Westerblad · News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society 2002 · narrative review · n=?

Muscle fatigue: lactic acid or inorganic phosphate the major cause?

Cited 563 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review discussing mechanism-based physiological studies without systematic synthesis.

PubMed 11821531 · doi:10.1152/physiologyonline.2002.17.1.17 · record verified 2026-08-30

What was done

This narrative review evaluates physiological literature on the causes of skeletal muscle fatigue, contrasting the traditional model of intracellular lactic acidosis with evidence regarding inorganic phosphate accumulation from creatine phosphate breakdown in mammalian muscle.

What was found

The abstract reports no numerical values or effect sizes. It states that recent studies in mammalian muscle at physiological temperatures demonstrate minimal direct impairment of muscle function from acidosis, whereas inorganic phosphate accumulation during fatigue emerges as a major causative factor.

Why it matters

It challenges the classical view that lactic acid is the primary driver of muscle fatigue, highlighting inorganic phosphate as a central mechanism in muscle performance limitation.

Limits

The abstract contains no quantitative data, search methodology, or study counts. The conclusions rely on mechanistic and preclinical mammalian muscle models rather than direct human clinical trials.

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