Muscle glycogen stores and fatigue
Journal of Physiology review: glycogen sits in distinct pools, and the intramyofibrillar pool near the SR is linked to reduced Ca²⁺ release in fatigue
Key Findings (contribution)
The importance of carbohydrate as an exercise fuel was shown at the beginning of the last century, and the importance of muscle glycogen for performance has been confirmed in numerous studies since (the classic biopsy evidence: Bergström & Hultman 1967 REF-452)
But how glycogen depletion ties in with impaired muscle function in fatigue is poorly understood, and a direct causal link from glycogen to muscle function has yet to be proven
Electron microscopy shows glycogen is not homogeneously distributed in muscle fibres but localized in distinct pools; each glycogen granule carries its own metabolic machinery (glycolytic enzymes and regulatory proteins)
One pool of these glycogenolytic complexes sits within the myofibrils, in close contact with key proteins of excitation–contraction coupling and Ca²⁺ release from the sarcoplasmic reticulum (SR)
The authors and others have provided experimental evidence for a direct role of decreased intramyofibrillar glycogen in the reduction of SR Ca²⁺ release during fatigue — consistent with compartmentalized energy turnover, where distinctly localized pools govern SR Ca²⁺ release and thereby contractility and fatigability
Key Mechanism
Depletion of the glycogen pool located within the myofibrils → reduced SR Ca²⁺ release → less force per activation → fatigue (the review's central proposition)
Pool names used in the literature — subsarcolemmal, intermyofibrillar, intramyofibrillar — are from the full text (not checked against the abstract)
Inference from the abstract: fatigue can develop while total glycogen is not exhausted, if the local pool near the SR is
Fibre-type-specific depletion patterns (type I at moderate, type II at high intensity) are not in this abstract — removed
Practical Application
Narrative review (Ørtenblad, Westerblad & Nielsen 2013): muscle glycogen sits in separate pools, and the pool inside the myofibrils — in contact with the excitation–contraction machinery — is the one experimentally linked to reduced SR Ca²⁺ release in fatigue; at the same time the authors state that a direct cause-and-effect link from glycogen to muscle function "remains to be established". Meaning: glycogen-related fatigue is about WHERE the glycogen is, not only how much — a cellular argument for keeping stores topped up during long or hard work, held with the review's own caution.
Explains why glycogen-depleted training (train-low, REF-157) can be a potent adaptive stimulus yet compromises high-quality work: the same depletion that signals also limits Ca²⁺ release
Adds cellular precision to the carb-loading rationale from Bergström & Hultman REF-452
Connects to the Ca²⁺-release fatigue mechanism favoured in Allen, Lamb & Westerblad REF-455 (same group)
Limitations
Narrative review, no systematic method; 2013 — refinements since (see REF-144)
Mechanism partly from animal/single-fibre work
The authors themselves state that a direct causal glycogen → function relationship remains to be established; no glycogen "threshold" for fatigue onset is given
How this entry was checked and changed
Why this level
regraded 2026-09-27 from A: authoritative narrative review from the leading group on glycogen compartmentation, no systematic method
Content correction 2026-09-27
Level A -> B+ (narrative review).
"Type I fibres deplete first at moderate intensity; type II at high intensity" -> not in the abstract; removed. Pool names marked as full text.
Added the abstract's explicit caution that a direct causal link from glycogen to muscle function is not yet established; added Tier/Sport lines and an abstract-based lead.
Descriptions of REF-144 repeated its pre-2026-09-26 version (muscle biopsies, glycogen/fibre-type depletion, fat oxidation doubling, power "preserved/maintained" at 100 g/h). The corrected entry took no biopsies and reports 6-min power FALLING ~10% after 4 h at 100 g/h; descriptions updated.