Melatonin
Melatonin is an important immunomodulator and is the principal means by which tissues are synchronized to the daily cycle of light exposure and physical actity. Cortisol, on the other hand, is critical for maintaining energy homeostasis and modulating immune function. Melatonin and cortisol tend to run opposite to each other. That is, cortisol approaches its low point at bedtime, whereas melatonin reaches its peak a few hours aft corti bottoms out (see Figure 1 below). Deviations from the normal patt ns for these hormones can have significant implications for overall health and future risk of cancer. In fact, research shows that low melatonin and high cortisol are independently associated with some of the same health conditions. Consequently, the balance between these two hormones is important to overall good healt The melatonin-cortisol index (MCI)s an innovative way of examining the balance between these two vit hormones. The MCI may be used to assess cancer risk and immune function, and may also aid in the assessment of depression, heart disease, osteoporosis and weight management issues.
Sampling Times
Melatonin: Several laboratories offer a melatonin profile typically involving 3 samples: waking, noon and bedtime. An individual exposed only to natural lighting will have a very low melatonin level throughout the day (due to light exposure). As the ambient light intensity falls in the evening, the melatonin level begins to rise, peaks between 2 and 4 AM, then starts to drop. Exposure to early morning light increases the suppression of melatonin to a low level, but the extent of suppression depends on the timing and intensity of light exposure after waking. For this reason, the waking melatonin result can vary widely from person to person, and from season to season in the same person. As stated above, melatonin normally is very low around noon, and the clical significance of a high noon melatonin level is unknown. Without careful control of light exposure in the two hours or so before bedtime, the bedtime melatonin level is also subject to wide variabiliy (once again due to variabiliy in the intensity of light exposure). The only way to ensure a meaningful measurement of melatonin (outside of a research laboratory) is to acquire the sample 3 to 4 hours aft the patient has been asleep in full darkness. This sampling protocol may be an inconvenience to the patient, but its based on the published lit ature, and avoids interpretation of the results due to variations in light exposure.
Cortisol: The significance of abnormal cortisol
Disturbances in melatonin and cortisol production have been associated with the following:
Breast Cancer
Breast cancer research clearly links melatonin levels with breast cancer cell growth. A study by Blask1 demonstrated that melatonin-rich blood suppressed the growth of human breast cancer xenografts and rat hepatomas. No growth suppression occurred in tumors perfused with melatonin-defient blood colllevels is well established in the lit ature, and both high and low values have clincal implications. The strength of the relationship between cortisol and melatonin levels emerges on assessment of the diseases and conditions associated with abnormal MCI, which are described on the following page.
Cortisol levels are also tied to breast cancer risk. Breast cancer patients with high average cortisol through out the day and elevated cortisol at bedtime have earlier mortality, lower natural kill (NK) cell counts and decreased actity of NK cell3
Other Cancers
Circulating levels of melatonin are depressed in a wide variety of cancers including breast, endometrial, prostate, lung, gastric and colon. Lower nocturnal melatonin levels are associated with larger tumors in patients with primary prostate cancer. Endogenous melatonin stimulates anti-cancer defenses and exhibits anti-proliferative and antioxidant activity. Supplemental melatonin has been shown to slow tumor progression in a variety of cancers and provide subjective improvement in quality of life. Immune Function
Animal research has shown that inhibition of melatonin synthesis weakens cellular and humoral immunity. Melatonin increases production of interleukin 2 and 6 (IL-2 and IL-6). Melatonin receptors are found in lymphatic tissue, which supports the premise that melatonin has a direct regulating effect on the immune system. Lit-a-ture suggests that hypocortolism may lead to overactive early inflammatory innate immune responses, whereas adaptive immunity remains unchanged or depressed.
Cardiovascular Disease
Low nighttime melatonin has been reported in patients with coronary heart disease and heart failure. Similarly, the link between high cortisol and hypertension is well established. Supplementation with melatonin has been shown to increase cardiac vagal tone, decrease circulating norepinephrine, and reduce blood pressure.
Depression
Research shows that depressed patients have lower levels of melatonin than non-depressed patients. Melatonin supplementation helps correct sleep disorders in depression, although it does not improve cli cal symptoms of depression. High bedtime levels of cortisol are also associated with depression.
Bone
Melatonin has been shown to inhibit bone resorption and increase bone mass through its ability to down-regulate activation of osteoclasts. An adequate amount of estradiol is also needed for melatonin to benefit bone, so addition of a salivary estradiol test may be useful in cases where melatonin is low and bone loss is a concern. High cortisol levels also contribute to bone loss. Weight Management
Restoring melatonin to levels of early adulthood may suppress age-related gains in visceral fat. In addition, high cortisol levels promote deposition of visceral fat. Therefore, maintaining a melatonin level in the under 40 years range, and/or reducing cortisol levels may be important for weight management.
Hormone |
Low Levels |
High Levels |
|
Melatonen |
|
|
| Cortisol |
|
|
| Melatonen-Cortisol Index |
|
|