The Complexities of Melatonin Supplementation

Melatonin is a hormone that helps regulate sleep. It is naturally produced in the body, but is also available as an over-the-counter dietary supplement. Melatonin supplements have become increasingly popular, but how do they compare to the melatonin our bodies make?

Here we break down what the research says about exogenous versus endogenous melatonin production, and the potential effects of regular melatonin supplementation.

Endogenous Melatonin Production

Melatonin is produced in the brain’s pineal gland as well as in the gut.

Pineal Gland

The pineal gland begins secreting melatonin a couple of hours before bedtime, and production peaks within the first hour of sleep. Levels remain elevated throughout the night before declining a few hours prior to waking. This pineal melatonin helps regulate sleep onset and maintenance.

Gut Production

Melatonin can also be produced in the gastrointestinal tract through conversion of the amino acid tryptophan. Tryptophan is found in many foods and can be converted to serotonin in the gut. Serotonin is then converted to melatonin. The role of gut-derived melatonin is not as well understood, but it may also help with sleep regulation.

Challenges Studying Endogenous Melatonin

There are several challenges involved in studying endogenous melatonin production:

• Melatonin exists in very low concentrations in the body. Sophisticated analytical techniques are required for measurement.
• Melatonin levels fluctuate on a circadian rhythm. Continuous sampling is required to accurately characterize production.
• Invasive blood sampling procedures are needed to measure melatonin. These are impractical for continuous long-term monitoring.

Due to these factors, there have been limited studies directly comparing endogenous and supplemental melatonin exposure.

Exogenous Melatonin Supplementation

Melatonin dietary supplements help promote sleep onset (falling asleep) in many people. However, there are some key differences in how exogenous melatonin acts compared to the body’s own melatonin:

Metabolism and Clearance

When taken as a supplement, 70-90% of melatonin is broken down by the liver and kidneys within an hour of ingestion. This rapid clearance limits its duration of action.

Sleep Onset Effects

Supplements can help reduce sleep latency (the time it takes to fall asleep), likely due to an initial rapid spike in melatonin levels. However, supplemental melatonin may be less effective for maintaining sleep throughout the night compared to endogenous melatonin.

Dosing Patterns

Typical melatonin supplements are taken as a single dose before bedtime. This results in a rapid spike in blood levels followed by clearance over several hours. In contrast, endogenous melatonin rises gradually in the evening, peaks during the middle of the night, and declines closer to wake time.

Long-Term Safety Concerns

Animal studies suggest melatonin supplementation is generally safe, even at very high doses. However, the long-term effects of habitual melatonin use are unknown. Potential concerns include:

• Tolerance – Could regular use cause decreased melatonin sensitivity over time, requiring higher doses for the same effect?
• Withdrawal – Could stopping melatonin after regular use lead to rebound insomnia or other negative effects?
• Hormonal effects – Could high nighttime melatonin from supplements alter hormone patterns long-term?

While major adverse events have not been reported, these areas warrant caution and further study.

Trends in Melatonin Use

Melatonin supplement use has increased dramatically over the past two decades. Surveys suggest 40-60% more Americans are using melatonin compared to just a few years ago. Additionally, higher dose formulations have become more prevalent:

• In the early 2000s, 1 mg tablets were common. Now these are rare.
• Most products today are 3-5 mg per tablet. Some fast-release formulations are 10 mg or higher.

Higher doses could lead to prolonged elevated melatonin levels at night and persistence into the morning hours. The implications of this altered pattern are unknown.

Key Takeaways

• Endogenous pineal and gut melatonin help regulate circadian rhythms and sleep.
• Measuring natural melatonin levels is challenging. More research is needed on how supplemental melatonin compares.
• Melatonin supplements can help with sleep onset, but may be less effective for sleep maintenance.
• The long-term safety of nightly melatonin supplementation requires further study.
• Use of higher dose melatonin supplements has increased dramatically in recent years.

Until more research is conducted, melatonin is likely safe for short-term use, but the effects of chronic supplementation remain unclear. As with any supplement, it is wise to use the lowest effective dose