Reduced dietary protein intake does not alter autophagy in human blood: A randomized crossover study in healthy adults

Singh S, Fourrier C, Hein LK, Bensalem J, Martin A, Hattersley KJ, King B, Teong XT, Baker K, Lange K, Barker G, …, Sargeant TJ · 2026 · Clinical Nutrition · Atlas ID SIN2026

What this study shows

In a rigorous randomized crossover trial, 63 healthy adults completed both a normal-protein (20% energy) and a reduced-protein (10% energy) diet for 4 weeks each. Despite preclinical evidence that dietary protein restriction should activate autophagy via mTORC1 inhibition, directly measured autophagic flux in blood immune cells did not change between the two diets. This is one of the few human studies to test the protein-restriction-to-autophagy link with a dynamic, flux-based (not just steady-state marker) readout, and the negative result suggests that moderate protein reduction alone, without an accompanying caloric deficit, is not sufficient to engage autophagy in humans the way it does in some animal models.

Abstract

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Autophagy activation is a promising strategy to counteract age-related cellular dysfunction. While preclinical studies suggest dietary protein restriction can induce autophagy via mTORC1 inhibition, direct human evidence using dynamic, flux-based measurements remains limited. The aim of this study was to determine whether a low protein diet could modulate autophagic flux in humans.

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At a glance

Evidence type	H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type	2 - Human Clinical Trial
Model system	Randomized crossover trial in healthy adults (n=63 completers, mean age ~29.5y); two 4-week interventions (average-protein 20% energy vs reduced-protein 10% energy) separated by a 4-week washout; autophagic flux measured in whole blood/PBMCs via a validated LC3B-II lysosomal-inhibition flux assay
Journal	Clinical Nutrition
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.clnu.2026.106778 · PMID 42721581

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Dietary protein restriction (10% vs 20% of energy) for 4 weeks each, randomized crossover, no caloric deficit
Target	mTORC1-mediated autophagy (autophagic flux)
Model	Human (healthy adults, n=63 completers)
Effect	No significant change in autophagic flux with protein restriction (negative result); suggests protein reduction alone, without caloric deficit, is insufficient to activate autophagy in human blood

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question A sensor/autophagy biomarker panel as a surrogate endpoint for human trials.

Cite this paper

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Singh, S., Fourrier, C., Hein, L. K., Bensalem, J., Martin, A., Hattersley, K. J., King, B., Teong, X. T., Baker, K., Lange, K., Barker, G., Gore, J. R., Heilbronn, L. K., & Sargeant, T. J. (2026). Reduced dietary protein intake does not alter autophagy in human blood: A randomized crossover study in healthy adults. Clinical Nutrition. https://doi.org/10.1016/j.clnu.2026.106778

@article{SIN2026,
  author       = {Singh, S. and Fourrier, C. and Hein, L. K. and Bensalem, J. and Martin, A. and Hattersley, K. J. and King, B. and Teong, X. T. and Baker, K. and Lange, K. and Barker, G. and Gore, J. R. and Heilbronn, L. K. and Sargeant, T. J.},
  title        = {{Reduced dietary protein intake does not alter autophagy in human blood: A randomized crossover study in healthy adults}},
  journal      = {Clinical Nutrition},
  year         = {2026},
  doi          = {10.1016/j.clnu.2026.106778},
  note         = {PMID: 42721581},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record SIN2026) [Data set]. https://mtor-atlas.org/study/SIN2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SIN2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SIN2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SIN2026/},
  doi          = {10.5281/zenodo.22059963}
}

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