nonspecific sur-
rogates of malnutrition such as dysphagia or weight loss (9).
SUBJECTS AND METHODS
Organization of the study
The goals and organization of the study and demographic
characteristics of the participants have been reported (14).
Briefly, we enrolled ALS participants with a forced vital capacity
$50% of predicted, reasoning that the subjects would be able to
complete the longitudinal study measurements every 16 wk over
the 48-wk study period despite disease progression. In addition,
we expected that participants would progress through varying
degrees of impaired ambulation, with some becoming wheel-
chair-bound. In this way, we anticipated that we would measure
TDEE as their ALS progressed through various combinations of
respiratory impairment and extremity weakness, assess impor-
tant clinical factors longitudinally, and perform statistical
modeling to create predictive equations to estimate TDEE.
We enrolled 80 ALS patients (Table 1; 35.0% female, 65.0%
male; mean 6 SD age: 58.7 6 11.0 y; range: 24–79 y) with
Characteristics of participants at baseline1
Men (n = 52)Women (n = 28)Total
Body mass (kg)
Lean body mass (kg)
ALSFRS-R (24) score
Mifflin-St Jeor (16)
Owen (17, 18)
Measured TDEE/measured RMR
Model 4, Rosenbaum (25)
Model 5, Wang (26)
Model 6, Harris-Benedict (15)
Model 7, Mifflin-St Jeor (16)
Model 8, Owen (17, 18)
Modeled TDEE 2 measured TDEE (kcal/d)
Model 4, Rosenbaum (25)
Model 5, Wang (26)
Model 6, Harris-Benedict (15)
Model 7, Mifflin-St Jeor (16)
Model 8, Owen (17, 18)
EI 2 measured TDEE (kcal/d)
57.8 6 12.2 (24.1–79.1)
86.0 6 14.1 (48.9–134.0)
27.0 6 4.1 (15.9–40.6)
57.0 6 7.1 (39.8–84.7)
35.7 6 5.5 (27–45)
60.1 6 11.6 (28.9–78.3)
70.0 6 16.5 (47.0–104.0)
27.4 6 5.7 (20.3–39.1)
39.8 6 7.8 (27.5–58.0)
36.9 6 5.8 (21–43)
58.7 6 11.9 (24.1–79.1)
80.1 6 16.8 (47.0–134.0)
27.1 6 4.7 (15.9–40.6)
50.7 6 11.1 (27.5–84.7)
36.1 6 5.6 (21–45)
1729 6 294 (1049–2470) 1240 6 251 (815–1712) 1539 6 366 (815–2470)
1601 6 147 (1186–1892)
1448 6 188 (1009–1727)
1744 6 217 (1178–2133)
1686 6 168 (1266–1948)
1754 6 129 (1377–2080)
1354 6 190 (1056–1716)
1090 6 219 (743–1510)
1348 6 191 (1021–1773)
1251 6 220 (861–1749)
1318 6 220 (1133–1684)
1508 6 203 (1056–1892)
1315 6 264 (743–1727)
1596 6 283 (1021–2133)
1523 6 283 (861–1948)
1589 6 250 (1133–2080)
2549 6 615 (1441–4175)
1.5 6 0.4 (0.7–2.4)
2046 6 582 (1199–3578)
1.6 6 0.3 (1.0–2.1)
2364 6 647 (1199–4175)
1.5 6 0.4 (0.7–2.4)
2428 6 324 (1634–3132)
2663 6 274 (1526–3070)
2560 6 329 (1341–3054)
2518 6 281 (1847–3084)
2531 6 271 (1924–3057)
2502 6 362 (1690–3621)
2247 6 317 (1738–2941)
2165 6 303 (1494–2823)
2016 6 337 (1266–2747)
2185 6 238 (1760–2643)
2174 6 259 (1808–2712)
2152 6 390 (1570–2953)
2361 6 331 (1634–3132)
2476 6 373 (1494–3070)
2356 6 423 (1266–3054)
2393 6 310 (1760–3084)
2397 6 317 (1808–3057)
2370 6 408 (1570–3621)
253 6 585 (21460 to +880)
84 6 577 (21251 to +901)
219 6 577 (21450 to 928)
261 6 549 (21475 to +691)
248 6 553(21373 to +802)
277 6 591 (21642 to +891)
2198 6 712 (617–4309)
2430 6 887 (22989 to +1395)
205 6 459 (2808 to +989)
109 6 516 (21060 to +1041)
239 6 478 (21138 to +826)
130 6 456 (21049 to 990)
119 6 443 (2991 to +813)
96 6 427 (2745 to +1006)
1609 6 512 (429–2499)
2466 6 697 (22016 to +638)
220 6 566 (21460 to +989)
93 6 552 (21251 to 1041)
227 6 539 (21450 to +928)
11 6 521 (21475 to +990)
15 6 518 (21373 to +813)
212 6 539 (21642 to +1006)
1974 6 701 (429–4309)
2436 6 816 (22989 to +1395)
1All values are means 6 SDs (range in parentheses). ALSFRS-R, revised amyotrophic lateral sclerosis functional rating scale; EI, energy intake; RMR,
resting metabolic rate; TDEE, total daily energy expenditure.
ENERGY EXPENDITURE IN ALS
nutritional intervention to prevent, or correct, energy in-
sufficiency has not been prospectively studied in ALS. The use
of a feeding gastrostomy as an alternative route of nutritional
intake to correct insufficient energy intake has been associated
with weight stabilization and, in some studies, improved sur-
vival (9, 48).
One barrier to acceptance of a feeding gastrostomy by ALS
patients appears to be one of perception. The ALS CARE da-
tabase showed that ALS patients who receive feeding tubes are in
a very advanced stage of disease, particularly with regard to
oropharyngeal dysfunction, indicating that the development of
dysphagia and other bulbar symptoms are the “triggers” in the
patient’s mind to find personal value in receiving nutrition via
a feeding gastrostomy (13, 14, 49). In this regard, the results of
this study address a major gap in the management of ALS pa-
tients by formulating ALS-specific equations to estimate TDEE
as the disease progresses. The modeled equations provide a basis
for recommending a feeding gastrostomy based on the adequacy
of EI to meet TDEE requirements. In this way, this approach
will refocus the discussion with ALS patients to place the em-
phasis on maintaining optimal nutritional intake throughout the
course of ALS, by the oral route if possible or supplemented
with gastrostomy feedings if needed.
Although model 7, which uses the Mifflin-St Jeor equation, is
statistically better than that based on the Harris-Benedict
equation, it requires a physical examination to rate muscle power
in the lower extremities, which precludes ALS patients com-
puting their own TDEE. Therefore, our equation from model 6
(using the Harris-Benedict equation) (15) may prove to be the
most practical overall for use in the care of the ALS patient at
home and in our multidisciplinary ALS clinics. In a typical clinic
workflow, an ALS patient will record his or her 24-h food diary
before a visit. During the clinic visit height, weight, age, sex, and
the responses to the questions in the ALSFRS-6 (Supplemental
Table 2 under “Supplemental data” in the online issue) will be
recorded and the TDEE will be calculated by using either the
equation from model 6 or model 7. EI will be determined from
the 24-h food diary. If EI , TDEE, clear EI targets can be set for
patients with nutritional counseling and dysphagia assessments
to identify foods to optimize oral EI. If a deficit of EI persists or
is severe, then a recommendation for feeding gastrostomy can be
made. Although our equations can form the basis for estimating
TDEE, clinical judgment will still be required for recommend-
ing a feeding gastrostomy because the ALS population is very
heterogeneous in terms of TDEE and EI.
To facilitate the use of this equation, we created a Web-based
calculator (https://mednet.mc.uky.edu/alscalculator/). The Web
page allows an individual ALS patient to create a personal ac-
count that can be accessed and updated privately or in a clinic
setting by the clinic staff. The calculations are shown in Sup-
plemental Table 3 under “Supplemental data” in the online issue
with the use of hypothetical clinical data. It remains to be de-
termined if this approach will improve function and survival in
ALS. The use of these equations in the context of ALS clinical
drug trials should standardize the approach for nutritional
management to make this factor less of an uncontrolled exper-
imental variable as it is at present.
The ALS Nutrition/NIPPV Study Group members and participating insti-
tutions are as follows—Nutrition sites: University of Kentucky Coordination
Center (Edward J Kasarskis, Richard J Kryscio, Marta S Mendiondo, Stephen
Wells, Christie Shrestha, Margaret Healey, Megan Thompson, Lan Chi
T Luu, Carmen Saylor, Kathryn Vanderpool, Irina Kasarskis, Maria Malguizo,
Renato Moreira, and Stephen Welch); Columbia University (Hiroshi
Mitsumoto, Jackie Montes, Daniel Bell, Wahida Karmally, Megan Tubman,
Kate Dalton, and Jonathan Hupf); Pennsylvania State University (Zachary
Simmons, Helen Stephens, Ally Brothers, Susan Deiling, and Michelle
Heckenluber); University of Utah (Mark B Bromberg and Summer Davis);
University of Vermont (Rup Tandan, Chris Potter, Dwight Matthews, Shannon
Lenox, and Jesse Gardner); NIPPV sites: Beth Israel Medical Center;
Albert Einstein College of Medicine (Stephen N Scelsa and Theresa Imperato);
University of Colorado (Yvonne D Rollins, Hans Neville, Bjorn Oskarsson,
Burleen Hewitt, and John Cumming); Drexel University (Terry D Heiman-
Patterson, Roseanne Sattazahn, Michael Sherman, Sara Feldman, and Melonie
Mitchell); Henry Ford (Daniel S Newman and Helen Foley); University of
Miami (Ashok Verma, Julie Steele, and Donald A Koggan); Upstate Medical
University, Syracuse (Jeremy M Shefner and Mary Lou Watson); University of
Texas Health Science Center at San Antonio (Carlayne Jackson and Pamela
Kittrell); Data and Safety Monitoring Board (Robert L Sufit, Laurie Gutmann,
Peng Huang, and Noah Lechtzin); NIH Program Management (Robin A Conwit
and Janice Cordell).
Lan Chi T Luu provided helpful discussions during the planning phase of
the study. The tremendous cooperation of the patients and caregivers is grate-
fully acknowledged. We thank Robin AConwit and Janice Cordell of the Na-
tional Institute of Neurological Disorders and Stroke, and the members of the
Data Safety Monitoring Board for their assistance during the course of the
study. The Web-based calculator was designed by Stephen Welch, Renato
Moreira, MSM, and EJK.
The authors’ responsibilities were as follows—EJK, MSM, and RJK:
designed the research; MSM and RJK: performed statistical analysis; EJK
and members of the ALS Nutrition/NIPPV Study Group: conducted the
research; DEM: conducted mass spectrometry; EJK, MSM, and RJK: wrote
the manuscript; and EJK: had primary responsibility for the final content. All
authors read and approved the final manuscript. The authors reported no
conflicts of interest and alone were responsible for the content and writing
of this manuscript. The nongovernmental funding sources had no role in the
design, implementation, analysis, or interpretation of the data.
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