Indications

Multiple human studies have measured the effects of melatonin supplements on sleep in healthy individuals. A wide range of doses has been used, often taken by mouth 30 to 60 minutes prior to sleep time. Most trials have been small, brief in duration, and have not been rigorously designed or reported. However, the weight of scientific evidence does suggest that melatonin decreases the time it takes to fall asleep (“sleep latency”), increases the feeling of “sleepiness,” and may increase the duration of sleep.

Ingredients

Each tablet contains:
Melatonin... 3 mg
Scored tablet for half dosages

Contains no: preservative, artificial flavor or color, sugar, milk, wheat, corn or yeast.

Description

Melatonin is a hormone (N-acetyl-5-methoxytryptamine) produced especially at night in the pineal gland. Its secretion is stimulated by darkness and inhibited by light. Melatonin, an indole, is synthesized from tryptophan via serotonin. The suprachiasmatic nuclei (SCN) of the hypothalamus have melatonin receptors and melatonin may have a direct action on SCN to influence circadian (sleep) rhythms.

MULTIFUNCTIONAL PROPERTIES
• Melatonin is also a powerful antioxidant that can easily cross cell membranes and the blood-brain barrier. Unlike other antioxidants, melatonin does not undergo redox cycling, the ability of a molecule to undergo reduction and oxidation repeatedly. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants, counterintuitively promoting free radical formation.
• Melatonin receptors appear to be important in mechanisms of learning and memory, and melatonin can alter electrophysiological processes associated with memory, such as long-term potentiation (LTP). Melatonin has been shown to prevent the hyperphosphorylation of the tau protein. Hyperphosphorylation of tau protein can result in the formation of neurofibrillary tangles, a pathological feature seen in Alzheimer's disease. Thus, melatonin may be effective for treating Alzheimer's disease.

PURITY, CLEANLINESS and STABILITY Third party testing on finished product to ensure Melatonin SAP is free of heavy metals, pesticides, volatile organics and other impurities. Melatonin is an indoleamine hormone whose precursor is the amino acid tryptophan. Recent research has revealed the many roles it plays in humans. Secreted by the pineal gland, it is also found in peripheral cells and organs. Physiological effects of melatonin include setting the circadian rhythm, seasonal adaptation and pubertal development. It also acts as an antioxidant, interacts with receptors in peripheral organs, and has direct mitochondrial effects. The diverse mechanisms of action renders melatonin of extreme importance in the aging and multiple disease processes, especially those associated with oxidative stress. Recent studies have shown the benefits of supplementing melatonin, emphasizing its importance in maintaining health and delaying the progression of certain diseases including sleep disorders, Alzheimer's Disease (AD) and Parkinson's Disease (PD).(1)

INSOMNIA The pineal gland secretes melatonin, and circulating levels of this hormone are responsible for setting the body's circadian rhythm. In a 24 hour cycle, melatonin production levels peak during sleep when it is dark, and are down-regulated by light. This rhythm may be disrupted with exposure to excessive light during dark hours, and/or insufficient amounts of light during the day. One of the major indications for melatonin is insomnia due to disrupted circadian rhythms or deficient melatonin levels, which naturally decline with age. Studies in those suffering from insomnia show that melatonin supplementation decreases the time it takes to fall asleep (sleep latency), increases the amount of time slept, and improves sleep quality compared to those given placebo.(2, 3, 4) Melatonin supplementation has been shown to be effective for insomnia in children suffering from autism,(2) ADHD(4), and in the elderly.(5) Long-term melatonin treatment was judged to be effective against sleep onset problems in 88% of the cases, but cessation of melatonin led to a relapse of chronic sleep onset disorder.(4) Supplementation of melatonin has also been used to regulate disrupted circadian rhythms in those with jet lag and people who work night shifts.(1)

COMBATING PARKINSON'S, ALZHEIMER'S AND ISCHEMIC INJURY ANTIOXIDANT AND ANTI-INFLAMMATORY Melatonin has free-radical scavenging ability that produces a cascade effect. Melatonin is oxidized when it reacts with hydrogen peroxide (H2O2), reactive oxygen species (ROS), or UV radiation to form a metabolite called N-acetyl-N-formyl-5-methoxykynuramine (AFMK). ROS stress consumes melatonin at a higher rate than other sources of oxidative stress, leading to higher levels of AFMK. Studies have shown that through the AFMK pathway, one molecule of melatonin can quench 10 molecules of ROS.(6) Various studies have found AFMK formation in cerebrospinal fluid, leukocytes, red blood cells, epithelial cells and keratinocytes.(6) AFMK has further been shown to inhibit lipid peroxidation, oxidative DNA damage and prevents neuronal cell injury caused by H2O2 and amyloid beta-peptide.(7) AFMK inhibits tumour necrosis factor-alpha (TNF- α )and interleukin 8 (IL 8) in neutrophils and peripheral blood mononuclear cells, and inhibits gene expression of cyclo-oxygenase 2 (COX 2).(6) AFMK and its metabolite AMK are effective at inhibiting the synthesis of prostaglandins.(8) When given melatonin, animal models of AD show a decrease in the expression of inflammatory cytokines (TNF- α ) in the hippocampus, as well as decreased beta-amyloid aggregation.(9) Humans trials also show an increase level of beta-amyloid aggregations and CNS inflammation when insulin levels are high.(10) Melatonin interacts with nitric oxide (NO); a compound important in the regulation of cellular signals in both physiological and pathological processes. NO promotes vasodilation. However; it also has a high affinity for superoxide anion radical (O2–), forming peroxynitrite (ONOO–). ONOO– is generated in times of chronic oxidative stress such as chronic hyperglycemia, hyperlipidemia, tobacco smoking and prolonged drug use.(11) Pathological effects include endothelial dysfunction leading to vasoconstriction, lipid peroxidation, protein oxidation and DNA damage. Furthermore, ONOO– inhibits superoxide dismutase and other antioxidants, which further exacerbates free radical damage. Melatonin is the only documented antioxidant able to quench ONOO– in addition to both oxygen and nitrogen based reactants, thereby inhibiting the pro-inflammatory and blocking transcription factors such as nuclear factor kappa B and activator protein 111. Melatonin regulates the glutathione redox status in isolated brain and hepatic mitochondria, correcting it when it is disrupted by oxidative stress.(11) The antioxidant properties of melatonin makes it an appropriate consideration in the treatment of AD and PD. In vitro models of AD have demonstated the neuroprotective effects of melatonin and has been shown to limit autooxidation of dopamine.(11)

NEURODEGENERATION AND ISCHEMIC INJURY/APOPTOSIS Neurodegeneration occurs with aging, but is highly exacerbated in diseases such as AD and PD. Excessive apoptosis of cells contributes to the disease process. Melatonin was found to inhibit apoptosis in immune cells, peripheral cells, and in neuronal models of PD and AD. It also was proven to be effective at inhibiting apoptosis in ischemia-reperfusion injury.(12) Melatonin can also be found in the mitochondria. Melatonin may improve ATP output efficiency via mitigation of oxidative stress, by acting directly on complexes I and IV in the electron transport chain (ETC),(12) while also limiting protein and DNA damage. Glutathione status is of great importance when considering neurodegeneration; melatonin may play a role in the restoration of glutathione levels and the reactivation of the enzymes glutathione peroxidase and superoxide dismutase. The effect of melatonin on GSH homeostasis have also been demonstrated in brain tissue(13) and in gastric mucosa and male testes.(14)

EXCITOTOXICITY Also impacted by melatonin is the GABA-benzodiazepine receptor complex and NMDA receptor.(12) Excitotoxicity contributes to the pathogenesis of PD and AD. Both in vivo and in vitro studies have found melatonin to have significant anti-excitotoxic effects. Melatonin reduces lipid peroxidation and stabilizes mitochondrial inner membranes, an effect that may improve ETC activity.

TAU PROTEIN AND AD Tau protein regulation plays a vital role in the pathogenesis of AD. Studies suggest that melatonin alters the function of certain protein kinase and phosphatase enzymes, thereby decreasing hyperphosphorylation of the tau protein found in neurofibrillary tangles.(15) Implications of this include neurodegenerative decline. Recent studies have shown melatonin to be effective at inhibiting the hyperphosphorylation of the tau protein.(15)

HYPERHOMOCYSTEINEMIA AND AD Hyperhomocyteinemia is a part of the pathogenesis of many disorders involving inflammation and oxidative stress. It is believed to contribute to cardiovascular disease and lipid peroxidation. Increased levels of homocysteine have been found to increase apoptosis in nerve cells, and have been linked to AD.(16) Melatonin has protective actions against hyperhomocysteinemia by reducing oxidative stress, preventing reactive gliosis, inhibiting apoptosis and contributing to the improvement of learning and memory performance.(16)

HYPERINSULINEMIA AND AD Results of melatonin as an adjuvant treatment of diabetes mellitus showed benefits in controlling complications of the diabetes mellitus (DM) and lipid profile improvement.(17) Insulin resistance also affects the brain and had been found to increase the risk of age-related impairment and AD. Hyperinsulinemia has an effect on memory, CNS inflammation, and regulation of the betaamyloid peptide, and has also been found to be correlated with hyperphosphorylation of the tau protein.(17, 18)

CANCER In cancer models, melatonin has been shown to have pro-apoptotic effects.(12) Alterations in melatonin receptor expression as well as changes in endogenous melatonin production have been shown in breast and prostate cancer, hepatoma and melanoma models.(19)

HORMONES Melatonin affects the release of gonadatrophins, which suggests its role in fertility treatment. High levels of oxidative stress and low levels of melatonin have been linked to infertility and delayed sexual maturation.(20) Furthermore, evidence of a relationship between light exposure and melatonin secretion and irregular menstrual cycles, menstrual cycle symptoms, and disordered ovarian function have been found.(21) Women with polycystic ovary syndrome seem to be more vulnerable to the influence of light/dark exposure.(20) Melatonin has been shown to protect against sperm apoptosis via ROS scavenging activities.(22) A recent study has shown that melatonin crosses the placenta and may be required for a successful pregnancy.(23) It also seems to be involved in correcting the pathophysiology of complications during pregnancy, including those due to abortion, pre-eclampsia and fetal brain damage.(23)

Quantity

90 tablets per bottle

Dose

1–3 tablets daily at or before bedtime

References

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