Functional decoupling of melatonin suppression and circadian phase resetting in humans

Abstract

Continuous experimental light exposures show that, in general, the conditions that produce greater melatonin suppression also produce greater phase shift, leading to the assumption that one can be used as a proxy for the other. We tested this association in 16 healthy individuals who participated in a 9-day inpatient protocol by assessing melatonin suppression and phase resetting in response to a nocturnal light exposure (LE) of different patterns: (i) dim-light control (<3 lux; n = 6) or (ii) two 12-min intermittent bright light pulses (IBL) separated by 36 min of darkness (∼9500 lux; n = 10). We compared these results with historical data from additional LE patterns: (i) dim-light control (<3 lux; n = 11); (ii) single continuous bright light exposure of 12 min (n = 9), 1.0 h (n = 10) or 6.5 h (n = 6); or (iii) an IBL light pattern consisting of six 15-min pulses with 1.0 h dim-light recovery intervals between them during a total of 6.5 h (n = 7). All light exposure groups had significantly greater phase-delay shifts than the dim-light control condition (P < 0.0001). While a monotonic association between melatonin suppression and circadian phase shift was observed, intermittent exposure patterns showed significant phase shifts with disproportionately less melatonin suppression. Each and every IBL stimulus induced a similar degree of melatonin suppression, but did not appear to cause an equal magnitude of phase shift. These results suggest unique specificities in how light-induced phase shifts and melatonin suppression are mediated such that one cannot be used as a proxy measure of the other.

Light Modulation of Human Clocks, Wake, and Sleep

“…Research has also shown that, on the opposite, inadequate light exposure (e.g., too much blue-enriched light) at inappropriate circadian times (e.g., before bedtime) can seriously alter sleep/circadian physiology and lead to disorders in chronic circumstances. In addition, recent work [103] has shown that acute melatonin suppression and circadian responses to light are specific and not proxies of each other. This suggests that NIF responses might not share a single sensitivity function to light and thus follow different illuminance-response and duration-response curves [34].…”

Randomized trial of polychromatic blue-enriched light for circadian phase shifting, melatonin suppression, and alerting responses

“…Munch and colleagues used a lower intensity (1 x 10 15 photons/cm 2 /s) closer to, but still an order of magnitude higher than that used in the current study (1 x 10 14 photons/cm 2 /s), and studied older adults who were likely to have reduced sensitivity to blue-light given pigmentation of the lens that would have blocked some of the short-wavelength light [46]. While we used a quantitative approach in selecting our light intensity, basing it on short-duration fluence response curves for melatonin suppression using the same light sources, it is possible that i) short duration exposures (1.5 h) do not always predict the effects of longer duration light (6.5 h) [19]; ii) the magnitude of melatonin suppression does not predict the magnitude of circadian phase shifting or vice versa [47,48]. Our pre-study power calculations based on monochromatic exposure data showed sufficient power to detect an effect on phase shifting but our posthoc power calculation for phase shifting, based on the actual variances measured, suggested that a greater number of participants was required.…”

Approaches to the Pharmacological Management of Jet Lag

“…This has been invoked as part of the mechanism of light effects but not confirmed. Major light-induced shifts in magnitude and direction were not associated with changes in melatonin suppression in one report [ 17 ] and this has been confirmed in a very recent publication [ 84 ]. Suitably timed administration of exogenous melatonin can partially counter the phase-shifting effects of light [ 85 ], but more importantly can act additively with regard to phase shifts, again when correctly timed [ 86 – 88 ].…”