Safety of two-year caloric restriction in non-obese healthy individuals

Romashkan SV, Das SK, Villareal DT, Ravussin E, Redman LM, Rochon J, Bhapkar M, Kraus WE · 2016 · Oncotarget · Atlas ID ROM2016

What this study shows

Two years of sustained 25% caloric restriction in healthy non-obese adults was safe overall, though it lowered bone density more than controls.

Abstract

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The extent to which sustained caloric restriction (CR) in healthy non-obese adults is safe has not been previously investigated. Assess the safety and tolerability of sustained two-year CR intervention in healthy, non-obese adults. A multi-center, randomized controlled trial. Participants were randomized using a 2:1 allocation in favor of 25% CR vs. Ad-Libitum intake (AL). Adverse and serious adverse events (AE, SAE), safety laboratory tests, and other safety parameters were closely monitored. Three participants were withdrawn from the CR intervention because of the safety concerns.

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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	Humans, RCT (CALERIE trial, n=218)
Journal	Oncotarget
Year	2016
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.18632/oncotarget.8093 · PMID 26992237 · Free full text (PMC4991370)

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	Caloric restriction (25%, 2 years)
Target	Nutrient-sensing / mTOR (indirect)
Model	Human – RCT (CALERIE, n=218, non-obese)
Effect	Sustained 25% caloric restriction was safe and well tolerated in healthy non-obese adults over 2 years
Dose	Caloric restriction ~25% (achieved ~480 kcal/day deficit in first 6 months) for 2 years vs ad libitum; multicenter RCT (CALERIE).
Sample size	218 participants in safety analysis (66 male / 152 female); 30 discontinued (26 CR, 4 AL).
Effect size	Sustained 25% CR was safe and well tolerated over 2 years; most lab abnormalities were small and not significantly different from control.
Limitations	Between-group differences mostly not statistically significant; a few treatment-resistant hematocrit decreases (2 withdrawn); healthy non-obese cohort only.

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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Romashkan, S. V., Das, S. K., Villareal, D. T., Ravussin, E., Redman, L. M., Rochon, J., Bhapkar, M., & Kraus, W. E. (2016). Safety of two-year caloric restriction in non-obese healthy individuals. Oncotarget. https://doi.org/10.18632/oncotarget.8093

@article{ROM2016,
  author       = {Romashkan, S. V. and Das, S. K. and Villareal, D. T. and Ravussin, E. and Redman, L. M. and Rochon, J. and Bhapkar, M. and Kraus, W. E.},
  title        = {{Safety of two-year caloric restriction in non-obese healthy individuals}},
  journal      = {Oncotarget},
  year         = {2016},
  doi          = {10.18632/oncotarget.8093},
  note         = {PMID: 26992237},
}

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 ROM2016) [Data set]. https://mtor-atlas.org/study/ROM2016/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ROM2016,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ROM2016},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ROM2016/},
  doi          = {10.5281/zenodo.22059963}
}

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