REF-053 · Cox et al., 2016 · Cell Metabolism, Vol. · Paper

Nutritional Ketosis Alters Fuel Preference and Lactate Production

Blimited evidenceMeasured on elite to world-class athletesWritten before October 2026, being re-checked

Participants

n=39 high-performance athletes across five separate studies. Ketosis was induced with a ketone-ester drink, not by fasting or carbohydrate restriction.

Overview

Cox et al. used a ketone ester to study nutritional ketosis in athletes without the confounds of starvation or a low-carbohydrate diet.

Across five studies in 39 high-performance athletes, ketosis changed fuel competition for oxidative respiration: muscle glycolysis and plasma lactate concentrations fell, ketone bodies served as an alternative oxidative substrate, and intramuscular triacylglycerol oxidation during exercise rose — even with normal muscle glycogen, co-ingested carbohydrate and elevated insulin.

The authors report that this metabolic state improved physical endurance in their tests. The abstract gives no percentages for the lactate reduction, no economy figure, and no statement about high-intensity efforts.

Key Findings

Ketosis decreased muscle glycolysis and plasma lactate concentration (magnitude not given in the abstract)
Ketosis increased intramuscular triacylglycerol oxidation during exercise, even with normal glycogen, co-ingested carbohydrate and elevated insulin
Ketone bodies provided an alternative substrate for oxidative phosphorylation
Authors' claim: the altered fuel selection improved physical endurance in these athletes

Practical Application

In 39 high-performance athletes across five acute studies, a ketone-ester drink lowered muscle glycolysis and plasma lactate and raised intramuscular fat oxidation during exercise even with carbohydrate on board; the authors report improved endurance — this is the mechanistic basis for ketone esters as an alternative fuel, not a performance recommendation.
Not from this paper; the base's own position: the acute-performance evidence for ketone esters since 2016 is mixed and the base does not recommend them for racing or high-intensity blocks — see REF-020 (UCI statement) and REF-054 (no effect on glycogen resynthesis). If an athlete wants to trial one, do it on a low-intensity endurance ride, not in a race, and watch for gastrointestinal tolerance and power.
Inference, not tested here: a lower lactate reading under a ketone ester is a shift in fuel selection, not a fitness change — do not read ketone-affected lactate values against the athlete's normal thresholds.

Limitations

Acute studies; no training intervention and no long-term outcome.
The abstract reports directions, not magnitudes; the endurance claim is the authors' and the specific test is not described in the abstract.
A ketone-ester drink is not the same state as dietary ketosis from carbohydrate restriction.
How this entry was checked and changed
Content correction 2026-09-27
Removed the unsourced "30-40% less lactate", "submaximal economy improved 2-4%", "high-intensity efforts (>85% VO2max) reverted to glycolytic reliance", "lactate clearance enhanced" and "long rides 2-3 h" — none is in the abstract.
The abstract says ketosis "improves physical endurance"; the entry's "limiting racing applications / cost-benefit unfavorable" is now labelled as the base's own position, not the paper's finding.
Type: "metabolic kinetics study" -> series of five acute studies (n=39).