Circadian rhythm of free melatonin in human plasma

J Clin Endocrinol Metab. 1998 Mar;83(3):1013-5. doi: 10.1210/jcem.83.3.4636.


The appearance of melatonin in saliva in concentrations up to 70% lower than those in blood has led to the suggestion that melatonin is bound to plasma protein and that saliva levels reflect the circulating free hormone. To test this directly, melatonin was measured in human plasma from 10 subjects after ultrafiltration through Centrifree micropartition tubes and compared to saliva melatonin levels in samples collected simultaneously. Melatonin was detected in the protein-free fraction and increased throughout the night in parallel with the saliva melatonin level. Peak concentrations ranged from 45-200 pmol/L (mean +/- SEM, 106 +/- 17 pmol/L) and averaged 23% of the total melatonin level. Across all samples, the correlation between the saliva levels and the free hormone levels was significant (r = 0.84; P < 0.05). These results provide the first direct evidence that endogenous melatonin is bound to plasma proteins and that saliva melatonin generally reflects the levels of this binding.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Proteins / metabolism
  • Circadian Rhythm / physiology*
  • Female
  • Humans
  • Male
  • Melatonin / analogs & derivatives
  • Melatonin / blood*
  • Melatonin / metabolism
  • Middle Aged
  • Osmolar Concentration
  • Saliva / metabolism


  • Blood Proteins
  • 2-iodomelatonin
  • Melatonin