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
Open accessAbstract
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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- Findingown data
Twice-daily supplementation with whey protein was effective at increasing muscle protein synthesis rates from the ER+SR phase during the RC phase, compared with collagen peptide supplementation.
“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.”
Quote in the paperSubstantial claim - Findingown data
IL-6 levels decreased significantly from the EB phase to the ER phase.
“Levels of IL-6 were significantly decreased at ER from EB (P = 0.049)”
Quote in the paperNot a substantial claim - Findingown data
There were no significant differences between the WP and CP groups in type I or type II fiber cross-sectional area.
“with no significant differences between groups (P > 0.05; Table 5)”
- Also stated in: § DISCUSSION · plain
“There were no significant differences in type I or II CSA at EB or ER + SR or between WP and CP.”
Quote in the paperNot a substantial claim - Also stated in: § DISCUSSION · plain
- Findingown data
HOMA-IR at the RC phase was not different from the EB and ER+SR phases.
“and then remained at levels no different to those of EB and ER + SR at RC (P > 0.05)”
Quote in the paperNot a substantial claim - Findingown data
CRP levels were significantly elevated at the ER+SR phase compared with the EB phase.
“Levels of CRP were significantly elevated at ER + SR from EB (P = 0.034)”
Quote in the paperNot a substantial claim
- Findingown data
HOMA-IR decreased significantly from the EB phase to the ER phase.
“HOMA-IR was significantly decreased from EB at ER (P < 0.001)”
Quote in the paperNot a substantial claim - Findingown data
IL-6 levels at the ER+SR phase were significantly elevated compared with all other time points.
“and elevated from all other time points at ER + SR (EB and ER P < 0.0001, ER + SR P = 0.018)”
Quote in the paperNot a substantial claim - Findingown data
Basal myofibrillar muscle protein synthesis rates did not differ significantly between groups during energy balance.
“There were no significant differences between basal rates of myofibrillar MPS between groups during EB (P > 0.05).”
Quote in the paperNot a substantial claim - Findingown data
Fractional synthetic rate fell significantly in both groups during energy restriction.
“ER resulted in a significant reduction in fractional synthetic rate in both groups (P < 0.001).”
Quote in the paperSubstantial claim - Findingown data
No dietary variable differed significantly between groups at any time point.
“There were no significant differences in any dietary variable between groups at any time points (P > 0.05) (Table 3).”
Quote in the paperSubstantial claim - Findingown data
Consuming a whey protein supplement, compared with a collagen peptide supplement, increased integrated muscle protein synthesis upon return to habitual physical activity.
“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.”
Quote in the paperSubstantial claim - Findingown data
CRP levels remained elevated at the RC phase compared with the ER phase.
“Levels of CRP were significantly elevated at ER + SR from EB (P = 0.034), and remained elevated at RC from EB (P = 0.003) and ER (P = 0.029).”
Quote in the paperNot a substantial claim - Findingown data
During the ER+SR phase, there was no further decline in integrated myofibrillar muscle protein synthesis beyond that seen at ER.
“and that during ER + SR there was no further decline.”
Quote in the paperSubstantial claim - Findingown data
Two weeks of physical inactivity (step reduction to fewer than 750 steps per day) combined with a mild energy deficit (-500 kcal/d) caused a significant reduction in leg lean mass in older men and women who consumed protein at twice the RDA.
“The novel finding of the present investigation was that 2 wk of physical inactivity (step reduction, <750 steps/d) in combination with a mild energy deficit (-500 kcal/d) resulted in a significant reduction in LLM in older men and women consuming a protein intake twice the RDA.”
Quote in the paperSubstantial claim - Findingown data
Lean body mass overall dropped significantly in energy restriction plus step reduction relative to energy balance.
“Total lean body mass (LBM) was significantly reduced in ER + SR in comparison to EB (P < 0.001).”
Quote in the paperSubstantial claim - Findingown data
TNF-α concentrations at the ER+SR phase were significantly elevated compared with all other phases.
“Concentrations of TNF-α at ER + SR were significantly elevated from all other phases.”
Quote in the paperNot a substantial claim - Findingown data
Muscle protein synthesis rates in the collagen peptide group remained suppressed after return to habitual activity.
“Interestingly, rates of MPS in the CP group remained suppressed following return to habitual activity.”
Quote in the paperSubstantial claim - Findingown data
There were no significant changes in type I or type II fiber cross-sectional area from the EB phase to the ER+SR phase.
“There were no significant changes in either type I or type II fiber CSA from EB to ER + SR (P > 0.05)”
Quote in the paperNot a substantial claim - Findingown data
Protein and calorie intakes did not differ significantly between the whey protein and collagen peptide groups at any phase.
“There were no significant differences in protein or calorie intake between WP and CP at any phase.”
Quote in the paperSubstantial claim - Findingown data
A reduction in energy intake caused a decline of approximately 16% in integrated myofibrillar muscle protein synthesis.
“Consistent with previous reports (36,37), we show that a reduction in energy intake induced a decline of ∼16% in integrated myofibrillar MPS”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [36] Murphy, 2015, Hypoenergetic diet-induced reductions in myofibrillar protein synthesis are restored with resistance training and balanced daily protein ingestion in older men, Am J Physiol Endocrinol Metab source
Not checked in the free run.
- cites [37] Hector, 2018, 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 source
Not checked in the free run.
- Findingown data
Protein from supplements made up 45% ± 9% of total protein intake during energy restriction, energy restriction plus step reduction, and recovery, while food provided the remaining 55% ± 9%.
“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.”
Quote in the paperNot a substantial claim - Findingown data
There were no significant differences between the WP and CP groups at any time point.
“There were no significant differences between the WP and CP groups at any time point.”
Quote in the paperNot a substantial claim - Findingown data
In recovery, total lean body mass rose only in the whey protein group.
“In RC, there was an increase in LBM, but only in WP (Figure 3A).”
Quote in the paperSubstantial claim - Findingown data
Plasma insulin concentration returned to levels similar to the EB phase during the ER+SR phase.
“but returned to levels similar to EB at ER + SR (P = 0.03)”
Quote in the paperNot a substantial claim - Findingown data
HOMA-IR was significantly elevated from the ER phase to the ER+SR phase, reaching levels similar to the EB phase.
“but then was significantly elevated from ER at ER + SR, similar to EB (P = 0.02)”
Quote in the paperNot a substantial claim - Findingown data
Plasma insulin concentration decreased again during the RC phase.
“before decreasing again at RC (P = 0.001)”
Quote in the paperNot a substantial claim - Findingown data
During recovery, leg lean mass rose from energy restriction plus step reduction only in the whey protein group.
“During RC, LLM increased from ER + SR, but in the WP group only.”
- Also stated in: § Body composition · plain
“Losses in LLM mimicked losses in LBM with a significant reduction at ER + SR in comparison to ER that was increased at RC compared with other times in WP, but not in CP (Figure 3B).”
Quote in the paperSubstantial claim - Also stated in: § Body composition · plain
- Findingown data
CRP levels remained elevated at the RC phase compared with the EB phase.
“Levels of CRP were significantly elevated at ER + SR from EB (P = 0.034), and remained elevated at RC from EB (P = 0.003) and ER (P = 0.029).”
Quote in the paperNot a substantial claim - Findingown data
Rates of muscle protein synthesis remained suppressed at energy restriction plus step reduction and recovery from energy balance in the collagen peptide group.
“Rates of MPS remained suppressed at ER + SR (P < 0.001), and RC (P < 0.001) from EB in the CP group (Figure 4).”
Quote in the paperSubstantial claim - Findingown data
Plasma insulin concentration decreased significantly from the EB phase to the ER phase.
“Plasma insulin concentration decreased significantly from EB at ER (P < 0.001)”
Quote in the paperNot a substantial claim - Findingown data
Energy restriction alone produced no marked changes in systemic inflammation.
“however, ER alone did not result in marked changes in systemic inflammation.”
Quote in the paperNot a substantial claim - Findingown data
TNF-α, IL-6, and CRP concentrations were significantly higher after the ER+SR phase.
“Mirroring changes in fasted blood glucose, we found that levels of TNF-α, IL-6, and CRP were significantly elevated following ER + SR”
Quote in the paperNot a substantial claim - Findingown data
Energy restriction alone can favorably reduce plasma insulin concentration in older adults.
“We report that ER alone is capable of inducing a favorable reduction in plasma insulin concentration in older adults”
Quote in the paperSubstantial claim - Findingown data
Two weeks of inactivity resulted in a decrement in muscle protein synthesis.
“In conclusion, we show here that 2 wk of inactivity resulted in the loss of LLM and a decrement in MPS.”
Quote in the paperSubstantial claim - Findingown data
Protein supplementation by itself could not prevent the absolute muscle mass loss caused by acute inactivity.
“Congruent with previous literature, we show that protein supplementation alone was insufficient to offset the absolute loss of muscle mass with acute inactivity”
Quote in the paperSubstantial claim - Findingown data
Men and women who received collagen peptide did not show these effects.
“that was not seen in men or women supplemented with CP.”
Quote in the paperSubstantial claim - Findingown data
Two weeks of reduced daily activity caused a significant impairment in glycemic control following the ER+SR phase that did not fully recover at the RC phase in both groups.
“Consistent with our work from our laboratory (4), we showed that 2 wk of reduced daily activity resulted in a significant impairment in glycemic control following ER + SR that did not fully recover at RC in both groups.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] McGlory, 2018, Failed recovery of glycemic control and myofibrillar protein synthesis with two weeks of physical inactivity in overweight, pre-diabetic older adults, J Gerontol A Biol Sci Med Sci source
Not checked in the free run.
- Findingown data
The changes in leg lean mass and lean body mass in this study do not show a significant benefit of protein supplementation for offsetting muscle loss during reduced activity.
“Congruent with these findings, our changes in LLM and LBM do not show a significant benefit of supplementation to offset muscle loss during a period of reduced activity”
Quote in the paperSubstantial claim - Findingown data
Adding step reduction to an energy-restricted phase did not cause a further decrease in lean body mass or leg lean mass compared with energy restriction alone, when participants consumed twice the RDA for protein.
“Another important finding 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.”
Quote in the paperSubstantial claim - Findingown data
Two weeks of inactivity resulted in loss of leg lean mass.
“In conclusion, we show here that 2 wk of inactivity resulted in the loss of LLM”
Quote in the paperSubstantial claim - Interpretationown data
Protein supplements provided no protection for leg lean mass.
“Protein supplementation did not confer a benefit in protecting LLM”
Quote in the paperSubstantial claim - Interpretationown data
Energy restriction and reduced activity do not act synergistically to lower rates of myofibrillar muscle protein synthesis.
“Thus, it appears that energy restriction and reduced activity do not synergistically lower rates of myofibrillar MPS”
Quote in the paperSubstantial claim - Interpretationcitation
The reduction in muscle protein synthesis rates observed in this study is similar to the approximately 13% decline reported in a previous study of two weeks of inactivity alone in older men and women.
“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 myofibrillar MPS in older men and women (4).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] McGlory, 2018, Failed recovery of glycemic control and myofibrillar protein synthesis with two weeks of physical inactivity in overweight, pre-diabetic older adults, J Gerontol A Biol Sci Med Sci source
Not checked in the free run.
- Study design and conductown data
No subject characteristic variable differed significantly between groups.
“There were no significant differences between groups for any variable.”
Quote in the paperNot a substantial claim - Premisecitation
Higher dietary protein intake might reduce muscle loss caused by inactivity.
“An increase in dietary protein intake may alleviate inactivityinduced muscle loss (9,10).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [9] Yang, 2012, Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men, Nutr Metab (Lond) source
Not checked in the free run.
- cites [10] Berggren, 2008, Skeletal muscle lipid oxidation and obesity: influence of weight loss and exercise, Am J Physiol Endocrinol Metab source
Not checked in the free run.
- Interpretationown data
A lower limit exists for the decline in muscle protein synthesis under these conditions, at least in healthy older adults.
“and that a lower limit exists to which MPS can decline in these scenarios, at least in healthy older adults.”
Quote in the paperSubstantial claim - Study design and conductown data
Participants adhered very well to the prescribed diets and supplements, consuming 98% ± 2% of what was provided.
“Overall, compliance with the prescribed diets and supplements was excellent with subjects consuming 98% ± 2% of what was provided.”
- Also stated in: § Diet · plain
“All required supplements were consumed by each participant and recorded in a dietary log.”
Quote in the paperSubstantial claim - Also stated in: § Diet · plain
- Premisecitation
Energy and protein underfeeding during hospitalization may worsen muscle breakdown.
“Hospitalization is also associated with energy and protein underfeeding that may further exacerbate muscle catabolism (8).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Drevet, 2014, Prevalence of protein-energy malnutrition in hospital patients over 75 years of age admitted for hip fracture, Orthop Traumatol Surg Res source
Not checked in the free run.
- Premisecitation
Previous work (reference 4) showed that returning to habitual activity without intervention was insufficient to restore muscle protein synthesis rates after two weeks.
“This finding is particularly relevant as our previous work (4) showed that a return to habitual activity in the absence of intervention was insufficient in restoring rates of MPS following 2 wk of return to habitual activity.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] McGlory, 2018, Failed recovery of glycemic control and myofibrillar protein synthesis with two weeks of physical inactivity in overweight, pre-diabetic older adults, J Gerontol A Biol Sci Med Sci source
Not checked in the free run.
- Premisecitation
Previous research has shown that daily whey protein supplementation at a dose considered suboptimal for older adults is ineffective at reducing skeletal muscle loss during immobilization.
“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).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [38] Moore, 2015, Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men, J Gerontol A Biol Sci Med Sci source
Not checked in the free run.
- cites [15] Dirks, 2014, Skeletal muscle disuse atrophy is not attenuated by dietary protein supplementation in healthy older men, J Nutr source
Not checked in the free run.
- May combine two claims. 28
- Classified as probably not a substantial claim. 16
May combine two claims.
Findingown dataIn older adults, leg lean mass fell significantly from energy balance to energy restriction and from energy restriction to energy restriction plus step reduction in both the whey protein and collagen peptide groups, with no between-group difference.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataTwo weeks of energy restriction plus step reduction decreased average daily steps by approximately 84% and 90% in the whey protein and collagen peptide groups, respectively.
“2 wk of ER + SR resulted in a decrease in average daily steps by ∼84% and ∼90% (P < 0.001).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataMuscle protein synthesis was significantly elevated from energy restriction at recovery in the whey protein group and compared with the collagen peptide group (P = 0.05).
“MPS was significantly elevated from ER at RC in the WP group and in comparison to the CP group (P = 0.05).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataFasted blood glucose increased significantly in the ER+SR phase compared with the EB and ER phases, and this elevation persisted into the RC phase.
“There was a significant increase in fasted blood glucose in ER + SR compared with EB and ER that remained elevated at RC (P < 0.001)”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataLosses in leg lean mass mirrored losses in total lean body mass, with a significant reduction at energy restriction plus step reduction compared with energy restriction, and a rise at recovery compared with other times in the whey protein group but not the collagen peptide group.
“Losses in LLM mimicked losses in LBM with a significant reduction at ER + SR in comparison to ER that was increased at RC compared with other times in WP, but not in CP (Figure 3B).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataSubjects returned to taking similar steps during recovery as in energy balance, with no significant difference.
“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).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIntegrated muscle protein synthesis rates fell during energy restriction and energy restriction plus step reduction in both groups, but rose during recovery only in the whey protein group.
“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).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe addition of inactivity during the ER+SR phase resulted in elevated plasma insulin and impaired glucose handling.
“however, the addition of inactivity during ER + SR resulted in the elevation of plasma insulin and impairment of glucose handling.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataCollagen peptide supplementation did not increase leg lean mass or lean body mass during the RC phase.
“However, supplementation with CP did not result in increases in LLM or LBM during RC.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataWhey protein supplementation increased leg lean mass and lean body mass from the ER+SR phase during the RC phase.
“We also show that supplementation with WP increased LLM and LBM from ER + SR during RC.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataWhey protein stimulated recovery of muscle protein synthesis and increased leg lean mass during one week of return to habitual activity.
“Importantly, we show that WP was able to stimulate recovery of MPS and increase LLM in 1 wk of return to habitual activity”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPeriods of inactivity and muscle disuse, such as bed rest and hospitalization, are more common in older persons.
“Periods of inactivity and muscle disuse, such as during bed rest and hospitalization or protracted illness, are more common in older persons (1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Naruishi, 2014, Predictors of improved functional outcome in elderly inpatients after rehabilitation: a retrospective study, Clin Interv Aging source
Not checked in the free run.
May combine two claims.
PremisecitationHospitalization-related loss of muscle mass and function can briefly worsen sarcopenia and lead to incomplete recovery, especially in older adults.
“The decline in muscle mass and function during hospitalization can transiently accelerate sarcopenic decline, resulting in incomplete recovery, particularly for older persons (2).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [2] Suetta, 2009, Effects of aging on human skeletal muscle after immobilization and retraining, J Appl Physiol (1985) source
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Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe trial was registered at clinicaltrials.gov as NCT03285737.
“The trial was registered at clinical trials.gov as NCT03285737.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationCutting total energy intake by 500 kcal/d below estimated requirements mimics the moderate energy restriction often seen in hospital.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Konturek, 2015, Malnutrition in hospitals: it was, is now, and must not remain a problem!, Med Sci Monit source
Not checked in the free run.
May combine two claims.
PremisecitationHospitalization or illness can be accompanied by decreased appetite and food intake, leading to energy deficit and muscle loss.
“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 deficit and muscle loss (5).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Tieland, 2011, Dietary protein intake in community-dwelling, frail, and institutionalized elderly people: scope for improvement, Eur J Nutr source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe target of ≤750 steps per day resembles the step counts seen in hospitalized older patients.
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] Fisher, 2011, Ambulatory activity of older adults hospitalized with acute medical illness, J Am Geriatr Soc source
Not checked in the free run.
May combine two claims.
Interpretationown dataWhey protein supplementation alone increased leg lean mass and muscle protein synthesis during recovery from inactivity and low energy intake.
“but only supplemental WP augmented LLM and muscle protein synthesis during recovery from inactivity and a hypoenergetic state.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataEthics approval came from the Hamilton Integrated Research Ethics Board, and the study followed human-subjects research standards.
“The study was approved by the Hamilton Integrated Research Ethics Board, and conformed to the standards for the use of human subjects in research”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataIntra-assay coefficients of variation were <5% for all blood analyses.
“Intra-assay coefficients of variation were all <5% for all blood analyses.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductown dataGroup assignment was hidden from both participants and researchers throughout the study and until analyses finished.
“Allocation was concealed from the participants and researchers for the duration of the study and until all analyses were complete.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataThis was a randomized controlled trial with a double-blind, parallel-group design.
“The study was a double-blind, parallel-group, randomized controlled trial.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationAbout a quarter of body mass lost during an energy deficit is fat-free mass, and some of that is probably muscle.
“Typically, ∼25% of body mass lost in an energy deficit can be attributed to fat-free mass (6), some of which is likely muscle (7).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [6] Leidy, 2007, Higher protein intake preserves lean mass and satiety with weight loss in pre-obese and obese women, Obesity source
Not checked in the free run.
- cites [7] Gallagher, 2000, Weight stability masks sarcopenia in elderly men and women, Am J Physiol Endocrinol Metab source
Not checked in the free run.
May combine two claims.
PremisecitationProtein sources high in essential amino acids and leucine are known to raise muscle protein synthesis and might help prevent muscle mass and strength loss during inactivity.
“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).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [12] Murphy, 2016, Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study, Am J Clin Nutr source
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- cites [13] Devries, 2015, Low-load resistance training during step-reduction attenuates declines in muscle mass and strength and enhances anabolic sensitivity in older men, Physiol Rep source
Not checked in the free run.
- cites [14] English, 2016, Leucine partially protects muscle mass and function during bed rest in middle-aged adults, Am J Clin Nutr source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataFiber type analysis used at least 300 fibers, and cross-sectional area was measured from at least 50 fibers per type.
“fiber typing was conducted using ≥300 fibers, and cross-sectional area (CSA) was based on ≥50 fibers/fiber type.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataA single investigator manually verified the DXA analysis regions while blinded.
“The analysis regions were standard regions where the head, torso, arms, and legs were subdivided by the software, but were subsequently checked manually, in a blinded manner, by a single investigator (SYO).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataEach testing day, the DXA scanner was calibrated using a 3-compartment Universal Whole Body DXA Phantom.
“The machine was calibrated each testing day with a 3-compartment Universal Whole Body DXA Phantom (Oscar, Jr; Orthometrix, Naples, FL).”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationCollagen provides an isonitrogenous and isoenergetic comparison and has shown considerable anabolic properties in older adults, though these have been questioned.
“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)].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [16] Phillips, 2016, The impact of protein quality on the promotion of resistance exercise-induced changes in muscle mass, Nutr Metab (Lond) source
Not checked in the free run.
- cites [17] Zdzieblik, 2015, 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 source
Not checked in the free run.
- cites [18] Phillips, 2016, Exceptional body composition changes attributed to collagen peptide supplementation and resistance training in older sarcopenic men, Br J Nutr source
Not checked in the free run.
May combine two claims.
PremisecitationWhey is rich in essential amino acids, especially leucine, and consuming it boosts muscle protein synthesis.
“Whey protein has a high essential amino acid (EAA) content, particularly leucine, and its ingestion stimulates muscle protein synthesis (MPS) (11).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Dickinson, 2011, Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids, J Nutr source
Not checked in the free run.
May combine two claims.
PremisecitationTaking fewer steps lowers anabolic sensitivity to protein and reduces leg lean mass.
“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).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [3] Breen, 2013, Two weeks of reduced activity decreases leg lean mass and induces “anabolic resistance” of myofibrillar protein synthesis in healthy elderly, J Clin Endocrinol Metab source
Not checked in the free run.
- cites [4] McGlory, 2018, Failed recovery of glycemic control and myofibrillar protein synthesis with two weeks of physical inactivity in overweight, pre-diabetic older adults, J Gerontol A Biol Sci Med Sci source
Not checked in the free run.
May combine two claims.
Interpretationown dataWhey protein supplementation may protect leg lean mass during inactivity accompanied by a hypocaloric diet and may even improve recovery after returning to habitual activity.
“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.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationExisting literature using a bedrest model found a significant mediating effect of bed rest on increases in systemic inflammation after 35 days of inactivity.
“These findings are congruent with existing literature using a bedrest model in which the authors found a significant mediating effect of bed rest on increases in systemic inflammation following 35 d of inactivity (39).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [39] Biolo, 2008, Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest, Am J Clin Nutr source
Not checked in the free run.
May combine two claims.
Interpretationown dataThe pronounced increase in leg lean mass and lean body mass with whey protein supplementation supports raising protein intake in older adults to overcome the age-related heightened anabolic resistance to protein feeding.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [38] Moore, 2015, Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men, J Gerontol A Biol Sci Med Sci source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductreasoningThe progression of dietary and activity phases in this study was a strength of the protocol because it allowed determination of the effects of energy restriction alone, and in combination with step reduction and high protein intake, on muscle metabolism in older adults.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataAll participants were healthy and free of chronic conditions, which restricts how far the intervention can be applied to older persons with common clinical chronic conditions.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductown dataThe study did not directly measure muscle protein breakdown rates, so the relative contributions of muscle protein synthesis and breakdown to changes in lean body mass and leg lean mass are unknown.
“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.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationcitationIf energy restriction and step reduction harm skeletal muscle strongly in healthy older adults, then a compromised older population would likely experience greater muscle loss and worse glycemic control.
“However, if the detrimental effects of ER and SR on skeletal muscle are significantly 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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] McGlory, 2018, Failed recovery of glycemic control and myofibrillar protein synthesis with two weeks of physical inactivity in overweight, pre-diabetic older adults, J Gerontol A Biol Sci Med Sci source
Not checked in the free run.
The paper relies on this without support.
Before this trial, no study had tested whether higher protein intake could prevent muscle loss during inactivity with low energy intake or aid recovery in older adults.
“Although studies have examined the influence of increased protein intake on muscle atrophy during immobilization (15), no study has examined the efficacy of increased protein consumption to offset loss of muscle mass during inactivity while hypoenergetic and to promote recovery in older adults.”
The paper relies on this without support.
No other study had compared whey protein and collagen peptides for their effect on muscle protein synthesis in older adults.
“To our knowledge, no other study had compared WP and CP for their effect on MPS in older adults.”
The paper relies on this without support.
This study is the first to look at how protein supplements from different sources affect older men and women during simulated hospitalization and convalescence with energy restriction.
“To our knowledge, this study is the first 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.”
The paper relies on this without support.
This is the first study to show an increase in leg lean mass and lean body mass with whey protein, but not collagen peptide, supplementation during recovery.
“however, this is the first study, to our knowledge, to show an increase in LLM and LBM with WP, but not CP, supplementation during recovery.”
The paper relies on this without support.
Step reduction combined with energy restriction simulates hospitalization and convalescence in older adults.
“during simulated hospitalization and convalescence concurrent with a state of energy restriction in older men and women”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Discussion reverses the reported leg lean mass loss during step reduction
MajorThe abstract and results report a significant decrease in leg lean mass from energy restriction to energy restriction plus step reduction. The discussion says adding step reduction caused no further decrease compared with energy restriction alone.
“Losses in LLM mimicked losses in LBM with a significant reduction at ER + SR in comparison to ER”
“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”
Protein grams in the intake table omit an unlabelled component
MinorFor the whey group during energy restriction, the table lists 87 g of protein and 1.6 g/kg, but 87 g divided by the group's 92.4 kg baseline mean is about 0.94 g/kg. Adding the separately prescribed 60 g/day supplement nearly reconciles the figures, indicating that the row labelled simply "Protein, g" excludes supplements without saying so.
Reported 1.6 · recomputed 0.941558
“| 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 |”
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“Energy intake during the ER + SR phase was adjusted to account for subjects’ inactivity (20).”
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Self-citationBurd, N. A., Tang, J. E., Moore, D. R., & Phillips, S. M. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91351.2008 · Cited by 390 · see citing works
Self-citationTieland, M., Borgonjen-Van den Berg, K. J., van Loon, L. J. C., & de Groot, L. C. P. G. M. (2012) · European Journal of Nutrition · doi:10.1007/s00394-011-0203-6 · Cited by 297 · see citing works
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Self-citationDickinson, J. M., Fry, C. S., Drummond, M. J., Gundermann, D. M., Walker, D. K., Glynn, E. L., Timmerman, K. L., Dhanani, S., Volpi, E., & Rasmussen, B. B. (2011) · The Journal of Nutrition · doi:10.3945/jn.111.139485 · Cited by 282 · see citing works
Higher Protein Intake Preserves Lean Mass and Satiety with Weight Loss in Pre‐obese and Obese Women
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Ambulatory activity of older adults hospitalized with acute medical illness
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The impact of protein quality on the promotion of resistance exercise-induced changes in muscle mass
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Self-citationLeucine partially protects muscle mass and function during bed rest in middle-aged adults
English, K. L., Mettler, J. A., Ellison, J. B., Mamerow, M. M., Arentson-Lantz, E., Pattarini, J. M., Ploutz-Snyder, R., Sheffield-Moore, M., & Paddon-Jones, D. (2016) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.115.112359 · Cited by 162 · cited 1× · see citing works
“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).”
BackgroundSkeletal muscle lipid oxidation and obesity: influence of weight loss and exercise.
Berggren, J. R., Boyle, K. E., Chapman, W. H., & Houmard, J. A. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00354.2007 · Cited by 151 · see citing works
The Acute Satellite Cell Response and Skeletal Muscle Hypertrophy following Resistance Training
Bellamy, L. M., Joanisse, S., Grubb, A., Mitchell, C. J., McKay, B. R., Phillips, S. M., Baker, S., & Parise, G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109739 · Cited by 149 · see citing works
Self-citationBiolo, G., Agostini, F., Simunic, B., Sturma, M., Torelli, L., Preiser, J. C., Deby-Dupont, G., Magni, P., Strollo, F., di Prampero, P., et al. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/88.4.950 · Cited by 138 · see citing works
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Murphy, C. H., Saddler, N. I., Devries, M. C., McGlory, C., Baker, S. K., & Phillips, S. M. (2016) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.136424 · Cited by 133 · see citing works
Self-citationMetabolic and Vascular Limb Differences Affected by Exercise, Gender, Age, and Disease
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Murphy, C. H., Churchward-Venne, T. A., Mitchell, C. J., Kolar, N. M., Kassis, A., Karagounis, L. G., Burke, L. M., Hawley, J. A., & Phillips, S. M. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00550.2014 · Cited by 124 · see citing works
Self-citationBell, K. E., Séguin, C., Parise, G., Baker, S. K., & Phillips, S. M. (2015) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu313 · Cited by 118 · see citing works
Self-citationMcGlory, C., von Allmen, M. T., Stokes, T., Morton, R. W., Hector, A. J., Lago, B. A., Raphenya, A. R., Smith, B. K., McArthur, A. G., Steinberg, G. R., et al. (2018) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glx203 · Cited by 113 · see citing works
Self-citationDevries, M. C., Breen, L., Von Allmen, M., MacDonald, M. J., Moore, D. R., Offord, E. A., Horcajada, M.-N., Breuillé, D., & Phillips, S. M. (2015) · Physiological Reports · doi:10.14814/phy2.12493 · Cited by 107 · see citing works
Self-citationDrevet, S., Bioteau, C., Mazière, S., Couturier, P., Merloz, P., Tonetti, J., & Gavazzi, G. (2014) · Orthopaedics & Traumatology: Surgery & Research · doi:10.1016/j.otsr.2014.05.003 · Cited by 94 · see citing works
Dufner, D. A., Bederman, I. R., Brunengraber, D. Z., Rachdaoui, N., Ismail‐Beigi, F., Siegfried, B. A., Kimball, S. R., & Previs, S. F. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00580.2004 · Cited by 92 · see citing works
Hector, A. J., McGlory, C., Damas, F., Mazara, N., Baker, S. K., & Phillips, S. M. (2018) · The FASEB Journal · doi:10.1096/fj.201700158rr · Cited by 91 · see citing works
Self-citationMalnutrition in hospitals: it was, is now, and must not remain a problem!
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“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).”
MethodJoanisse, S., Gillen, J. B., Bellamy, L. M., McKay, B. R., Tarnopolsky, M. A., Gibala, M. J., & Parise, G. (2013) · The FASEB Journal · doi:10.1096/fj.13-229799 · Cited by 82 · see citing works
Self-citationA novel oral tracer procedure for measurement of habitual myofibrillar protein synthesis
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Satellite cell activity, without expansion, after nonhypertrophic stimuli
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Self-citationThe effect of exercise mode on the acute response of satellite cells in old men
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Self-citationMuscular Performance after Concentric and Eccentric Exercise in Trained Men
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Self-citation
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Plant Proteins: Assessing Their Nutritional Quality and Effects on Health and Physical Function
Hertzler, S. R., Lieblein-Boff, J. C., Weiler, M., & Allgeier, C. (2020) · Nutrients · doi:10.3390/nu12123704 · Cited by 594 · see citing works
Strategies to Prevent Sarcopenia in the Aging Process: Role of Protein Intake and Exercise
Rogeri, P. S., Zanella, R., Martins, G. L., Garcia, M. D. A., Leite, G., Lugaresi, R., Gasparini, S. O., Sperandio, G. A., Ferreira, L. H. B., Souza-Junior, T. P., et al. (2021) · Nutrients · doi:10.3390/nu14010052 · Cited by 181 · see citing works
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Monteyne, A. J., Coelho, M. O. C., Murton, A. J., Abdelrahman, D. R., Blackwell, J. R., Koscien, C. P., Knapp, K. M., Fulford, J., Finnigan, T. J. A., Dirks, M. L., et al. (2023) · The Journal of Nutrition · doi:10.1016/j.tjnut.2023.02.023 · Cited by 64 · see citing works
Oikawa, S. Y., Bahniwal, R., Holloway, T. M., Lim, C., McLeod, J. C., McGlory, C., Baker, S. K., & Phillips, S. M. (2020) · Nutrients · doi:10.3390/nu12051235 · Cited by 41 · see citing works
Self-citationAl-Rawhani, A. H., Adznam, S. N., Abu Zaid, Z., Md. Yusop, N. B., M. Sallehuddin, H., & Alshawsh, M. A. (2024) · Clinical Nutrition · doi:10.1016/j.clnu.2024.08.033 · Cited by 13 · see citing works
- Authors
- Oikawa, S. Y., McGlory, C., D'Souza, L. K., Morgan, A. K., Saddler, N. I., Baker, S. K., Parise, G., & Phillips, S. M.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Phillips, Stuart M
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 108
- Issue
- 5
- Pages
- 1060-1068
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2894552307
- Semantic Scholar
- ed94b02029c841ccb1d8e6bf3fd3e9a252bc9eb1
- Cited by
- 76
- References
- 41
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 10 · 2023: 11 · 2022: 8 · 2021: 13 · 2020: 12 · 2019: 10
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Whey Protein Research Consortium
- US National Dairy Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- protein supplementation, muscle protein synthesis, leg lean mass, muscle mass loss, older adults, physical inactivity, caloric restriction, whey protein, collagen peptides
- MeSH terms
- Whey Proteins, Aged, Energy Intake, Collagen, Convalescence, Energy Metabolism, Female, Hospitalization, Humans, Leg, Male, Motor Activity, Muscle Proteins, Peptides, Rest, Protein Biosynthesis, Walking, Muscle, Skeletal, Dietary Supplements, Caloric Restriction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
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