Clinical Nutrition 35 (2016) 41e47

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Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Randomized control trials

Changes in body composition in heart failure patients after

a resistance exercise program and branched chain amino acid
supplementation
Juan Antonio Pineda-Jua
rez a, Ne

stor Alonso Sa

nchez-Ortiz a, Lilia Castillo-Martínez a,
a, *
n b, Candace Keirns-Davis c,
Arturo Orea-Tejeda , Rocío Cervantes-Gayta

rez-Ocampo , Karla Quiroz-Bautista b, Mo
Carlos Pe b
nica Tenorio-Dupont b,
b
Alberto Ronquillo-Martínez
a
Heart Failure Clinic, Instituto Nacional de Ciencias M

n “SZ”, Mexico City, Mexico
edicas y Nutricio
b
Rehabilitation Service, Instituto Nacional de Ciencias M

n “SZ”, Mexico City, Mexico
edicas y Nutricio
c
Massachusetts General Hospital Interpreter Services, Boston, MA 02114, USA

a r t i c l e i n f o s u m m a r y

Article history: Background & aims: Heart Failure (HF) is a complex syndrome, which can include the physiological,
Received 8 October 2014 neural hormonal and metabolic complications known as “Cardiac Cachexia” (CC). In the development of
Accepted 8 February 2015 CC there is a release of catabolic cytokines (Tumor Necrosis Factor-a, interleukins 1 and 6) that cause a
decrease of fat free mass and fat mass. These changes in body composition might be reversed with a
Keywords: therapeutic combination of resistance exercise and branched chain amino acid supplementation (BCAA).
Resistance exercise
Aim: Evaluate changes in body composition after a resistance exercise program and BCAA supplemen-
Branched chain amino acids
tation in patients with HF.
Heart failure
Methods: In a randomized clinical trial with 3 month of follow-up anthropometric body composition
analysis and stress tests were evaluated at the beginning and in the end of the study. Patients were
divided into two groups; the experimental group performed the resistance exercise program and
received 10 g/day BCAA supplementation, and the control group only performed the resistance exercise
program. Both groups were provided with individualized diets and conventional medical treatment.
Results: Changes were found in hip circumference between the groups (p ¼ 0.02), and muscle strength
was increased in the experimental group (8%) and the control group (11.4%) with no difference between
them. METS and VO2Max also increased in experimental and control groups (16.6% and 50.1% respec-
tively). Regarding changes in symptoms, improvements in fatigue (45.4%), decubitus intolerance (21.8%)
and dyspnea (25.4%) were observed in the overall sample.
Conclusion: Improvements in physical and functional capacities are attributed to resistance exercise
program but not to the BCAA supplementation.
Clinical Trials Identifier: NCT02240511.
© 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

1. Introduction respond to physiological demands [1]. These abnormalities involve

Heart failure (HF) is a complex syndrome which results from
structural and/or functional alterations that limit the ability to
* Corresponding author. Heart Failure Clinic Director at INCMNSZ, Providencia
1218-A 402 Col. del Valle, Benito Ju

arez, CP 03100 Mexico City, Mexico. Tel./fax: þ52
55 55 13 93 84.
E-mail addresses: oreatart@gmail.com (A. Orea-Tejeda), mieshe@comcast.net
(C. Keirns-Davis).
metabolic and neuro-hormonal factors such as tumor necrosis
factor-a (TNF-a), one of the most important catabolic cytokines
related with changes in body composition, interleukin 1 (IL-1), IL-6,
interferon Y, and transmission growth factor b [2], which produce
catabolic and anabolic imbalance and promote loss of fat free mass
(FFM) with or without loss of fat mass (FM) in patients with HF. This
syndrome is called “Cardiac Cachexia” (CC) [3]. Signs and symptoms
such as fatigue, anorexia and decreased muscle strength reflect
altered body composition [3].

http://dx.doi.org/10.1016/j.clnu.2015.02.004
0261-5614/© 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
42
rez et al. / Clinical Nutrition 35 (2016) 41e47
J.A. Pineda-Jua
There are two possible ways to counteract these catabolic fac-
tors and restore body compartments. In one of them, protein sup-
plementation promotes protein synthesis and inhibits proteolysis
[4]; in the other resistance exercise (RE) increases muscle mass
and muscle strength, maintaining heart rate [5].
Previous studies report the association of protein supplemen-
tation [6,7] and exercise [8e10] with changes in muscle strength in
some cases and exercise capacity in HF patients. However, these
therapies were not combined, and the studies did not provide
enough information about changes in body composition.
Based on these reports, our hypothesis was that the combina-
tion of RE and protein supplementation in form of branched chain
amino acids (BCAA) might have an anabolic effect in patients with
HF since the supplementation of BCAA could be helpful as “fuel”
during the exercise and maintain the muscle mass metabolism [11].
2. Materials and methods
2.1. Population
A group of 66 patients from the Heart Failure Clinic at “Instituto
Nacional de Ciencias Me
dicas y Nutricio
n Salvador Zubira
n”
(INCMNSZ) in Me
xico City, more than 18 years of age enrolled in the
study according to the following criteria: confirmed stable heart
failure [1], no myocardial revascularization, unstable angina or
stroke in the previous 3 months, patients with no other chronic
illness which contributed to loss of muscle mass (arthritis, renal
failure, cancer, HIV) previous study inclusion, or extra cardiac
conditions that made patients unable to perform exercise.
2.2. Assignment to study groups
A member of our clinic randomly assigned patients to: the
experimental group with the resistance exercise program (RE) plus
Amino 2000 BCAA supplementation (PRONAT® laboratory)
(Table 1) or the control group with only RE. The supplementation
group received 180 packets of 5 grams (g) and ingested 10 g/day
(5 g after breakfast and 5 g before RE).
The present study was approved by the Institutional Ethics
Committee of Biomedical Research in Humans of the INCMNSZ.
2.3. Study procedures
An initial interview was conducted on all selected patients to
obtain demographic information, signs and symptoms related to HF
and pharmacological treatment. Anthropometric variables, muscle
strength, bioelectrical impedance, stress test and dietetic assess-
ment were evaluated as described below:
Table 1
AMINO 2000 BCAA nutritional information.
Portion per container: 30
Portion size: 4 tablets (5 g)
Content per serving:
Energy: 18.1 Kcal
Carbohydrates: .49 g
Fat: .12 g
Protein: 3.75 g
- Glutamine: 975 mg
- Leucine: 556 mg
- Isoleucine: 257.33 mg
- Sodium: .01 mg
2.3.1. Anthropometric measurements
Body weight and height were measured by a calibrated scale
(TORINO®) and stadiometer (SECA®) respectively, and both mea-
surements were used to calculate body mass index (BMI). Arm,
waist and hip circumferences were measured by an ergonomic tape
(SECA®). All anthropometric variables were measured according to
the reference manual anthropometric standardization [12]. Muscle
strength was measured by a handgrip dynamometer (TAKEI®);
three consecutive measurements were obtained from the domi-
nant hand [13], and the average of these was obtained and reported
in kilograms.
2.3.2. Body composition
This was evaluated by bioelectrical impedance analysis (BIA)
using multi frequency equipment (Body Stat Quad Scan 4000). The
method consisted of putting four electrodes (two on the hand and
the other two on the foot) on the right side to evaluate whole body
composition [14]. Patients had fasted 1 h and should not have
exercised for 12 h before the study. The BIA values were obtained at
frequencies of 5, 50, 100 and 200 kHz. The 50 kHz frequency was
used to obtain resistance (R), reactance (Xc) and phase angle by the
Phase Angle Software 1.0. R and Xc (standardized by height) were
processed by bioelectrical vector analysis (BIVA) [15] to classify the
body composition of each patient using the RXc graph in a Mexican
reference healthy population [16]. Impedance index (II) was
calculated diving 5 kHz/200 kHz frequencies. Total body water
(TBW), extra cellular water (ECW) and third space water (TSW)
were also measured by BIA.
2.3.3. Stress test
Patients were evaluated on an automatic treadmill (modified
Bruce protocol test) and monitored by a cardiologist. Heart rate and
blood pressure were measured at the beginning and at the end of
the test, calculating: metabolic equivalents (METS), maximal oxy-
gen consumption (VO2MAX) and time on the treadmill. The test
was stopped if the patients reported fatigue or their heart rate
increased abruptly.
2.3.4. Diet measurement
Patients of both groups performed a 24-h recall prior to start the
intervention (baseline measurement); an individualized and stan-
dardized diet was prescribed to all patients according to energy
expenditure for their age, sex, ideal weight and height which
consisted in 50% of carbohydrates, 20% of protein and 30% of fat in
order to prevent different Kilocalories and macronutrients con-
sumption, especially in protein intake in the supplemented group
during the study. It is noteworthy that the supplemented group was
subtracted the quantity of protein (10 g) that was prescribed in
their diet to prevent further consumption. The diet was divided into
4 meals as follows: breakfast, morning snack, lunch and dinner.
General recommendations about sodium intake (2400e3000 mg/
day) and liquid consumption (2000e3000 ml/day) were also pro-
vided. At the end of study another 24-h recall also was performed
for evaluate the diet adherence that was defined as 20% more or
20% less than the recommended total Kcal. These data were
analyzed by the Food Processor® version 7. The same trained and
standardized Nutritionist performed all measurements.
The duration of the therapy was 12 weeks for each patient; all
measurements were taken at the beginning and end of the study.
2.3.5. Resistance exercise therapy
Patients underwent an evaluation by a physiotherapist before
starting the therapy and were supervised during all exercises ses-
sions. Exercise sessions were of 1 h duration twice a week. RE
therapy was divided in four parts: stretching: arms, hands, wrists,

rez et al. / Clinical Nutrition 35 (2016) 41e47
J.A. Pineda-Jua 43

legs, knees and ankles, each one for 10e20 s with resting intervals Table 2
of 5 s (4 series), warming and flexion: the same muscle groups, Baseline demographic, clinical and drug treatment characteristics.

making small circles forward and backward for 5e10 s with resting Total RE þ BCAA RE p Value
intervals of 5 s (4 series), resistance exercises: flexion, contractions n ¼ 66 n ¼ 34 n ¼ 32 between
and twisting of the same muscle groups worked in the two previ- groups

ous sections. In this part resistance was increased with the aid of Sex (f/m) 27/39 (40.9/59.1) 34 (44.4/56.4) 32 (55.6/43.6) NS
dumbbells (500 ge1500 g), barbells and bands, and patients per- Age(years) 73 (61.7e80.2) 74.5 (64.2e84) 71 (58e79) NS
Decubitus 25 (37.9) 11 (44) 14 (56) NS
formed the same exercises with 15e20 repetitions with resting
Intolerance
intervals of 10 s (4 series), relaxation: involved the same exercises Dyspnea 31 (47) 16 (51.6) 15 (48.4) NS
as “stretching” to rest all muscle groups worked. Edema 33 (50) 14 (42.4) 19 (57.6) NS
Fatigue 55 (83.3) 25 (45.5) 30 (54.5) 0.02a
NYHA
2.3.6. Statistical analysis
I 39 (60.9) 21 (53.8) 18 (46.6)
All data obtained were analyzed with the Statistical Program II 20 (31.3) 9 (45) 11 (55) NS
Package for the Social Sciences (SPSS) version 17 (SPSS, Inc., Chi- III 4 (6.3) 3 (75) 1 (25)
cago, IL, USA). Continuous variables were presented as IV 1 (1.6) 1 (100) 0
mean ± standard deviation when data had a normal distribution or Dysfunction
Systolic 4 (6.1) 2 (5.9) 2 (6.3)
as medians (p 50) and interquartile ranges (p25 e p75) otherwise. Diastolic 4 (6.1) 2 (5.9) 2 (6.3) NS
Categorical variables were presented in frequency and percentage Mixed 56 (84.4) 30 (88.2) 26 (86.7)
(n/%). For the comparison between the groups on continuous var- Co-morbidities
iables an independent “T” test (parametric distribution) or U- CVE 34 (51.5) 20 (58.8) 14 (43.8) NS
Diabetes 27 (40.9) 12 (35.3) 15 (46.9) NS
Mann-Whitney (no parametric distribution) were used and the
Hypertension 45 (68.9) 26 (76.5) 19 (59.4) NS
Pearson X2 test for categorical variables. For the comparisons after Renal diseases 14 (21.2) 10 (29.4) 4 (12.5) NS
intervention, percentage changes were obtained for continuous Cancer history 11 (16.7) 9 (26.5) 2 (6.3) 0.04a
variables, and a McNemar test was used for categorical variables. Liver diseases 4 (6.1) 2 (5.9) 2 (6.3) NS
Obesity 16 (24.2) 7 (20.6) 9 (28.1) NS
Dyslipidemia 16 (24.2) 7 (20.6) 9 (28.1) NS
3. Results Beta-blockers 58 (87.9) 32 (94.1) 26 (81.2) NS
ACEI's 23 (34.8) 14 (41.4) 9 (28.1) NS
Figure 1 is a flow chart of patient participation in the study. ARB's 33 (50%) 16 (47.1) 17 (33) NS
There were 5 dropouts in the experimental group and 6 in the Diuretics 29 (43.9) 14 (41.1) 15 (46.8) NS
Digital 32 (48.5) 16 (47.1) 16 (5) NS
control group. Thus, the analysis included 55 patients (29 in the Nitrate 26 (39.4) 12 (35.2) 14 (43.7) NS
experimental group and 26 in the control group). The demographic,
Abbreviations: f: female, m: male, NYHA: New York Heart Association, CVE: cerebral
clinical, anthropometric, body composition, stress test, biochemical
vascular event, ACEI's: angiotensin converting enzyme inhibitors, ARB's: angio-
and treatment characteristics of the patients at baseline are sum- tensin II blockers, Categorical variables are presented in No. (percentage) and
marized in Tables 2 and 3. Continuous variables are presented in median (p25 e p75).
a
According to the baseline characteristics, the majority of the Statistically significant difference <.05, NS: not significant.
patients reported more fatigue (83.3%) at the beginning with sig-
nificant differences between the groups (p ¼ 0.02). NYHA func-
tional classes, I (60.9%) and II (31.1%) were predominant, and the hydration (62.1%). The rest of baseline characteristics were not
most common ventricular dysfunction was mixed (84.4%). Cerebral significantly different between the groups (see Tables 2 and 3).
vascular events (51.4%) and hypertension (68.9%) were the main co- After intervention, we observed that the hip circumference in
morbidities in the patients; cancer history was statistically different the experimental group had decreased markedly (3.1%) in com-
between the groups (p ¼ 0.04). Most of the patients were taking parison with that of the control group (1.5%), (p ¼ 0.02). Although
beta receptor blockers (87.9%). On the basis of the BIVA findings, differences in the rest of anthropometric variables were not sta-
most of the patients were classified as cachectic (62.1%) with over- tistically significant, arm (2% vs. 4%) and waist (just in
controls, 1.7%) circumferences decreased, and muscle strength
increased in both groups (8% vs 11.4%). Body composition showed
reduction in TSW (14.6% vs. 33.3%) and increase in phase angle
(2.5% vs. 2%) in both groups; however these differences and those of
the rest of the body composition variables were not significant.
Regarding the stress tests, RHR and EHR were shown to be reduced
little more than 6% in both groups, while time on the treadmill,
METS and VO2Max were reduced in both with no statistically sig-
nificant changes. In contrast, changes in EDBP were statistically
different (p ¼ 0.0001), as were increased concentrations of plasma
albumin and nitrogen balance. The control group had a reduction in
the urea level (Table 4).
As far as the clinical manifestations of HF were concerned, sta-
tistically significant changes (Fig. 2) occurred in decubitus intoler-
ance, dyspnea (p ¼ 0.03) and fatigue (p < 0.0001) with a tendency
to decreased dyspnea (p ¼ 0.07) in the population as a whole after
12 weeks intervention. Fatigue decreased in both groups
(p ¼ 0.007); dyspnea only decreased in the experimental group
(p ¼ 0.03). Muscle strength was increased in 34.5% in the total
population (statistical tendency, p ¼ 0.08) with no changes be-
Fig. 1. Flow chart of the participated patients in the study. tween the groups (Fig. 3).
44
rez et al. / Clinical Nutrition 35 (2016) 41e47
J.A. Pineda-Jua

Table 3
Baseline anthropometric, body composition, stress test, diet and biochemical markers characteristics.

Total RE þ BCAA RE p Value between groups

n ¼ 66 n ¼ 34 n ¼ 32

Anthropometry
Weight (Kg) 69.9 ± 17.3 68.8 ± 15.7 67.5 ± 15.5 NS
Height (cm) 158.7 ± 9.7 158.9 ± 8.7 158.5 ± 10.9 NS
BMI (Kg/m2) 27.6 ± 5.6 27.0 ± 5.1 28.2 ± 6.1 NS
Arm (cm) 28.9 ± 4.3 28.6 ± 4.0 29.4 ± 4.7 NS
Waist (cm) 94.7 ± 14.4 93.8 ± 14.6 95.6 ± 14.0 NS
Hip (cm) 100 (93.7e109.2) 99.7 (93.7e110.6) 100.5 (93.5e107.7) NS
Strength (Kg) 24.5 ± 9.1 24.8 ± 8.7 24.1 ± 9.6 NS
Body composition
Obese 9 (13.6) 2 (5.8) 7 (21.8) NS
Cachexia 41 (62.1) 25 (73.5) 16 (50)
Over hydration 41 (62.1) 23 (67.6) 18 (56.2) NS

I.I .82 (.81e.86) .82 (.81e.86) .82 (.81e.86) NS
TBW (%) 54.2 ± 8.0 55.7 ± 7.76 52.6 ± 8.1 NS
ECW (%) 24.4 ± 3.0 24.8 ± 3.0 24.0 ± 3.0 NS
TSW .51 (.30e.90) .60 (.15e.84) .31 (.50e.91) NS
Phase angle 5.2 (3.8e5.7) 5.3 (3.8e5.7) 5.1 (3.8e5.7) NS
R/H 318.5 (274.6e375.85) 315.1 (267.5e351.7) 323.6 (291.9e385.9) NS
Xc/H 28.3 ± 8.3 27.7 ± 8.1 28.9 ± 8.5 NS
Diet
Kcal 1423.3 ± 502.7 1447.0 ± 582.5 1398.1 ± 409.2 NS
Fat (g) 408.0 ± 238.2 459.2 ± 268.6 353.7 ± 190.6 NS
Protein (g) 60.2 ± 21.8 60.4 ± 24.5 60.0 ± 18.9 NS
CH (g) 201.0 ± 82.4 193.4 ± 83.4 209.1 ± 81.8 NS
Leucine(g) 3.4 ± .21 3.4 ± 1.8 3.5 ± 1.5 NS
Isoleucine (g) 1.1 ± .7 1.1 ± .69 1.1 ± .53 NS
Valine (g) 2.2 ± .13 2.13 ± 1.2 2.26 ± 1.0 NS
Stress test
RHR (b/m) 75.1 ± 18.4 73.8 ± 18.5 76.5 ± 18.5 NS
EHR (b/m) 121.5 ± 31.3 117.8 ± 33.3 125.4 ± 29.2 NS
RSBP (mm/Hg) 120.1 ± 20.6 119.2 ± 18.1 121.0 ± 23.2 NS
RDBP (mm/Hg) 70 (60e80) 70 (60e80) 76 (60e90) NS
ESBP (mm/Hg) 140 (130e149.5) 140 (130e146) 140 (130e160) NS
EDBP (mm/Hg) 78.3 ± 15.4 75.2 ± 16.7 81.6 ± 13.4 NS
Treadmill Time (min) 5.5 ± 3.8 5.8 ± 4.3 5.1 ± 3.3 NS
METSb 4.5 (2e6.7) 4.6 (2.6e7.0) 3.7 (1.9e6.2) NS
VO2 Max (ml/kg/min) 15.9 (7e23.6) 16.1 (9.2e24.5) 12.9 (6.8e21.9) NS
Biomarkers
Albumin (g/dL) 3.9 (3.5e4.2) 3.9 (3.3e4.2) 3.9 (3.5e4.2) NS
Hemoglobin (g/dL) 14.2 (12.7e15.3) 14.5 (12.9e15.6) 13.8 (12.4e15.3) NS
Hematocrit (%) 42.0 (37.7e45.9) 42.6 (38.5e42.6) 41.4 (35.7e45.7) NS
Nitrogen balance (mg/dL) 22.4 ± 9.6 21.5 ± 7.4 23.3 ± 11.5 NS
Urea (mg/dL) 47.8 ± 20.7 45.6 ± 15.6 50.2 ± 25.0 NS
Creatinine (mg/dL) 1.1 (.82e1.3) 1.1 (1.08e1.4) 1.1 (.80e1.3) NS
GFR (mL/min/m2) 52.8 (40.4e74.4) 52.5 (39.7e79.0) 52.8 (39.5e70.6) NS

Abbreviations: BMI: body mass index, I.I: impedance index, TBW: total body water, ECW: extra cellular water, TSW: third space water, R: resistance, Xc: reactance, H: height,
METS: metabolic equivalents, VO2MAX: maximal oxygen consumption, Kcal: Kilocalories, CH: carbohydrates, RHR: resting heart rate, EHR: effort heart rate, RSBP: resting
systolic blood pressure, ESBP: effort systolic blood pressure, RDBP: resting diastolic blood pressure, ESBP: effort diastolic blood pressure, GFR: glomerular filtration rate.
Categorical variables are presented in No. (percentage) and Continuous variables are presented in median ± standard deviation or median (p25 e p75), NS: not significant.

4. Discussion intervention, though not in muscle quantity. Therefore, there were

In this clinical trial with stable HF patients we found that
anthropometry variables changed after 12 weeks of intervention,
with reductions in waist (2.2%), arm (3.5%) and hip circumfer-
ences (1.1%) and increase in muscle strength (11.1%). Maionara et al.
[17] found similar results; the sum of the five circumferences (arm,
hip, waist, thigh and calf) diminished from 325.5 mm to 322.3 mm
and muscle strength (sum of the large muscle groups) increased
from 392 Kg to 429 Kg. Okura et al. [18] also observed reductions in
hip and waist circumferences of 9.3% and 6.3% respectively after 14
weeks. On the basis of these changes, we assume that fat mass
decreased (through lipolytic activation [19]) and muscle mass (and
function) increased, considering that last two variables are related
[20] and RE is an anabolic therapy by definition. Additionally, 34.5%
of the total population had improved muscle strength, even when
we could not measure the exact amount of muscle mass gained by
the HF patients. Similar findings were obtained by Osbak et al. [21],
who had noted a muscle strengthening after 12 weeks of exercise
important changes in body composition.
Another important consideration in our analysis of body
composition was water distribution. Usually these patients tend to
have fluid retention and abnormal fluid distribution outside cells
(extra cellular water) [22]. RE training improves body water dis-
tribution, incorporating it into cellular space. Hip and waist re-
ductions maybe related to decreased third space water in both
groups (14.6% and 33.3% in experimental and control group
respectively), probably associated with the increased albumin
concentration (experimental: 6.5%, controls: 5.1%).
From the standpoint of exercise tolerance evaluated by stress test,
the notable reductions in resting and exercise heart rate after 12
weeks (6e6% and 7.4%) in the experimental and control groups
(6.4% and 14.2%) support the conclusions of Keyhani et al. [23] about
their results, i.e., diminished heart rate after 8 weeks with increased
treadmill time (11.6% and 9.5), METS (16.6% and 50.1%) and VO2Max
(16.6% and 50.1%) in experimental and control groups. These im-
provements were comparable to those of Maionara et al. [17].

rez et al. / Clinical Nutrition 35 (2016) 41e47
J.A. Pineda-Jua 45

Table 4
Percentage changes comparison between groups after 12 weeks.

Total BCAA þ RE RE p Value between groups

n ¼ 55 n ¼ 29 n ¼ 26

Anthropometry
Weight (Kg) 3.8 (2.3e2.3) .38 (2.7e2.2) .67 (2.1e2.3) NS
BMI (Kg/m2) .47 (2.7e2.5) .59 (4.4e2.1) .47 (2.4e2.7) NS
Arm (cm) 3.5 (7.5e1.9) 2.0 (7.4e3.3) 4.0 (7.6e.20) NS
Waist (cm) 1.1 (3.4e2.5) .68 (3.2e3.3) 1.7 (3.7e2.5) NS
Hip (cm) 2.2 (4.4 e .05) 3.1 (6.6 e 1.1) 1.5 (3.7e1.8) 0.02a
Strength (Kg) 11.1 (4.1e18.5) 8 (6.8e15.3) 11.4 (3.6e21.4) NS
Body composition

I.I 1.1 (2.4e1.2) 1.1 (2.4e1.2) 1.1 (1.7e1.2) NS
TBW (%) .16 (3.3e3.4) .98 (3.7e3.1) .29 (3.0 e 3.8) NS
ECW (%) -.42 (3.4e2.8) .96 (3.6e3.7) 1.3 (3.4e1.8) NS
TSW (Lt) 15.6 (61.7e16.9) 14.6 (50e19.6) 33.3 (70.8e10.9) NS
Phase angle 2.5 (5.5e8.1) 2.5 (6.9e15.6) 2.0 (1.9e12.3) NS
R/H 1.1 (5.5e8.1) 1.1 (5.5e6.9) 1.0 (8.2e12.2) NS
Xc/H 1.2 (8.0e9.7) .93 (9.7e9.7) 4.4 (5.9e9.7) NS
Diet
Kcal 6.4 (18.1e23.6) 18.0 (1.6e23.6) 7.2 (20.2e25.6) NS
Fat (g) 2.3 (34.8e27.9) 3.2 (45.5e25.0) 6.6 (32.3e62.1) NS
Protein (g) 1.1 (24.4e38.5) 5.5 (22.2e31.2) 6.0 (24.9e46.8) NS
CH(g) 6.1 (18.6e6.9) 2.0 (17.4e8.0) 11.4 (23.4e7.3) NS
Leucine (g) 13.5 (16.4e55.7) 14.2 (9.8e55.7) 9.6 (31.3e57.1) NS
Isoleucine (g) 17.2 (11.3e60.1) 11.7 (5.2e37.5) 17.3 (31.1e69.8) NS
Valine (g) 9.6 (15.8e60.1) 11.7 (12.5e60.1) 6.2 (32.1e57.2) NS
Stress test
RHR (b/m) 6.6 (17.6) 6.6 (16.1e15.2) 6.4 (23.2e9.8) NS
EHR (b/m) 12.4 (27.1e9.0) 7.9 (27.7e7.6) 14.2 (.24.4e25.8) NS
RSBP (mm/Hg) 4.1 (9.7e11.1) 1.6 (10.0e11.1) 5.2 (10.7e13.5) NS
RDBP (mm/Hg) 7.5 (13.3e20.8) 6.6 (11.1e26.6) 9.2 (15.2e17.7) NS
ESBP (mm/Hg) 5.6 (12.8e12.1) 2.3 (11.4e12.1) 8.0 (14.7e10) NS
EDBP (mm/Hg) 2.5 (11.5e20.0) 15.4 (7.5e25) 12.0 (17.6e10.2) 0.0001a
Treadmill Time (min) 10.4 (18.2e71.5) 11.6 (31.0e82.1) 9.5 (11.8e73.5) NS
METS 28.7 (2.0e72.4) 16.6 (.18e30.7) 50.1 (11.2e94.0) NS
VO2 Max (ml/kg/min) 28.7 (2.0e72.4) 16.6 (.18e38.5) 50.1 (11.2e94.0) NS
Biomarkers
Albumin (g/dL) 5.2 (5.1e13.8) 6.5 (10.2e13.7) 5.1 (5.0e13.8) NS
Hemoglobin (g/dL) 1.2 (7.0e8.3) 1.3 (8.4e8.8) 1.2 (4.3e7.2) NS
Hematocrit (%) -.53 (6.8 9.3) -.75 (7.8e9.3) .14 (4.4e9.2) NS
Nitrogen balance (mg/dL) 5.9 (10.3e26.0) 6.0 (5.6e27.8) 2.3 (19.1e25.2) NS
Urea (mg/dL) 5.7 (10.5e26.1) 9.5 (7.2e31.3) 3.1 (15.7e20.2) NS
Creatinine (mg/dL) 5.9 (9.6e24.4) 6.3 (9.4e27.7) 5.9 (10.1e23.9) NS
GFR (mL/min/m2) .7 (.24e.12) .8 (.24e.14) .6 (.23e.13) NS

Abbreviations: BMI: body mass index, I.I: impedance index, TBW: total body water, ECW: extra cellular water, TSW: third space water, R: resistance, Xc: reactance, H: height,
METS: metabolic equivalents, VO2MAX: maximal oxygen consumption, Kcal: Kilocalories, CH: carbohydrates, RHR: resting heart rate, EHR: effort heart rate, RSBP: resting
systolic blood pressure, ESBP: effort systolic blood pressure, RDBP: resting diastolic blood pressure, ESBP: effort diastolic blood pressure, GFR: glomerular filtration rate.
Continuous variables are presented as percentage changes in median (p25 e p75).
a
Statistically significant difference <.05, NS: not significant.

Fig. 2. Clinical changes after 12 weeks intervention, *p < 0.05: statistically significant, **p < 0.10: tendency toward statistical significance, BCAA: branched chain amino acids, RE:
resistance exercise.
46
rez et al. / Clinical Nutrition 35 (2016) 41e47
J.A. Pineda-Jua

Fig. 3. Muscle strength changes after 12 weeks intervention, **p < 0.10: statistically significant difference, BCAA: branched chain amino acids, RE: resistance exercise.

An increase in diastolic blood pressure at rest and on effort (6.6% group at the end of the study, maybe this is the main reason why BCAA
and 15.4% respectively) was observed in the experimental group. did not have the expected effect, even so we believe that it takes more
These changes could be caused by inappropriate endothelial studies suggesting the use of these AA.
behavior during increased flow, depending on the exercise type. Our trial was limited by the fact that we only evaluated handgrip
These changes could be expected because vascular resistance in- strength and not other muscle groups (legs, back or chest), and the
creases in patients with HF. However, with training this vascular lack of the follow up may have precluded finding more significant
dynamic tends to stabilize, and peripheral resistances decrease changes. Finally the sample size was very small.
with improvement in capillary vasodilatation and secondary blood
pressure stabilization [24].
5. Conclusion
The BCAA may have an effect on blood pressure as mentioned by
Takemoto [25]; amino acids play a role as neurotransmitters on
In our study, clinical and physical improvements were caused by
brain centers that regulate blood pressure and blood flow, and this
the RE program independently from BCAA supplementation.
could influence the cardiovascular system. It is also plausible that
However, beyond of these changes, uncertainty persists about
the improvement of physical variables could result from increased
whether the best way to modify body composition in HF patients is
muscle mass as proposed by Wilson et al. [26] In addition, our study
to provide an optimal physical-dietary regimen. To our knowledge
showed clear improvement in HF symptoms after intervention,
in HF physical activity and energy expenditure decreased, and they
suggesting better patient functional capacity.
are the principal causes of muscle mass loss.
With regard to the amino acids, we did not find that their (10 g)
The essential points could be: a) The implementation of an ex-
supplementation had an impact on the experimental group
ercise program, because it increases total energy expenditure and
compared to the controls at the end of intervention. These results
therefore nutritional requirements, is a worthwhile addition to
agree with those of Perillo et al. [27], who did not observe changes in
therapy, and, b) Dietary intake in HF could be favored by an anti-
functional capacity (VO2Max, pulse oximetry and 6 min walk test)
inflammatory (fruits, vegetables, whole grains, mono and poly-
after creatinine supplementation (5 g/day). However, for other au-
unsaturated fatty acids) and pro anabolic (including adequate
thors, 4 g/day of essential amino acid supplementation improves
intake of essential amino acids including BCAA) food effect that
aerobic capacity and major exercise capacity [28]. Kuethe et al. [29]
help to counteract the constant catabolic process caused by the
reported amelioration of metabolic abnormalities (muscle mass)
release of catabolic cytokines.
when creatinine supplementation (4 g/day) was used. However, it
should be mentioned that none of these studies involved any exercise
program. Even so and as far as we know, the BCAA metabolism in Conflict of interest
“normal” conditions is based on their degradation by the BCAA
transferase which is the responsible to transform the BCAA to keto All authors state no conflict of interest.
acids branched chain (KABC) and subsequently by the action of KABC
dehydrogenase converts the KABC to Acetyl Co-A and Succinyl Co-A
Acknowledgments
and finally this two substrates go to the Krebs Cycle for its use as
energy, but also we know that BCAA excess in blood can cause
We appreciated PRONAT® industry for donated the supplement
metabolic acidosis and hence rise ammonium blood levels [30]. With
that we use in this trial.
this two prior considerations it could explain that patients with heart
failure have a constant catabolic process and this results in a state of
malnutrition and therefore a bad state of absorption, i.e.; the pre- Appendix A. Supplementary data
scribed BCAA could not have absorbed in adequately way and
remaining in the periphery, this data can substantiate the observation Supplementary data related to this article can be found at http://
that levels of BUN and urea had an increase in the supplemented dx.doi.org/10.1016/j.clnu.2015.02.004.

rez et al. / Clinical Nutrition 35 (2016) 41e47
J.A. Pineda-Jua 47

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