Benefits of Immediate-and Extended-Release MelatoninJuly 2018
By Michael Downey
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
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.
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 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.
- Bellesi M, de Vivo L, Chini M, et al. Sleep Loss Promotes Astrocytic Phagocytosis and Microglial Activation in Mouse Cerebral Cortex. J Neurosci. 2017;37(21):5263-73.
- Institute of Medicine Committee on Sleep M, Research. The National Academies Collection: Reports funded by National Institutes of Health. In: Colten HR, Altevogt BM, eds. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Washington (DC): National Academies Press (US) National Academy of Sciences.; 2006.
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- Cirelli C. Brain plasticity, sleep and aging. Gerontology. 2012;58(5):441-5.
- Jackowska M, Hamer M, Carvalho LA, et al. Short sleep duration is associated with shorter telomere length in healthy men: findings from the Whitehall II cohort study. PLoS One. 2012;7(10):e47292.
- Pandi-Perumal SR, BaHammam AS, Brown GM, et al. Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes. Neurotox Res. 2013;23(3):267-300.
- Lahiri DK, Chen D, Lahiri P, et al. Melatonin, metals, and gene expression: implications in aging and neurodegenerative disorders. Ann N Y Acad Sci. 2004;1035:216-30.
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- Wu YH, Swaab DF. The human pineal gland and melatonin in aging and Alzheimer’s disease. J Pineal Res. 2005;38(3):145-52.
- Amaral FG, Turati AO, Barone M, et al. Melatonin synthesis impairment as a new deleterious outcome of diabetes-derived hyperglycemia. J Pineal Res. 2014;57(1):67-79.
- Gupta YK, Gupta M, Kohli K. Neuroprotective role of melatonin in oxidative stress vulnerable brain. Indian J Physiol Pharmacol. 2003;47(4):373-86.
- Liu RY, Zhou JN, van Heerikhuize J, et al. Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-epsilon4/4 genotype. J Clin Endocrinol Metab. 1999;84(1):323-7.
- Atanassova PA, Terzieva DD, Dimitrov BD. Impaired nocturnal melatonin in acute phase of ischaemic stroke: cross-sectional matched case-control analysis. J Neuroendocrinol. 2009;21(7):657-63.
- Manufacturer Dissolution Profile. Data on File. 2017.
- Garfinkel D, Laudon M, Nof D, et al. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995;346(8974):541-4.
- Oliver SJ, Costa RJ, Laing SJ, et al. One night of sleep deprivation decreases treadmill endurance performance. Eur J Appl Physiol. 2009;107(2):155-61.
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- Hibi M, Kubota C, Mizuno T, et al. Effect of shortened sleep on energy expenditure, core body temperature, and appetite: a human randomised crossover trial. Sci Rep. 2017;7:39640.
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- von Zglinicki T, Martin-Ruiz CM. Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med. 2005;5(2): 197-203.
- Sukegawa T, Itoga M, Seno H, et al. Sleep disturbances and depression in the elderly in Japan. Psychiatry Clin Neurosci. 2003;57(3):265-70.
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- Gutierrez-Cuesta J, Sureda FX, Romeu M, et al. Chronic administration of melatonin reduces cerebral injury biomarkers in SAMP8. J Pineal Res. 2007;42(4):394-402.
- Bondy SC, Lahiri DK, Perreau VM, et al. Retardation of brain aging by chronic treatment with melatonin. Ann N Y Acad Sci. 2004;1035:197-215.
- Reiter RJ, Sainz RM, Lopez-Burillo S, et al. Melatonin ameliorates neurologic damage and neurophysiologic deficits in experimental models of stroke. Ann N Y Acad Sci. 2003;993:35-47; discussion 8-53.
- Lahiri DK, Chen DM, Lahiri P, et al. Amyloid, cholinesterase, melatonin, and metals and their roles in aging and neurodegenerative diseases. Ann N Y Acad Sci. 2005;1056:430-49.
- Feng Z, Qin C, Chang Y, et al. Early melatonin supplementation alleviates oxidative stress in a transgenic mouse model of Alzheimer’s disease. Free Radic Biol Med. 2006;40(1):101-9.
- Niranjan R, Nath C, Shukla R. The mechanism of action of MPTP-induced neuroinflammation and its modulation by melatonin in rat astrocytoma cells, C6. Free Radic Res. 2010;44(11):1304-16.
- Ma J, Shaw VE, Mitrofanis J. Does melatonin help save dopaminergic cells in MPTP-treated mice? Parkinsonism Relat Disord. 2009;15(4):307-14.
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- Ayer RE, Sugawara T, Zhang JH. Effects of melatonin in early brain injury following subarachnoid hemorrhage. Acta Neurochir Suppl. 2008;102:327-30.
- Wang Z, Ma C, Meng CJ, et al. Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model. J Pineal Res. 2012;53(2):129-37.
- Liu WC, Wang X, Zhang X, et al. Melatonin Supplementation, a Strategy to Prevent Neurological Diseases through Maintaining Integrity of Blood Brain Barrier in Old People. Front Aging Neurosci. 2017;9:165.
- Wang X, Xue GX, Liu WC, et al. Melatonin alleviates lipopolysaccharide-compromised integrity of blood-brain barrier through activating AMP-activated protein kinase in old mice. Aging Cell. 2017;16(2):414-21.
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