What is the effect of "coffee + melatonin"? The result is not what you think

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When we feel sleepy and tired, a cup of coffee will always awaken your mind.

At night, when many people are nervous and difficult to sleep due to insomnia, they will choose melatonin (melatonine) to assist sleep.

The two seem to be a "hostile" relationship that is "incompatible".

But this "hostile" relationship may be more harmonious than you might think: relevant pharmacokinetic studies suggest that caffeine increases endogenous and oral melatonin levels in the human body.

Related findings[1][2]:

In one crossover study, 12 healthy subjects were given a single dose of 200 mg of caffeine (equivalent to one large or two small cups of coffee) 1h before a single dose of 6 mg of melatonin and 1 h to 3 h after oral administration.

The results found that caffeine increased the average AUC and maximum levels of melatonin by 120% and 137%, respectively, but the half-life of melatonin was not significantly affected.

Compared with non-smokers (6 cases), the interaction between smokers (6 cases) was less obvious.

In a similar study, caffeine intake 12h or 24h before melatonin administration did not affect melatonin levels, although melatonin levels were elevated when 2 subjects ingested caffeine 12h before melatonin administration.

Twelve healthy subjects, after taking a single dose of 200 mg of caffeine at night, found an increase in endogenous, nocturnal melatonin levels and a 32% increase in melatonin AUC.

The specific mechanism analyzed in the article is due to the fact that 90% of caffeine is cleared by the metabolism of the CYP1A2 enzyme, and the pituitary hormone melatonine is also a selective substrate of the CYP1A2 enzyme.

The experimental results showed that caffeine had a significant effect on melatonine's Cmax, which more than doubled on average, but its Tmax was not affected, suggesting that caffeine could compete with melatonine in the CYP1A2 enzyme, affecting melatonine's first-pass metabolism, resulting in higher oral bioavailability.

Fig. 1 Serum concentration of melatonine in volunteers over time

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bibliography:

[1] H rtter S, Nordmark A, Rose D-M, Bertilsson L, Tybring G, Laine K. Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Br J Clin Pharmacol(2003) 56, 679–682.

[2] H rtter 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*1F polymorphism on CYP1A2 phenotyping by melatonin. Basic Clin Pharmacol Toxicol (2006) 99, 300–4.

[3] Ursing C, Wikner J, Brismar K, R jdmark S. Caffeine raises the serum melatonin level in healthy subjects: an indication of melatonin metabolism by cytochrome P450 (CYP)1A2. J Endocrinol Invest (2003) 26, 403–6.

[4] Kalow W, Tang BK. Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 1991; 50: 508–519.

[5] Facciolá G, Hidestrand M, von Bahr C, Tybring G. Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. Eur J Clin Pharmacol 2001; 56: 881–888.

First published: Clinical Decision Assistant

Author: Xiao Dangdang, Red Oil Hot Sauce

Editor-in-Charge: Little Dangdang

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