REF-054 · Vandoorne et al., 2017 · Frontiers in Physiology, · Paper · PubMed

Ketone Ester in Recovery: Promotes mTORC1 Signaling but NOT Glycogen Resynthesis

Blimited evidenceMeasured on trained to highly trained athletesWritten before October 2026, being re-checked

Participants

n=8 healthy trained males, randomized double-blind placebo-controlled crossover. Each session: intense one-leg glycogen-depleting exercise, then a 5-hour recovery during which subjects ingested a protein/carbohydrate mixture plus either a ketone ester (KE) or an isocaloric placebo (PL).

Protocol

Randomized double-blind placebo-controlled crossover in eight healthy trained males (from the abstract).
Each session: intense one-leg glycogen-depleting exercise, then a 5-h recovery period with a protein/carbohydrate mixture plus either a ketone ester (KE) or an isocaloric placebo (PL).
Measures: muscle glycogen resynthesis; AMPK phosphorylation; mTORC1 activation (phosphorylation of S6K1 and 4E-BP1).
Follow-up in vitro: myogenic C2C12 cells, testing ketone bodies on leucine-mediated mTORC1 activation and protein synthesis.

Overview

Vandoorne et al. directly tested whether co-ingesting a ketone ester with post-exercise carbohydrate + protein alters muscle recovery signalling and glycogen resynthesis.

Adding the ketone ester did not affect muscle glycogen resynthesis, but it lowered post-exercise AMPK phosphorylation more rapidly and produced higher mTORC1 activation (higher phosphorylation of its downstream targets S6K1 and 4E-BP1). In myogenic C2C12 cells the authors then confirmed that ketone bodies increase leucine-mediated mTORC1 activation and protein synthesis.

Their conclusion: KE in a standard recovery beverage enhances post-exercise mTORC1 activation but does not affect muscle glycogen resynthesis; whether chronic use helps training adaptation remains to be tested.

Key Findings

Glycogen resynthesis: NO effect of adding ketone ester to CHO+protein over 5 h of recovery (the key correction — the previous "5-15% faster" claim was erroneous)
Ketone ester increased mTORC1 activation (higher p-S6K1 and p-4E-BP1) and lowered AMPK phosphorylation more rapidly during recovery
In vitro (C2C12 myotubes): ketone bodies potentiated leucine-stimulated mTORC1 activation and protein synthesis
Effect is on anabolic signalling, not carbohydrate storage; no performance or training outcome was measured

Practical Application

In 8 trained males (double-blind crossover), a ketone ester added to a post-exercise carbohydrate + protein drink did not change muscle glycogen resynthesis over 5 hours but raised mTORC1 signalling — do not use ketone esters to speed refuelling; the only rationale left is a mechanistic anabolic-signalling effect that has not been tied to performance.
Optimized carbohydrate + protein timing remains the established, lower-cost approach to refuelling — see REF-056 (timing of carbohydrate after exercise) and REF-055 (recovery-nutrition review).
Not a standard recommendation of the base; the authors themselves call for chronic-intake studies before any adaptation claim.

Limitations

n=8 men, one-leg exercise model, 5-hour window; signalling markers, not protein synthesis rates in vivo or training outcomes.
Isocaloric placebo controls energy, not ketone-specific taste or gastrointestinal effects.
How this entry was checked and changed
Why this level

regraded 2026-09-27 from A: crossover, n=8

Content correction 2026-09-27
Added the design and sample from the abstract (randomized double-blind placebo-controlled crossover, n=8 healthy trained males, 5-h recovery) and the AMPK and in-vitro results; Level A -> B (crossover, n=8).
Removed the unsourced "consistent with Poffé 2020 (ketone ester affects neither muscle glycogen utilization nor performance)" — no entry in the base carries that paper.
2026-09-28: added Protocol from the abstract (Europe PMC PMID 28588499).
2026-09-28: PMID 28536533 belonged to an unrelated paper; replaced with 28588499, the PubMed record for this entry's own DOI.