REF-482 · Nybo, 2003 · Medicine & Science in Sports & Exercise, · Paper · PubMed

CNS fatigue and prolonged exercise: effect of glucose supplementation

Experimental linking of substrate to the CNS

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

Participants

n=8 endurance-trained males.

Protocol

A 2-min sustained maximal knee extension (voluntary force + central activation ratio by twitch interpolation) at baseline and immediately after 3 h of cycling, randomized to be with or without glucose supplementation.

Key Findings

Direct experimental evidence of the link CHO availability ↔ CNS activation of muscle.

1

Without glucose, blood glucose fell from 4.5 ± 0.2 to 3.0 ± 0.2 mM over the 3 h; with glucose, glucose homeostasis was maintained.

2

Mean force in the sustained MVC: 248 ± 23 N at baseline, 222 ± 20 N after the glucose trial, 197 ± 21 N after the placebo trial (P < 0.05 between conditions).

3

In the placebo trial the lower force came with a reduced level of CNS activation (central activation ratio) versus both other conditions (P < 0.05); in the glucose trial the central activation ratio was similar to baseline.

4

Conclusion of the paper: exercise-induced hypoglycaemia attenuates CNS activation during a sustained maximal contraction, whereas 3 h of moderately intense exercise does not affect central activation when euglycaemia is kept by carbohydrate ingestion.

Practical Application

Nybo 2003 (n=8 endurance-trained men, crossover): after 3 h of cycling without glucose, blood glucose fell to 3.0 mM and maximal force dropped to 197 N with reduced central activation; with glucose, central activation stayed at baseline (force 222 N vs 248 N at baseline). Fuelling a long ride protects the brain's drive to the muscle, not just the muscle's fuel.
Explains the athlete who "cannot push" late in a long ride with legs that are not wrecked: the deficit can be central and glucose-dependent.
Not from this paper; the base's own practice: keep blood glucose up with steady carbohydrate intake through long efforts — dose per SYNTH-02; at race fuelling rates fat-oxidation capacity stops predicting durability (REF-474, >90 g/h).
The paper does not test a dose, timing or caffeine; it shows the mechanism under one 3-h protocol.

Limitations

Small cohort (n=8), male only
Central activation measured by twitch interpolation during a knee-extension MVC, not during cycling itself
The specific glucose dose was not studied for optimization
How this entry was checked and changed
Why this level

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

Content correction 2026-09-27
Level A -> B: crossover, n=8.
Removed "EEG changed (↑ alpha)": the study used twitch interpolation / central activation ratio, not EEG. Removed "glucose is almost the only brain fuel" and "gel every 20 min", "hour 4", "90-100 g/h target" as findings; fuelling advice relabelled as the base's own practice.
"MVC preserved with CHO" corrected to the abstract's numbers (248 -> 222 N with glucose, 197 N placebo); what was preserved was central activation. Added blood-glucose values and n=8. Cross-reference byline REF-461 Roberts -> Reynolds.
2026-10-01: cross-reference repointed from a merged framework to the one that replaced it (SYNTH-01→31, 05→34, 09→70, 12/15→32, 19→26).