Skubic · Biomolecules 2025 · narrative review · n=?

Circadian Biomarkers in Humans: Methodological Insights into the Detection of Melatonin and Cortisol.

Cited 22 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative methodological review without primary human trial data or meta-analysis.

PubMed 40723877 · doi:10.3390/biom15071006 · record verified 2026-08-30

What was done

The authors reviewed methodological approaches for quantifying the circadian hormones melatonin and cortisol in humans. The review evaluated different biological matrices (blood, saliva, urine) and analytical platforms (immunoassays versus liquid chromatography–tandem mass spectrometry [LC-MS/MS]), focusing on protocol requirements for Dim Light Melatonin Onset (DLMO) and the Cortisol Awakening Response (CAR), alongside pre-analytical confounders like ambient light, posture, and exact timing.

What was found

The abstract reports no numerical values or quantitative comparisons. It qualitatively notes differences in sensitivity, specificity, and feasibility between immunoassays and LC-MS/MS and emphasizes the necessity of controlled sampling conditions to eliminate confounding in DLMO and CAR measurements.

Why it matters

Melatonin and cortisol are core biochemical markers for evaluating circadian misalignment in sleep, metabolic, and psychiatric disorders. Establishing standardized sampling and assay selection helps avoid measurement errors in clinical and research settings.

Limits

The abstract provides no primary data, sample sizes, or quantitative assay performance metrics (such as detection limits or cross-reactivity rates). Search strategy and systematic inclusion criteria are not described.

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