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Non-Pharmacological Treatment of Sarcopenia: A Systematic Review

Tratamento não farmacológico da sarcopenia: uma revisão sistemática

DOI:10.34117/bjhr2n5-077

Recebimento dos originais: 10/09/2019

Aceitação para publicação: 29/10/2019

Leonardo Manoel de Carvalho

Médico do Esporte pelo Hospital de Clínicas da Faculdade de Medicina da USP
Instituição :Clínica Stronger
Endereço :Clínica Stronger – Rua Augusta, 101, Conjunto 210. Consolação. São Paulo
– SP.
E-mail :clinicastronger@gmail.com

Samuel Rodrigues Buniatti

Médico pela Universidade Federal do Rio Grande do Sul
Instituição :Clínica Stronger
Endereço :Clínica Stronger – Rua Augusta, 101, Conjunto 210. Consolação. São Paulo
– SP.
E-mail :clinicastronger@gmail.com

Cassiano Rodrigues Santiago

Médico pela Universidade Federal de Ciências da Saúde de Porto Alegre
Instituição : Clínica Stronger
Endereço: Clínica Stronger – Rua Augusta, 101, Conjunto 210. Consolação. São Paulo
– SP.
E-mail : clinicastronger@gmail.com

Rafael Victor Guiron

Nutricionista pelo Centro Universitário São Camilo
Instituição : Clínica Stronger
Endereço : Clínica Stronger – Rua Augusta, 101, Conjunto 210. Consolação. São Paulo
– SP.
E-mail : clinicastronger@gmail.com

ABSTRACT

Introduction: Sarcopenia, which is defined by loss of both muscular mass and strength
associated with aging, has been of great interest in the last decades, but has no approved
pharmacological treatment yet. The target of the present research is to review and
systematize the data that supports non-pharmacological treatment of the pathology.
Methodology: Randomized Clinical Trials (RCT) of Sarcopenic patients was searched in
MEDLINE, EMBASE and LILACS databases using pre-defined terms. Results and
Conclusion: 17 RCT were included in the present research covering nutritional therapy,

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physical training, electrostimulation and combined therapies. The present data suggests
that all therapies (i. e. nutrition therapy, physical training and electrostimulation) have
positive impact in the treatment of the pathology, and the combined therapies seem to
increase even further the benefits in comparison to isolated approaches.

Keywords: sarcopenic obesity, nutrition therapy, physical training, electrostimulation,

nutrition.

RESUMO

Introdução: A sarcopenia, definida pela perda de massa muscular e força associada ao

envelhecimento, tem sido de grande interesse nas últimas décadas, mas ainda não possui
tratamento farmacológico aprovado. O objetivo da presente pesquisa é revisar e
sistematizar os dados que apóiam o tratamento não farmacológico da patologia.
Metodologia: Os ensaios clínicos randomizados (ECR) de pacientes sarcopênicos foram
pesquisados nas bases de dados MEDLINE, EMBASE e LILACS usando termos pré-
definidos. Resultados e Conclusão: 17 ECR foram incluídos na presente pesquisa,
abrangendo terapia nutricional, treinamento físico, eletroestimulação e terapias
combinadas. Os presentes dados sugerem que todas as terapias (isto é, terapia nutricional,
treinamento físico e eletroestimulação) têm impacto positivo no tratamento da patologia,
e as terapias combinadas parecem aumentar ainda mais os benefícios em comparação com
abordagens isoladas.

Palavras-chave: obesidade sarcopênica, terapia nutricional, treinamento físico,

eletroestimulação, nutrição .
1 INTRODUCTION
The aging process generates a collective of physiological changes that, when not
correctly counterbalanced, result in shortage of functional capacity in an individual 1.
Muscular tissue follows this pattern, presenting an 8% depletion in its mass each ten-year
period after 40 years of age, and 15% depletion each ten-year period after 70 years of age.
Muscular strength follows a similar pattern, with a peak around 30 years of age, a
reduction of 15% per ten-year period after 50 years of age, increasing to 30% per ten-year
period after 70 years of age 2. Although depletion of muscular mass and function are
related, it can be observed that the shortage of strength exceeds the loss of muscular mass,
which evidences the importance of the reduction of the central activation and reduction
of the intrinsic force-generation capacity of skeletal muscle, which are the
pathophysiological basis of the concept of dynapenia (loss of muscle strength)3.
It is important to remark that muscle strength is related to negative events such as
falls, limitation of movement and hospitalization 3, but in a nonlinear way: small

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decreases in muscle strength in older people can have serious effects in functional
performance, which would not be observed in younger patients.
In the last decades, there has been considerable effort to reach a precise clinical
definition including reliable parameters and their confidence intervals to measure the
expected physiological changes with aging and determine a threshold for the pathology.
In 1984, Irwin Rosenberg created the term “Sarcopenia”, defined until then as an aging
related depletion of muscle mass related with aging 4. Posteriorly, muscle weakness was
added to the definition 5. Currently, there is still debate about the most accurate and
clinical expressive diagnostic criteria, but to some extent there is consensus that both
muscle mass and muscle strength or function should be considered 5. A wide review of
diagnostic criteria or sarcopenia definition isn’t the target of the present research and can
be found in this reference 5, but our group concur with the European Working Group on
Sarcopenia in Older People (EWGWOP): “a syndrome characterized by progressive and
generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes
such as physical disability, poor quality of life and death” 6. The loss of lean body mass
associated with aging can also be related to an increase in fat mass, generating a
phenotype known as “Sarcopenic obesity” 7. The physiopathology of Sarcopenia is not
yet fully comprehended, but there is moderate evidence relating it to a decrease of
muscular activity (e. g. sedentarism, bedridden patients, hospitalizations), chronic
7
diseases (e. g. endocrinological diseases, neoplasia, inflammatory diseases) and
nutritional deficits 8. In fact, about 40% of elders above 70 years old do not achieve the
mark of 0,8g/kg/day of protein in diet, what can be related to a variety of factors:
masticatory disorders, dental and oral diseases, delayed gastric emptying (Gastroparesis),
early satiety and elevated cost of protein-rich products 8.
The treatment of sarcopenia is currently a high interest field. There are clinical
trials in progress testing various pharmacologic agents, such as Testosterone 9, Selective
10
Androgen Receptor Modulator (MK-0773) , myostatin human monoclonal antibody
11
(Bimagrumab) , however, there is still no consensus for pharmacological therapy.
Therefore, life habits modification focused on physical training and nutritional treatment
remains the therapeutic option for sarcopenia. There are several published papers
covering this approach in older people, however there are few covering specifically
sarcopenia patients. It is important to note that it is not clear whether the results obtained
in healthy elderly can be extended to sarcopenic elderly. Although some previously
published review proposes to investigate the effects of nutritional therapy and physical

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exercise in the elderly, this is the first review including only clinical trials performed
exclusively on sarcopenic individuals, in addition to presenting a session on
electrostimulation therapy, not discussed in previous reviews.

2 METHODOLOGY
The search of papers was made on 06/06/2017 in the databases MEDLINE,
EMBASE and LILACS with the terms “Sarcopenia” and/or “Sarcopenic”, using the
restrictor “Clinical Trials”, without restriction of languages or date. A search with the
restrictor “Reviews” was also made to further search for clinical trials in its references.
The papers found were united in MENDELEY reference management software, being
excluded duplicates and then the titles and abstracts were analyzed individually by two
researchers. On this phase, the selection of one researcher is enough to the selected paper
ingress in the next phase of analysis. The inclusion criteria were as follows 1)
Randomized clinical trials; 2) Minimum intervention time of 4 weeks; 3) Average age >
60 years, no individual younger than 50 years; 4) Non-pharmacological treatment of
Sarcopenia. The exclusion criteria were as follows 1) Sarcopenia secondary to specific
pathologies; 2) Papers with no presentation of results; 3) Papers that did not discuss the
diagnostic criteria used. In the second phase of the review, the papers included were fully
read and the data extracted, and a final decision was made on the inclusion of papers in
the review. The same researchers made the full analysis of papers, with discrepancies
being resolved by the analysis of a third researcher. This study conforms to all PRISMA
guidelines and reports the required information accordingly (see Supplementary
Checklist).

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3 RESULTS

A total of 484 papers were found in the initial search. After exclusion of duplicates
(85), there were 399 papers. The titles and abstracts were than read and 39 were selected
for full reading. Fourteen papers were excluded for not being randomized trials; three for
not presenting treatment data; two for including individuals not suffering from
Sarcopenia; one for age mean being lower than 60 years old; one for not specify the
diagnostic criteria; one for not being able to find the full text (paper unavailable for
purchase and the authors couldn’t be reached). Only seventeen papers were included in
this review. There wasn’t disagreement between the researchers related to what papers
should be included.For better discussion of the references, we chose to organize them in
types of intervention: Nutritional intervention only (4), Physical training only (3),
Nutritional intervention and physical training (7), electrostimulation (3).

4 NUTRITIONAL INTERVENTION
TABLE 1 HERE
Only four papers were included in this category, two of those relating to the same study.
All of those requires individual comments. Alemán-Mateo et al elaborated a study with
supplementation of 70g of ricotta three times a day with the main meals. The study did
not result in any statistical significant differences between the groups on the analyzed
variables. It was seen a possible increase in hand grip strength in the intervention group,

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but without statistical significance (p=0,06). This study raises a series of questions:
having the patients take 70g of ricotta with the main meals generates a possibility of
shortening protein intake from other sources in the meal because of the volume of ricotta
and the satiety it could bring. The study did not measure other aspects of food intake pre
and post intervention to control this bias. Furthermore, each dose of ricotta consists in
17
5,2g of protein, potentially insufficient to overcome anabolic resistance of aging .
Finally, 40% of the intervention group were lost in follow up, 10% because they would
not eat the ricotta and 30% for other reasons not related to the study, which can
compromise the results. In addition, one cannot ignore the use of handgrip as the sole
measure of strength in the study, since its correlation with the overall strength is not
perfect 6.Cramer et al. carried out a protocol comparing two isocaloric products consumed
2 times a day, containing 330kcal, with different macro and micronutrient balance, as can
be observed in table 1. Both groups had similar results. Increase in knee extension
strength, hand grip strength and gait speed were found without statistical difference in the
groups. In spite of the protocol distinguishing the control and intervention group, the
products tested were similar with some differences in protein, carbohydrate, Vitamin D3
and the presence of CaHMB in one of them. There wasn’t one isolated variable being
tested. There was no real control group free of intervention. The study does not explain
the reason for this group composition, creating doubts about the specific objectives of the
comparison.
Bauer et al compared the consumption of a product composed mainly of whey
protein with an isocaloric control in his protocol. The study had a satisfactory sample and
had a good control of the variables related to the complete nutritional intake of the
patients. Both groups presented best results in SPBB score, gait speed and chair-stand
test, being the last the most relevant in the intervention group. The intervention group
also presented significant increase in hand grip strength and in appendicular muscle mass.
At the end of the study period, nutritional control showed increase in calories intake in
both studies but increase of proteins only in the intervention group. The increase in the
results of control group can be related to the increase in calories intake and the additional
benefits in the intervention group can be related to higher protein intake and/or increase
in 25-hydroxy vitamin D (25(OH)D). Further analysis of the study by Verlaan et al
showed that patients who, before intervention, had higher protein intake (≥ 1g/kg/day) or
higher serum 25(OH)D (≥50nmol/L) levels had higher gains in appendicular muscle
mass, showing that a proper protein intake in everyday diet of sarcopenic patients aside

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from supplementation is of capital significance. In summary, there are few studies
focused exclusively in nutritional interventions of sarcopenic patients, but the evidences
of the stronger study seen in this review are promising. Studies that focus on protein
intake in an isolated form to clearly determine the ideal dose of protein of the sarcopenic
elderly patient lack in the literature. It is interesting to note that merely prescribing a
particular food supplement or type of food without adequate dietary control to ensure that
there is indeed an increase in protein-calorie intake cannot be considered an effective
strategy. Elderly people present several physiological changes that decrease the volume
of food ingested, such as masticatory disorders, dental and oral diseases, delayed gastric
emptying and early satiety 8, which could lead the elderly to simply replace their
traditional meal with food supplement, not generating a real increase consumption.
Another essential point is to ensure that the elderly exceed the protein-calorie threshold
needed to overcome the "anabolic resistance" associated with aging 3. Recently, several
consensuses have suggested higher protein intakes than the current recommended dietary
allowance (RDA) of 0.8g / kg / day, with recommendations exceeding twice that value
for some conditions 8. The use of dietary supplements should not be made as a quick exit
rather than a complete dietary assessment, but a tool that complements (does not replace)
a balanced diet at opportune moments in which the patient does not usually have an
adequate intake.

TABLE 2 HERE
In this subject, three researches comparing results of different types of physical
training were included. Despite a satisfactory methodology, all researches presented small
samples varying from 10 to 25 patients each group.Bellomo et al compared three
modalities of training against a control group: lower limbs resistance training,
sensorimotor training and vibration therapy of the quadriceps. All groups showed increase
in isometric quadriceps strength and half-step length in gait. Sensorimotor and vibrational
training showed better balance with decrease of sway area and ellipse surface. Body
composition was not measured in this paper.Balachandran et al compared
Strength/Hypertrophy Training (SHT) with High-Speed Circuit training (HSC), using as
parameter SPPB score, leg press and chest press strength and functional tests. The results
can be observed in Table 2. Only HSC showed best results in SPPB score, compatible
with evidences that peak power has a stronger relation to function than strength
1
.Difference in body composition was not found. Chen et al used three modalities of

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training against a control group (CON): resistance training (RT), aerobic training (AT)
and combined training (CT). All intervention groups presented increase in appendicular
muscle mass, decrease in body fat and visceral fat. RT and CT group presented increase
in knee extension strength, being RT > CT > AT = CON.It is clear that physical training
results in strength improvement, power and functional tests, being the results different
between distinct types of training. There is already ample evidence that aerobic and
resistance training has positive effects in the elderly population, and the sparse evidence
in sarcopenic elderly seems to suggest that these effects also exist in this subpopulation.
There are several physiological mechanisms that mediate these modifications, such as
increased muscle capillarity, increased mitochondrial compartment, increased number
and size of fast muscle fibers and better neuromuscular activation. The proper type of
training to reverse the effects of sarcopenia remains controversial. Aerobic training has
undeniable benefits in the elderly population in reducing cardiovascular risk and
mortality, however, the fact that sarcopenia is a disease related to decreased muscle mass
and strength suggests that resistance training is more efficient, as we observed in the work
of Chen et al 20, in which the resistance training volume is related to greater gain of knee
extension force. Analyzing the modalities of resistance training, there is ample evidence
in the elderly population that muscle power is more related to functionality than muscle
strength, which was also found in the subpopulation of sarcopenic elderly in the work of
Balachandran et al 19, in which only the HSC group showed improvement in SPPB. The
questioning about the possible superior benefits of hypertrophy training is valid, since
sarcopenia is a disease with decreased muscle mass, however, the outcome that is directly
important to the patient is functionality, not mass gain 3.Two of the three studies analyzed
isolated effects of training in body composition with conflicting results, showing
necessity of further research to clarify the matter. However, it should be noted that
Balachandran's study 19, which did not find differences in body composition in relation to
the baseline, had a very small sample, which does not allow to affirm the inexistence of
this effect.

5 INTERVENTIONS WITH NUTRITION AND PHYSICAL TRAINING

TABLE 3 HERE
Six trials addressing nutritional and physical interventions were included. A great
heterogeneity can be observed on the studies either of nutritional interventions as physical
training protocols. Kin HK et al compared exercise only, EAA supplementation only,

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combined intervention and a control group. Combined intervention group showed best
results with statistical difference. This same group, in other study, tested isolated tea
catechins versus exercise versus combined intervention. Isolated catechins showed no
change in outcomes. When added to exercises, tea catechins amplified the outcomes of
exercises only, showing the best results in combined intervention. Again, the same group
later performed another study comparing isolated exercise, EAA associated with
catechins supplementation and combined interventions. Within group analysis showed
loss of fat mass, an increase of 17,8% on quadriceps strength in combined therapy, 12,8%
in exercise and 9% in supplementation, however those findings were not statistical
significant between groups. It should be noted that there is no definition of the
pharmacodynamic mechanisms through which the catechins exert their potentialization
of the gains generated by the physical exercise and none of Kim's studies presented a
placebo for nutritional intervention, raising the question whether the benefits of groups
that included nutritional strategy were exclusively due to the placebo effect.
Zdzieblik et al tested collagen supplementation effects in elderly sarcopenic men utilizing
an exercise only group versus a 15g/day collagen supplementation added to the same
exercises routine. The exercises consisted of resistance training of large muscle groups.
The collagen plus exercise group showed higher loss of fat mass and higher increase both
in muscle mass and strength. The study had no control or isocaloric placebo given to the
exercise group and collagen is known to be a protein of low biological value, which raises
questions about the mechanisms through which collagen could generate these effects. It
is impossible to rule out that these benefits are due solely to the placebo effect.
Two papers published by Maltais et al referring to the same study data. In the
study, all elderly overweight sarcopenic men were submitted to resistance training with a
post training supplementation. The subjects were divided in three groups: a high protein
dairy supplementation with chocolate cow milk; a high protein soy supplementation with
chocolate soy beverage added EAA powder; a control with isocaloric rice milk. All
groups showed increase in muscle mass, without statistical difference between groups.
The dairy group had higher decrease in fat mass. It is worth stressing the study had 8-10
patients each group, a fairly low number, which could mask the higher gain of muscle
mass in protein supplementation groups in view of muscle mass gain in soy and dairy
groups are, respectively, 35% and 21% higher than control group.
Rondanelli et al compared effects of whey protein supplementation versus
placebo, both combined with a physical training program. Only the intervention group

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showed better results, with increase in fat free mass (FFM), increase in hand grip strength,
better Katz Index and SF-36. The physical training did not include resistance exercises,
what could explain the outcomes of the exercise plus placebo group.
The analysis of the results of the studies above as a group is challenging, in view
of the discrepancies in them. Not only the nutritional interventions are very
heterogeneous, the physical training is not very similar between studies. However, it is
fair to admit a tendency of better results in combined interventions.Studies with higher
numbers of individuals and standardized interventions are needed to confirm the
superiority of combined over isolated therapy in sarcopenic elderly. However, there is
ample evidence in the general population that increased protein intake, through dietary
supplements or food, potentiates the anabolic effects of resistance training, leading to
increased protein synthesis, muscle mass gain, and strength development. Kim's first
study 21 corroborates this trend, since only the group that associated resistance training
with amino acid supplementation showed significant improvement in knee extension
strength, as well as in the Rondanelli study 26. A similar effect was observed in the other
studies by Kim 22,27, in which training with catechins of tea and / or EAA was performed,
although the mechanisms through which the catechins exert this effect still unclear.
23
Zdzieblik found a similar effect in the association of collagen supplementation with
resistance exercise, however, we recommend caution in the interpretation of this study
since it was not controlled by placebo, so the results found may have been generated by
greater dedication to the training of patients receiving supplementation or by the mere
increase in the caloric intake. Maltais’ studies 24,25, despite an increase in functional tests
with the addition of supplementation, failed to demonstrate an additional strength gain,
perhaps due to the low protein dose used in these studies (up to 13.5g), possibly unable
to overcome the anabolic resistance related to aging.
In summary, despite the methodological heterogeneity, it seems reasonable to
assume that, as in the general population and in the healthy elderly, the population of
sarcopenic elderly also presents benefits in the association of nutritional approach with
resistance training for gains of muscle mass, strength and functional performance. Also,
the low methodological quality of the studies does not allow us to reach a definitive
conclusion.
In addition, considering that, at the moment, there is not a well-defined variable
to evaluate the treatment of sarcopenia, the use of any of the variables presented in these
studies (palmar grip strength, knee extension force, muscle mass, SPPB, quality

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questionnaires life and functionality, isolated functional tests) deserves specific criticism.
For a better interpretation of the results of these studies, we recommend the combined
analysis of all these variables.

6 ELECTROSTIMULATION
TABLE 4 HERE
Kemmler et al developed FORMOsA protocol for the study of electrostimulation
in obese sarcopenic patients, comparing electrostimulation alone, electrostimulation plus
supplement and a control without any intervention. Both intervention groups improved Z
score to sarcopenia and lean mass. Analysis made by Wittmann et al showed the group
with electrostimulation plus supplementation had better results than electrostimulation
alone in relation to fat mass decrease and improvement of Metabolic Syndrome Z-score
(MetS Z-score), calculated by ([50 – HDL-C]/SD – HDL-C) + ([TGs – 150]/SD – TGs)
+ ([FPG – 100]/SD – FPG) + ([WC – 88]/SD – WC) + ([MAP – 100]/SD – MAP), being
HDL-C: High-density lipoprotein cholesterol; SD: standard deviation; TGs:
Triglycerides; FPG: Fasting plasma glucose; WC: Waist circumference; MAP: Mean
arterial pressure. Wei et al tested three different combinations of frequency/time ratios in
the study. The groups were LG (20Hz x 720s), MG (40Hz x 360s), HG (60Hz x 240s)
and a control without intervention. LG and MG groups presented increased in knee
extension isokinetic strength, more pronounced in MG group, but without statistical
difference between groups. However, despite the small number of studies, the results look
promising. Whole body electrostimulation is attractive to treatment of older people with
low functional capacity or any other condition preventing the patient to perform resistance
training with good results. Questions can be raised about the tolerability of the method,
28,29
however, the first two studies had treatment intensity controlled by patient
tolerability, generating positive results. The study by Wei et al 30, despite not describing
tolerability control, reported no loss of follow-up related to cessation of treatment for this
reason, which generates positive expectations. In addition, it is important to consider that
there are no studies comparing this therapy with traditional resistance exercise, which
currently consists of standard therapy, therefore, the electrostimulation is not intended to
replace the resistance training, but to approach the group of patients that are too weak for
traditional approaches. However, more studies are needed to establish electrostimulation

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as a valid and well-founded therapy for sarcopenia, since the research is in the early
stages.

7 CONCLUSION
The small number of studies encompassing treatment of sarcopenic individuals
combined to the small number of individuals in each study and inconsistency
methodology hinders a strong analysis of the subject.That alone prevents us an
unequivocal position in the impact of non-pharmacological interventions of sarcopenia.
However, the available evidences indicate electrostimulation, nutritional intervention and
physical training all present a positive impact. The present evidence could suggest that
combined therapies show better results than isolated approaches. Studies with greater
samples and stronger methodology are required to further support the findings and
conclusion of the present review.

FIGURE LEGENDS

Figure 1: Schematic of the study selection process

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