In ICU survivors with persistent muscle loss and weakness, the increase in muscle protein synthesis after combined resistance exercise and protein intake was smaller than in controls, in the context of a higher baseline fractional synthetic rate, but post-intervention synthesis rates were similar between groups, providing the first mechanistic support for structured exercise-nutrition rehabilitation after critical illness.
Key Findings
Results
ICU survivors had lower quadriceps muscle thickness and handgrip strength than age- and sex-matched controls 3 to 6 months after ICU discharge.
Twenty ICU survivors (60 ± 12 years, 30% female, BMI 26.9 [IQR 22.9-28.7], SAPS 3 62.3 ± 15.8) were compared with 20 age- and sex-matched controls.
Quadriceps muscle thickness was significantly lower in ICU survivors (p = 0.02).
Handgrip strength was significantly lower in ICU survivors (p = 0.04).
Former patients were enrolled within 3 to 6 months of ICU discharge.
Results
Baseline muscle protein synthesis from plasma precursor amino acids was higher in ICU survivors than in controls.
Baseline fractional synthetic rate was 0.041%/hour in ICU survivors vs. 0.030%/hour in controls (p = 0.009).
Synthesis was measured by incorporation of [ring-2H5]phenylalanine into mixed-muscle protein during a primed continuous intravenous infusion.
Results
The increase in muscle protein synthesis after resistance exercise plus protein intake was smaller in ICU survivors than in controls.
The change was Δ 0.031%/hour in ICU survivors vs. Δ 0.040%/hour in controls (p = 0.04).
This pre-to-post change was the primary comparison, analysed by group-by-time linear mixed models.
The intervention was flywheel leg extension resistance exercise combined with 24 g hydrolysed protein, with muscle biopsies before and after.
Results
Post-intervention muscle protein synthesis rates were similar in ICU survivors and controls.
Post-intervention rates were 0.071%/hour in ICU survivors vs. 0.070%/hour in controls (p = 0.70).
The smaller increase in ICU survivors occurred against a higher baseline rate, so the final rates converged.
Results
At baseline, ICU survivors showed lower activation of the autophagy-lysosomal pathway than controls.
Anabolic and proteolytic pathways were measured using standard assays on muscle biopsies.
Results
In both groups, the exercise and protein intervention increased anabolic signalling, decreased initiation of autophagy and increased parts of the ubiquitin-proteasome pathway.
These molecular responses were seen in both ICU survivors and controls.
Pathways were assessed in muscle biopsies taken before and after the intervention.
Conclusions
The authors conclude that ICU survivors retain substantial anabolic capacity, supporting structured exercise-nutrition rehabilitation, although the hypothesis of residual anabolic resistance was only partially supported.
The blunted increase in synthesis was set against a higher baseline rate and equal post-intervention rates.
The authors describe the findings as the first mechanistic support for structured exercise-nutrition rehabilitation to promote muscle recovery after critical illness.
Registered prospectively at ClinicalTrials.gov (NCT05261984).
What This Means
Many people who survive a stay in intensive care are left with weak, thinner muscles for months. This study asked whether their muscles have lost the ability to respond to the usual building signals of exercise and protein. Researchers compared 20 ICU survivors, tested 3 to 6 months after discharge, with 20 similar people who had never been critically ill. Everyone did a leg resistance exercise session and drank 24 g of protein, and muscle samples were taken before and after to measure how fast muscle protein was being made.
The survivors did have less muscle and weaker grip strength. Their muscles were building protein faster than controls at rest, but increased less after exercise and protein (about 0.031 vs. 0.040 percentage points per hour). After the intervention, both groups were building protein at nearly the same rate. Cell signalling in muscle also responded in the same general direction in both groups, with growth signals turning up.
This research suggests that muscles of ICU survivors can still respond well to exercise combined with protein, even months later, although the response is somewhat smaller. This supports the idea that structured exercise and nutrition programmes could help recovery. The study was small and measured a single session, so it cannot show whether longer programmes actually restore muscle size or strength.
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Fischer-Hammerschmied A, Tardif N, Mandić M, Gustafsson T, Apro W, Helleberg J, et al.. (2026). Preserved anabolic skeletal muscle capacity in response to exercise and protein intake after critical illness.. Critical care (London, England). https://doi.org/10.1186/s13054-026-06418-7