Intra- and inter-individual variation of the human lipidome

Lipids play essential roles in cellular functions such as membrane structure, signaling, and energy storage. Lipidomics—global study of lipids in cells and tissues—seeks to identify biomarkers and uncover underlying metabolic pathways. Human lipid concentrations in cells and biofluids can fluctuate at multiple temporal scales, reflecting normal biochemical and physiological variation, or responses to various internal and external stimuli. Understanding both intra- and inter-individual lipid variability is crucial for accurate lipidomics study design and interpretation. This knowledge also supports personalized healthcare, moving beyond static reference ranges. Here, we review key drivers of intra-individual variation, including diet, circadian rhythms, sleep, environmental exposures, and physiological states. We also examine inter-individual factors such as genetics, age, sex, microbiome composition, and medications. Finally, we discuss how these variables interact and influence lipidomics outcomes, aiming to enhance reproducibility and guide future research.