Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis
Abstract
Sepsis is a massive inflammatory response mediated by infection, characterized by oxidative stress, release of cytokines, and mitochondrial dysfunction. Melatonin accumulates in mitochondria, and both it and its metabolites have potent antioxidant and anti-inflammatory activities and may be useful in sepsis. We undertook a phase I dose escalation study in healthy volunteers to assess the tolerability and pharmacokinetics of 20, 30, 50, and 100 mg oral doses of melatonin. In addition, we developed an ex vivo whole blood model under conditions mimicking sepsis to determine the bioactivity of melatonin and the major metabolite 6-hydroxymelatonin at relevant concentrations. For the phase I trial, oral melatonin was given to five subjects in each dose cohort (n = 20). Blood and urine were collected for measurement of melatonin and 6-hydroxymelatonin, and symptoms and physiological measures were assessed. Validated sleep scales were completed. No adverse effects after oral melatonin, other than mild transient drowsiness with no effects on sleeping patterns, were seen, and no symptoms were reported. Melatonin was rapidly cleared at all doses with a median [range] elimination half-life of 51.7 [29.5-63.2] min across all doses. There was considerable variability in maximum melatonin levels within each dose cohort, but 6-hydoxymelatonin sulfate levels were less variable and remained stable for several hours. For the ex vivo study, blood from 20 volunteers was treated with…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 20 participants or records.
Read the paper
Related studies
- Chaos and quantum thermalization
- The Dalton quantum chemistry program system
- Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study
- Quantitative metabolomics by H-NMR and LC-MS/MS confirms altered metabolic pathways in diabetes
- Stable adiabatic quantum batteries
- A novel self-lipid antigen targets human T cells against CD1c(+) leukemias
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.