The dark side of apnea: altered 24-hour melatonin secretion in obstructive sleep apnea (OSAS) is disease severity dependent

Abstract

Purpose: Melatonin aids in the synchronization of the circadian rhythm to the external environment. Few studies have tried to elucidate the relationship between melatonin and obstructive sleep apnea syndrome (OSAS). These often include few patients, do not differentiate between OSAS severity and/or do not analyse a 24-h melatonin profile. This study set out to investigate disease severity dependent differences in 24-h salivary melatonin secretion of OSAS patients compared to a reference population in a retrospective design.

Methods: 24-h salivary melatonin profiles of 169 OSAS patients were analysed (55 light, 66 moderate, 48 severe) as well as 91 reference patients. Several aspects of the melatonin curve were analysed and stratified according to OSAS severity. Parameters included: dim light melatonin onset (DLMO), time of returning below DLMO (DLMOoff), peak melatonin concentration and time, and total melatonin exposure.

Results: Significant effects were corrected for confounding by age and sex using linear regression. Our analysis shows that, compared to reference and in a disease dependent manner, OSAS patients have a significantly lower 24-h melatonin curve, lower melatonin peak concentration, lower total melatonin exposure and a smaller proportion of patients reach DLMO. The differences in peak melatonin production and total melatonin exposure were resistant to confounding by age and/or sex.

Conclusion: This study describes clear OSAS severity dependent abnormalities in melatonin production in OSAS patients, independent of sex and/or age. Future research should indicate whether oral melatonin supplementation has beneficial effects in OSAS patients with attenuated endogenous melatonin production.

Keywords: Circadian rhythm; OSAS; Obstructive sleep apnea; Salivary melatonin.

Fig. 1

Overview of included patients

Fig. 2

Lower 24-h salivary melatonin secretion in OSAS patients. Data represented as average ± SEM. Melatonin secretion profile of reference group (open circles), light OSAS (light grey squares), moderate OSAS (dark grey triangles), and severe OSAS (black diamonds). Overall repeated measures ANOVA results for all groups and only OSAS groups (^###p < 0.001). For post-hoc analysis results see main text

Fig. 3

Differences in DLMO related parameters in OSAS patients. A: data represented as % of patients, B-D: data represented as boxplots with the box consisting of 25th, 50th (median) and 75th percentile of data, whiskers indicate minimum and maximum values. Individual patient data is plotted as open circles (reference), light grey squares (light OSAS), dark grey triangles (moderate OSAS), or black diamonds (severe OSAS). A: percentage of patients not reaching DLMO, B: DLMO time of remaining patients, C: DLMOoff time, D: total time spent above DLMO. Statistics: &: chi-square, #: univariate ANOVA, *: Tukey HSD post-hoc. Number of symbols denotes level of significance (single: p < 0.05, double: p < 0.01, triple: p < 0.001), NS: non-significant. L: light, M: moderate, S: severe

Fig. 4

Reduced melatonin peak height and total melatonin exposure in OSAS patients. data represented as boxplots with the box consisting of 25th, 50th (median) and 75th percentile of data, whiskers indicate minimum and maximum values. Individual patient data is plotted as open circles (reference), light grey squares (light OSAS), dark grey triangles (moderate OSAS), or black diamonds (severe OSAS). A: peak salivary melatonin, B: time of peak melatonin, C: Total melatonin exposure (measured as area under the 24-h melatonin curve). Statistics: #: univariate ANOVA, * and solid line: Tukey HSD post-hoc, $ and dashed line: LSD post-hoc. Number of symbols denotes level of significance (single: p < 0.05, double: p < 0.01, triple: p < 0.001), NS: non-significant. L: light, M: moderate, S: severe