Bioavailability of Oral Melatonin in Humans

Abstract

We administered crystalline melatonin (80 mg) in gelatin capsules to 5 young male volunteers and measured serum and urinary melatonin levels at intervals. Changes in serum melatonin levels were best described by a biexponential equation with an absorption constant (k_a) of 1.72 h^-1 (half-life = 0.40 h) and an elimination constant (k_el) of 0.87 h^-1 (half-life = 0.80 h). Peak serum melatonin levels, ranging from 350 to 10,000 times those occurring physiologically at nighttime, were observed 60–150 min after its administration, remaining stable for approximately 1.5 h. The fraction of ingested melatonin that was absorbed, estimated from the area under the curve describing serum melatonin concentrations as a function of time after melatonin administration (the concentration-time curve), varied by 25-fold among subjects. 3 additional volunteers received three melatonin-containing capsules (80 mg each) at 60-min intervals. This regimen extended the duration of elevated serum melatonin levels to 4–6 h. Melatonin excretion closely paralleled serum melatonin levels until 9 h after the hormone’s administration, after which urinary levels tended to be higher than those predicted from serum levels. However, the area under the concentration-time curve for serum melatonin correlated well (r = 0.96) with the cumulative melatonin excretion during the initial 15 h after melatonin’s administration, indicating that either approach can be used to estimate the absorption of orally administered melatonin.

Melatonin improves memory acquisition under stress independent of stress hormone release

“…Consistent with numerous previous studies (Deacon and Arendt 1995;Dollins et al 1994;Nickelsen et al 1989;Rutledge et al 2004;Waldhauser et al 1984;Wright et al 1986), melatonin compared to placebo decreased wakefulness. As this effect was not in relation to the memory effects of melatonin, wakefulness can be ruled out as a possible confound.…”

“…Second, none of these studies tested memory function during stress, which per se affects memory encoding and retrieval (de Quervain et al 1998;Elzinga et al 2005;Kuhlmann et al 2005b;Leeuwenberg et al 1992). Concurring with the present observations, in adult male rats, melatonin facilitated social recognition (Argyriou et al 1998), and in humans several studies failed to reveal effects of melatonin on memory using free recall procedures (Rutledge et al 2004;Waldhauser et al 1984;Wesensten et al 2005). However, Lieberman et al (1984) found no effect of 240 mg melatonin on both free recall as well as recognition memory of words.…”

“…Concurring with the present observations, in adult male rats, melatonin facilitated social recognition (Argyriou et al 1998), and in humans several studies failed to reveal effects of melatonin on memory using free recall procedures (Rutledge et al 2004;Waldhauser et al 1984;Wesensten et al 2005). However, Lieberman et al (1984) found no effect of 240 mg melatonin on both free recall as well as recognition memory of words. In that study both encoding and retrieval were measured at times of enhanced melatonin concentration, and the melatonin dose was distinctly higher, which may account for the divergent findings.…”

“…In the second session (day 2) hormonal responses to the Trier Social Stress Test (TSST) as well as memory under conditions of stress ("memory retrieval after stress") were tested after subjects had received either placebo or melatonin (3 mg, orally, "Melatonin Standard" purchased from PhysioLogics, Northglenn, CO, 80234 USA). Drugs were administered 60 min before the TSST, based on the known kinetics of melatonin after oral intake of 1-5 mg indicating that at this time blood levels of melatonin reach maximum values that are maintained for at least 2-4 hours (Dollins et al 1994;Waldhauser et al 1984). The third session (day 3) served to test memory retrieval of items (objects distributed in the test room) that the subjects had encoded under conditions of stress ("memory encoding under stress") on the second session on day 2.…”

Double-blind randomized study on the myeloprotective effect of melatonin in combination with carboplatin and etoposide in advanced lung cancer

“…The ingestion of 40-mg capsules is, in fact, known to result in plasma concentrations much above the physiological ones for more than 8 h (Waldhauser et al, 1984;Aldhous et al, 1985), and which have been associated with some biological activities, such as activation of some lymphocyte subsets in cancer patients .…”