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A randomized controlled trial of the impact of protein supplementation on leg lean mass and integrated muscle protein synthesis during inactivity and energy restriction in older persons

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Background: In older persons, muscle loss is accelerated during physical inactivity and hypoenergetic states, both of which are features of hospitalization. Protein supplementation may represent a strategy to offset the loss of muscle during inactivity, and enhance recovery on resumption of activity. Objective: We aimed to determine if protein supplementation, with proteins of substantially different quality, would alleviate the loss of lean mass by augmenting muscle protein synthesis (MPS) while inactive during a hypoenergetic state. Design: Participants (16 men, mean ± SD age: 69 ± 3 y; 15 women, mean ± SD age: 68 ± 4 y) consumed a diet containing 1.6 g protein · kg-1 · d-1, with 55% ± 9% of protein from foods and 45% ± 9% from supplements, namely, whey protein (WP) or collagen peptides (CP): 30 g each, consumed 2 times/d. Participants were in energy balance (EB) for 1 wk, then began a period of energy restriction (ER; -500 kcal/d) for 1 wk, followed by ER with step reduction (ER + SR; <750 steps/d) for 2 wk, before a return to habitual activity in recovery (RC) for 1 wk. Results: There were significant reductions in leg lean mass (LLM) from EB to ER, and from ER to ER + SR in both groups (P < 0.001) with no differences between WP and CP or when comparing the change from phase to phase. During RC, LLM increased from ER + SR, but in the WP group only. Rates of integrated muscle protein synthesis decreased during ER and ER + SR in both groups (P < 0.01), but increased during RC only in the WP group (P = 0.05). Conclusions: Protein supplementation did not confer a benefit in protecting LLM, but only supplemental WP augmented LLM and muscle protein synthesis during recovery from inactivity and a hypoenergetic state. This trial was registered at http://www.clinicaltrials.gov as NCT03285737.
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Original Research Communications
A randomized controlled trial of the impact of protein supplementation
on leg lean mass and integrated muscle protein synthesis during
inactivity and energy restriction in older persons
Sara Y Oikawa,1Chris McGlory,1Lisa K D’Souza,1Adrienne K Morgan,1Nelson I Saddler,1Steven K Baker,2
Gianni Parise,1and Stuart M Phillips1
1Department of Kinesiology, and and 2Department of Neurology, Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
ABSTRACT
Background: In older persons, muscle loss is accelerated during
physical inactivity and hypoenergetic states, both of which are
features of hospitalization. Protein supplementation may represent
a strategy to offset the loss of muscle during inactivity, and enhance
recovery on resumption of activity.
Objective: We aimed to determine if protein supplementation, with
proteins of substantially different quality, would alleviate the loss
of lean mass by augmenting muscle protein synthesis (MPS) while
inactive during a hypoenergetic state.
Design: Participants (16 men, mean ±SD age: 69 ±3 y; 15 women,
mean ±SD age: 68 ±4 y) consumed a diet containing 1.6 g protein ·
kg–1 ·d–1, with 55% ±9% of protein from foods and 45% ±9% from
supplements, namely, whey protein (WP) or collagen peptides (CP):
30 g each, consumed 2 times/d. Participants were in energy balance
(EB) for 1 wk, then began a period of energy restriction (ER; –500
kcal/d) for 1 wk, followed by ER with step reduction (ER + SR; <750
steps/d) for 2 wk, before a return to habitual activity in recovery (RC)
for 1 wk.
Results: There were signicant reductions in leg lean mass (LLM)
from EB to ER, and from ER to ER + SR in both groups (P<0.001)
with no differences between WP and CP or when comparing the
change from phase to phase. During RC, LLM increased from
ER + SR, but in the WP group only. Rates of integrated muscle
protein synthesis decreased during ER and ER + SR in both
groups (P<0.01), but increased during RC only in the WP group
(P=0.05).
Conclusions: Protein supplementation did not confer a benet in
protecting LLM, but only supplemental WP augmented LLM and
muscle protein synthesis during recovery from inactivity and a
hypoenergetic state. This trial was registered at clinicaltrials.gov as
NCT03285737. Am J Clin Nutr 2018;108:1–9.
Keywords: muscle protein synthesis, older adults, whey protein,
collagen peptides, step reduction
INTRODUCTION
Periods of inactivity and muscle disuse, such as during bed
rest and hospitalization or protracted illness, are more common in
older persons (1). The decline in muscle mass and function during
hospitalization can transiently accelerate sarcopenic decline,
resulting in incomplete recovery, particularly for older persons
(2). We have shown that periods in which fewer steps are
taken, as a model of inactivity but not outright muscle disuse,
result in reductions in anabolic sensitivity to protein (3,4)and
declines in leg lean mass (3). Such periods of inactivity are, we
suggest, more common than bed rest and complete disuse, and
may be deleterious in older persons particularly if frequent and
incomplete recovery occurs.
In addition to reduced ambulation, hospitalization or illness
can be accompanied by a decrease in appetite and food intake,
which can lead to an energy decit and muscle loss (5).
Typically, 25% of body mass lost in an energy decit can be
attributed to fat-free mass (6), some of which is likely muscle
(7). Hospitalization is also associated with energy and protein
underfeeding that may further exacerbate muscle catabolism (8).
Funding for this study was provided by the Whey Protein Research
Consortium and the US National Dairy Council.
Address correspondence to SMP (e-mail: phillis@mcmaster.ca).
Abbreviations used: APE, atomic percentage excess; CP, collagen peptide;
CRP, C-reactive protein; CSA, cross-sectional area; DXA, dual-energy X-ray
absorptiometry; EAA, essential amino acid; EB, energy balance phase; ER,
energy-restricted phase; ER + SR, energy-restricted and step-reduction phase;
LBM, lean body mass; LLM, leg lean mass; MPS, muscle protein synthesis;
PASE, physical activity scale for the elderly; RC, recovery phase; RDA,
Recommended Dietary Allowance; SR, step reduction; WP, whey protein.
Received April 14, 2018. Accepted for publication July 16, 2018.
First published online 0, 2018; doi: https://doi.org/10.1093/ajcn/nqy193.
Am J Clin Nutr 2018;108:1–9. Printed in USA. ©2018 American Society for Nutrition. All rights reserved. 1
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2OIKAWA ET AL.
An increase in dietary protein intake may alleviate inactivity-
induced muscle loss (9,10). Whey protein has a high essential
amino acid (EAA) content, particularly leucine, and its ingestion
stimulates muscle protein synthesis (MPS) (11). Supplementing
the diet with protein sources rich in EAA and leucine is known
to enhance rates of MPS (12,13), and may serve to offset losses
in muscle mass and strength during periods of physical inactivity
(14). Although studies have examined the inuence of increased
protein intake on muscle atrophy during immobilization (15),
no study has examined the efcacy of increased protein
consumption to offset loss of muscle mass during inactivity while
hypoenergetic and to promote recovery in older adults.
We investigated whether providing healthy older adults with
twice the Recommended Dietary Allowance (RDA) of protein
(1.6 g ·kg–1 ·d–1) would attenuate the inactivity-induced loss
of leg lean mass (LLM) and integrated rates of MPS while
energy restricted. We also examined whether supplementation
with proteins of different quality would affect muscle outcomes.
Supplements were high-quality whey protein (WP) or lower-
quality collagen peptides (CP). We selected collagen as a
comparator as it provides an isonitrogenous and isoenergetic
comparison (as opposed to carbohydrate, which is often used)
(16), and as it has shown considerable and impressive anabolic
properties in older adults (17) [which have been questioned (18)].
To our knowledge, no other study had compared WP and CP for
their effect on MPS in older adults. We hypothesized that energy
restriction and step reduction would result in reductions in LLM
and MPS as primary outcomes. Further, we hypothesized that
WP, but not CP, would mitigate declines in LLM and maintenance
of MPS. As secondary outcomes, we believed that ER + SR
would induce an increase in levels of systemic inammation
independent of supplement type. We also hypothesized that
ER + SR would result in impaired glucose handling congruent
with previous ndings from our laboratory (4).
METHODS
Ethical approval
The study was approved by the Hamilton Integrated Research
Ethics Board, and conformed to the standards for the use
of human subjects in research as outlined by the Canadian
Tri-Council Policy on the ethical use of human subjects in
research (http://www.pre.ethics.gc.ca/pdf/eng/tcps2/TCPS_2_F
INAL_Web.pdf). Each participant was informed of the purpose
of the study, experimental procedures, and potential risks before
written consent was provided. The trial was registered at clinical
trials.gov as NCT03285737.
Participants
Thirty-two older adults were recruited from the greater
Hamilton area, in response to local advertisements, to participate
in this study. Potential participants were screened rst by
telephone to ensure they were nonsmokers, nondiabetic, and
between the ages of 65 and 80 y. Exclusion criteria included
signicant loss or gain of body mass in the past 6 mo (>2 kg);
regular use of: nonsteroidal anti-inammatory drugs (with the
exception of daily low-dose aspirin); use of simvastatin or
atorvastatin; use of anticoagulants; the use of a walker, cane,
or assistive walking device; current or recently remised cancer;
infectious disease; or gastrointestinal disease. Figure 1 shows
the Consolidated Standards of Reporting Trials (CONSORT)
diagram for subject ow through the protocol.
Study overview
An overview of the study is shown in Figure 2. The study
was a double-blind, parallel-group, randomized controlled trial.
Eligible participants were allocated to consume 1 of 2 types of
protein supplement: 30 g 2 times/d of WP or CP. Allocation was
concealed from the participants and researchers for the duration
of the study and until all analyses were complete. After baseline
testing and familiarization with all study measures, participants
commenced the 5-wk-long protocol during which they consumed
a controlled diet provided by the study investigators. The protocol
was divided into 4 distinct phases. The rst phase was a week-
long run-in phase in which subjects were in energy balance
(EB) with protein intake equal to the RDA (0.8 g protein ·
kg–1 ·d–1). Subjects were then placed in an energy restriction
phase (ER) for 1 wk where they consumed an energy-restricted
diet (–500 kcal/d) and protein intake was increased to twice
the RDA (1.6 g ·kg–1 ·d–1) by consumption of a twice-daily
supplement (30 g/dose) of either WP or CP. Inactivity, as step
reduction (SR), was superimposed on ER (ER + SR) for 2 wk.
During the ER + SR phase, participants were instructed to reduce
their daily step count to 750 steps/d, which is a daily step
count similar to what is observed in older hospitalized patients
(19). Participants monitored their daily step counts with the
use of a waist-mounted pedometer (PiezoX, Deep River, ON,
Canada) and recorded their steps at the end of each day on a log
sheet that was checked at each visit. Energy intake during the
ER + SR phase was adjusted to account for subjects’ inactivity
(20). Finally, during recovery (RC, 1 wk), participants returned to
their habitual levels of activity (matching their average daily step
count seen in EB and ER). During RC, participants maintained
their high protein intake (1.6 g ·kg–1 ·d–1) while consuming the
same supplements and an energy intake matching their activity
levels during EB. Before and after each dietary phase, participants
had blood collected for fasting serum and plasma. Before and at
the end of each phase participants underwent a dual-energy X-ray
absorptiometry (DXA) scan (GE-Lunar iDXA; Aymes Medical,
Newmarket, ON, Canada).
Baseline testing
Before study commencement, participants were asked to
complete a physical activity and weighed food record (Nutribase
version 11.5; Cybersoft Inc., Phoenix, AZ) for 3 d (2 weekdays
and 1 weekend day) to assess habitual physical activity levels and
dietary intakes.
Diets
Each participants’ energy requirement was determined with
the use of the Oxford prediction equations for basal metabolic
rate (21) using height and body mass for men and women aged
>60y(20). Activity factors were determined for each participant
on the basis of their baseline physical activity records, daily step
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WHEY PROTEIN AND MUSCLE RECOVERY IN OLDER ADULTS 3
n
Did not meet inclusion criteria (n = 64)
Randomly assigned (n = 32)
Analyzed Analyzed
n
n
n
n
n
n
n
n
nn
n
n
n
n
n
n
FIGURE 1 CONSORT ow diagram. CONSORT, Consolidated Standards of Reporting Trials.
counts, and Physical Activity Scale for the Elderly questionnaire
(PASE) (22) for energy intake during the EB, ER, and RC phases.
During the ER + SR phase, a reduced activity factor (of 1.3)
was applied to the basal metabolic rate in order to match caloric
intake to activity level. During the ER and ER + SR phases, a
reduction in total energy intake of 500 kcal/d below the estimated
energy requirement was applied to the diet to simulate a moderate
energy restriction that is common during hospitalization (23).
During the EB phase of the study, participants were provided
with a protein intake of 0.8 g ·kg–1 ·d–1, which reects the
current RDA for protein in adults 19y(24). For the ER,
ER + SR, and RC phases, participants were provided with a
0.8 g · kg-1 · d-1 1.6 g · kg-1 · d-1
FIGURE 2 Schematic of study design. CP, collagen peptide supplement; DXA, dual-energy X-ray absorptiometry; WP, whey protein supplement.
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4OIKAWA ET AL.
protein intake of 1.6 g ·kg–1 ·d–1, in line with recommendations
from a number of expert committees for optimal protein intake
for older adults who are hospitalized (25). Increasing protein
intake during the ER, ER + SR, and RC phases of the study
was achieved by reducing the proportion of food energy provided
from carbohydrates, whereas the proportion of energy from fat
was maintained at 25% of total energy across all phases.
Dietary protein was derived via a combination of plant- and
animal-based protein sources throughout the 5-wk trial. During
phases ER, ER + SR, and RC, participants were provided with
their prepackaged protein supplements (either WP or CP) to be
consumed 2 times/d, once in the morning prior to breakfast and
once in the evening 1–2 h before sleep.
Participants were prescribed a customized meal plan according
to food preferences and food was supplied at the beginning of
each week. Food consisted of prepackaged frozen meals (Heart
to Home Frozen Meals, Brampton, ON) and items that required
minimal preparation. Participants were provided with a dietary
log where they were to indicate the percentage of the provided
food consumed during the day and were strongly encouraged
to consume only the study diet. If food outside of the provided
diet was consumed, additions were recorded in the dietary log.
Overall, compliance with the prescribed diets and supplements
was excellent with subjects consuming 98% ±2% of what was
provided.
Supplementation
Supplements contained WP isolate (Whey Protein Isolate
895, Nealanderes International Inc., Mississauga, ON, Canada),
or hydrolyzed collagen peptide (Gelita, Eberbach, Germany).
Individual servings were identically avored and packaged by
Innit Nutrition (Windsor, ON, Canada) in powdered form.
Participants were instructed to mix each package with 300 mL of
water before ingestion, and were asked to consume the beverage
within a 5-min period. Supplements were isonitrogenous and
energy-matched; their contents appear in Tab le 1.
Isotope protocol
Oral consumption of 2H2O (70 at.%; Cambridge Isotope
Laboratories) was used to label newly synthesized myobrillar
proteins as previously described (26). Participants reported to the
laboratory in the fasted state on day 0, and after the collection of a
saliva sample (26) and a muscle biopsy from the vastus lateralis,
participants consumed a single 100-mL oral bolus of 2H2O. This
process was repeated at the beginning of each dietary phase of
the study. An additional 100 mL dose of 2H2O was provided to
participants at the beginning of the second week of ER + SR.
Total body water enrichment of 2H was used as a surrogate of
the precursor for plasma alanine labeling, which remains in a
constant ratio of 3.7 with water. This has been conrmed in
our laboratory (data not shown) and by others (26–28), and was
determined from saliva swabs that were collected by participants
between 0700 and 0900 each morning.
All muscle biopsies were obtained with the use of a 5-mm
Bergström needle that was adapted for manual suction under
1% xylocaine local anesthesia. Muscle tissue samples were freed
from any visible connective and adipose tissue, rapidly frozen in
TABLE 1
Amino acid composition of protein supplements1
WP supplement CP supplement
g/100 g g/30 g g/100 g g/30 g
Alanine 5.7 1.7 8.6 2.6
Arginine 3.0 0.9 7.3 2.2
Aspartic acid 12.5 3.8 5.8 1.7
Cystine 4.0 1.2 0 0
Glutamic acid 17.6 5.3 10.2 3
Glycine 1.8 0.5 22.2 6.7
Histidine 2.0 0.6 1.0 0.3
Proline 4.5 1.4 12.7 3.8
Serine 4.5 1.4 3.2 1.0
Tyrosine 4.2 1.3 0.8 0.2
Tryptophan 2.4 0.7 0 0
Isoleucine 6.3 1.9 1.4 0.4
Leucine 14.34.32.70.8
Lysine 11.2 3.4 3.6 1.1
Methionine 2.4 0.7 0.9 0.3
Phenylalanine 3.8 1.1 2.1 0.6
Threonine 5.3 1.6 1.8 0.5
Valine 5.6 1.7 2.4 0.7
EAAs 51.3 15.4 14.9 4.5
NEAAs 59.8 17.9 71.8 21.5
1CP, collagen peptide; EAA, essential amino acid; NEAA, nonessential
amino acid; WP, whey protein.
liquid nitrogen for measurement of MPS, and mounted in optimal
cutting temperature medium for immunohistochemistry; samples
were then stored at –80C for further analysis.
Analytic methods
Myobrillar proteins were isolated from the muscle biopsies
as previously described (29). The incorporation of deuterium
into protein-bound alanine was determined and rates of protein
synthesis were calculated as detailed previously (30).
Saliva samples were analyzed for 2H enrichment by cavity
ring-down spectroscopy with the use of a liquid isotope analyzer
(Picarro L2130-i analyzer, Picarro, Santa Clara, CA) with an
automated injection system. The water phase of saliva was
injected 6 times and the average of the last 3 measurements was
used for data analysis (coefcient of variation 0.5%). Standards
were measured before and after each participant run. The 2H
isotopic enrichments for muscle and saliva initially expressed as
δ2H were converted to atomic percentage excess (APE) using
standard equations (27).
Body composition
Body composition was assessed following an overnight fast
(12 h). DXA measurements were conducted using a GE Lunar
iDXA total body scanner (GE Medical Systems Lunar, Madison,
WI) and analyzed (Lunar enCORE version 14.1, GE Medical
Systems) in medium-scan mode. The machine was calibrated
each testing day with a 3-compartment Universal Whole Body
DXA Phantom (Oscar, Jr; Orthometrix, Naples, FL). The analysis
regions were standard regions where the head, torso, arms, and
legs were subdivided by the software, but were subsequently
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WHEY PROTEIN AND MUSCLE RECOVERY IN OLDER ADULTS 5
checked manually, in a blinded manner, by a single investigator
(SYO).
Blood metabolites and hormones
Serum glucose concentrations were measured with the use
of the glucose oxidase method (YSI 2300; YSI Life Sciences,
Yellow Springs, OH). Plasma insulin concentrations were mea-
sured with the use of the dual-site chemiluminescent method (Im-
mulite 2000 immuno-assay system; Siemens, Germany). High-
sensitivity C-reactive protein (CRP) levels were measured with
an Express Plus autoanalyzer (Chrion Diagnostics Co, Walpole,
MA) and using a commercially available high-sensitivity CRP-
Latex kit (Pulse Scientic, Burlington, ON). IL-6 and TNF-α
levels were measured with a Bio-Plex reagent kit on a Bio-
Plex 200 (Bio-Rad Laboratories, Hercules, CA). Intra-assay
coefcients of variation were all <5% for all blood analyses.
Calculations
The fractional synthetic rate of myobrillar protein was
determined from the incorporation of deuterium-labeled alanine
into protein with the use of enrichment of body water, corrected
for the mean number of deuterium moieties incorporated
per alanine (27), as the surrogate precursor labeling between
subsequent biopsies. In brief, the following standard equation
was used: FSR(%/d) =[(APEAla)]/[(APEp)×t]×100 where
FSR is the fractional synthetic rate, APEAla is the deuterium
enrichment of protein-bound alanine, APEpis the mean precursor
enrichment over the time period, and tis the time between
biopsies.
The HOMA-IR was calculated with fasted glucose and insulin
levels using the standard equation [(glucose ×insulin)/22.5] (31).
Histologic staining
Muscle cross-sections, 7-μm thick, were prepared from
optimal cutting temperature medium–embedded samples and
allowed to air-dry for 30 min before being stored at –80C.
Tissue sections were thawed and xed as previously described
(32). Primary antibodies used were A4.951 (MHCI; slow
isoform; neat; DSHB); myosin heavy-chain type II (MHCII; fast
isoform; 1:1000; ab91506; Abcam, Cambridge, MA); laminin
(1:500; ab11575; Abcam). Secondary antibodies used were
MHCI (Alexa Fluor 488 anti-mouse, 1:500); MHCII (Alexa Fluor
647 anti-rabbit, 1:500), and laminin (Alexa Fluor anti-rabbit 488,
1:500). Slides were rexed with 4% PFA in between the MHCII
and laminin staining steps to limit cross-reactivity. Nuclei were
labeled with 4,6-diamidino-2-phenylindole (DAPI, 1:20,000;
Sigma-Aldrich) before slides were coverslipped with uorescent
mounting media (DAKO, Burlington, ON, Canada). Images were
observed with a Nikon Eclipse 90i microscope and captured
with a Photometrics Cool SNAP HQ2 uorescent camera (Nikon
Instrument, Melville, NY). Analysis was completed per our
previous work (32–35), ber typing was conducted using 300
bers, and cross-sectional area (CSA) was based on 50
bers/ber type. Muscle bers on the periphery of muscle cross-
sections were not used in the analysis.
TABLE 2
Participants’ characteristics1
WP supplement
(n=16, 8F)
CP supplement
(n=15, 7F)
Age, y 69 ±468±2
Height, m 1.71 ±0.09 1.70 ±0.10
Body mass, kg 92.4 ±14.2 82.0 ±17.9
BMI, kg/m231.2 ±5.2 28.0 ±4.8
Body fat, % 41.1 ±8.6 37.2 ±8.6
LBM, kg 52.3 ±9.7 49.3 ±11.0
Steps/d 6237 ±2890 8392 ±4290
Knee extensor MVC, Nm 143 ±62 146 ±43
Chair stands, stands/30 s 15 ±316±3
TUG, s 7.8 ±2.0 7.1 ±1.2
6MWT distance, m 542 ±99 562 ±67
Gait speed, m/s 1.5 ±0.3 1.6 ±9.2
1Values are means ±SDs. CP, collagen peptide; LBM, lean body mass;
MVC, maximum voluntary contraction; TUG, timed up and go test; WP,
whey protein; 6MWT, 6-min walk test.
Statistics
Data were compared using a 2-way mixed-model ANOVA
with between (group) and within (time, EB, ER, ER + SR,
and RC) factors. The ANOVA revealed no interaction between
group and sex, and thus groups were collapsed across sex for all
measures. All signicant interaction terms for the ANOVA were
further tested with the use of Tukey’s post hoc test. Signicance
was set at P<0.05. All statistical analyses were completed using
SPSS (IBM SPSS Statistics for Mac, version 21; IBM Corp.,
Armonk, NY). Data in tables are presented as means ±SDs.
Graphical representation of data is in box and whisker plots with
the box representing the IQR, the line indicating the median
and the cross indicating the mean, and the whiskers indicate the
maximum and minimum values.
RESULTS
Subjects’ characteristics
Subjects’ characteristics are presented in Table 2. There were
no signicant differences between groups for any variable. The
baseline step counts of participants were 6237 ±2890 and
8392 ±4290 in the WP and CP groups, respectively and 2
wk of ER + SR resulted in a decrease in average daily steps
by 84% and 90% (P<0.001). Subjects returned to taking
similar steps during RC (6336 ±2348 and 8473 ±3586) in
both groups, showing no difference during RC compared with EB
(P>0.05).
Diet
There were no signicant differences in any dietary variable
between groups at any time points (P>0.05) (Tab le 3). All
required supplements were consumed by each participant and
recorded in a dietary log. Supplemental protein accounted for
45% ±9% of total protein intake in ER, ER + SR, and RC with
the remaining 55% ±9% derived from food sources.
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6OIKAWA ET AL.
TABLE 3
Nutrient intake during each dietary phase of the study1
WP supplement CP supplement
EB ER ER + SR RC EB ER ER + SR RC
Intake, kcal 2535 ±305 1986 ±353 1406 ±244 2337 ±350 2442 ±431 1989 ±466 1394 ±343 2193 ±457
Intake, kcal/kg 30 ±422±416±327±429±521±515±426±5
Protein, g/kg 0.8 ±0.1 1.6 ±0.1 1.6 ±0.1 1.6 ±0.1 0.8 ±0.1 1.6 ±0.1 1.6 ±0.1 1.6 ±0.1
Protein, g 75 ±12 87 ±20 86 ±21 87 ±20 67 ±15 71 ±29 71 ±29 71 ±29
1There were no signicant differences in protein or calorie intake between WP and CP at any phase. Values are means ±SDs. CP, collagen peptide; EB,
energy balance phase; ER, energy-restricted high-protein diet phase; ER + SR, energy-restricted high-protein diet and step-reduction phase; RC, habitual
activity and caloric consumption, combined with high-protein intake recovery phase; WP, whey protein.
Body composition
Total lean body mass (LBM) was signicantly reduced in
ER + SR in comparison to EB (P<0.001). In RC, there was an
increaseinLBM,butonlyinWP(Figure 3A). Losses in LLM
mimicked losses in LBM with a signicant reduction at ER + SR
FIGURE 3 Changes in (A) LBM between sequential study phases, and
(B) LLM between sequential study phases. The box plot shows the median
(line) and mean (+), with the box representing the IQR, and the whiskers
representing the maximum and minimum values. Data were analyzed with
2-factor ANOVA with group as a between factor, and repeated measures
for phase. WP (n=16),CP(n=15). Means that do not share a letter
are signicantly different within the group, P<0.05. Differences between
groups at that time point, P<0.05. Pvalue indicates the interaction of WP
and CP at RC. CP, collagen peptide; ER, energy-restricted phase; ER + SR,
energy-restricted and step-reduction phase; LBM, lean body mass; LLM, leg
lean mass; RC, recovery phase; WP, whey protein.
in comparison to ER that was increased at RC compared with
other times in WP, but not in CP (Figure 3B).
Myobrillar protein synthesis
There were no signicant differences between basal rates of
myobrillar MPS between groups during EB (P>0.05). ER
resulted in a signicant reduction in fractional synthetic rate in
both groups (P<0.001). MPS was signicantly elevated from
ER at RC in the WP group and in comparison to the CP group
(P=0.05). Rates of MPS remained suppressed at ER + SR
(P<0.001), and RC (P<0.001) from EB in the CP group
(Figure 4).
Glycemic control and inammation
There was a signicant increase in fasted blood glucose in
ER + SR compared with EB and ER that remained elevated at
RC (P<0.001) (Table 4). There were no signicant differences
FIGURE 4 Rates of integrated myobrillar muscle protein synthesis
(%/d) during EB, ER, ER + SR, and RC. The box plot shows the median
(line) and mean (+), with the box representing the IQR and the whiskers
representing the maximum and minimum values. Data were analyzed with
2-factor ANOVA with group as a between factor and repeated measures
for phase. WP (n=16), CP (n=15). Means that do not share a letter
are signicantly different within the group, P<0.05. Differences between
groups at that time point, P<0.05. Pvalue indicates the interaction of WP and
CP at RC. CP, collagen peptide; EB, energy balance; ER, energy restriction;
ER + SR, energy restriction and step reduction; RC, recovery; WP, whey
protein.
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WHEY PROTEIN AND MUSCLE RECOVERY IN OLDER ADULTS 7
TABLE 4
Fasted glucose, insulin, and levels of systemic inammation during each dietary phase of the study1
WP supplement CP supplement
EB ER ER + SR RC EB ER ER + SR RC
Glucose, mM 4.9 ±0.5a5.0 ±0.6a6.2 ±1.2b5.6 ±0.9b4.6 ±0.6a5.1 ±0.6a6.2 ±0.9b5.7 ±0.8b
Insulin, ulU/mL 9.9 ±2.3a6.9 ±1.5b9.2 ±3.6a,c 8.0 ±2.3b,c 10.0 ±1.8a6.5 ±1.7b7.9 ±2.8a,c 8.0 ±2.6b,c
HOMA-IR 2.2 ±0.5a1.5 ±0.4b2.5 ±1.1a2.0 ±0.7a2.1 ±0.5a1.6 ±0.4b2.2 ±0.9a2.1 ±0.8a
TNF-α, pg/mL 15.1 ±3.9a16.8 ±2.9a23.5 ±5.9b16.17 ±3.8a16.3 ±3.6a16.9 ±3.6a22.8 ±6.1b17.3 ±4.8a
IL-6, pg/mL 7.4 ±1.6a6.1 ±1.7b12.2 ±4.8c8.2 ±3.3a7.4 ±1.7a6.9 ±1.2b11.9 ±5.7c8.7 ±3.4a
CRP, mg/L 9.0 ±3.2a10.2 ±2.9a,b 12.7 ±4.9b,c 13.9 ±4.6c9.1 ±2.4a11.3 ±2.5a,b 12.4 ±4.4b,c 11.4 ±4.3c
1Data were analyzed with 2-factor ANOVA with repeated measures on time. There were no signicant differences between the WP and CP groups at any
time point. Values are mean ±SD. Means that do not share a letter are signicantly different within the group, P<0.05. CP, collagen peptide; CRP,
c-reactive protein;EB, energy balance phase; ER, energy-restricted high-protein diet phase; ER + SR, energy-restricted high-protein diet and step-reduction
phase; RC, habitual activity and caloric consumption, combined with high protein intake recovery phase; WP, whey protein.
between groups for any measures of insulin sensitivity or
inammation (P>0.05).
Plasma insulin concentration decreased signicantly from EB
at ER (P<0.001) but returned to levels similar to EB at ER + SR
(P=0.03) before decreasing again at RC (P=0.001).
The calculation of HOMA-IR demonstrated a similar trend
to fasted insulin levels where HOMA-IR was signicantly
decreased from EB at ER (P<0.001), but then was signicantly
elevated from ER at ER + SR, similar to EB (P=0.02) and then
remained at levels no different to those of EB and ER + SR at RC
(P>0.05).
Concentrations of TNF-αat ER + SR were signicantly
elevated from all other phases. Levels of IL-6 were signicantly
decreased at ER from EB (P=0.049) and elevated from all
other time points at ER + SR (EB and ER P<0.0001, ER + SR
P=0.018). Levels of CRP were signicantly elevated at ER + SR
from EB (P=0.034), and remained elevated at RC from EB
(P=0.003) and ER (P=0.029).
Type I and II ber CSA
There were no signicant changes in either type I or type II
berCSAfromEBtoER+SR(P>0.05) with no signicant
differences between groups (P>0.05; Tab le 5).
DISCUSSION
The novel nding of the present investigation was that 2 wk of
physical inactivity (step reduction, <750 steps/d) in combination
with a mild energy decit (–500 kcal/d) resulted in a signicant
reduction in LLM in older men and women consuming a protein
intake twice the RDA. Importantly, we observed that consuming
a WP supplement, in comparison to the consumption of a CP
supplement, resulted in an increase in integrated MPS with return
to habitual levels of physical activity. To our knowledge, this
study is the rst to examine the impact of protein supplementation
with different protein sources during simulated hospitalization
and convalescence concurrent with a state of energy restriction
in older men and women.
Consistent with previous reports (36,37), we show that
a reduction in energy intake induced a decline of 16% in
integrated myobrillar MPS, and that during ER + SR there
was no further decline. The reduction in rates of MPS in the
present investigation are similar to those from our previous
study in which 2 wk of inactivity alone resulted in an 13%
decline in integrated rates of myobrillar MPS in older men and
women (4). Thus, it appears that energy restriction and reduced
activity do not synergistically lower rates of myobrillar MPS,
and that a lower limit exists to which MPS can decline in these
scenarios, at least in healthy older adults. Importantly, in the
present investigation, we report that twice-daily supplementation
with WP was effective at increasing rates of MPS from ER + SR
during RC in comparison to the consumption of a CP supplement.
Interestingly, rates of MPS in the CP group remained suppressed
following return to habitual activity. This nding is particularly
relevant as our previous work (4) showed that a return to habitual
activity in the absence of intervention was insufcient in restoring
rates of MPS following 2 wk of return to habitual activity.
Another important nding of the present study was that the
introduction of SR, in addition to a period of ER, did not result in a
further decrease in LBM or LLM in comparison to ER alone when
participants consumed twice the RDA for dietary protein intake.
TABLE 5
Fiber CSA of type I and type II bers at EB and ER + SR1
WP supplement CP supplement
EB ER + SR EB ER + SR
Type I CSA, μm25570 ±1987 6479 ±2912 5501 ±940 4533 ±1699
Type II CSA, μm24377 ±1758 4334 ±1897 4533 ±1699 4375 ±1588
1Data were analyzed with 2-factor ANOVA with repeated measures on time. There were no signicant differences in type I or II CSA at EB or ER + SR
or between WP and CP. Values are means ±SDs. CP, collagen peptide supplement; CSA, cross-sectional area; EB, energy balance phase; ER + SR, energy
restricted high protein diet and step reduction phase; WP, whey protein.
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8OIKAWA ET AL.
We also show that supplementation with WP increased LLM
and LBM from ER + SR during RC. However, supplementation
with CP did not result in increases in LLM or LBM during RC.
Previously, daily supplementation with WP, albeit at what we
would consider a suboptimal dose for an older adult population
(38), has been shown to be ineffective at reducing losses in
skeletal muscle with immobilization (15). Congruent with these
ndings, our changes in LLM and LBM do not show a signicant
benet of supplementation to offset muscle loss during a period of
reduced activity; however, this is the rst study, to our knowledge,
to show an increase in LLM and LBM with WP, but not CP,
supplementation during recovery. The pronounced increase in
LLM and LBM with WP supplementation provides support for
increasing protein intake in older adults in an effort to overcome
the heighted anabolic resistance to protein feeding that occurs
with age (38).
Consistent with our work from our laboratory (4), we showed
that 2 wk of reduced daily activity resulted in a signicant
impairment in glycemic control following ER + SR that did not
fully recover at RC in both groups. We report that ER alone
is capable of inducing a favorable reduction in plasma insulin
concentration in older adults; however, the addition of inactivity
during ER + SR resulted in the elevation of plasma insulin and
impairment of glucose handling. Mirroring changes in fasted
blood glucose, we found that levels of TNF-α, IL-6, and CRP
were signicantly elevated following ER + SR; however, ER
alone did not result in marked changes in systemic inammation.
These ndings are congruent with existing literature using a bed-
rest model in which the authors found a signicant mediating
effect of bed rest on increases in systemic inammation following
35 d of inactivity (39).
The progression of dietary and activity phases in the present
study was a strength of this protocol as it allowed us to
determine the effects of ER alone, and in combination with
ER + SR with high protein intake, on muscle metabolism in
older adults. However, there are some limitations of the current
investigation that we acknowledge. First, we did not directly
measure rates of muscle protein breakdown, and therefore the
relative contributions of MPS and muscle protein breakdown
to changes in LBM and LLM are unknown. Second, all the
participants in the current study were healthy and free of
any chronic condition, thus limiting the applicability of the
intervention to older persons with clinically prevalent chronic
conditions. However, if the detrimental effects of ER and SR
on skeletal muscle are signicantly pronounced in a cohort of
healthy older adults, we propose that losses in muscle mass
and impairments in glycemic control would be worsened in a
compromised older adult population as we have reported (4).
In conclusion, we show here that 2 wk of inactivity resulted
in the loss of LLM and a decrement in MPS. Importantly,
we show that WP was able to stimulate recovery of MPS and
increase LLM in 1 wk of return to habitual activity that was
not seen in men or women supplemented with CP. Congruent
with previous literature, we show that protein supplementation
alone was insufcient to offset the absolute loss of muscle mass
with acute inactivity, but that supplementation with WP may be
protective on LLM from a bout of inactivity combined with a
hypocaloric diet and even enhance recovery following return to
habitual activity.
We thank Todd Prior for his technical assistance.
The authors’ responsibilities were as follows—SYO, CM, and SMP:
conceived and designed the study, and drafted the manuscript; and all authors:
participated in some aspect of data collection and/or analysis, provided
content and/or editorial corrections, and read and approved the nal version
of the manuscript. SMP has received competitive research funding, travel
expenses, and honoraria for speaking from the US National Dairy Council.
The remaining authors had no conicts of interest to declare.
REFERENCES
1. Naruishi K, Kunita A, Kubo K, Nagata T, Takashiba S, Adachi
S. Predictors of improved functional outcome in elderly inpatients
after rehabilitation: a retrospective study. Clin Interv Aging 2014;9:
2133–41.
2. Suetta C, Hvid LG, Justesen L, Christensen U, Neergaard K, Simonsen
L, Ortenblad N, Magnusson SP, Kjaer M, Aagaard P. Effects of aging
on human skeletal muscle after immobilization and retraining. J Appl
Physiol (1985) 2009;107(4):1172–80.
3. Breen L, Stokes KA, Churchward-Venne TA, Moore DR, Baker
SK, Smith K, Atherton PJ, Phillips SM. Two weeks of reduced
activity decreases leg lean mass and induces “anabolic resistance” of
myobrillar protein synthesis in healthy elderly. J Clin Endocrinol
Metab 2013;98(6):2604–12.
4. McGlory C, von Allmen MT, Stokes T, Morton RG, Hector AJ, Lago
BA, Raphenya AR, Smith BK, McArthur AG, Steinberg GR, et al.
Failed recovery of glycemic control and myobrillar protein synthesis
with two weeks of physical inactivity in overweight, pre-diabetic older
adults. J Gerontol A Biol Sci Med Sci 2018;73(8):1070–7.
5. Tieland M, Borgonjen-Van den Berg, van Loon KJ, de Groot
LCPGM LJC. Dietary protein intake in community-dwelling, frail, and
institutionalized elderly people: scope for improvement. Eur J Nutr
2011;51(2):173–9.
6. Leidy HJ, Carnell NS, Mattes RD, Campbell WW. Higher protein intake
preserves lean mass and satiety with weight loss in pre-obese and obese
women. Obesity 2007;15(2):421–9.
7. Gallagher D, Ruts E, Visser M, Heshka S, Baumgartner RN, Wang
J, Pierson RN, Pi-Sunyer FX, Heymseld SB. Weight stability masks
sarcopenia in elderly men and women. Am J Physiol Endocrinol Metab
2000;279(2):E366–75.
8. Drevet S, Bioteau C, Maziere S, Couturier P, Merloz P, Tonetti
J, Gavazzi G. Prevalence of protein-energy malnutrition in hospital
patients over 75 years of age admitted for hip fracture. Orthop
Traumatol Surg Res 2014;100(6):669–74.
9. Yang Y, Churchward-Venne TA, Burd NA, Breen L, Tarnopolsky MA,
Phillips SM. Myobrillar protein synthesis following ingestion of soy
protein isolate at rest and after resistance exercise in elderly men. Nutr
Metab (Lond) 2012;9(1):57.
10. Berggren JR, Boyle KE, Chapman WH, Houmard JA. Skeletal muscle
lipid oxidation and obesity: inuence of weight loss and exercise. Am
J Physiol Endocrinol Metab 2008;294(4):E726–32.
11. Dickinson JM, Fry CS, Drummond MJ, Gundermann DM, Walker
DK, Glynn EL, Timmerman KL, Dhanani S, Volpi E, Rasmussen BB.
Mammalian target of rapamycin complex 1 activation is required for
the stimulation of human skeletal muscle protein synthesis by essential
amino acids. J Nutr 2011;141(5):856–62.
12. Murphy CH, Saddler NI, Devries MC, McGlory C, Baker SK, Phillips
SM. Leucine supplementation enhances integrative myobrillar protein
synthesis in free-living older men consuming lower- and higher-
protein diets: a parallel-group crossover study. Am J Clin Nutr
2016;104(6):1594–606.
13. Devries MC, Breen L, Von Allmen M, MacDonald MJ, Moore
DR, Offord EA, Horcajada MN, Breuille D, Phillips SM. Low-load
resistance training during step-reduction attenuates declines in muscle
mass and strength and enhances anabolic sensitivity in older men.
Physiol Rep 2015;3(8):E12493 1–13. doi: 10.14814/phy2.12493.
14. English KL, Mettler JA, Ellison JB, Mamerow MM, Arentson-Lantz E,
Pattarini JM, Ploutz-Snyder R, Shefeld-Moore M, Paddon-Jones D.
Leucine partially protects muscle mass and function during bed rest in
middle-aged adults. Am J Clin Nutr 2016;103(2):465–73.
Downloaded from https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqy193/5115704 by guest on 05 October 2018
WHEY PROTEIN AND MUSCLE RECOVERY IN OLDER ADULTS 9
15. Dirks ML, Wall BT, Nilwik R, Weerts DH, Verdijk LB, van Loon
LJ. Skeletal muscle disuse atrophy is not attenuated by dietary protein
supplementation in healthy older men. J Nutr 2014;144(8):1196–203.
16. Phillips SM. The impact of protein quality on the promotion of
resistance exercise-induced changes in muscle mass. Nutr Metab (Lond)
2016;13:64.
17. Zdzieblik D, Oesser S, Baumstark MW, Gollhofer A, Konig D.
Collagen peptide supplementation in combination with resistance
training improves body composition and increases muscle strength
in elderly sarcopenic men: a randomised controlled trial. Br J Nutr
2015;114(8):1237–45.
18. Phillips SM, Tipton KD, van Loon LJ, Verdijk LB, Paddon-Jones D,
Close GL. Exceptional body composition changes attributed to collagen
peptide supplementation and resistance training in older sarcopenic
men. Br J Nutr 2016;116(3):569–70.
19. Fisher SR, Goodwin JS, Protas EJ, Kuo YF, Graham JE, Ottenbacher
KJ, Ostir GV. Ambulatory activity of older adults hospitalized with
acute medical illness. J Am Geriatr Soc 2011;59(1):91–5.
20. Henry CJK. Basal metabolic rate studies in humans: measurement
and development of new equations. Public Health Nutr 2007;8(7a):
1133–52.
21. Vikne H, Refsnes PE, Ekmark M, Medb JI, Gundersen V, Gundersen K.
Muscular performance after concentric and eccentric exercise in trained
men. Med Sci Sports Exerc 2006;38(10):1770–81.
22. Washburn RA, Smith KW, Jette AM, Janney CA. The Physical Activity
Scale for the Elderly (PASE): development and evaluation. J Clin
Epidemiol 1993;46(2):153–62.
23. Konturek PC, Herrmann HJ, Schink K, Neurath MF, Zopf Y.
Malnutrition in hospitals: it was, is now,and must not remain a problem!
Med Sci Monit 2015;21:2969–75.
24. Council NR. Recommended Dietary Allowances. 10 ed. Washington
(DC): National Academy Press, 1989.
25. Deutz NE, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-
Westphal A, Cederholm T, Cruz-Jentoft A, Krznaric Z, Nair KS,
et al. Protein intake and exercise for optimal muscle function with
aging: recommendations from the ESPEN Expert Group. Clin Nutr
2014;33(6):929–36.
26. MacDonald AJ, Small AC, Greig CA, Husi H, Ross JA, Stephens NA,
Fearon KC, Preston T. A novel oral tracer procedure for measurement of
habitual myobrillar protein synthesis. Rapid Commun Mass Spectrom
2013;27(15):1769–77.
27. Wilkinson DJ, Franchi MV, Brook MS, Narici MV, Williams JP,
Mitchell WK, Szewczyk NJ, Greenhaff PL, Atherton PJ, Smith
K. A validation of the application of D(2)O stable isotope tracer
techniques for monitoring day-to-day changes in muscle protein
subfraction synthesis in humans. Am J Physiol Endocrinol Metab
2014;306(5):E571–9.
28. Dufner DA, Bederman IR, Brunengraber DZ, Rachdaoui N, Ismail-
Beigi F, Siegfried BA, Kimball SR, Previs SF. Using 2H2Oto
study the inuence of feeding on protein synthesis: effect of isotope
equilibration in vivo vs. in cell culture. Am J Physiol Endocrinol Metab
2005;288(6):E1277–83.
29. Burd NA, Tang JE, Moore DR, Phillips SM. Exercise training and
protein metabolism: inuences of contraction, protein intake, and sex-
based differences. J Appl Physiol (1985) 2009;106(5):1692–701.
30. Bell KE, Seguin C, Parise G, Baker SK, Phillips SM. Day-to-day
changes in muscle protein synthesis in recovery from resistance,
aerobic, and high-intensity interval exercise in older men. J Gerontol
A Biol Sci Med Sci 2015;70(8):1024–9.
31. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF,
Turner RC. Homeostasis model assessment: insulin resistance and β-
cell function from fasting plasma glucose and insulin concentrations in
man. Diabetologia 1985;28(7):412–9.
32. Joanisse S, Gillen JB, Bellamy LM, McKay BR, Tarnopolsky MA,
Gibala MJ, Parise G. Evidence for the contribution of muscle stem cells
to nonhypertrophic skeletal muscle remodeling in humans. FASEB J
2013;27(11):4596–605.
33. Bellamy LM, Joanisse S, Grubb A, Mitchell CJ, McKay BR, Phillips
SM, Baker S, Parise G. The acute satellite cell response and
skeletal muscle hypertrophy following resistance training. PLoS One
2014;9(10):e109739.
34. Nederveen JP, Joanisse S, Seguin CM, Bell KE, Baker SK, Phillips SM,
Parise G. The effect of exercise mode on the acute response of satellite
cells in old men. Acta Physiol (Oxf) 2015;215(4):177–90.
35. Joanisse S, McKay BR, Nederveen JP, Scribbans TD, Gurd BJ, Gillen
JB, Gibala MJ, Tarnopolsky M, Parise G. Satellite cell activity, without
expansion, after nonhypertrophic stimuli. Am J Physiol Regul Integr
Comp Physiol 2015;309(9):R1101–11.
36. Murphy CH, Churchward-Venne TA, Mitchell CJ, Kolar NM, Kassis
A, Karagounis LG, Burke LM, Hawley JA, Phillips SM. Hypoenergetic
diet-induced reductions in myobrillar protein synthesis are restored
with resistance training and balanced daily protein ingestion in older
men. Am J Physiol Endocrinol Metab 2015;308(9):E734–43.
37. Hector AJ, McGlory C, Damas F, Mazara N, Baker SK, Phillips SM.
Pronounced energy restriction with elevated protein intake results in
no change in proteolysis and reductions in skeletal muscle protein
synthesis that are mitigated by resistance exercise. FASEB J 2018;32(1):
265–75.
38. Moore DR, Churchward-Venne TA, Witard O, Breen L, Burd NA,
Tipton KD, Phillips SM. Protein ingestion to stimulate myobrillar
protein synthesis requires greater relative protein intakes in healthy
older versus younger men. J Gerontol A Biol Sci Med Sci
2015;70(1):57–62.
39. Biolo G, Agostini F, Simunic B, Sturma M, Torelli L, Preiser JC, Deby-
Dupont G, Magni P, Strollo F, di Prampero P, et al. Positive energy
balance is associated with accelerated muscle atrophy and increased
erythrocyte glutathione turnover during 5 wk of bed rest. Am J Clin
Nutr 2008;88(4):950–8.
Downloaded from https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqy193/5115704 by guest on 05 October 2018
... Periods of reduced skeletal muscle loading are inevitable and can arise from various situations, including limb immobilization, bed rest, spaceflight, or spinal cord injury. While not complete muscle disuse or unloading, we have discovered that reduced physical activity (i.e., step reduction) is also a disuselike stimulus and recapitulates some of the same effects (31,167,200,201,246). Mechanistically, the loss of skeletal muscle mass can be underpinned by imbalances in MPS and MPB (8). ...
... While not complete muscle disuse or unloading, we have discovered that reduced physical activity (i.e., step reduction) is also a disuselike stimulus and recapitulates some of the same effects (31,167,200,201,246). Mechanistically, the loss of skeletal muscle mass can be underpinned by imbalances in MPS and MPB (8). Work from our group (31,166,167,201,263) and others (91,92,135,288,290), have attributed the loss of muscle mass with muscle disuse, for the most part, to a reduction in rates of MPS. Gibson et al. (91) were the first to report a 25% reduction in fasted rates of MPS following 5 weeks of unilateral lower-limb immobilization, in healthy young men with tibial fractures. ...
... Consistent with the notion of skeletal muscle disuse-induced "anabolic resistance," integrated rates of MPS (i.e., fed and fasting) are rapidly decreased during periods of reduced skeletal muscle activity. As little as 2 weeks of step reduction (<1000 steps/day) was sufficient to reduce integrated rates of MPS by 13%-26% from baseline, in healthy older adults, which is not recovered following 2 weeks of return to habitual activity (167,201). We demonstrated that 2 weeks of single-leg immobilization was sufficient to depress integrated rates of MPS by a similar but opposite magnitude as 10 weeks of RT in healthy young men (263). ...
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Skeletal muscle is the organ of locomotion, its optimal function is critical for athletic performance, and is also important for health due to its contribution to resting metabolic rate and as a site for glucose uptake and storage. Numerous endogenous and exogenous factors influence muscle mass. Much of what is currently known regarding muscle protein turnover is owed to the development and use of stable isotope tracers. Skeletal muscle mass is determined by the meal- and contraction-induced alterations of muscle protein synthesis and muscle protein breakdown. Increased loading as resistance training is the most potent nonpharmacological strategy by which skeletal muscle mass can be increased. Conversely, aging (sarcopenia) and muscle disuse lead to the development of anabolic resistance and contribute to the loss of skeletal muscle mass. Nascent omics-based technologies have significantly improved our understanding surrounding the regulation of skeletal muscle mass at the gene, transcript, and protein levels. Despite significant advances surrounding the mechanistic intricacies that underpin changes in skeletal muscle mass, these processes are complex, and more work is certainly needed. In this article, we provide an overview of the importance of skeletal muscle, describe the influence that resistance training, aging, and disuse exert on muscle protein turnover and the molecular regulatory processes that contribute to changes in muscle protein abundance. © 2021 American Physiological Society. Compr Physiol 11:2249-2278, 2021.
... Totally 686 subjects were examined in the studies which varied from 12 to 146 people. The studies were published from 2006 to 2020 and conducted in Italy [9], Denmark [2,35], Brazil [29], China [30,31], Canada [32,36], USA [33,34] and Australia [19]. All the studies had parallel design. ...
... The WP dose varies from 4 to 60 g per day and the duration of supplement administration ranged from 4 to 72 weeks. RCTs included elderly [32], overweight and obese participants [2,19,35], people with diabetes mellitus type 2 (DMT2) [9], sarcopenic obesity [29], hypertension [30], postmenopausal condition [34], alcoholic liver injury [31], chronic obstructive pulmonary disease (COPD) [36], and hemodialysis [33]. Participants in control groups took carbohydrate (maltodextrin [2,29,30,34], corn starch [31] and glucose [19]) or other type of proteins (casein [9,19,35,36], collagen [32], corn peptide [31] and soy protein [33]) as placebo. ...
... RCTs included elderly [32], overweight and obese participants [2,19,35], people with diabetes mellitus type 2 (DMT2) [9], sarcopenic obesity [29], hypertension [30], postmenopausal condition [34], alcoholic liver injury [31], chronic obstructive pulmonary disease (COPD) [36], and hemodialysis [33]. Participants in control groups took carbohydrate (maltodextrin [2,29,30,34], corn starch [31] and glucose [19]) or other type of proteins (casein [9,19,35,36], collagen [32], corn peptide [31] and soy protein [33]) as placebo. ...
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... Although in some cases, ambulation and some rehabilitation therapies are sufficient to restore lost muscle following a disuse event, in other populations, such as older individuals and those having undergone prolonged disuse or catabolic event, a multifaceted approach is necessary. Studies in animal models seeking to identify nutritional strategies to prevent or, at least, curtail disuse-induced muscle atrophy are promising (199,200), but human investigations using various nutritional approaches, including supplementation with protein (166,201), essential amino acids (EAA) (20,37,202), leucine (21,165,203,204), branched-chain amino acids (BCAA) (205), and b-hydroxy b-methyl-butyrate (HMB) (206) are inconsistent. Importantly, manipulating nutritional intake during disuse is not always possible. ...
... Mitchell and colleagues (166) showed that supplemental consumption of dairy protein (20 g/day) did not assist in the recovery of lost muscle with 2 wk of passive reambulation (i.e., no structured rehabilitation) or 2 wk of resistance training in middle-aged males, despite augmenting myofibrillar fractional synthetic rate. Conversely, although whey protein supplementation (2 Â 30 g/day) did not protect against muscle loss during step reduction and energy restriction, it did facilitate an enhanced rate of integrated MPS and a rapid regain of whole body and leg lean mass during return to habitual activity in older men and women (201). The consumption of whey protein also facilitated the recovery of knee extensor strength following 7 days of bed rest and 5 days of progressive rehabilitation (consisting of 45 min/day stretching and balance/strength-focused exercises) (209). ...
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Decreased skeletal muscle contractile activity (disuse) or unloading leads to muscle mass loss, also known as muscle atrophy. The balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB) is the primary determinant of skeletal muscle mass. A reduced mechanical load on skeletal muscle is one of the main external factors leading to muscle atrophy. However, endocrine and inflammatory factors can act synergistically in catabolic states, amplifying the atrophy process and accelerating its progression. Additionally, older individuals display aging-induced anabolic resistance, which can predispose this population to more pronounced effects when exposed to periods of reduced physical activity or mechanical unloading. Different cellular mechanisms contribute to the regulation of muscle protein balance during skeletal muscle atrophy. This review summarizes the effects of muscle disuse on muscle protein balance and the molecular mechanisms involved in muscle atrophy in the absence or presence of disease. Finally, a discussion of the current literature describing efficient strategies to prevent or improve the recovery from muscle atrophy is also presented.
... 8 Growth hormone regulates a number of metabolic processes, with which IGF-1 assists, including protein metabolism. 9 Furthermore, muscle protein synthesis is also suppressed by an energy deficient status, 10 an impairment often accompanied by the loss of LM. 11 For a more comprehensive review of the effects of low energy availability, the reader is referred to a recent review. 3 In a field of research containing a large number of small studies, synthesis of results using methods like meta-analyses is important to objectively evaluate the effectiveness of these interventions and provide strong evidence of directions for future research. ...
... This result aligns with previous literature showing the commonly prescribed energy deficit of 500 kcal day −1 impairs LM retention. 11 The relationship between RT and LM was influenced by the severity of the energy deficit, weight status, and age, but not sex or duration of the intervention. As a result of the regression analysis, we represented the negative association between LM gains and the strength of energy deficit as a linear relationship. ...
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Short‐term energy deficits impair anabolic hormones and muscle protein synthesis. However, the effects of prolonged energy deficits on resistance training (RT) outcomes remain unexplored. Thus, we conducted a systematic review of PubMed and SportDiscus for randomized controlled trials performing RT in an energy deficit (RT+ED) for ≥3 weeks. We first divided the literature into studies with a parallel control group without an energy deficit (RT+CON; Analysis A) and studies without RT+CON (Analysis B). Analysis A consisted of a meta‐analysis comparing gains in lean mass (LM) and strength between RT+ED and RT+CON. Studies in Analysis B were matched with separate RT+CON studies for participant and intervention characteristics, and we qualitatively compared the gains in LM and strength between RT+ED and RT+CON. Finally, Analyses A and B were pooled into a meta‐regression examining the relationship between the magnitude of the energy deficit and LM. Analysis A showed LM gains were impaired in RT+ED vs RT+CON (effect size (ES) = ‐0.57, p = .02), but strength gains were comparable between conditions (ES = ‐0.31, p = .28). Analysis B supports the impairment of LM in RT+ED (ES: ‐0.11, p = .03) vs RT+CON (ES: 0.20, p < .001) but not strength (RT+ED ES: 0.84; RT+CON ES: 0.81). Finally, our meta‐regression demonstrated that an energy deficit of ~500 kcal · day‐1 prevented gains in LM. Individuals performing RT to build LM should avoid prolonged energy deficiency, and individuals performing RT to preserve LM during weight loss should avoid energy deficits >500 kcal · day‐1.
... However, the hydrolysis of this by-product has become a sustainable way to revalue it. In this sense, researchers have investigated the effect of specific collagen peptides (SCP) by their biological properties (98,99), some of them related to joint soreness. Clark et al. (100), pioneered the analysis of the effect of SCP supplementation in sportsmen's joint soreness. ...
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Nutrition and sport play an important role in achieving a healthy lifestyle. In addition to the intake of nutrients derived from the normal diet, some sport disciplines require the consumption of supplements that contribute positively to improved athletic performance. Protein intake is important for many aspects related to health, and current evidence suggests that some athletes require increased amounts of this nutrient. On the other hand, society's demand for more environmentally friendly products, focus on the search for alternative food sources more sustainable. This review aims to summarize the latest research on novel strategies and sources for greener and functional supplementation in sport nutrition. Alternative protein sources such as insects, plants or mycoproteins have proven to be an interesting substrate due to their high added value in terms of bioactivity and sustainability. Protein hydrolysis has proven to be a very useful technology to revalue by-products, such as collagen, by producing bioactive peptides beneficial on athletes performance and sport-related complications. In addition, it has been observed that certain amino acids from plant sources, as citrulline or theanine, can have an ergogenic effect for this target population. Finally, the future perspectives of protein supplementation in sports nutrition are discussed. In summary, protein supplementation in sports nutrition is a very promising field of research, whose future perspective lies with the search for alternatives with greater bioactive potential and more sustainable than conventional sources.
... One such model is step reduction (SR). In the SR experiment, subjects reduce the amount of daily walking (while counting each step with a pedometer) to the minimum values (750-5000 steps) [37,38]. The lower threshold for the number of steps (~750) approximately corresponds to the activity of outpatients [39]. ...
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Skeletal muscle is capable of changing its structural parameters, metabolic rate and functional characteristics within a wide range when adapting to various loading regimens and states of the organism. Prolonged muscle inactivation leads to serious negative consequences that affect the quality of life and work capacity of people. This review examines various conditions that lead to decreased levels of muscle loading and activity and describes the key molecular mechanisms of muscle responses to these conditions. It also details the theoretical foundations of various methods preventing adverse muscle changes caused by decreased motor activity and describes these methods. A number of recent studies presented in this review make it possible to determine the molecular basis of the countermeasure methods used in rehabilitation and space medicine for many years, as well as to identify promising new approaches to rehabilitation and to form a holistic understanding of the mechanisms of gravity force control over the muscular system.
... These findings corroborate data from a previous study conducted by the same research group that showed higher rates of integrated MPS and better recovery of leg lean mass with consumption of whey versus collagen protein in healthy older individuals after a period of energy restriction and step reduction (<750 daily steps) [181]. The results of these two studies regarding the anabolic potential of whey and collagen proteins might be explained by the differences in the quality of the protein sources consumed. ...
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Sarcopenia is one of the main issues associated with the process of aging. Characterized by muscle mass loss, it is triggered by several conditions, including sedentary habits and negative net protein balance. According to World Health Organization, it is expected a 38% increase in older individuals by 2025. Therefore, it is noteworthy to establish recommendations to prevent sarcopenia and several events and comorbidities associated with this health issue condition. In this review, we discuss the role of these factors, prevention strategies, and recommendations, with a focus on protein intake and exercise.
... The results of these studies suggest that CP supplementation, which has a protein quality score lower than both soy and rice protein (Phillips, 2017), is also effective in improving RTinduced muscle adaptations, contradicting the thesis that protein sources with a higher quantity of EAAs, in particular leucine, are crucial for hypertrophic gains. However, comparisons of CP supplementation with high-quality WP protein have shown a superiority of WP to increase the MPS in both rest and exercise in older women (Oikawa et al., 2020) and only WP increased leg lean mass and MPS during recovery from inactivity and hypoenergetic state in older persons (Oikawa et al., 2018). ...
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Collagen is the central structural component of extracellular connective tissue, which provides elastic qualities to tissues. For skeletal muscle, extracellular connective tissue transmits contractile force to the tendons and bones. Connective tissue proteins are in a constant state of remodeling and have been shown to express a high level of plasticity. Dietary-protein ingestion increases muscle protein synthesis rates. High-quality, rapidly digestible proteins are generally considered the preferred protein source to maximally stimulate myofibrillar (contractile) protein synthesis rates. In contrast, recent evidence demonstrates that protein ingestion does not increase muscle connective tissue protein synthesis. The absence of an increase in muscle connective tissue protein synthesis after protein ingestion may be explained by insufficient provision of glycine and/or proline. Dietary collagen contains large amounts of glycine and proline and, therefore, has been proposed to provide the precursors required to facilitate connective tissue protein synthesis. This literature review provides a comprehensive evaluation of the current knowledge on the proposed benefits of dietary collagen consumption to stimulate connective tissue remodeling to improve health and functional performance.
Chapter
This chapter discusses the uses of biologically active peptides in sports nutrition and their potential mechanisms. In the beginning, it presents physiological parameters that determine athletic performance and how they may be positively influenced by nutrition and potentially the intake of bioactive peptides. It then discusses the potential effects of bioactive peptides on first body composition and muscular performance, second muscle damage, and lastly adaptions of connective tissue. The following section outlines the limitations of previous research about bioactive peptides and their potential mechanisms. By the end of the chapter, it presents practical applications that may help athletes to integrate bioactive peptides into sports nutrition to improve athletic performance as well as injury prevention and rehabilitation.
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Preservation of lean body mass (LBM) may be important during dietary energy restriction (ER) and requires equal rates of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Currently, the relative contribution of MPS and MPB to the loss of LBM during ER in humans is unknown. We aimed to determine the impact of dietary protein intake and resistance exercise on MPS and MPB during a controlled short-term energy deficit. Adult men (body mass index, 28.6 ± 0.6 kg/m(2); age 22 ± 1 yr) underwent 10 d of 40%-reduced energy intake while performing unilateral resistance exercise and consuming lower protein (1.2 g/kg/d, n = 12) or higher protein (2.4 g/kg per d, n = 12). Pre- and postintervention testing included dual-energy X-ray absorptiometry, primed constant infusion of ring-[(13)C6]phenylalanine, and (15)[N]phenylalanine to measure acute postabsorptive MPS and MPB; D2O to measure integrated MPS; and gene and protein expression. There was a decrease in acute MPS after ER (higher protein, 0.059 ± 0.006 to 0.051 ± 0.009%/h; lower protein, 0.061 ± 0.005-0.045 ± 0.006%/h; P < 0.05) that was attenuated with resistance exercise (higher protein, 0.067 ± 0.01%/h; lower protein, 0.061 ± 0.006%/h), and integrated MPS followed a similar pattern. There was no change in MPB (energy balance, 0.080 ± 0.01%/hr; ER rested legs, 0.078 ± 0.008%/hr; ER exercised legs, 0.079 ± 0.006%/hr). We conclude that a reduction in MPS is the main mechanism that underpins LBM loss early in ER in adult men.-Hector, A. J., McGlory, C., Damas, F., Mazara, N., Baker, S. K., Phillips, S. M. Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise.
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Protein supplementation during resistance exercise training augments hypertrophic gains. Protein ingestion and the resultant hyperaminoacidemia provides the building blocks (indispensable amino acids – IAA) for, and also triggers an increase in, muscle protein synthesis (MPS), suppression of muscle protein breakdown (MPB), and net positive protein balance (i.e., MPS > MPB). The key amino acid triggering the rise in MPS is leucine, which stimulates the mechanistic target of rapamycin complex-1, a key signalling protein, and triggers a rise in MPS. As such, ingested proteins with a high leucine content would be advantageous in triggering a rise in MPS. Thus, protein quality (reflected in IAA content and protein digestibility) has an impact on changes in MPS and could ultimately affect skeletal muscle mass. Protein quality has been measured by the protein digestibility-corrected amino acid score (PDCAAS); however, the digestible indispensable amino acid score (DIAAS) has been recommended as a better method for protein quality scoring. Under DIAAS there is the recognition that amino acids are individual nutrients and that protein quality is contingent on IAA content and ileal (as opposed to fecal) digestibility. Differences in protein quality may have important ramifications for exercise-induced changes in muscle mass gains made with resistance exercise as well as muscle remodelling. Thus, the purpose of this review is a critical appraisal of studies examining the effects of protein quality in supplementation on changes in muscle mass and strength as well as body composition during resistance training.
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Exceptional body composition changes attributed to collagen peptide supplementation and resistance training in older sarcopenic men - Volume 116 Issue 3 - Stuart M. Phillips, Kevin D. Tipton, Luc J. C. van Loon, Lex B. Verdijk, Douglas Paddon-Jones, Graeme L. Close
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Background: Physical inactivity triggers a rapid loss of muscle mass and function in older adults. Middle-aged adults show few phenotypic signs of aging yet may be more susceptible to inactivity than younger adults. Objective: The aim was to determine whether leucine, a stimulator of translation initiation and skeletal muscle protein synthesis (MPS), can protect skeletal muscle health during bed rest. Design: We used a randomized, double-blind, placebo-controlled trial to assess changes in skeletal MPS, cellular signaling, body composition, and skeletal muscle function in middle-aged adults (n = 19; age ± SEM: 52 ± 1 y) in response to leucine supplementation (LEU group: 0.06 g ∙ kg(-1) ∙ meal(-1)) or an alanine control (CON group) during 14 d of bed rest. Results: Bed rest decreased postabsorptive MPS by 30% ± 9% (CON group) and by 10% ± 10% (LEU group) (main effect for time, P < 0.05), but no differences between groups with respect to pre-post changes (group × time interactions) were detected for MPS or cell signaling. Leucine protected knee extensor peak torque (CON compared with LEU group: -15% ± 2% and -7% ± 3%; group × time interaction, P < 0.05) and endurance (CON compared with LEU: -14% ± 3% and -2% ± 4%; group × time interaction, P < 0.05), prevented an increase in body fat percentage (group × time interaction, P < 0.05), and reduced whole-body lean mass loss after 7 d (CON compared with LEU: -1.5 ± 0.3 and -0.8 ± 0.3 kg; group × time interaction, P < 0.05) but not 14 d (CON compared with LEU: -1.5 ± 0.3 and -1.0 ± 0.3 kg) of bed rest. Leucine also maintained muscle quality (peak torque/kg leg lean mass) after 14 d of bed-rest inactivity (CON compared with LEU: -9% ± 2% and +1% ± 3%; group × time interaction, P < 0.05). Conclusions: Bed rest has a profoundly negative effect on muscle metabolism, mass, and function in middle-aged adults. Leucine supplementation may partially protect muscle health during relatively brief periods of physical inactivity. This trial was registered at clinicaltrials.gov as NCT00968344.
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Aim: A dysregulation of satellite cells may contribute to the progressive loss of muscle mass that occurs with age; however, older adults retain the ability to activate and expand their satellite cell pool in response to exercise. The modality of exercise capable of inducing the greatest acute response is unknown. We sought to characterize the acute satellite cell response following different modes of exercise in older adults. Methods: Sedentary older men (n=22; 67±4yrs; 27±2.6kg*m(-2) ) were randomly assigned to complete an acute bout of either resistance exercise, high intensity interval exercise on a cycle ergometer or moderate intensity aerobic exercise. Muscle biopsies were obtained before, 24 and 48h following each exercise bout. The satellite cell response was analyzed using immunofluorescent microscopy of muscle cross sections. Results: Satellite cell expansion associated with type I fibres was observed 24 and 48h following resistance exercise only (p˂0.05) while no expansion of type II associated satellite cells was observed in any group. There was a greater number of activated satellite cells 24h following resistance exercise (pre: 1.3±0.1, 24h: 4.8±0.5Pax7+/MyoD+cells/100 fibres) and high intensity interval exercise (pre: 0.7±0.3, 24h: 3.1±0.3Pax7+/MyoD+cells/100 fibres) (p˂0.05). The percentage of type I associated SC co-expressing MSTN was reduced only in the RE group 24h following exercise (pre: 87±4, 24h: 57±5%MSTN+ Type I SC) (p<0.001). Conclusion: Although resistance exercise is the most potent exercise type to induce satellite cell pool expansion, high intensity interval exercise was also more potent than moderate intensity aerobic exercise in inducing satellite cell activity. This article is protected by copyright. All rights reserved.
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Protein supplementation in combination with resistance training may increase muscle mass and muscle strength in elderly subjects. The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia. A total of fifty-three male subjects (72·2 (sd 4·68) years) with sarcopenia (class I or II) completed this randomised double-blind placebo-controlled study. All the participants underwent a 12-week guided resistance training programme (three sessions per week) and were supplemented with either collagen peptides (treatment group (TG)) (15 g/d) or silica as placebo (placebo group (PG)). Fat-free mass (FFM), fat mass (FM) and bone mass (BM) were measured before and after the intervention using dual-energy X-ray absorptiometry. Isokinetic quadriceps strength (IQS) of the right leg was determined and sensory motor control (SMC) was investigated by a standardised one-leg stabilisation test. Following the training programme, all the subjects showed significantly higher (P<0·01) levels for FFM, BM, IQS and SMC with significantly lower (P<0·01) levels for FM. The effect was significantly more pronounced in subjects receiving collagen peptides: FFM (TG +4·2 (sd 2·31) kg/PG +2·9 (sd 1·84) kg; P<0·05); IQS (TG +16·5 (sd 12·9) Nm/PG +7·3 (sd 13·2) Nm; P<0·05); and FM (TG -5·4 (sd 3·17) kg/PG -3·5 (sd 2·16) kg; P<0·05). Our data demonstrate that compared with placebo, collagen peptide supplementation in combination with resistance training further improved body composition by increasing FFM, muscle strength and the loss in FM.
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Background Physical inactivity impairs insulin sensitivity, which is exacerbated with aging. We examined the impact of two weeks of acute inactivity and recovery on glycemic control, integrated rates of muscle protein synthesis (MPS) in older men and women. Methods Twenty-two overweight, pre-diabetic older adults (12 men, 10 women, 69 ± 4 yr) undertook 7 d of habitual activity (baseline; BL), step reduction (SR; <1000 steps .d⁻¹ for 14 d), followed by 14d of recovery (RC). An oral glucose tolerance test was used to assess glycemic control and deuterated water ingestion to measure integrated rates of MPS. Results Daily step count was reduced (all P<0.05) from BL at SR (7362±3294 to 991±97) and returned to BL levels at RC (7117±3819). Homeostasis model assessment-insulin resistance increased from BL to SR and Matsuda insulin sensitivity index decreased and did not return to BL in RC. Glucose and insulin are under the curve were elevated from BL to SR and did not recover in RC. Integrated MPS was reduced during SR and did not return to BL in RC. Conclusions Our findings demonstrate that two weeks of SR leads to lowered rates of MPS and a worsening of glycemic control that unlike younger adults, is not recovered during return to normal activity in overweight, pre-diabetic elderly humans. Clinical Trials Registration ClinicalTrials.gov identifier: NCT03039556.
Article
Background: Leucine co-ingestion with lower-protein (LP)-containing meals may overcome the blunted muscle protein synthetic response to food intake in the elderly but may be effective only in individuals who consume LP diets. Objective: We examined the impact of leucine co-ingestion with mixed macronutrient meals on integrated 3-d rates of myofibrillar protein synthesis (MyoPS) in free-living older men who consumed higher protein (HP) (1.2 g · kg(-1) · d(-1)) or LP (0.8 g · kg(-1) · d(-1)) in rested and resistance exercise (REX) conditions. Design: In a crossover design, 20 healthy older men [aged 65-85 y] were randomly assigned to receive LP or HP diets while ingesting a placebo (days 0-2) and Leu supplement (5 g leucine/meal; days 3-5) with their 3 main daily meals. A bout of unilateral REX was performed during the placebo and Leu treatments. Ingested (2)H2O and skeletal muscle biopsies were used to measure the 3-d integrated rate of MyoPS during the placebo and Leu treatments in the rested and REX legs. Results: Leucinemia was higher with Leu treatment than with placebo treatment (P < 0.001). MyoPS was similar in LP and HP during both treatments (P = 0.39) but was higher with Leu treatment than with placebo treatment in the rested (pooled mean ± SD: Leu, 1.57% ± 0.11%/d; placebo, 1.48% ± 0.08%/d; main effect of treatment: P < 0.001) and REX (pooled mean: Leu, 1.87% ± 0.09%/d; placebo, 1.71 ± 0.10%/d; main effect of treatment: P < 0.001) legs. Conclusions: Leu co-ingestion with daily meals enhances integrated MyoPS in free-living older men in rested and REX conditions and is equally effective in older men who consume daily protein intakes greater than or equal to the RDA. This trial was registered at clinicaltrials.gov as NCT02371278.
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Background: Malnutrition is an under-recognized problem in hospitalized patients. Despite systematic screening, the prevalence of malnutrition in the hospital did not decrease in the last few decades. The aim of our study was to evaluate the prevalence of malnutrition and to determine the explicit daily calorie intake of hospitalized patients, to identify the risk factors of developing malnutrition during hospitalization and the effect on the financial reimbursement according to the German DRG-system. Material/Methods: 815 hospitalized patients were included in this study. The detection of malnutrition was based on the nutritional-risk-screening (NRS) and subjective-global-assessment (SGA) scores. A trained investigator recorded the daily calorie and fluid intake of each patient. Furthermore, clinical parameters, and the financial reimbursement were evaluated. Results: The prevalence of malnutrition was 53.6% according to the SGA and 44.6% according the NRS. During hospitalization, patients received on average 759.9 +/- 546.8 kcal/day. The prevalence of malnutrition was increased in patients with hepatic and gastrointestinal disease and with depression or dementia. The most important risk factors for malnutrition were bed rest and immobility (OR=5.88, 95% CI 2.25-15.4). In 84.5% of patient records, malnutrition was not correctly coded, leading to increased financial losses according to the DRG-system (94.908 Euros). Conclusions: Hospitalized patients suffer from inadequate nutritional therapy and the risk for developing malnutrition rises during the hospital stay. The early screening of patients for malnutrition would not only improve management of nutritional therapy but also, with adequate coding, improve financial reimbursement according to the DRG-system.
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Background Malnutrition is an under-recognized problem in hospitalized patients. Despite systematic screening, the prevalence of malnutrition in the hospital did not decrease in the last few decades. The aim of our study was to evaluate the prevalence of malnutrition and to determine the explicit daily calorie intake of hospitalized patients, to identify the risk factors of developing malnutrition during hospitalization and the effect on the financial reimbursement according to the German DRG-system.