Intramuscular Fat as a Biomarker of Muscle Health: Strengths, Limitations and Open Challenges.

Intramuscular fat (IMF), also known as myosteatosis, refers to the accumulation of lipids within and around skeletal muscle fibres. Excess IMF is increasingly recognised as a sign of poor muscle quality, linked to reductions in strength, power and mobility, and associated with adverse outcomes in metabolic disease, osteoarthritis, cardiovascular diseases and cancer. It is important to note that an increase in intramuscular fat is not always pathological. These associations and the ongoing uncertainty have sparked growing interest in IMF as a biomarker of muscle health beyond muscle mass and cross-sectional area. This narrative review synthesises current evidence on IMF as a biomarker of muscle health, critically evaluating its definition, measurement, biological variability, responsiveness to intervention and ongoing challenges for clinical application. We first clarify terminology, distinguishing intramyocellular lipids, extramyocellular lipids, intermuscular adipose tissue and subcutaneous adipose tissue. Advances in imaging techniques are assessed: Magnetic resonance imaging and spectroscopy provide accurate compartmental lipid quantification; computed tomography offers practical, reproducible estimates of muscle density; and ultrasound presents an accessible, though operator-dependent, alternative. Across populations, IMF shows considerable variability: Levels increase with age, differ by sex and ethnicity and have strong associations with adiposity and activity. Normative values are emerging but are lacking standardisation and population-specific reference ranges. Interventional studies show that IMF is modifiable. Acute endurance exercise reduces intramyocellular lipid stores, while long-term aerobic and resistance training prevent or lower fat infiltration but increase levels of intramyocellular lipids. Dietary restriction and bariatric surgery reliably decrease IMF but may also cause loss of lean mass without sufficient resistance training or protein intake. Pharmacological therapies, particularly glucagon-like peptide-1 receptor agonists such as liraglutide and semaglutide, have recently been shown to lower IMF while enhancing muscle quality, despite some overall muscle reduction. These findings support IMF as a flexible biomarker that indicates intervention success and correlates with functional outcomes including strength, gait speed and insulin sensitivity. Key barriers remain: lack of standardised imaging protocols, no universally defined pathological thresholds and the complex challenge of interpreting IMF across different age groups, sexes and ethnicities. Overcoming these obstacles through consensus definitions, prospective multi-ethnic research and the integration of advanced imaging with functional outcomes will be vital. If achieved, IMF could become a clinically important biomarker, complementing mass and strength-based measures to guide treatments, assess risk and track muscle health throughout life.