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Effects of β-hydroxy-β-methylbutyrate (HMB) supplementation in addition to multicomponent exercise in adults older than 70 years living in nursing homes, a cluster randomized placebo-controlled trial: The HEAL study protocol

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Background: Evidence supports the fact that multicomponent exercise and HMB supplementation are, separately, effective in improving older adult's health and palliate functional metabolic diseases in older people. However, the true effect of HMB supplementation combined with a tailored exercise program in frail older adults is still unknown. Thus, the aim of the HEAL (HMB + Exercise = Adults Living longer) study is to assess the effects of the combination of a daily multicomponent exercise and resistance training (VIVIFRAIL program) intervention in addition to HMB supplementation on older adults' health. Methods/design: A 24-week cluster randomized, double-blind, placebo-controlled study will be conducted on 104 adults ≥70 years. Nursing homes will be randomized to either of four groups: Ex-HMB (exercise intervention with HMB), Ex-Plac (exercise intervention with placebo), NoEx-HMB (no exercise intervention with HMB), and Controls (No exercise and no HMB). Intervention groups which include exercise will complete the individualized multicomponent (strength, balance and cardiovascular exercises) training program VIVIFRAIL. Intervention groups which include HMB supplementation will receive a 3 g/daily dose of free acid HMB in powder form. The primary outcome measure is the functional capacity. Secondary outcome measures are muscle strength and power, frailty and fall risk, body composition, biochemical analyses and cardiometabolic risk factor, disability and comorbidity, cognitive function and depression. Discussion: The findings of the HEAL study will help professionals from public health systems to identify cost-effective and innovative actions to improve older people's health and quality of life, and endorse exercise practice in older adults and people living in nursing homes. Trial registration: NCT03827499 ; Date of registration: 01/02/2019.
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S T U D Y P R O T O C O L Open Access
Effects of β-hydroxy-β-methylbutyrate
(HMB) supplementation in addition to
multicomponent exercise in adults older
than 70 years living in nursing homes, a
cluster randomized placebo-controlled trial:
the HEAL study protocol
Javier Courel-Ibáñez
*
, JG Pallarés and on behalf of the HEAL study group
Abstract
Background: Evidence supports the fact that multicomponent exercise and HMB supplementation are, separately,
effective in improving older adults health and palliate functional metabolic diseases in older people. However, the
true effect of HMB supplementation combined with a tailored exercise program in frail older adults is still unknown.
Thus, the aim of the HEAL (HMB + Exercise = Adults Living longer) study is to assess the effects of the combination
of a daily multicomponent exercise and resistance training (VIVIFRAIL program) intervention in addition to HMB
supplementation on older adultshealth.
Methods/design: A 24-week cluster randomized, double-blind, placebo-controlled study will be conducted on 104
adults 70 years. Nursing homes will be randomized to either of four groups: Ex-HMB (exercise intervention with
HMB), Ex-Plac (exercise intervention with placebo), NoEx-HMB (no exercise intervention with HMB), and Controls
(No exercise and no HMB). Intervention groups which include exercise will complete the individualized
multicomponent (strength, balance and cardiovascular exercises) training program VIVIFRAIL. Intervention groups
which include HMB supplementation will receive a 3 g/daily dose of free acid HMB in powder form. The primary
outcome measure is the functional capacity. Secondary outcome measures are muscle strength and power, frailty
and fall risk, body composition, biochemical analyses and cardiometabolic risk factor, disability and comorbidity,
cognitive function and depression.
Discussion: The findings of the HEAL study will help professionals from public health systems to identify cost-
effective and innovative actions to improve older peoples health and quality of life, and endorse exercise practice
in older adults and people living in nursing homes.
Trial registration: NCT03827499; Date of registration: 01/02/2019.
Keywords: Healthy ageing, Physical activity, Physical fitness, Falls, Dynapenia
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reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
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(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
* Correspondence: Javier.courel.ibanez@gmail.com
Human Performance and Sports Science Laboratory, Faculty of Sport
Sciences, University of Murcia, Calle Argentina, 19, 30720 San Javier, Murcia,
Spain
Courel-Ibáñez and Pallarés BMC Geriatrics (2019) 19:188
https://doi.org/10.1186/s12877-019-1200-5
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Background
To date, people are living more years than ever before in
history and the worlds aging is rising at a staggering rate
[1]. Thus, strategies focused on health maintenance for
aging people through exercise and proper nutrition are
required to contribute to lifelong wellbeing and prevent
ageing diseases and chronic illness. Frailty, sarcopenia,
dynapenia and sarcopenic obesity states are the main
metabolic complications in older people and represent a
major public health challenge [24]. A recent estimation
from the Eurostat online database (28 European countries)
suggests increments from 60 to 70% of individuals with
sarcopenia in 2045 affecting 12.9 to 22.3% of people over
65 years old [5]. These diseases are caused by a degenera-
tive loss of muscle mass (muscle wasting), strength and
mobility. The combination of exercise with protein dietary
supplementation is proven to be highly effective to in-
crease muscle mass and strength in older adults [68].
Evidence states that exercise in older people is a main
component in frailty prevention (increases strength and
decreases falls incidence) and functional capacity preserva-
tion (increases mobility and autonomy) [810]. In turn,
weak elders have greater risk of disability, hospitalization,
morbidity and death [3,11]. In addition to a better phys-
ical condition, exercise has a clear impact on psychological
well-being in older people [12]. Although much remains
to be done, the possibility of physical exercise as the new
medication for the twenty-first century is truly inspiring.
The first step of this revolution is that the question is
turning from may I prescribe physical activity for older
people?to what kind of exercise must I prescribe?[13].
Reducing sedentary behaviours and promoting exercise
training in older adults living in nursing homes stands as a
main global challenge [14,15].
Very recently, the ERAMUS+ co-funding VIVIFRAIL
project (http://www.vivifrail.com) has developed a multi-
component exercise program (strength, balance and car-
diovascular exercises), carefully adapted, for improving
functional capacity for older people above 70 years [16].
The program includes a practical guide for testing and
prescribing the physical training according to each spe-
cific condition (serious, moderate, slight or no limitation,
and with or without risk of falling). Furthermore, the
VIVIFRAIL App allows individualsmonitoring and pro-
vides clear instructions to effectively complete the pro-
gram within the everyday environment. Now that long-
term exercise interventions in older adults are more pos-
sible than ever [17], what is now required is to examine
the effectiveness of this program on relevant health and
functional outcomes for older adults and nursing homes
residents [15].
The β-hydroxy-β-methylbutyrate (HMB) dietary is a
bioactive metabolite formed from the decomposition of
leucine, an essential branched-chain amino acid. The
importance of leucine has anti-catabolic properties and
plays an important role in protein metabolism, glucose
homeostasis, insulin action and recovery from exercise
[1820]. A dose of 3 g of HMB dietary supplementation
provides 60 g of leucine, which otherwise would imply
600 g of high biological value protein [21]. The HMB
supplementation is affordable (around 50/kg) and its
consumption is safe with no adverse effects [22,23]. In
older adults > 60 years old, HMB is demonstrated to
have anti-catabolic effect, enhance protein synthesis, at-
tenuate proteolysis, increase muscle mass and decrease
muscle damage [2426]. Despite the fact that HMB effi-
cacy varies [25], a meta-analysis concluded that HMB
supplements contribute to the preservation of muscle
mass in old age [27]. Based on these findings, the sup-
plementation of HMB appears to be an effective strat-
egy to prevent metabolic and physical complications in
ageing (frailty, dynapenia, sarcopenia and sarcopenic
obesity) and preserve health, functional capacity and
strength in older people.
A recent investigation [28] reported for the first time a
significant reduction of 50% in whole body plasma con-
centration of HMB and reductions of 25% on the conver-
sion of leucine to HMB in older adults (~ 65 y-old). At the
moment, there is limited understanding why this happens,
but it seems clear than reductions in HMB conversion are
associated with age [29]. These decrements on high qual-
ity protein synthesis importantly accounted for a decline
in muscle weakness in older people [30]. Hence, the possi-
bility of palliating muscle and functional losses in the age-
ing by HMB supplementation is truly inspiring and
encourages further studies [26,27].
To date, only five Randomized Control Trial (RCT)
studies have examined the effectiveness of exercise train-
ing combined with HMB dietary supplementation in
older adults > 60 years old [3135]. Whereas it seems
clear that HMB supplements contribute to the preserva-
tion of muscle mass in old age, contradictory evidence
on its effects on strength increments [3134] and func-
tional performance [3335] in older adults exists. These
equivocal outcomes may be attributed to the protocols
applied, with discrepancies in the training volume (num-
ber of sessions, time per session, number of reps), inten-
sity (load monitoring and progression) and exercises.
Besides, sample sizes explored are reduced (n< 32)
and only one RCT [32] conducted an exercise inter-
vention > 8 weeks. Consequently, there is a need for
longer and larger studies to fully determine the potential
effects of HMB supplementation on physical performance,
translating to a functional benefit [34]. In this sense, the
HEAL (HMB + Exercise = Adults Living longer) study will
be the first RCT conducting a specific, individualized,
multicomponent exercise intervention for the older adult
population such as the VIVIFRAIL [16]. Because this
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evidence-based program has been proven as effective and
safe in adults aged 65 years or over [17], it represents an
excellent opportunity to determine the true effects of
HMB supplementation in enhancing training perform-
ance. Furthermore, the promising results of HMB sup-
plementation to mitigate age-related cognitive deficits
[36,37] and the lack of studies exploring its impact on
people with very limited or no mobility [25,38]encourage
adopting this strategy in vulnerable people such as older
nursing homes patients. Therefore, the aim of the HEAL
study is to assess the effects of the combination of a daily
multicomponent exercise and resistance training (VIVIF-
RAIL program) in addition to HMB supplementation on
older adultshealth.
Methods/design
Study design and settings
This is a cluster randomized, placebo-controlled study
with four parallel groups. The study has been designed
to determine the efficacy of HMB supplementation in
addition to 24-weeks of multicomponent exercise and
resistance training (the VIVIFRAIL program) in adults
70 years. Flowchart of the trial is shown in Fig. 1.
Enrollment, intervention allocation, follow-up, and data
analysis will be conducted according to the SPIRIT
(Standard Protocol Items: Recommendations for Inter-
ventional Trials) statement [39,40].
Eligibility criteria
Inclusion criteria for enrollment will be: men and
women aged 70 years, be able to follow an active phys-
ical rehabilitation program and voluntary participation.
Enrollment of cognitively impaired older adults will re-
quire proxy permission (family member or caregiver)
[41]. All potential participants will provide a medical
history and undergo a medical examination to identify
cardiovascular or metabolic conditions that would ex-
clude participation (for full list, see Table 1).
Sample size
The required sample size will be determined on the basis
on the functional capacity, using the Short Physical Per-
formance Battery (SPPB) [42]. According to previous re-
search on subjects with similar characteristics [17], a
clinically relevant change is about 1.5 ± 1.0 points incre-
ments after 12-weeks. Differences of 2 point in total SPBB
Fig. 1 Flowchart of the trial
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with a standard deviation of 3 points with a power of 80%
and αof 0.05 can be estimated with 20 participants using
the R software (v. 3.2.1) and the package samplesize.As-
suming a maximum loss of follow-up of 30%, we will re-
cruit 26 adults 70 years per group (n= 104). Similar
interventions had an adherence rate of 75%, and a mean
attendance of 80% to the sessions [17]. Therefore, the
current estimation is realistic and affordable.
Recruitment process and measurements procedures
A schematic overview of the outcomes, measures and
timeline is shown in Table 2. Recruitment will be carried
out in nursing homes in Murcia (Spain) located within a
radius of 15 km or less than 20 min by car from the assess-
ment sites. There are over 15 nursing homes among this
radius that ensure recruitment of enough participants. Ini-
tial assessment will be carried out in the Human Perform-
ance & Sports Science Lab, Faculty of Sport Sciences,
University of Murcia (Murcia, Spain). Body composition
and biochemical analyses will be performed in the Medical
Centre Virgen de la Caridad (Murcia, Spain). Participants
will be scheduled in small groups to be taken to the
laboratory for the initial assessment and medical centre.
Dependent people will be transported in adapted vehicles
with a caregiver. All measurements will be performed
under technical and medical supervision.
The VIVIFRAIL exercise program will be administered
by a training team (experienced and qualified personal
trainers and physical therapists), under nursing supervi-
sion. After the initial assessment and one week before
the start of the intervention, participants will attend a
familiarization session at the place in which the testing
and training will be conducted.
Randomization and blinding
After recruitment and baseline measurements, nursing
home will be randomized to either of the four groups in
clusters, according to a computer-generated sequence
using the Sealed Envelope Ltd. online system. The clus-
ter design is chosen to prevent influences on partici-
pantsbehaviours within a given nursing home unit. A
stratified randomization will be used according to their
initial functional status (A, B, C or D, see Fig. 2) to re-
duce imbalance between groups. The allocation will be
concealed in a password protected computer file. Given
the nature of the treatment (i.e., daily exercise and diet-
ary supplementation program), participants will be aware
of their group allocation. Outcome assessors and data
analysts will be blinded to the treatment group assign-
ment. Assessors will not be involved in intervention ac-
tivities. A dedicated protocol will be defined to protect
the confidentiality of data.
Interventions
Dietary supplementation
Intervention groups including HMB supplementation
(Ex-HMB and NoEx-HMB) will receive a 3 g daily dose
of free acid HMB in powder form (myprotein.co.uk,
Cheadle, Cheshire, UK) dissolved freely into 250 mL of
water during a 24-week intervention [34,43]. Nursing
staff will supply the doses as a part of their daily diet
routine. Ex-Plac and Control groups will receive stevio-
side. Supplements will be packaged in indistinguishable
envelopes and boxes, with an identification code for each
participant and group. The compliance of supplementa-
tion will be monitored and ensured by medical staff
working at the nursing home. Oral supplement and
Vitamin D will be provided to maintain an acceptable
nutritional status.
Multicomponent physical exercise program
Intervention groups including exercise (Ex-HMB and
Ex-Plac) will complete an individualized multicompo-
nent training program, VIVIFRAIL [16], 5 days a
week during 24 weeks. Free on-line resources and
program guidelines are available online (http://www.
vivifrail.com/resources). The VIVIFRAIL program has
been carefully designed for people 70 years and in-
cludes six programs or Passportsadapted for each
participants condition according to their functional
limitation (serious [A], moderate [B], slight [C] and
no limitation [D]) and risk of falling (B+ and C+).
Individualization is made based on the baseline test-
ing scores (i.e., the VIVIFRAIL test). Each program
combines strength, power, balance, walking, stretching
and cardiovascular exercises, in the named VIVIF-
RAIL Wheel. Training sessions are daily and weekly
organized (type of exercise, steps and reps) in
Table 1 Exclusion criteria for the HEAL study
Exclusion criteria
- Acute heart attack (recent 36 months) or unstable angina
- Uncontrolled atrial or ventricular arrhythmias
- Aortic dissecting aneurysm
- Severe aortic stenosis
- Acute endocarditis / pericarditis
- Uncontrolled high blood pressure (> 180/100 mmHg)
- Acute thromboembolism
- Acute or severe heart failure
- Acute or severe respiratory failure
- Uncontrolled postural hypotension
- Uncontrolled acute decompensated diabetes mellitus
or low blood sugar
- A recent fracture in the last month.
- Coincident participation in any intervention trial
- HMB contraindication, intolerance, or allergy
- Have regularly performed exercise (> 20min > 3days/week)
in the last 3 months
- Malignant diseases (exceptions: basal or squamous-cell
skin carcinoma or carcinoma in situ of the uterine cervix)
- Revascularization within 1 year
- Severe loss of vision, hearing, or communicative ability
- Conditions preventing cooperation
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individual Passports. A summary of the exercise
program is shown in Fig. 2.
The VIVIFRAIL program has a free mobile app avail-
able on iOS and Android, the latest version of which,
(launched in January, 2019) allows the recording of the
results of the test to automatically assign each partici-
pant to a training program. The App includes a calendar
with a daily progression, training monitoring and rate of
perceiving effort assessment.
Outcome measures
Functional capacity (primary outcome): The Short Phys-
ical Performance Battery (SPPB) [42] scores from 1 (low
mobility) and 12 (full mobility) points based on three
Table 2 Schedule of enrollment, interventions, and assessments
TIMEPOINT Enrollment
-t
1
Allocation
0
Baseline
t
1
Intervention Follow-up
12th week post
baseline
t
2
Close-out
25th week post
baseline
t
3
ENROLLMENT
Eligibility screen
Informed consent
Randomized Allocation
INTERVENTION
Ex-HMB
NoEx-HMB
Ex-Plac
Control
ASSESSMENTS
Functional capacity (primary outcome)
SPPB: Gait speed, balance, and 5-sit-to-stand ✓✓
Muscle strength and power
Grip strength ✓✓
1RM seated leg press ✓✓
1RM vertical bench press ✓✓
Sit-to-stand muscle power ✓✓
Frailty and fall risk
Frailty phenotype ✓✓
Falls history ✓✓
Fall risk assessment ✓✓
Body composition ✓✓
Blood pressure and resting heart rate ✓✓
Haematology ✓✓
Biochemical analyses ✓✓
Nutritional status ✓✓
Sarcopenia ✓✓
Disability and comorbidity
Barthel index ✓✓
Lawton index ✓✓
Comorbidity ✓✓
Cognitive function ✓✓
Depression ✓✓
Ex: 12-week of VIVIFRAIL multicomponent exercise program. HMB: dietary supplementation of HMB. Plac Placebo. SPPB Short Physical Performance Battery; 1RM
one-repetition maximum
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tests: balance tests (tandem, semi-tandem and one foot
next to the other), gait speed and 5-sit-to-stand test.
The SPPB has been extensively administrated in older
adults [17,44]. The resulting scores are part of the
VIVIFRAIL test to determine each individualsphys-
ical exercise program [16].
Maximal muscle strength and power output: grip
strength measurement (Jamar digital dynamometer,
NexGen ergonomics, Pointe Claire, Quebec, Canada)
[45], one repetition maximum (1RM) seated leg press
and vertical bench press strength (Salter Ltd., Barce-
lona, Spain) and muscle power (T-Force Dynamic
Fig. 2 Summary of the VIVIFRAIL multicomponent exercise intervention program. Individualization based on baseline testing scores. Full
guidelines: www.vivifrail.com
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Measurement System, Ergotech Consulting SL,
Murcia, Spain) [46,47], sit-to-stand muscle power
[48], in the same order with a 3-min rest between
tests in order to diminish fatigue [49].
Frailty and fall risk: frailty phenotype determination
[50], complete falls history and fall risk assessment,
physical examination [16].
Body composition: Body composition will be assessed
using dual-energy x-ray absorptiometry - DXA (Hologic,
Bedford, MA; Discovery A), between 6:00 AM and 9:00
AM after a 10-h fast and after participants had voided
their bladders [51].
Blood pressure and resting heart rate: Systolic and dia-
stolic blood pressure, as well as resting heart rate will be
measured after 10 min of rest, two times 2 min apart
(M6 upper arm blood pressure monitor Omron. Omron
Health Care Europe B.V. Hoofddorp, The Netherlands).
Haematology: Erythrocyte count, haematocrit, haemo-
globin, platelets, leukocytes and erythrocyte mean cor-
puscular volume will be quantified by Coulter Cell
Counter.
Biochemical analyses: glucose, high-density lipoprotein
(HDL), total cholesterol (TC), triglycerides (TG), glyco-
sylated haemoglobin (HbA
1c
), thyroid-stimulating hormone
(TSH), C-reactive protein (CRP), albumin, prealbumine,
transferrin, insulin-like growth factors (IGF-1 and IGFBP-
3), creatine phosphokinase (CPK) and 25-hydroxyvitamin
D (25[OH]D). Blood analysis will be conducted with stand-
ard methods using an autoanalyzer. Insulin sensitivity will
be derived from the homeostatic model assessment for in-
sulin resistance (HOMA-IR).
Nutritional status: The Mini-Nutritional Assessment
(MNA-SF) [52] will be used to evaluate nutrition status
and malnutrition risk.
Sarcopenia: The SARC-F will be used to diagnose sar-
copenia [53].
Disability and comorbidity: Barthel index [54] and
Lawton index [55] will be used to assess disability in
basic activities and instrumental activities of daily living,
respectively. Given the limitations of comorbidity in-
dexes in older people [56], we will consider comorbidity
when a participant presents two or more geriatric syn-
dromes from a list of selected geriatric syndromes, as
previously proposed [57].
Cognitive function and depression: the validated Spanish
version of the Mini-Mental State Examination (MMSE)
[58] will be used to assess cognitive function. Depression
will be assess with the Spanish version of the 15-item Yea-
savage geriatric depression scale [59].
Statistical analysis
Analysis will be performed on participants who
attended at least 80% the training sessions and
completed all the measurements. Treatment effects
will be tested using generalized linear models. All
models will be adjusted for the baseline outcome
value and repeated adjusting for gender, age, the
group effect, and confounding factors.
Trial registration
The trial was registered on ClinicalTrials.gov (identifier:
NCT03827499) on 01/02/2019.
Discussion
This paper outlines the protocol for a randomized,
placebo-controlled study to determine the efficacy of
HMB supplementation in addition to 24-weeks of
multicomponent exercise and resistance training in
adults 70 years old. At the time of writing, the
study was ongoing (recruitment status). Baseline as-
sessment is planned to started in March 2019.
Maintaining old peoples health and protecting
them from frailty, muscle waist and cardiovascular
diseases will save billions in public care costs by
lengthening peoples healthy life, reducing the loss of
income due to premature death and reducing nursing
dependency [60]. Evidence supports that multicompo-
nent exercise [810,17,61] and HMB supplementa-
tion [2426] are effective in improving older adults
health and palliating functional metabolic diseases in
older people. However, thetrueeffectofHMBsup-
plementation combined with a tailored exercise pro-
gram is still unknown. Just a few trials have
investigated the combination of both [3133], show-
ing promising results. Moreover, the implementation
of the new VIVIFRAIL multicomponent exercise pro-
gram for frail old people in addition to HMB supple-
mentation is still to be done.
The study results will be of high relevance to old
people living in nursing homes and their health care
providers. If the benefits of the combined VIVIFRAIL
and HMB are proven, this could be an alternative man-
agement strategy to consider in nursing homes with
older adults and people with functional metabolic dis-
eases and muscle-wasting conditions. In addition, the
current exercise intervention is inexpensive and freely
available (http://www.vivifrail.com/), which permits its
replication. The findings of the HEAL study will help
professionals from public health systems to identify cost-
effective and innovative actions to improve older peo-
ples health and quality of life, and endorse exercise
practice in older adults living in nursing homes.
Abbreviations
1RM: One-repetition maximum; CRP: C-reactive protein; DXA: Dual-energy x-
ray absorptiometry; Ex-HMB: Exercise intervention with HMB; Ex-Plac: Exercise
intervention with placebo; HDL: High-density lipoprotein; HMB: β-hydroxy-β-
methylbutyrate; MMSE: Mini-Mental State Examination; NoEx-HMB: No
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exercise intervention with HMB; RCT: Randomized Control Trial;
SPIRIT: Standard Protocol Items: Recommendations for Interventional Trials;
SPPB: Short Physical Performance Battery; TC: Total cholesterol;
TG: Triglycerides; TSH: Thyroid-stimulating hormone
Acknowledgements
*The HEAL study group:
Jesús García Pallarés Human Performance and Sports Science Laboratory,
Department of Physical Activity and Sport, Faculty of Sport Sciences,
University of Murcia, Spain.
Javier Courel Ibáñez Human Performance and Sports Science Laboratory,
Department of Physical Activity and Sport, Faculty of Sport Sciences,
University of Murcia, Spain.
Ricardo Morán Navarro Human Performance and Sports Science Laboratory,
Department of Physical Activity and Sport, Faculty of Sport Sciences,
University of Murcia, Spain.
Elena Saura Guillén Endocrinology and Nutrition Service, University
Hospital Virgen de la Arrixaca, Murcia, Spain.
Alejandro Martínez Cava Human Performance and Sports Science
Laboratory, Department of Physical Activity and Sport, Faculty of Sport
Sciences, University of Murcia, Spain.
Alejandro Sánchez Pay Human Performance and Sports Science Laboratory,
Department of Physical Activity and Sport, Faculty of Sport Sciences,
University of Murcia, Spain.
Ángel Buendía Romero Faculty of Sport Sciences, University of Murcia, Spain.
Silverio García Conesa Faculty of Sport Sciences, University of Murcia, Spain.
Authorscontributions
JGP contributed in the conception of the idea for the study. JCI and JGP
contributed in the development of the protocol, organization and writing
the manuscript. All the authors read the draft, made contributions and
approved the final manuscript.
Funding
This protocol has been peer-reviewed and funded by the Autonomous Com-
munity of the Region of Murcia, Regional Program for the Promotion of Sci-
entific and Technical Research (Action Plan 2018), Seneca Foundation-
Agency of Science and Technology, Region of Murcia (ID: 20872/PI/18).
Availability of data and materials
Data are not available due to EU General Data Protection Regulation. Please,
contact the corresponding author if you are interested in study materials.
Ethics approval and consent to participate
This study was reviewed and approved by the Ethics Commission of the
University of Murcia, Spain (code: 2131/2018). All participants will sign an
informed consent according to the Declaration of Helsinki prior to data
collection.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Received: 9 February 2019 Accepted: 30 June 2019
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... Experimental Gerontology xxx (xxxx) 111521 analysis revealed a small effect size of HMB and HMB-containing supplements in increasing muscle mass and strength (Bear et al., 2019). An RCT investigating the effects of HMB supplementation combined with an exercise program in older persons (≥70 y) living in nursing homes is ongoing (Courel-Ibanez et al., 2019). Similar to the findings on leucine, an umbrella review found strong effects of HMB on muscle mass in older persons without a clear effect on muscle strength or physical performance. ...
Article
Full-text available
Old age is associated with declines in bone density and muscle mass and function, which predisposes to mobility disability, falls, and fractures. Poor nutritional status, a risk factor for several age-related pathologies, becomes prevalent in old age and contributes to the structural and functional changes of the musculoskeletal system that increases the risk of osteoporosis, sarcopenia, osteosarcopenia, and physical frailty. The biological mechanisms underpinning these pathologies often overlap and include loss of proteostasis, impaired redox functioning, and chronic low-grade inflammation. Thus, provision of nutrients with anabolic/anticatabolic, antioxidant, and anti-inflammatory properties may be an effective strategy to offset these age-related pathologies. We searched PUBMED for pre-clinical and clinical work examining the effects of nutrients with a combined effect on muscle and bone. This review summarizes recent evidence on the mechanisms of action and potential clinical use of nutrients that concomitantly improve muscle and bone health in older persons.
... Twenty-four participants underwent a medical examination to identify cardiovascular or metabolic conditions that would exclude participation, met the inclusion criteria according to the HEAL study protocol, 28 were informed of the characteristics of the study, and provided signed consent. Sarcopenia was identified according to the Foundation for the National Institutes of Health diagnosis algorithm 29 : gait speed <0.8 m/s, handgrip strength <26 kg for men and <16 kg for women, and appendicular lean mass (aLM) adjusted by body mass index (BMI) < 0.789 in men and <0.512 in women. ...
Article
Objectives: We aimed to determine whether the benefits of long (24 weeks) and short (4 weeks) training programs persisted after short (6 weeks) and long (14 weeks) periods of inactivity in elderly nursing home residents with sarcopenia. Design: Multicenter randomized trial. Intervention: The Vivifrail tailored, multicomponent exercise programme (http://vivifrail.com) was conducted to individually prescribe exercise for frail older adults, depending on their functional capacity. The training included four levels combining strength/power, balance, flexibility and cardiovascular endurance exercises. Setting and Participants: Twenty-four institutionalized older adults (87.1±7.1 years, 58.3% women) diagnosed with sarcopenia were allocated into two groups: the Long Training-Short Detraining (LT-SD) group completed 24 weeks of supervised Vivifrail training followed by 6 weeks of detraining; the Short Training-Long Detraining (ST-LD) group completed 4 weeks of training and 14 weeks of detraining. Measures: Changes in functional capacity and strength were evaluated at baseline, and after short and long training and detraining periods. Results: Benefits after short and long exercise interventions persisted when compared with baseline. Vivifrail training was highly effective in the short term (4 weeks) in increasing functional and strength performance (effects size=0.32–1.44, p<0.044) with the exception of handgrip strength. Continued training during 24 weeks produced 10–20% additional improvements (p<0.036). Frailty status was reversed in 36% of participants, with 59% achieving high self-autonomy. Detraining resulted in a 10–25% loss of strength and functional capacity even after 24 weeks of training (effects size=0.24–0.92, p<0.039). Conclusions and Implications: Intermittent strategies such as 4 weeks of supervised exercise 3 times yearly with no more than 14 weeks of inactivity between exercise periods appears as an efficient solution to the global challenge of maintaining functional capacity and can even reverse frailty in vulnerable institutionalized older adults.
... National Institute for Health and Care Excellence (NICE) recommended guidance for the treatment of HMB The emphasis has shifted from quantitative measurement to overall quality of life impact assessment. However, meaning the understanding of the situations of women life in relation to their goals, Advancements, Novel Researches and Best Practices in Nursing and health care and health care desires, and values within their cultural value (Courel, Pallares, 2019& El-Sabaa, Ibrahim, Hassan, 2013& Gokyildiz, Aslan, Beji, Mecdi, 2013. ...
... A recent systematic review demonstrated that HMB may have a small positive impact on fat-free mass in athletes and no significant effect on body mass or fat mass [59]. In the elderly, HMB supplements have been proven to preserve muscle mass, but have conflicting evidence on muscle strength and functional performance [60][61][62]. There is some evidence that HMB reduces exerciseinduced muscle damage, as evidenced by decrease in indirect markers like lactate dehydrogenase and creatine kinase [63]. ...
Article
Full-text available
Purpose of Review Decades of research on nutrition and exercise on athletes and bodybuilders has yielded various strategies to promote anabolism and improve muscle health and growth. We reviewed these interventions in the context of muscle loss in critically ill patients. Recent Findings For critically ill patients, ensuring optimum protein intake is important, potentially using a whey-containing source and supplemented with vitamin D and leucine. Agents like hydroxyl β-methylbutyrate and creatine can be used to promote muscle synthesis. Polyunsaturated fatty acids stimulate muscle production as well as have anti-inflammatory properties that may be useful in critical illness. Adjuncts like oxandralone promote anabolism. Resistance training has shown mixed results in the ICU setting but needs to be explored further with specific outcomes. Summary Critically ill patients suffer from severe proteolysis during hospitalization as well as persistent inflammation, immunosuppression, and catabolism syndrome after discharge. High protein supplementation, ergogenic aids, anti-inflammatories, and anabolic adjuncts have shown potential in alleviating muscle loss and should be used in intensive care units to optimize patient recovery.
... Thus, it seems that HMB supplementation in addition to exercise would be particularly effective to optimize physical rehabilitation treatments and accelerate mobility recovery in frail people and muscle wasting conditions. Although evidence supporting the positive impact of HMB to enhance exercise training adaptations and increase health benefits in frail or sarcopenic people is lacking, the results of ongoing clinical trials [54][55][56] will likely provide additional evidence in the near future to support treatment choices for older people. ...
Article
Full-text available
Both regular exercise training and beta-hydroxy-beta-methylbutyrate (HMB) supplementation are shown as effective treatments to delay or reverse frailty and reduce cognitive impairment in older people. However, there is very little evidence on the true benefits of combining both strategies. The aim of this meta-analysis was to quantify the effects of exercise in addition to HMB supplementation, on physical and cognitive health in older adults. Data from 10 randomized controlled trials (RCTs) investigating the effect of HMB supplementation and physical function in adults aged 50 years or older were analyzed, involving 384 participants. Results showed that HMB supplementation in addition to physical exercise has no or fairly low impact in improving body composition, muscle strength, or physical performance in adults aged 50 to 80 years, compared to exercise alone. There is a gap of knowledge on the beneficial effects of HMB combined with exercise to preserve cognitive functions in aging and age-related neurodegenerative diseases. Future RCTs are needed to refine treatment choices combining HMB and exercises for older people in particular populations, ages, and health status. Specifically, interventions in older adults aged 80 years or older, with cognitive impairment, frailty, or limited mobility are required.
Article
We aimed to analyze the isometric knee extension test (IKE) test in terms of i) intra- and inter-session repeatability, and ii) relationship with functional and body composition factors of sarcopenia among institutionalized older adults. Thirteen institutionalized older adults (age = 87 ± 10 years, body mass [BM] = 73.1 ± 10.9 kg, body mass index [BMI] = 28.5 ± 3.8 kg·m2) were recruited from a nursing home. Variability of maximal isometric force registered in three IKE trials performed on the same day was used to examine intra-session repeatability, whereas inter-session repeatability was analyzed by comparing maximal isometric force from two different days. Furthermore, functional (Handgrip, 6-m Gait Speed, Time Up and Go [TUG], and Sit-to-stand tests) and body composition (appendicular lean mass adjusted by BMI, ALM/BMI) evaluations were conducted. Statistics included the intraclass correlation coefficient (ICC) and the standard error of measurement (SEM), expressed in both absolute (N·kg-1) and relative terms (coefficient of variation, CV = 100 × SEM / mean). High to very high intra-session repeatability was found for both the dominant and non-dominant legs (CV ≤ 6.0%, ICC ≥ 0.989). Similarly, both legs showed high inter-session repeatability (SEM ≤ 0.26 N·kg-1, ICC ≥ 0.959). On the other hand, significant relationships were found between Dominant and Non-dominant IKE tests and 6-m Gait Speed (r = 0.77; r = 0.58), ALM/BMI (r = 0.62; r = 0.58), and Non-dominant Handgrip/BM (r = 0.60; r = 0.68). In addition, a significant association was found between Dominant IKE/BM and TUG (r = -0.74), as well as between Non-dominant IKE/BM and Dominant Handgrip/BM (r = 0.67). These findings suggest that the IKE test is a repeatable and suitable strategy for lower-limb screening in institutionalized older adults.
Article
Purpose of review: The interest in the use of beta-hydroxy-beta-methylbutyrate (HMB) as an intervention to prevent and treat sarcopenia has increased over recent years. The purpose of this review is to explore recent evidence pertaining to the mechanism of action of HMB and how this may influence changes in lean mass and strength in older persons who are both hospitalized and living in the community. Recent findings: No new studies have been published over the last 2 years investigating the effect of HMB in older persons who are hospitalized, aside from one posthoc analysis of a randomized controlled trial exploring the effect of a high protein oral nutrition supplement containing HMB on handgrip strength and nutritional status. Three studies recruiting community-dwelling older adults have been published, but results are influenced by suboptimal methodological quality. Summary: Recent data suggest the need for high-quality studies investigating the effectiveness of HMB to improve outcomes related to sarcopenia in both hospitalized and community-dwelling older persons.
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This is a randomized trial on sarcopenic older adults aged ≥ 75 years living in nursing homes. Participants completed 4 weeks of the tailored multicomponent exercise training program Vivifrail© (www.vivifrail.com).One group continued the intervention for a further 14 weeks, while the other interrupted the intervention for 14 weeks because of the COVID-19 lockdown. Functional capacity and strength were evaluated at baseline, after 4 weeks of exercise and after 14 weeks of training or detraining. This study is part of an ongoing multicenter trial (NCT03827499). The main findings are: i) The Vivifrail© multicomponent tailored exercise program was very effective in the short-term (4 weeks) and produced a similar response to training in two groups of sarcopenic, frail and institutionalized adults aged ≥ 75 years from two different nursing homes. This uniform improvement demonstrates the robustness of the Vivifrail© tailored prescription guidelines (http://vivifrail.com/resources/); ii) short-term health improvements after 4 weeks of Vivifrail© seemed to persist after 14 weeks of inactivity due to COVID-19 confinement, and may have prevented severe functional decline and strength loss in institutionalized older adults; iii) while overall functional capacity and strength declined along the 14-week confinement, the benefits of the previous exercise training persisted, with older adults in a better physical condition as compared with baseline; iv) frailty reversion (i.e., recovery of autonomy) after 4 weeks of exercise was mostly maintained during the 14-week training cessation period
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This study determined the effects of a 4-week individualized multicomponent exercise program (Vivifrail) on physical frailty and functional disability in older adults living in nursing homes. Fourteen institutionalized older adults (aged 81.7 ± 9.7 years) volunteered to completed 4 weeks of the individualized Vivifrail exercise program (5 days a week) according to their initial level: A, disability; B, frailty; C, pre-frailty and D, robust. Training sessions were directed by strength and conditioning trainers. Eleven participants completed the pre and post evaluations with very high levels of attendance (96% of the training sessions). Functional capacity (SPPB scores) significantly improved in all the participants (+48.2%, p < 0.001) and tests: sit-to-stand (24.1% faster, p = 0.003), gait speed 4 m (9.8% faster, p = 0.033) and 6 m (7.2% faster, p = 0.017) and Up and Go (11.2% faster, p = 0.004). Disability and sarcopenia decreased significantly (SARC-F, p = 0.026; Lawton index, p = 0.013). People with initial levels of disability (A), frailty (B) and pre-fragility (C) shown the greatest improvements. Six of the nine participants who started with physical frailty or pre-frailty status (66.7%) reversed this condition after the intervention. In addition, 33% of participants with disability, who were unable to perform the functional tests (sit-stand and walk), became able to complete them after the intervention. These important benefits found in such a shorter period of time (4 weeks) could be related to three key elements: individualization of the program, daily frequency and face-to-face coaching motivation by physical conditioning professionals.
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En este estudio se determinaron los efectos de un programa de ejercicio multicomponente individualizado de 4 semanas (Vivifrail) sobre la fragilidad física y la discapacidad funcional en adultos mayores que viven en hogares de ancianos. Catorce personas institucionalizadas (edad 81,7 ± 9,7 años) se ofrecieron voluntarios para completar 4 semanas del programa de ejercicio individualizado Vivifrail (5 días a la semana) de acuerdo con su nivel inicial: A, discapacidad; B, fragilidad; C, pre-fragilidad y D, robusto. Los entrenamientos fueron dirigidos por educadores físico-deportivos titulados. Once participantes completaron las 4 semanas con niveles muy altos de asistencia (96%). La capacidad funcional (puntuación del SPPB) mejoró en todos los participantes (+46,6%, p < 0,001, ES = 0,79) y tests: levantarse de la silla (45,6% faster, p = 0,003, ES = 1,43), velocidad de marcha 4 m (19,3% faster, p = 0,033, ES = 0,38) y test Timed Up-and-Go (23,2% faster, p = 0,004, ES = 0,35). La discapacidad y sarcopenia disminuyeron significativamente (SARC-F, p = 0,026, ES = 0,59; Lawton index, p = 0,013, ES = 0,87). Las personas que empezaron con niveles de discapacidad (A), fragilidad (B) y pre-fragilidad (C) mostraron mejores resultados. Seis de los nueve participantes que comenzaron con fragilidad física o pre-fragilidad (66,7%) revirtieron esta condición tras la intervención. Además, el 33% de los participantes que fueron incapaces de realizar las pruebas funcionales (sentarse, levantase y caminar) al inicio, pudieron completarlas tras la intervención. Estos importantes beneficios en tan poco tiempo (4 semanas) podrían estar relacionados con tres elementos clave: individualización del programa, frecuencia diaria y motivación del entrenamiento dirigido. En este estudio se determinaron los efectos de un programa de ejercicio multicomponente individualizado de 4 semanas (Vivifrail) sobre la fragilidad física y la discapacidad funcional en adultos mayores que viven en hogares de ancianos. Catorce personas institucionalizadas (edad 81,7 ± 9,7 años) se ofrecieron voluntarios para completar 4 semanas del programa de ejercicio individualizado Vivifrail (5 días a la semana) de acuerdo con su nivel inicial: A, discapacidad; B, fragilidad; C, pre-fragilidad y D, robusto. Los entrenamientos fueron dirigidos por educadores físico-deportivos titulados. Once participantes completaron las 4 semanas con niveles muy altos de asistencia (96%). La capacidad funcional (puntuación del SPPB) mejoró en todos los participantes (+46,6%, p < 0,001, ES = 0,79) y tests: levantarse de la silla (45,6% faster, p = 0,003, ES = 1,43), velocidad de marcha 4 m (19,3% faster, p = 0,033, ES = 0,38) y test Timed Up-and-Go (23,2% faster, p = 0,004, ES = 0,35). La discapacidad y sarcopenia disminuyeron significativamente (SARC-F, p = 0,026, ES = 0,59; Lawton index, p = 0,013, ES = 0,87). Las personas que empezaron con niveles de discapacidad (A), fragilidad (B) y pre-fragilidad (C) mostraron mejores resultados. Seis de los nueve participantes que comenzaron con fragilidad física o pre-fragilidad (66,7%) revirtieron esta condición tras la intervención. Además, el 33% de los participantes que fueron incapaces de realizar las pruebas funcionales (sentarse, levantase y caminar) al inicio, pudieron completarlas tras la intervención. Estos importantes beneficios en tan poco tiempo (4 semanas) podrían estar relacionados con tres elementos clave: individualización del programa, frecuencia diaria y motivación del entrenamiento dirigido. Neste estudo, foram determinados os efeitos de um programa individualizado de exercícios multicomponentes de quatro semanas (Vivifrail) sobre a fragilidade física e a incapacidade funcional em idosos residentes em casas de repouso. Quatorze indivíduos institucionalizados (idade 81,7 ± 9,7 anos) se voluntariaram para completar 4 semanas do programa de exercícios individualizado Vivifrail (5 dias por semana), de acordo com seu nível inicial: A, incapacidade; B, fragilidade; C, pré-fragilidade e D, robusto. Os treinamentos foram conduzidos por educadores físicos e esportivos certificados. Onze participantes completaram as 4 semanas com níveis muito altos de participação (96%). A capacidade funcional (escore SPPB) melhorou em todos os participantes (+46,6%, p < 0,001, ES = 0,79) e testes: levantar da cadeira (45,6% faster, p = 0,003, ES = 1,43), velocidade de caminhada 4m (19.3% faster, p = 0,033, ES = 0,38) e 6 m (19,3% faster, p = 0,033, ES = 0,38) e teste Timed Up and Go (23,2% faster, p = 0,004, ES = 0,35). Incapacidade e sarcopenia diminuíram significativamente (SARC-F, p = 0,026, ES = 0,59; Lawton index, p = 0,013, ES = 0,87). Pessoas que iniciaram com níveis de incapacidade (A), fragilidade (B) e pré-fragilidade (C) apresentaram melhores resultados. Seis dos nove participantes que iniciaram com a condição física ou pré-fragilidade (66,7%) reverteram essa condição após a intervenção. Além disso, 33% dos participantes que não conseguiram realizar os testes funcionais (sentar, levantar e andar) na linha de base, conseguiram concluí-los após a intervenção. Esses importantes benefícios em tão pouco tempo (4 semanas) podem estar relacionados a três elementos principais: individualização do programa, frequência diária e motivação do treinamento direcionado.
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Age-related sarcopenia and dynapenia are associated with frailty and metabolic diseases Resistance exercise training (RET) adjuvant to evidence-based nutritional intervention(s) have been shown as mitigating strategies. Given that b-hydroxy-b-methyl-butyrate (HMB) supplementation during RET improves lean body mass in younger humans, and that we have shown that HMB acutely stimulates muscle protein synthesis (MPS) and inhibits breakdown; we hypothesized that chronic supplementation of HMB free acid (HMB-FA) would enhance MPS and muscle mass/function in response to RET in older people. We recruited 16 healthy older men (Placebo (PLA): 68.5 ± 1.0 y, HMB-FA: 67.8 ± 1.15 y) for a randomised double-blind-placebo controlled trial (HMB-FA 3 x 1 g/day vs. PLA) involving a 6-week unilateral progressive RET regime (6 x 8 repetitions, 75% 1-RM, 3 . wk-1). Deuterium oxide (D2O) dosing was performed over the first two weeks (0-2 wk) and last two weeks (4-6 wk) with bilateral vastus lateralis (VL) biopsies at 0-2 and 4-6 wk (each time 75 ± 2 min after a single bout of resistance exercise (RE)) for quantification of early and later MPS responses and post-RE myogenic gene expression. Thigh lean mass (TLM) was measured by DXA, VL thickness and architecture (fibre length and pennation angle)by ultrasound at 0/3/6 wk, and strength by knee extensor 1-RM testing and MVC by isokinetic dynamometry (approx. every 10 days). RET induced strength increases (1-RM) in the exercised leg of both groups (398 ± 22N to 499 ± 30N HMB-FA vs. 396 ± 29N to 510 ± 43N PLA (both P < 0.05)). In addition, maximal voluntary contraction (MVC) also increased (179 ± 12 Nm to 203 ± 12 Nm HMB-FA vs. 185 ± 10 Nm to 217 ± 11 Nm PLA (both P < 0.05); with no group differences. VL muscle thickness increased significantly in the exercised leg in both groups, with no group differences. TLM (by DXA) rose to significance only in the HMB-FA group (by 5.8%e5734 ± 245 g p ¼ 0.015 vs. 3.0% to 5644 ± 323 g P ¼ 0.06 in PLA). MPS remained unchanged in the untrained legs (UT) 0e2 weeks being 1.06 ± 0.08%.d-1 (HMB-FA) and 1.14 ± 0.09%.d-1 (PLA), the trained legs (T) exhibited increased MPS in the HMB-FA group only at 0-2 weeks (1.39 ± 0.10%.d-1, P < 0.05) compared with UT: but was not different at 4e6-weeks: 1.26 ± 0.05%.d-1. However, there were no significant differences in MPS between the HMB-FA and PLA groups at any given time point and no significant treatment interaction observed. We also observed significant inductions of c-Myc gene expression following each acute RE bout, with no group differences. Further, there were no changes in any other muscle atrophy/hypertrophy or myogenic transcription factor genes we measured. RET with adjuvant HMB-FA supplements in free-living healthy older men did not enhance muscle strength or mass greater than that of RET alone (PLA). That said, only HMB-FA increased TLM, supported by early increases in chronic MPS. As such, chronic HMB-FA supplementation may result in long term benefits in older males, however longer and larger studies may be needed to fully determine the potential effects of HMB-FA supplementation; translating to any functional benefit.
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Ingestion of proteins with high leucine content during resistance training (RT) can augment hypertrophy. Some data suggest that a leucine metabolite, β-hydroxy, β-methylbutyrate (HMB), is substantially more anabolically efficacious than leucine. Purpose: We aimed to test whether supplementation with HMB versus leucine, added to whey protein, would result in differential muscle hypertrophy and strength gains in young men performing resistance training. Methods: Twenty-six resistance-trained men (23 ± 2 y) performed 12 wk of RT with 3 phases. Phase 1: 8 wk of periodized RT (3 training sessions/wk). Phase 2: 2 wk overreaching period (5 sessions/wk). Phase 3: 2 wk taper (3 sessions/wk). Participants were randomly assigned to twice daily ingestion of: whey protein (25 g) plus HMB (1.5 g) (Whey+HMB; n=13) or whey protein (25 g) plus leucine (1.5 g) (Whey+Leu; n=13). Skeletal muscle biopsies were performed before and after RT. Measures of fat and bone-free mass (FBFM), vastus lateralis (VL) muscle thickness and muscle cross-sectional area (CSA - both by ultrasound), muscle fiber CSA, and 1-repetition maximum (1-RM) strength tests were determined. Results: We observed increases in FBFM, VL muscle thickness, muscle CSA and fiber type CSA and 1-RM strength with no differences between groups at any phase. We observed no differences between groups or time-by-group interactions in hormone concentrations at any phase of the RT program. Conclusion: HMB added to whey did not result in greater increases in any measure of muscle mass, strength, or hormonal concentration compared to leucine added to whey. Our results show that HMB is no more effective in stimulating RT-induced hypertrophy and strength gains than leucine.
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2018): Cognitive function is preserved in aged mice following long-term β-hydroxy β-methylbutyrate supplementation, Nutritional Neuroscience, β-hydroxy β-methylbutyrate (HMB) is a nutritional supplement purported to enhance skeletal muscle mass and strength, as well as cognitive function in older adults. The purpose of this study was to determine the potential for long-term HMB supplementation to preserve muscle function and cognition in aged mice, as well as provide evidence of a link between vessel-associated pericyte function and outcomes. Four-(Adult/Ad) and 17 month-old (Aged/Ag) C57BL/6J mice consumed chow containing 600 mg/kg BW/day of either Ca-HMB (Ad, n=16; Ag, n=17) or Ca-Lactate (Ad, n=16; Ag, n=17) for 6 months. HMB did not prevent age-related reductions in muscle mass, strength and coordination (Age main effect, P<0.05). The rate of muscle protein synthesis decreased within the mitochondrial fraction (age main effect, P<0.05), and this decline was not prevented with HMB. Despite no change in muscle mass or function, an age-dependent reduction in active avoidance learning was attenuated with HMB (Age and HMB main effects, P<0.05). Age detrimentally impacted muscle-resident pericyte gene expression with no recovery observed with HMB, whereas no changes in brain-resident pericyte quantity or function were observed with age or HMB. The findings from this study suggest that prolonged HMB supplementation starting in adulthood may preserve cognition with age.
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Purpose: Frailty, polypharmacy, and underprescription are considered a major matter of concern in nursing homes, but the possible relationships between them are not well known. The aim is to examine the possible association between medication underprescription, polypharmacy, and frailty in older people living in nursing homes. Methods: A cross-sectional analysis from a concurrent cohort study, including 110 subjects ≥ 65 years living in two nursing homes. Four frailty scales were applied; polypharmacy was defined as ≥ 5 medications and underprescription was measured with Screening Tool to Alert to Right Treatment (START) criteria. Logistic regression models were performed to assess the associations. Results: The mean age was 86.3 years (SD 7.3) and 71.8% were female. 73.6% of subjects took ≥ 5 chronic medications and 60.9% met one or more START criteria. The non-frail participants took more medications than the frail subjects according to the imputated frailty Fried criteria (8.1 vs 6.7, p = 0.042) and the FRAIL-NH scale (7.8 vs 6.8, p = 0.026). Multivariate analyses did not find an association between frailty and polypharmacy. Frail participants according to the Fried criteria met a higher number of START criteria (1.9 vs 1.0, p = 0.017), and had a higher prevalence of underprescription (87.5 vs 50.0%), reaching the limit of statistical significance in multivariate analysis. Conclusion: The positive association found in previous studies between frailty and polypharmacy cannot be extrapolated to institutionalized populations. There is a trend towards higher rates of underprescription in frail subjects. Underprescription in frail older adults should be redefined and new strategies to measure it should be developed.
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Aim: Exercise is one of the most important components in frailty prevention and treatment. Therefore, we systematically reviewed the effect of resistance training (RT) alone or combined with multimodal exercise intervention on muscle hypertrophy, maximal strength, power output, functional performance, and falls incidence in physically frail elderly. Methods: MEDLINE, Cochrane CENTRAL, PEDro, and SPORTDiscus databases were searched from 2005 to 2017. Studies must have mentioned the effects of RT (i.e., included or not in multimodal training) on at least one of the following parameters: muscle mass, muscle strength, muscle power, functional capacity, and risk of falls in frail elderly. Results: The initial search identified 371 studies and 16 were used for qualitative analysis for describing the effect of strength training performed alone or in a multimodal exercise intervention. We observed that RT alone or in a multimodal training may induce increases of 6.6-37% in maximal strength; 3.4-7.5% in muscle mass, 8.2% in muscle power, 4.7-58.1% in functional capacity and risk of falls, although some studies did not show enhancements. Conclusion: Frequency of 1-6 sessions per week, training volume of 1-3 sets of 6-15 repetitions and intensity of 30-70%1-RM promoted significant enhancements on muscle strength, muscle power, and functional outcomes. Therefore, in agreement with previous studies, we suggest that supervised and controlled RT represents an effective intervention in frailty treatment.
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Background: Loss of skeletal muscle mass and muscle weakness are common in a variety of clinical conditions with both wasting and weakness associated with an impairment of physical function. β-Hydroxy-β-methylbutyrate (HMB) is a nutrition supplement that has been shown to favorably influence muscle protein turnover and thus potentially plays a role in ameliorating skeletal muscle wasting and weakness. Objectives: The aim of this study was to investigate the efficacy of HMB alone, or supplements containing HMB, on skeletal muscle mass and physical function in a variety of clinical conditions characterized by loss of skeletal muscle mass and weakness. Methods: A systematic review and meta-analysis of randomized controlled trials reporting outcomes of muscle mass, strength, and physical function was performed. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment. Outcome data were synthesized through meta-analysis with the use of a random-effects model and data presented as standardized mean differences (SMDs). Results: Fifteen randomized controlled trials were included, involving 2137 patients. Meta-analysis revealed some evidence to support the effect of HMB alone, or supplements containing HMB, on increasing skeletal muscle mass (SMD = 0.25; 95% CI: -0.00, 0.50; z = 1.93; P = 0.05; I2 = 58%) and strong evidence to support improving muscle strength (SMD = 0.31; 95% CI: 0.12, 0.50; z = 3.25; P = 0.001; I2 = 0%). Effect sizes were small. No effect on bodyweight (SMD = 0.16; 95% CI: -0.08, 0.41; z = 1.34; P = 0.18; I2 = 67%) or any other outcome was found. No study was considered to have low risk of bias in all categories. Conclusion: HMB, and supplements containing HMB, increased muscle mass and strength in a variety of clinical conditions, although the effect size was small. Given the bias associated with many of the included studies, further high-quality studies should be undertaken to enable interpretation and translation into clinical practice. The trial was registered on PROSPERO as CRD42017058517.
Article
Introduction: Skeletal muscle power has been demonstrated to be a stronger predictor of functional limitations than any other physical capability. However, no validated alternatives exist to the usually expensive instruments and/or time-consuming methods to evaluate muscle power in older populations. Our aim was to validate an easily applicable procedure to assess muscle power in large cohort studies and the clinical setting and to assess its association with other age-related outcomes. Methods: Forty community dwelling older adults (70-87 years) and 1804 older subjects (67-101 years) participating in the Toledo Study for Healthy Aging were included in this investigation. Sit-to-stand (STS) velocity and muscle power were calculated using the subject's body mass and height, chair height and the time needed to complete five STS repetitions, and compared with those obtained in the leg press exercise using a linear position transducer. In addition, STS performance, physical (gait speed) and cognitive function, sarcopenia (skeletal muscle index (SMI)) and health-related quality of life (HRQoL) were recorded to assess the association with the STS muscle power values. Results: No significant differences were found between STS velocity and power values and those obtained from the leg press force-velocity measurements (mean difference ± 95% CI = 0.02 ± 0.05 m·s-1 and 6.9 ± 29.8 W, respectively) (both p > 0.05). STS muscle power was strongly associated with maximal muscle power registered in the leg press exercise (r = 0.72; p < 0.001). In addition, cognitive function and SMI, and physical function, were better associated with absolute and relative STS muscle power, respectively, than STS time values after adjusting by different covariates. In contrast, STS time was slightly more associated with HRQoL than STS muscle power measures. Conclusion: The STS muscle power test proved to be a valid, and in general, a more clinically relevant tool to assess functional trajectory in older people compared to traditional STS time values. The low time, space and material requirements of the STS muscle power test, make this test an excellent choice for its application in large cohort studies and the clinical setting.
Article
Background/objectives: Multicomponent exercise programs are the cornerstone in preventing gait and balance impairments and falls in older adults. However, the effects of these programs in usual clinical practice have been poorly analyzed. Design: 4-Month, twice-a-week multicomponent exercise program cohort study in real-life. Setting: Falls Unit, Complejo Hospitalario Universitario of Albacete, Spain. Participants: Sixty-seven participants who had experienced a fall in the previous year were included. Measurements: Pre- and post-intervention measurements were collected for leg press, gait speed, the Short Physical Performance Battery (SPPB), the Falls Efficiency Scale International, fat mass percentage, body mass index, the Geriatric Depression Scale by Yesavage (GDS), the Mini Mental State Examination, and the number of falls. Results: Fifty participants completed the program (adherence rate 75%, attendance 80%). Their mean age was 77.2 (SD 5.8) years; 39 were women. The participants reduced the mean number of frailty criteria from 2.1 to 1.3 (95%CI 0.4-1.1) and increased mean gait speed from 0.65 m/s to 0.82 m/s (95%CI 0.11-0.22), increasing their median SPPB scores from 8.5 to 10.0 points (p < 0.001), leg press strength from 62.5 kg to 80.0 kg (p < 0.001), and leg press power at 60% load from 76 W to 119 W (p < 0.001). There was also an improvement in GDS scores from 5.3 to 4.4 (95%CI 0.1-1.7). Body mass index did not change, but fat-free mass increased from 43.7 kg to 44.2 kg (95%CI 0.1-1.0), and fat mass percentage declined from 36.7% to 36.0% (95% CI 0.1-1.4). Seventeen patients (34%) had a fall during the six-month follow-up, and there was a reduction in the median number of falls from 3.0/year to 0.0/six months. Conclusions: A multicomponent Falls Unit-based exercise program as part of usual clinical practice in real life, improved physical function, reduced depressive symptoms, improved body composition and decreased the number of falls in older adults with previous falls.
Article
Background: Muscle power has been proposed to be the primary therapeutic target for resistance training interventions aimed at enhancing physical function in older adults. However, no recommendations exist on ideal testing protocols to assess muscle power in older adults, and the safety of this procedure has not been adequately evaluated in the literature. Methods: A systematic review was conducted to identify studies evaluating muscle power exerted by older people in resistance exercises through May 2017. Information from muscle power testing protocols regarding familiarization, warm-up, measuring instrument, exercise, intensity, volume, rest intervals, data collection, and analysis was collected, as well as that regarding adverse events. Reporting bias was evaluated according to the recommendations given by the Cochrane Collaboration group. Results: From 65 studies that met inclusion criteria, 3,484 older subjects and 11,841 muscle power tests distributed in 6,105 testing sessions were identified. A full description of the different muscle power testing protocols was conducted. In addition, a risk of adverse events of 0.15%-0.69% (one adverse event every 144-658 muscle power tests) was found. However, adverse events were poorly reported, with most of the studies showing a high risk of reporting bias. Conclusions: Major discrepancies were found in muscle power testing protocols among studies. This might limit consensus on designing optimal training programs to improve muscle power and physical function in older adults, and understanding the main mechanisms involved in the age-related loss of muscle power. Finally, muscle power testing was found to be safe in older people with a broad range of health and functional states.
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Sarcopenia is defined as an age-related loss of skeletal muscle mass and function and is recognized as a major clinical problem for older people. Essential amino acid supplementation, particularly β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine that is produced in skeletal muscle, has been evaluated in several studies as a nutritional approach to enhancing muscle protein synthesis in healthy or frail elderly subjects. Studies performed in in vitro conditions show that HMB may be effective in the treatment of muscle wasting, increasing myogenesis, reducing muscle apoptosis, and having a positive effect on muscle protein turnover; however, studies of the effects of HMB conducted in old animals have reported conflicting results. Clinical trials performed in older adults confirm that HMB can attenuate the progression of sarcopenia in elderly subjects. HMB supplementation results in an increase in skeletal muscle mass and strength in the elderly and its effect is even greater when combined with physical exercise. The role of HMB in sarcopenic obesity management is still under debate and a general lack of intervention studies in this population must be recognized. In conclusion, HMB appears to be effective for enhancing muscle mass and strength in the elderly. Less certain is the role of HMB supplementation in reducing fat mass and, thus, in the treatment of sarcopenic obesity.