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Interpreting Dim Light Melatonin Testing Results

Understanding the Phase Response Curve

In humans, a properly functioning circadian rhythm is an intrinsic, ~24-hour biological cycle that governs various physiological and behavioral processes within the body. It is often referred to as the “body clock.” These rhythms are endogenously generated, meaning they arise from internal biological mechanisms, and persist even in the absence of external cues such as light and dark.

However, irregular sleep-wake routines, societal responsibilities, seasonal changes, aging, medications, light exposure, medical conditions, neurological/neurodegenerative disorders, diet/meal timing, genetic factors, and environmental factors can all result in disruptions to the normal circadian timing, which contributes to chronic misalignment, phase length changes, or overall dysregulation. This often results in in sleep disturbances, chronic fatigue, mood changes, and impairments in cognitive and physical performance.

Melatonin is the current gold standard by which the human body clock is measured. By monitoring melatonin levels in saliva at strategically timed intervals, the resulting dataset can be presented as a Phase Response Curve (PRC). The PRC in turn can be divided into distinct sections that reflect an individual’s approximate circadian timing. The example profile below provides an overview of a typical 24-HR Circadian Phase Map, highlighting 2 distinct phases; the wake phase and sleep phase, as well as 2 transitional periods; onset and offset.

Fig.1 – Typical 24-HR Circadian Phase Map with highlighted phases: wake phase & sleep phase, and transitional periods of onset & offset.

Quite simply interpreted; melatonin levels should be low during the wake phase, rising during melatonin onset, high during the sleep phase, and fall back to wake phase levels (offset) after waking up. While the overall amplitude and duration of each phase may exhibit variability based on the individual’s genetic makeup, environment, and sleep-wake behavior, the sleep or wake phase should not extend far beyond wake time or bedtime. Anything outside of this window may represent disruption of the circadian system, melatonin synthesis, secretion, metabolism, and/or clearance.

Understanding Dim Light Melatonin Onset and Offset

While a 24-HR Circadian Phase Map is ideal for capturing highly irregular sleep-wake cycles, a more amenable approach for most individuals is to perform a shorter assessment with more precision centered around dim light melatonin onset or offset. Capturing phase changes between the wake and sleep phase (Onset) or the sleep and wake phase (Offset) can be an ideal approach when evaluating suspected circadian misalignment during highly symptomatic periods. Both onset and offset should occur approximately 1-3 hours pre-bed, or post-wake time respectively. While this number can range significantly, correlation with symptoms of misalignment can be a cause for concern. As such, levels that are consistently too high, too low, or oscillating may also represent significant disruption to circadian regulation.

The assessment of dim light melatonin onset (DLMO) is the most common method used in circadian rhythm research and clinical practice to assess circadian timing. DLMO is the time at which melatonin secretion begins in dim light conditions and serves as a robust marker of the beginning of an individual’s biological night. This is a good option for those having routine sleep disruptions in the evening. Below is an example of an aligned onset, notated and highlighted for reference.

Fig.2 – Typical 7-Sample Dim Light Melatonin Onset (DLMO) Profile with ranges highlighted

Any disruption to an individuals’ regulation of melatonin can provide valuable information for clinicians working in the field of sleep-medicine, as they present the opportunity to aid in the design of interventions and treatments for resolving disruption and circadian rhythm sleep-wake disorders.

What’s Inside a Comprehensive DLMO Results Report

When sampled over time, a salivary Dim Light Melatonin Onset (DLMO) profile will enable the characterization of an individual’s circadian sleep physiology. The DLMO Results Report effectively provides baseline melatonin levels (while awake), melatonin onset (triggered by dim light exposure) and peak bedtime levels. Taken together these metrics compliment patient reported sleep behavior with sleep physiology. This information can lead to a more complete picture of causes of insomnia and/or circadian rhythm sleep disorders such as dysregulation and sleep phase shifts. Corrective actions to improve sleep quality may include strategically timed melatonin supplements, timed light exposure therapy sessions and/or specific improvements in sleep hygiene.

In general, a DLMO assessment will allow sleep-health providers to evaluate some key parameters:

Normal Sleep Onset
Typically, the melatonin onset should occur around two hours before bedtime, when melatonin levels have increased significantly enough to begin the sleep process. Some sleep disturbances are non-circadian sleep disorders and may not be directly tied to a sleep phase shift. A robust peak melatonin level and low baseline or waking level are both important aspects of a normal sleep onset. Normal Sleep Phase results need to be considered in the context of the patient’s overall presentation and available diagnostic data.

Phase Advanced
An advanced sleep phase, indicated by a DLMO that is earlier than ~3 hrs before habitual bedtime and an offset that is ~3 earlier than wake time, is often seen in individuals who have difficulty staying awake until their desired bedtime in the evenings and often have problems staying asleep in the early morning hours. Often, therapy involving strategically timed exposure to blue light can inhibit melatonin production and delay the onset until the patient’s desired bedtime.

Phase Delayed
A delayed sleep phase, indicated by a DLMO that is later than ~1 hrs before habitual bedtime and an offset this is later than ~3 hours post-waking, is often seen in individuals who have problems falling asleep at their desired bedtime and difficulty waking up in the morning. Here, strategically timed treatment with proper melatonin supplementation can pinpoint the necessary increase in melatonin levels to help patients fall asleep at their desired bedtime.

No Onset / Undetermined
In profiles where the threshold is never crossed, such as flat-line results or atypically elevated levels, the interpretation of the DLMO cannot be calculated. This may indicate poor sleep hygiene, poor circadian entertainment, pharmacological disruption, psychiatric conditions, or low levels of daytime light exposure. Atypically elevated thresholds can occur if one or more of the first 3 baseline values are abnormally elevated. Retesting is recommended for accurate results, ensuring careful adherence to test instructions.

Baseline Average
A high or elevated baseline indicates that melatonin levels were rising prior to the beginning of sampling. In this case, patients may have entered into a dim light area early or may be experiencing dysregulation from abnormal daytime levels of melatonin, often caused by supplementing higher doses than required. An interesting observation is the slow clearance of supplemental melatonin relative to endogenously produced melatonin. Supplements can cause high melatonin levels (above 50 pg/ml) for up to 10 days depending on the dose taken. These supplements can affect a person’s chronotype which has also been described as a melatonin hangover.

Peak Level
The peak level reported during the sampling regimen can be an important indication of sufficient melatonin production. A low peak level can indicate a suppressed melatonin onset and can result from inadequate daytime light exposure, cataracts, or poor sleep hygiene related to blue light exposure from screens or other sources. Children and adolescents should have very robust melatonin peak levels, in some cases above 50 pg/ml. Melatonin peak levels may also decrease with age.