The time course of disuse muscle atrophy of the lower limb in health and disease

We aimed to quantify declines from baseline in lower limb skeletal muscle size and strength of uninjured adults following single‐leg disuse. We searched EMBASE, Medline, CINAHL, and CCRCT up to 30 January 2022. Studies were included in the systematic review if they (1) recruited uninjured participants; (2) were an original experimental study; (3) employed a single‐leg disuse model; and (4) reported muscle strength, size, or power data following a period of single‐leg disuse for at least one group without a countermeasure. Studies were excluded if they (1) did not meet all inclusion criteria; (2) were not in English; (3) reported previously published muscle strength, size, or power data; or (4) could not be sourced from two different libraries, repeated online searches, and the authors. We used the Cochrane Risk of Bias Assessment Tool to assess risk of bias. We then performed random‐effects meta‐analyses on studies reporting measures of leg extension strength and extensor size. Our search revealed 6548 studies, and 86 were included in our systematic review. Data from 35 and 20 studies were then included in the meta‐analyses for measures of leg extensor strength and size, respectively (40 different studies). No meta‐analysis for muscle power was performed due to insufficient homogenous data. Effect sizes (Hedges' gav) with 95% confidence intervals for leg extensor strength were all durations = −0.80 [−0.92, −0.68] (n = 429 participants; n = 68 aged 40 years or older; n ≥ 78 females); ≤7 days of disuse = −0.57 [−0.75, −0.40] (n = 151); >7 days and ≤14 days = −0.93 [−1.12, −0.74] (n = 206); and >14 days = −0.95 [−1.20, −0.70] (n = 72). Effect sizes for measures of leg extensor size were all durations = −0.41 [−0.51, −0.31] (n = 233; n = 32 aged 40 years or older; n ≥ 42 females); ≤7 days = −0.26 [−0.36, −0.16] (n = 84); >7 days and ≤14 days = −0.49 [−0.67, −0.30] (n = 102); and >14 days = −0.52 [−0.74, −0.30] (n = 47). Decreases in leg extensor strength (cast: −0.94 [−1.30, −0.59] (n = 73); brace: −0.90 [−1.18, −0.63] (n = 106)) and size (cast: −0.61[−0.87, −0.35] (n = 41); brace: (−0.48 [−1.04, 0.07] (n = 41)) following 14 days of disuse did not differ for cast and brace disuse models. Single‐leg disuse in adults resulted in a decline in leg extensor strength and size that reached a nadir beyond 14 days. Bracing and casting led to similar declines in leg extensor strength and size following 14 days of disuse. Studies including females and males and adults over 40 years of age are lacking.

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Single‐leg disuse decreases skeletal muscle strength, size, and power in uninjured adults: A systematic review and meta‐analysis

Preobrazenski

Seigel

Halliday

et al. 2023

“…Twenty-three healthy males (age: 22 ± 1 year; height: 179.4 ± 1.3 cm; body mass: 73.4 ± 1.5 kg; body mass index 22.8 ± 0.5 kg•m À2 ) volunteered to take part in this study. Prior to inclusion, participants attended the Nutritional Physiology Research Unit at the University of Exeter for routine medical screening to ensure they did not contravene the following exclusion criteria: diagnosed metabolic impairment (e.g., type 1 or type 2 diabetes); cardiovascular disease; hypertensive (≥140/90 mmHg); chronic use of prescribed or over-the-counter pharmaceuticals; personal or family history of epilepsy, schizophrenia, or seizures; presence of an ulcer in the stomach or gut; pre-existing liver or kidney condition; musculoskeletal injury within 6 months prior to enrolment; having previously received a stable isotope tracer containing 15 N; regular use of nutritional supplements; and/or an allergy or intolerance to lidocaine or amino acids. Written consent was obtained from all participants following full explanation of the experimental procedures, which were approved by the University of Exeter's Sport and Health Sciences Ethics Committee (180509/B/01).…”

Section: Participantsmentioning

confidence: 99%

“…5,10,12 In support, our recent work demonstrated that the decrease in daily MPS rates, which capture multiple postabsorptive and postprandial periods, positively correlate with reductions in muscle volume after 7 days of unilateral leg immobilization (r 2 = 0.417, P < 0.05). 13 It is therefore suggested that this decline in MPS quantitatively accounts for only ~25-50% of the measured muscle loss with short-term (<14 days) disuse 13,14 when the rate of atrophy is greatest, 15,16 although some work has argued MPS can potentially explain an even greater proportion. 12,17 Moreover, marked reductions in muscle volume are evident after only 2 days of immobilization (i.e., ~0.85% per day 18 ) despite less a pronounced decline in daily MPS 13 and can occur in the absence of any changes in MPS if high-volume and high-intensity eccentric contractions are performed before immobilization.…”

Section: Introductionmentioning

confidence: 99%

Short‐term disuse does not affect postabsorptive or postprandial muscle protein fractional breakdown rates

Pavis

Abdelrahman

Murton

et al. 2023

BackgroundThe decline in postabsorptive and postprandial muscle protein fractional synthesis rates (FSR) does not quantitatively account for muscle atrophy during uncomplicated, short‐term disuse, when atrophy rates are the highest. We sought to determine whether 2 days of unilateral knee immobilization affects mixed muscle protein fractional breakdown rates (FBR) during postabsorptive and simulated postprandial conditions.MethodsTwenty‐three healthy, male participants (age: 22 ± 1 year; height: 179 ± 1 cm; body mass: 73.4 ± 1.5 kg; body mass index 22.8 ± 0.5 kg·m−2) took part in this randomized, controlled study. After 48 h of unilateral knee immobilization, primed continuous intravenous l‐[15N]‐phenylalanine and l‐[ring‐2H5]‐phenylalanine infusions were used for parallel determinations of FBR and FSR, respectively, in a postabsorptive (saline infusion; FAST) or simulated postprandial state (67.5 mg·kg body mass−1·h−1 amino acid infusion; FED). Bilateral m. vastus lateralis biopsies from the control (CON) and immobilized (IMM) legs, and arterialized‐venous blood samples, were collected throughout.ResultsAmino acid infusion rapidly increased plasma phenylalanine (59 ± 9%), leucine (76 ± 5%), isoleucine (109 ± 7%) and valine (42 ± 4%) concentrations in FED only (all P < 0.001), which was sustained for the remainder of infusion. Serum insulin concentrations peaked at 21.8 ± 2.2 mU·L−1 at 15 min in FED only (P < 0.001) and were 60% greater in FED than FAST (P < 0.01). Immobilization did not influence FBR in either FAST (CON: 0.150 ± 0.018; IMM: 0.143 ± 0.017%·h−1) or FED (CON: 0.134 ± 0.012; IMM: 0.160 ± 0.018%·h−1; all effects P > 0.05). However, immobilization decreased FSR (P < 0.05) in both FAST (0.071 ± 0.004 vs. 0.086 ± 0.007%·h−1; IMM vs CON, respectively) and FED (0.066 ± 0.016 vs. 0.119 ± 0.016%·h−1; IMM vs CON, respectively). Consequently, immobilization decreased net muscle protein balance (P < 0.05) and to a greater extent in FED (CON: −0.012 ± 0.025; IMM: −0.095 ± 0.023%·h−1; P < 0.05) than FAST (CON: −0.064 ± 0.020; IMM: −0.072 ± 0.017%·h−1).ConclusionsWe conclude that merely 2 days of leg immobilization does not modulate postabsorptive and simulated postprandial muscle protein breakdown rates. Instead, under these conditions the muscle negative muscle protein balance associated with brief periods of experimental disuse is driven near exclusively by reduced basal muscle protein synthesis rates and anabolic resistance to amino acid administration.

The time course of disuse muscle atrophy of the lower limb in health and disease

Hardy

Inns

Hatt

et al. 2022

Short, intermittent episodes of disuse muscle atrophy (DMA) may have negative impact on age related muscle loss. There is evidence of variability in rate of DMA between muscles and over the duration of immobilization. As yet, this is poorly characterized. This review aims to establish and compare the time‐course of DMA in immobilized human lower limb muscles in both healthy and critically ill individuals, exploring evidence for an acute phase of DMA and differential rates of atrophy between and muscle groups. MEDLINE, Embase, CINHAL and CENTRAL databases were searched from inception to April 2021 for any study of human lower limb immobilization reporting muscle volume, cross‐sectional area (CSA), architecture or lean leg mass over multiple post‐immobilization timepoints. Risk of bias was assessed using ROBINS‐I. Where possible meta‐analysis was performed using a DerSimonian and Laird random effects model with effect sizes reported as mean differences (MD) with 95% confidence intervals (95% CI) at various time‐points and a narrative review when meta‐analysis was not possible. Twenty‐nine studies were included, 12 in healthy volunteers (total n = 140), 18 in patients on an Intensive Therapy Unit (ITU) (total n = 516) and 3 in patients with ankle fracture (total n = 39). The majority of included studies are at moderate risk of bias. Rate of quadriceps atrophy over the first 14 days was significantly greater in the ITU patients (MD −1.01 95% CI −1.32, −0.69), than healthy cohorts (MD −0.12 95% CI −0.49, 0.24) (P < 0.001). Rates of atrophy appeared to vary between muscle groups (greatest in triceps surae (−11.2% day 28), followed by quadriceps (−9.2% day 28), then hamstrings (−6.5% day 28), then foot dorsiflexors (−3.2% day 28)). Rates of atrophy appear to decrease over time in healthy quadriceps (−6.5% day 14 vs. −9.1% day 28) and triceps surae (−7.8% day 14 vs. −11.2% day 28), and ITU quadriceps (−13.2% day 7 vs. −28.2% day 14). There appears to be variability in the rate of DMA between muscle groups, and more rapid atrophy during the earliest period of immobilization, indicating different mechanisms being dominant at different timepoints. Rates of atrophy are greater amongst critically unwell patients. Overall evidence is limited, and existing data has wide variability in the measures reported. Further work is required to fully characterize the time course of DMA in both health and disease.