Melatonin Caffeine

Caffeine increases the levels of both endogenous and orally administered melatonin. 

A crossover study in 12 healthy subjects found that a single 200-mg dose of caffeine (equivalent to one large or two small cups of coffee), taken 1 hour before and 1 and 3 hours after a single 6-mg oral dose of melatonin, increased the average AUC and maximum levels of melatonin by 120% and 137%, respectively, although the half-life of melatonin was not significantly affected. The interaction was less pronounced in smokers (6 subjects) than in non-smokers (6 subjects). ... 

Another crossover study in 12 healthy subjects (by the same authors) found that a single 200-mg dose of caffeine, taken 12 or 24 hours before a single 6-mg dose of melatonin, did not affect the melatonin levels, although 2 subjects had raised melatonin levels when caffeine was taken 12 hours, but not 24 hours, before melatonin. ... 

In 12 healthy subjects given a single 200-mg dose of caffeine, taken in the evening, endogenous, nocturnal melatonin levels were found to be increased, and the AUC of melatonin was increased by 32%. ... 

Caffeine is thought to reduce the metaholism of melatonin by competing for metabolism by the cytochrome P450 isoenzyme CYP1A2. ... 

Melatonin is produced by the pineal gland in the body and is also available as a supplement in some parts of the world. However, the effects of longterm use of this supplement are unknown. From the above studies, it appears that caffeine significantly increases the levels of single doses of supplementary melatonin, however the long-term effects of caffeine and concurrent multiple dosing of melatonin do not appear to have been studied. Melatonin can cause drowsiness when taken on its own, so patients who take melatonin should be advised that this effect may be increased if they also take caffeine. This increased drowsiness may oppose the stimulating effect of caffeine. 

Hartter S, Nordmark A, Rose D-M, BertilssonL, Tybring G, Laine K. Effects of caffeine intake on die pharmacokinetics of melatonin, aprobe drug for CYP1A2 activity. BrJ Clin Pharmacol... 

Hartter S, Korhonen T, Lundgren S, Rane A, Tolonen A, Turpeinen M, Laine K. Effect of caffeine intake 12 or 24 hours prior to melatonin intake and CYP1A2 IF polymorphism on C YPl A2 phenot5 ing by melatonin. Basic Clin Pharmacol Toxicol (2006) 99, 300-4. 

Ursing C, Wikner J, Brismar K, Rqjdmark S. Caffeine raises the serum melatonin level in healthy subjects an indication of melatonin metabolism by c3 chrome P450 (C YP) 1A2. J Endocrinol Invest (2003) 26, 403-6. 

Melatonin (V-acetyl-5-methoxytryptamine) is a pineal gland hormone which aggregates melanin granules in the dermal melanophores and is capable of lightening the color of frog melanocytes by reversing the darkening action of MSH, ACTH, and caffeine (116, 149). Its effect on the human and other mammalian melanocytes is, however, questionable (253). 

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