The endogenous melatonin profile as a marker for circadian phase position

Several circadian rhythms have been used to assess the phase of the endogen ous circadian pacemaker (ECP). However, when more than one marker rhythm is ' measured, results do not always agree. Questions then inevitably arise. A re there multiple oscillators? Are some markers more reliable than others? Masking is a problem for all marker rhythms. Masking of melatonin is minimi zed by sampling under dim light. The dim-light melatonin onset (DLMO) is pa rticularly convenient since it can usually be obtained before sleep. Howeve r, assessing the DLMO in low melatonin producers may be problematic, partic ularly with the commonly used operationally defined threshold of 10 pg/ml. This study evaluates various circadian phase markers provided by the plasma melatonin profile in 14 individuals, several of whom are low melatonin pro ducers. The amount (amplitude) of melatonin production appears to influence the phase of many points on the melatonin profile. Accordingly, when low p roducers are in a data set, we now prefer a lower DLMO threshold than the o ne previously recommended (10 pg/ml). Indeed, there are some low producers who never exceed this threshold at any time. Radioimmunoassays are now avai lable that have the requisite sensitivity and specificity to support the us e of a lower threshold. Nevertheless, the dim-light melatonin offset (DLMOf f), even when operationally defined at thresholds less than 10 pg/ml, appea rs to be confounded by amplitude in this study; in such cases, it may be pr eferable to use the melatonin synthesis offset (SynOff) because it is not c onfounded by amplitude and because, theoretically, it is temporally closer to the endogenous mechanism signaling the offset of production. The questio n of whether the termination mechanism of melatonin synthesis is related to an interval timer or to a second oscillator loosely coupled to the onset o scillator is probably best answered using the SynOff rather than the DLMOff . It is hoped that these findings will make a useful contribution to the de bate on the best ways to use points on the melatonin profile to assess circ adian phase position in humans.