Life Extension Magazine®

Woman sleeping with help from immediate and extended melatonin

Benefits of Immediate-and Extended-Release Melatonin

Micronized melatonin provides immediate- and extended-release to help one fall asleep—and stay asleep.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in August 2023. Written by: Michael Downey, Health & Wellness Author.

Many people have trouble falling and staying asleep, and sleep interruptions worsen with age.

A mouse study published in 2017 showed that lack of sleep can cause parts of synapses—the connections between brain cells—to break down, leading to cognitive issues.1

Insufficient sleep is linked to diabetes, hypertension, heart attack, shortened telomeres, and premature death.2-5

In 1992, Life Extension® introduced melatonin as an alternative to sleep medications. It has benefited many people who suffer from insomnia, but not all forms of sleep problems respond to melatonin.

For individuals who continue to have sleep issues, a micronized melatonin provides immediate release and extended release to help fall and stay asleep.

What you need to know

  • Inadequate sleep duration and quality might be caused by an age-related decline in melatonin levels.
  • Prescription sleeping pills come with extensive side effects, addiction potential, and a higher risk of premature mortality.
  • Melatonin supplementation has been clinically demonstrated to improve sleep onset, duration, and quality.
  • For those who have difficulty staying asleep, extended-release melatonin can deliver a full night’s sleep without interruptions.
  • A new micronized melatonin is specially formulated to release 0.75 mg of melatonin immediately to help one fall asleep fast, and another 0.75 mg of melatonin over the next seven hours to help one stay asleep.

A Root Cause of Insufficient or Disrupted Sleep

The pineal gland acts as the body’s central clock, telling the brain and other organs when it’s time to rest.6-9

Pineal gland production of melatonin declines with age.3,6 Impaired melatonin production has been seen in chronic conditions like elevated blood sugar.10

This poses a health risk for millions of people, since low melatonin levels are associated with a potentially higher risk of neurodegenerative diseases,6,11 including Alzheimer’s,12 and a greater chance of stroke.13

Compounding the problem, lack of sleep itself—the result of inadequate melatonin—can cause a long list of its own negative health effects.

For Those Who Have Trouble Staying Asleep

For Those Who Have Trouble Staying Asleep  

Supplementing with melatonin can help keep circadian rhythms in tune. There are many forms of melatonin available. People can pick a formulation that works best for their nighttime needs.

For those with problems falling and then staying asleep, a new dual-action form of melatonin may resolve problematic issues.

Immediate-release melatonin can help one get to sleep faster and experience more restful and regenerative sleep.

For others, insufficient melatonin release throughout the night may result in difficulty staying asleep or difficulty getting back to sleep after awakening in the night. For these individuals, extended-release melatonin may support a full night of uninterrupted sleep.

Using micronized melatonin and a proprietary encapsulation technology, a new melatonin formula gradually delivers precise amounts of melatonin over a period of 7 hours.14

In a double-blind, crossover study involving 12 elderly subjects who had complained of insomnia, participants took extended-release melatonin for three weeks. After a washout period, they then took a placebo for three weeks. The study authors concluded that:

“Controlled-release melatonin replacement therapy effectively improves sleep quality in this [elderly] population.”15

Many practitioners recommend starting with a low dosage of melatonin. Once one knows how one’s body reacts to it, the dosage can be increased to suit the individual’s needs. The total dose of a new dual-action formula is 1.5 mg, comprised of:

  • 0.75 mg of immediate-release melatonin
  • 0.75 mg of extended-release melatonin.

Since everyone’s biochemistry and sleep patterns are different, it may take trial and error before the ideal dosage and supplement formulation is found, i.e. immediate, extended, liquid, or immediate/extended-release.

Do You Have Trouble Staying Asleep?
Do You Have Trouble Staying Asleep?

The secretion of melatonin declines with age, which can interfere with your ability to get to sleep. Supplementing with melatonin helps keep your circadian rhythm in tune.

  • The immediate-release form of melatonin can help initiate sleep faster and induce more restful and regenerative sleep.
  • For some people, the liquid form of melatonin achieves adequate results.
  • But for others, reduced levels of melatonin at night may result in difficulty staying asleep or difficulty getting back to sleep after awakening in the night. For these individuals, extended-release melatonin supplements support a full night of uninterrupted sleep.
  • A novel immediate/extended-release (IR/XR) melatonin supplement combines an immediate burst of melatonin to help initiate sleep—along with an extended-release dose to keep melatonin levels from falling during the night and to help one sleep. The total dose of this dual-action product is 1.5 mg, comprised of 0.75 mg of immediate-release melatonin and 0.75 mg of extended-release melatonin. It is best to take one to two 1.5 mg capsules, 30-120 minutes before desired sleep onset.

Since everyone’s biochemistry and sleep patterns are different, it may take some trial and error before one finds the ideal dosage and supplement formulation—immediate, extended, liquid, or immediate/extended-release—to match individual body rhythm and sleep needs.

Wide-Ranging Health Risks of Poor Sleep

The effects of sleep inadequacy go far beyond simple fatigue or reduced endurance.16 They include:

  • Decreased feeling of fullness, increased hunger and food consumption, weight gain, and a higher risk of obesity.17,18
  • Increased fine lines and wrinkles.19
  • A shortening of telomeres5 (the chromosome “caps” that shorten with time and may serve as an indicator of aging20).
  • Enhanced susceptibility to stress and anxiety, which disrupts circadian rhythms, leading to poor sleep and (in a typical vicious cycle) more stress!21-25
  • Neuroprotective Effect of Melatonin

    Melatonin has been shown to protect the brain against oxidative stress and the neurodegeneration that occurs as a result of aging.26

    In addition, scientists are finding that the age-related decline in melatonin levels may be a critical factor in the age-related increase in neurodegenerative diseases.6,11,27

    Numerous animal studies have shown the brain-protective effects of melatonin, including: shrinking the size of the infarct, or damaged area, after a stroke, guarding against Alzheimer’s disease and Parkinson’s, and improving blood-brain barrier impairment and swelling after a brain injury.28-35

    The blood-brain barrier is essential to neural function. Damage to it is considered an early event in the process of various neurological diseases.36

    Melatonin has been shown to preserve the integrity and permeability of the blood-brain barrier in old mice.37 This study led a group of researchers to suggest that “melatonin supplementation may help prevent neurological diseases through maintaining the integrity of [the blood-brain barrier] in old people.”36

    Migraine is a neurological disease which can dramatically impact quality of life. In a recent review of the literature, melatonin supplementation was found to be effective in preventing migraines and was superior to placebo in preventing cluster headaches. Melatonin may also play a role in preventing tension headaches.38

    Inadequate Sleep and Alzheimer’s Risk
    Inadequate Sleep and Alzheimer’s Risk

    Excessive daytime sleepiness in elderly adults with normal cognitive function has been shown in a new study to be linked with the buildup of beta-amyloid in the brain.42

    The implications are cause for real concern, since the accumulation of beta-amyloid is a precursor to the development of Alzheimer’s disease. This buildup begins before symptoms are apparent.

    The study conducted by the Mayo Clinic included 283 subjects, average age of 77. Over a period of two years, the subjects’ brains were measured for levels of beta-amyloid, and they regularly reported the amount of daytime sleepiness they experienced. Results showed that subjects who developed the highest amounts of beta-amyloid were also the ones who reported the most daytime drowsiness. The amyloid levels were particularly high in brain areas associated with memory, behavior, and emotion.

    The researchers say their study is the first to specifically show that excessive daytime sleepiness in cognitively normal elderly people leads to a buildup of amyloid in the brain.

    “We know that sleep is necessary to clear toxins and beta-amyloid in the brain,” said study author Prashanthi Vemuri. “We also know that beta-amyloid causes sleep disruptions. So it’s been a chicken-and-an-egg problem.”43

    Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian was impressed with the study. “In fact,” he said, “the findings will change the way I care for patients, as I will now proactively ask about excessive daytime sleepiness as one of many potentially modifiable risk factors for the disease.”43



    Inadequate sleep is associated with an increased risk of obesity, diabetes, cognitive decline, and stroke, shortened telomeres, and premature death.2-5

    Prescription sleeping pills come with side effects, addiction risk, and increased risk of premature mortality.

    Supplementation with melatonin is clinically shown in some studies to enhance onset, duration, and quality of sleep, but does not work for every kind of sleep problem.39-41

    A unique form of micronized melatonin has been developed that provides immediate release and extended release to help one fall asleep and stay asleep.

    If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.


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