Pooling 11 controlled trials (nine randomized, 548 adults with MASLD), melatonin supplementation lowered total cholesterol by 16.8 mg/dL, LDL by 52.4 mg/dL, and the inflammatory markers IL-1, IL-6 and TNF-α, alongside modest reductions in body weight and waist circumference. Grade III steatosis was less common at follow-up (RR 0.23, two trials). ALT, AST, GGT, ALP, triglycerides, HDL, glucose, blood pressure and hs-CRP did not differ significantly; enzyme gains appeared only in exploratory sensitivity analyses.
The headline numbers deserve skepticism. An LDL drop of 52 mg/dL would rival a moderate-dose statin, yet the confidence interval runs from about 4 to 100 mg/dL and heterogeneity reached I² of 96%, which signals trials that differ too much to trust a single pooled figure. The steatosis result rests on just two trials. Most telling, the outcomes clinicians actually use to track liver injury, the transaminases, showed nothing in the primary analysis, and no trial measured fibrosis, cirrhosis, liver-related events or mortality. Melatonin's antioxidant and anti-inflammatory profile makes biological sense for MASLD, and the cytokine signal fits that, but surrogate lipid and cytokine changes do not establish liver benefit. Small, short trials with mixed designs and background therapies also invite bias. Editorially, this is hypothesis-generating rather than practice-changing. Weight loss, exercise, diet quality and treating cardiometabolic risk factors remain the proven foundation for fatty liver; anyone considering melatonin for it should discuss it with their clinician, especially if already taking a statin or other medicines, and treat it as an experimental add-on until larger trials with histologic endpoints exist.