REF-1142 · Franchi et al., 2025 · The Journal of Physiology · Paper · PubMed

Strength back after short disuse

10 days with one leg unloaded cost young men 29% of quadriceps force and 4% of muscle volume; nine sessions of 3 × 10 at 70% 1RM over 21 days restored the force and took volume above baseline, while the muscle shifted toward an oxidative, slow-fibre profile rather than the usual strength-training one

Blimited evidenceMeasured on recreational people

Franchi et al. suspended the dominant leg of 11 young men (22.1 ± 2.9 y, recreationally active) for 10 days (unilateral lower-limb suspension, ULLS: crutches, the other foot on a raised sole), then retrained the leg for 21 days with nine supervised sessions of unilateral leg press and leg extension, 3 sets of 10 at 70% of an estimated 1RM, three times a week (usually every other day).

Knee-extensor isometric MVC fell 29.3% with suspension (797 → 563 N) and was fully restored after retraining (792 N). Quadriceps volume fell 3.7% and then rose 18.7% above the suspended value — 14.1% above baseline — but fibre cross-sectional area did not increase (type I fibre CSA ended 19% BELOW baseline).

Instead, the proportion of type I fibres rose 34% after retraining (38% in the abstract), muscle glycogen rose ~15-16%, total body water ~3%, SDH (an oxidative enzyme) ~20%, mitochondrial fusion and fission proteins rose, and the most changed gene pathways after retraining were oxidative phosphorylation and fatty-acid metabolism.

The authors conclude that prior short-term disuse may "dictate" the adaptations to subsequent resistance training, with metabolic recovery coming before hypertrophy; they attribute part of the volume gain to glycogen-bound water and possible oedema.

Protocol

Participants: 12 healthy recreationally active men recruited (18-35 y, BMI 20-28, activity one to three times a week; professional athletes, smokers and anyone with DVT history or musculoskeletal, metabolic or cardiovascular disorders excluded); 1 dropped out before suspension, 2 declined the post-retraining biopsy. Men only because ULLS carries a deep-vein-thrombosis risk that is higher in women. Sample size from an a priori power calculation.
Disuse (LS0 → LS10): 10 days of ULLS of the dominant leg (strapped at ~15-20° knee flexion, 50 mm raised sole on the other shoe, crutches), compression sock, daily ankle range-of-motion exercise, Doppler check at day 5, compliance checked by daily calls and calf circumference and skin temperature.
Retraining (LS10 → AR21): started 3 days after the LS10 tests; three sessions a week (usually every other day, at least 24 h apart), nine sessions in all; unilateral leg press and leg extension, 3 sets of 10 reps at 70% of 1RM estimated from a 4-6RM (Brzycki), re-estimated at the start of each week; 2 s concentric and 2 s eccentric by metronome; 2 min between sets; supervised.
Measures at LS0, LS10 and AR21 (3 days after the last session): isometric knee-extensor MVC at 90° (data published earlier in Sarto et al. 2022, same cohort); quadriceps and vastus lateralis volume by panoramic ultrasound; VL architecture; DXA and bioimpedance; vastus lateralis biopsies (fibre CSA and type by immunofluorescence, glycogen by PAS staining, SDH, western blots of mitochondrial proteins, RNA sequencing); 3-day food diaries; GPAQ activity questionnaire.

Key Results

OutcomeAfter 10 days of suspension (vs baseline)After 21 days of retraining (vs end of suspension)Retraining vs baseline
Isometric MVC−29.3% (797 ± 111 → 563 ± 101 N, P < 0.001)+42.9% (to 792 ± 106 N, P < 0.001)back to baseline
Quadriceps volume−3.67 ± 4% (P = 0.028)+18.68 ± 6.87% (P < 0.001)+14.1 ± 5.1% (P < 0.001)
Vastus lateralis volume−3.47 ± 3.98% (P = 0.051)+24.15 ± 10.4% (P < 0.001)+19.6 ± 8% (P < 0.001)
Thigh lean mass (DXA)no change+2.75 ± 2.13% (P = 0.006)+2.12 ± 2.35% (P = 0.029)
Type I fibre CSAno change—−19.3 ± 5.52% (P = 0.031)
Type II fibre CSAno changesmall, non-significant fall—
Type I fibre proportionno change+33.96% (P = 0.015); abstract 38%—
Type II fibre proportionno change−20.76% (P = 0.015)—
MyHC isoform protein (SDS-PAGE)no significant changeMyHC-I +18.58 ± 33.5%, not significant—
Muscle glycogen (PAS)no change+16.11 ± 15.51% (P = 0.0314)+14.62 ± 14.8% (P = 0.0375)
Total body water (BIA)no change+3.1 ± 3.23% (P = 0.022)—
SDH stainingno change+20.5 ± 9.1% (P < 0.001)+18.69% (P = 0.028)
MYH7 / MYH1 mRNAMYH7 −47.56% (P = 0.0167)MYH7 +208.99% (P = 0.0022); MYH1 −85.11% (P < 0.001)MYH1 −85.57% (P < 0.01)
Physical activity (GPAQ)−86.4%above baseline (P = 0.013 vs LS0)—
Training loads rose fast: estimated leg-press 1RM +16.8 ± 10.8% by week 2 and +28.8 ± 14.6% by week 3 versus the post-suspension value.
Diet unchanged: ~1950 kcal a day before, during and after suspension, carbohydrate ~3 g/kg, no macronutrient change.
Mitochondrial proteins: MFN1, MFN2, OPA1 and DRP1 rose after retraining; PGC-1α only a trend (P = 0.056); respiratory-chain complexes did not change. 882 genes changed with suspension and 891 with retraining (q < 0.05).

Mechanisms

Measured: force fell about eight times more than muscle volume (−29% vs −3.7%); for the same participants the group earlier reported reduced activation and altered motor-unit properties, i.e. a large neural share of the loss.
Measured: whole-muscle volume rose ~19% in 21 days (~0.85-1% a day, against ~0.4% a day in the fastest strength-training studies the authors cite) without any rise in fibre CSA.
Authors' interpretation: part of the volume gain is probably water — glycogen supercompensation (each gram stored with 3-4 g of water) and possibly exercise-induced inflammation and oedema — so ultrasound volume likely overstates true hypertrophy.
Measured: after retraining the muscle moved toward an oxidative, slow profile: more type I fibres by immunostaining, more SDH, more glycogen, mitochondrial dynamics proteins up, oxidative and fatty-acid gene pathways up, the fast MYH1 gene almost silenced.
Authors' interpretation: prior short-term disuse may decide the nature of the adaptation to subsequent resistance training — "metabolic recovery before hypertrophy" — a recovery programme the muscle runs whatever the loading modality. They speculate the type I rise reflects hybrid (I/IIa) fibres, since MyHC protein did not change significantly.
Inference: without a control leg or a group that trained without prior disuse, "different from usual strength training" is a comparison with other studies, not a measured contrast; some of the shift could be the time course of recovery itself, or more everyday activity (questionnaire activity at AR21 was above baseline, P = 0.013).

Practical Application

How fast does strength come back after a short layoff? Ten days with one leg unloaded cost young men 29% of quadriceps force; nine sessions of 3 × 10 at 70% 1RM over 21 days restored it (one uncontrolled study, n=11). The muscle meanwhile shifted, unusually for lifting, toward an oxidative, slow-fibre profile.That supports "a short immobilisation costs a lot of force fast, and a few weeks of ordinary lifting restores it". It is one uncontrolled study of 11 young men with one leg suspended, not a training break or an older athlete.
Expect force to fall far more than size after a few days off a leg. −29% force against −3.7% volume points to a large neural share; a brace or crutches week is a strength problem first (Measured; for one leg in young men).
Retrain with load, about twice as long as the disuse. The 21-day block was chosen because full restoration had been seen after retraining twice as long as the disuse; here nine sessions at 70% 1RM sufficed for force (study design, not a tested ratio).
Do not read the quick "growth" on a scan as muscle. Volume rose 14% above baseline while fibres did not grow; the authors attribute part of it to glycogen-bound water and possibly oedema (DXA thigh lean mass was still +2% above baseline).
For a whole-body training break rather than a limb in a brace, the base's detraining evidence and return rules are in REF-374, REF-375 and SYNTH-36; for strength losses after stopping training, more over 65 (REF-375).

Limitations

No control: no contralateral control leg in the analyses and no group that trained without prior suspension, so "in contrast with what is usually observed after resistance training" rests on other studies.
n = 11 for function and volume, n = 9 for biopsies after retraining and n = 8 for SDH; young, recreationally active men only (women excluded for DVT risk); no older adults.
ULLS of one leg while walking on crutches is a partial, single-limb unloading model; it is not bed rest, a cast or a planned training break.
The MVC data were already published from the same cohort (Sarto et al. 2022); this paper adds the structural and molecular data.
Fibre type by immunostaining moved without a significant change in MyHC isoform protein; the abstract (38% type I, 14% glycogen, 42% MVC restoration) and the results text (33.96%, 16.11% vs end of suspension, 42.9%) report slightly different figures for the same outcomes.
Muscle volume from panoramic ultrasound with CSA at 10%, 80% and 90% of femur length extrapolated by spline; volume converted to mass by an assumed density; water shifts can masquerade as hypertrophy (the authors' own point).
Ethics approval by the local committee; the study was not registered in a database (stated). Funding: Italian Space Agency, Italian Ministry of University and Research (PRIN, NextGenerationEU), NIH intramural programme; no competing interests declared.
How this entry was checked and changed
Why this level

uncontrolled pre-post, n=11 (9 for the biopsy data after retraining, 8 for SDH), no control leg or control group, young recreationally active men only; read from the full text (open access, CC BY)

Full text (checked 2026-10-15)
Eleven males (22.09 ± 2.91 years); 10 days of ULLS followed by 21 days of knee extensor RT, three times a week, nine training sessions (full text).
AR programme: three sets of 10 repetitions of unilateral leg press and leg extension at 70% of 1RM; the usual weekly scheme was to train every other day (full text).
MVC −29.3% (563 ± 101 N at LS10 vs. 797 ± 111 N at LS0, P < 0.001); full restoration 42.9% after 21 days of AR (792 ± 106 N, P < 0.001) (full text).
Quadriceps volume −3.67 ± 4% at LS10 (P = 0.028); +18.68 ± 6.87% at AR21 vs LS10; 14.1 ± 5.1% above LS0; VL +24.15 ± 10.4%, 19.6 ± 8% above LS0 (full text).
Type I fibre CSA at AR21 −19.3 ± 5.52% vs LS0 (P = 0.031); type I fibre proportion +33.96% (P = 0.015), type II −20.76% (full text).
Glycogen +16.11 ± 15.51% (P = 0.0314) vs LS10 and +14.62 ± 14.8% vs LS0; total body water +3.1 ± 3.23%; SDH +20.5 ± 9.1% vs LS10 (full text).
Estimated leg-press 1RM +16.8 ± 10.8% at week 2 and +28.8 ± 14.6% at week 3; total physical activity −86.4% during ULLS (full text).
Volume increase ∼0.85–1% day−1 vs ∼0.4% day−1 in the fastest strength-training studies cited; carbohydrate ∼3 g per kg kept constant (full text).