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Home > Anti-aging Research > Melatonin


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  • 'Shocking' Data on What's Really in Melatonin Gummies - Medscape, 4/26/23 - "The vast majority of melatonin gummies sold in the US may contain up to 347% more melatonin than is listed on the label, and some products also contain CBD" - See melatonin at Amazon.com.
  • Melatonin a New Way to Reduce Self-Harm? - Medscape, 3/27/23 - "While there were no statistically significant changes in relative risk for body injuries, falls, and transport accidents, the relative risk for self-injury was statistically significantly lower during the months following melatonin-treatment initiation ... The incidence rate ratio (IRR) in the month following treatment was 0.58 (95% CI, 0.46-0.73) for self-harm and 0.59 (95% CI, 0.45-0.78) for poisoning" - See melatonin at Amazon.com.
  • Melatonin Can Do More Harm Than Good. Try These 3 Sleep Supplements Instead - CNET, 1/1/23 - "If you experience side effects like next-day drowsiness when you take melatonin, does that mean you should never take it? According to Axe, you might be able to try a few adjustments first. To start, he says to avoid taking it in the middle of the night. "After you take melatonin it starts working within about an hour and lasts for about 5 hours in your body, so taking it in the middle of the night isn't the best idea if you want to wake up with energy," he explains - Note: It just seems like some of these articles talk in circles. "It doesn't make you sleepy but on the other hand, it makes you sleepy". You can't believe every article you read. CBD? Studies don't support that. So melatonin is the placebo effect but CBD isn't even though studies say it is (with CBD).
  • The Role of Melatonin in Chronic Kidney Disease and Its Associated Risk Factors: A New Tool in Our Arsenal? - NTK Papers, 6/28/22 - "The combined use of stem cells with melatonin is an appealing therapeutic approach which ought to be assessed further" - See melatonin at Amazon.com.
  • In-Depth: Melatonin helps people with severe COVID recover. How about long haulers? - 10News, 1/7/22 - "In October, a clinical trial involving 150 hospitalized COVID patients in Iraq found those taking 10 mG of melatonin each night before bed had a lower risk of COVID-related blood clots, sepsis, and death. Just one hospitalized patient taking melatonin died compared to 13 deaths in the control group ... A retrospective study in Spain found hospitalized COVID patients who received melatonin early in the pandemic had a nearly 40 percent lower risk of death. A randomized, controlled trial on about 100 hospitalized COVID patients in Iran found it improved sleep quality and blood oxygen levels but was inconclusive on survival rates ... This week, researchers in France released data showing that high doses of melatonin blocked the coronavirus from entering the brains of mice. Melatonin also reduced swelling there ... About 55 percent of COVID patients have at least one lingering symptom for at least six months after their infection, she said. Those symptoms include fatigue, headaches, and difficulty concentrating or “brain fog.” ... Scientists think these neurological issues happen when the coronavirus enters brain cells via a receptor called ACE-2. The French study found melatonin changed the shape of the ACE-2 receptors, preventing the virus from getting in ... A study early in the pandemic by the Cleveland Clinic found people taking melatonin had a 28 percent lower chance of getting infected with COVID in the first place ... Last year, doctors in Texas published a paper arguing that newly infected COVID patients should start taking melatonin daily, as early as the first night they test positive ... “Our recommendation is to administer melatonin 2.5 to 10 mg at night to all adults diagnosed with SARS-CoV-2 as early as on the first day of diagnosis, especially for those at increased risk for morbidity or mortality,” they wrote" - See melatonin at Amazon.com. My favorite is the Source Naturals Sleep Science Melatonin 1 mg Peppermint Flavor - Helps Promote Sleep - 300 Lozenge Tablets because the small dosage allows you to adjust the dose easily. Just take 3 tablets if you want 3 mg.
  • Melatonin exacerbates asthma, study finds - Science Daily, 12/10/21 - "a research group led by Kentaro Mizuta from Tohoku University Graduate School of Dentistry has discovered that melatonin, a sleep hormone, worsens asthma ... Asthma patients suffer from bronchoconstriction, where the smooth muscles of the bronchus -- the pathway that moves air to and from your lungs -- contract. To ease this, many take a bronchodilator, a medicine which widens the bronchus ... However, melatonin, which is often prescribed for insomnia, favors a state of bronchoconstriction and weakens the relaxing effect of a bronchodilator through the activation of the melatonin MT2 receptor."
  • Melatonin Improves Sleep in MS - Medscape, 10/15/21 - "The study was a double-blind, placebo-controlled, crossover study. Participants had a Pittsburgh Sleep Quality Index (PSQI) score of 5 or more, or an Insomnia Severity Index (ISI) score higher than 14 at baseline. Other baseline assessments included patient-reported outcomes for sleep disturbances, sleep quality, daytime sleepiness, fatigue, walking ability, and mood. Half of the participants received melatonin for the first 2 weeks and then switched to placebo. The other half started with placebo and moved over to melatonin at the beginning of week 3 ... During the second and fourth weeks, participants wore an actigraph watch to measure their physical and sleep activities, and then repeated the patient-reported outcome measures at the end of weeks 2 and 4. Melatonin improved average sleep time (6.96 vs. 6.67 hours; P = .03) as measured by the actigraph watch. Sleep efficiency was also nominally improved (84.7% vs. 83.2%), though the result was not statistically significant (P = .07). Other trends toward statistical significance included improvements in ISI (–3.5 vs. –2.4; P = .07), change in PSQI component 1 (–0.03 vs. 0.0; P = .07), and change in the NeuroQoL-Fatigue score (–4.7 vs. –2.4; P = .06)"
  • In-Depth: Could melatonin help with COVID-19 infections and vaccinations? - 10News, 3/1/21 - "The paper, published in late January, says that taking melatonin "for at least two weeks prior to vaccination can be a useful approach to improve sleep quality and to ensure that the vaccination is performed at a moment of optimal sleep conditions."" - See melatonin at Amazon.com.
  • Melatonin is effective against polycystic kidney disease - Science Daily, 1/26/21 - "Though Gamberi says melatonin has not been previously used to treat PKD, she does think it holds some promise. PKD is a chronic disease, so treatment cannot include any toxic components. This rules out chemotherapy and tumour-killing antineoplastics used in oncology, for instance. However, melatonin is entirely non-toxic and shares certain properties with antineoplastics and anti-inflammatory agents."
  • Doctors Say Their COVID-19 Protocol Saves Lives. Others Want Proof - Medscape, 7/16/20 - "MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The "+" holds a place for additional therapies like vitamin D, zinc, and melatonin. The protocol originated as a variation of the "HAT therapy," a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis." - See Vitamin C products at Amazon.com and vitamin C at iHerb.com and Jarrow Zinc Balance at Amazon.com and iHerb and melatonin at Amazon.com and iHerb and vitamin D at Amazon.com and vitamin D at iHerb.
  • Melatonin: Magic Potion or Unregulated Danger? - Medscape, 12/5/19 - "Natural melatonin levels are low early in the evening, rise steadily through the night, and peak in the last third of sleep. Because melatonin has a short half-life (about 30-45 minutes), taking a standard-release tablet around bedtime results in a peak early in the night and a tail toward morning — precisely the opposite of the natural pattern" - See melatonin at Amazon.com.
  • Is Melatonin Safe to Take Every Night? - Time, 10/1/19 - "A 0.5 mg dose may be all that’s needed for sleep-cycle regulation, and should be taken three to five hours before bed, he says. For people who want to take melatonin just before bed, a 5 mg dose is appropriate. “Some people report headaches or stomach problems at higher doses, but those side-effects are uncommon,” he says ... Still, there are other concerns. “Melatonin has an incredible safety record, no doubt about it,” says Dr. Mark Moyad, the Jenkins/Pomkempner director of preventive and alternative medicine at the University of Michigan. “But it’s a hormone, and you don’t want to mess around with hormones until you know what they’re doing.” ... People with existing medical problems should discuss melatonin with their doctor before using it" - Err! That last line raised my blood pressure.  Do doctors even have any training is supplements?  I had a run-in with some doctors over supplements. They’ve been putting out the same line my entire life. It reminds me of my second-grade teacher talking about communism and how their leaders put of the communist line when even they don’t believe it. Most doctors and nurses even take supplements. Things like saying the supplements aren’t tested for impurities when ConsumberLab and CVS test them all the time. Have they read the news on valsartan and Zantac being recalled for cancer causing impurities?
  • Benefits of Melatonin (increase your longevity?) - 10 minute YouTube Video
  • Melatonin's heart protective effects not related to its antioxidant properties - Science Daily, 4/9/19  - "Antiarrhythmic agents are substances that treat irregular electrical activity in the heart. Melatonin has previously been shown to have antiarrhythmic effects, with the assumption that this was due to its known antioxidant properties ... One group of rats was given 10 mg of melatonin daily for seven days, while another received a placebo. Researchers then measured the electrical activity in the rats' hearts before, during and after a cardiac event. They later examined the hearts for measures of oxidative stress and antioxidant activity ... Ventricular tachycardia (VT) and ventricular fibrillation (VF) are two kinds of dangerous irregular electrical activity in the heart that can result from a heart attack. Incidence of both VT and VF was reduced in melatonin-treated rats. A marker of antioxidant activity was also higher in the treated rats. However, there was no association between the presence of oxidative stress and incidence of irregular electrical activity ... In previous work, the research team observed that blocking melatonin-specific receptors removed the antiarrhythmic benefit of melatonin. When taken together with this current study, these results suggest that melatonin's protective effects for the heart "are related to its antiarrhythmic action, and this effect is related not to antioxidative properties but to melatonin receptor stimulation,"" - See melatonin at Amazon.com.
  • Melatonin 'Should Be a Last Resort' in Tackling Sleep Issues - Medscape, 12/20/18
  • Guidelines for the therapeutic use of melatonin - Science Daily, 12/11/18 - "According to the authors, most oral formulations require approximately 45 minutes to an hour to become bioavailable, so a dose should be taken about an hour before the usual reported bedtime. Given that melatonin is a powerful timer of the organism's physiology, it should be taken strictly at the same time every day"
  • As Melatonin Use Rises, So Do Safety Concerns - WebMD, 11/12/18 - "One review of 15 studies involving 284 otherwise healthy subjects found that those who took melatonin before bed fell asleep 3.9 minutes faster on average and slept 13 minutes longer. Another, of 19 studies involving 1,700 people, found that melatonin users fell asleep 7 minutes faster on average and slept 8 minutes longer ... circadian rhythm disorders ... One study, published in June in the journal PLOS Medicine, looked at 116 men with the disorder and found that those who took 0.5 milligrams of fast-release melatonin 1 hour before their desired bedtime at least 5 nights per week fell asleep 34 minutes earlier on average, slept more soundly, and saw their sleep patterns normalize after 4 weeks" - See melatonin at Amazon.com.
  • Melatonin for Migraine Headache Prophylaxis - Medscape, 4/30/18 - "Overall, the evidence supporting melatonin for migraine prevention is promising but still preliminary. Nonetheless, given the favorable tolerability and low risk for side effects, melatonin is an option that may be worth considering for reducing migraine frequency, severity, and duration in patients with frequent migraine headaches" - See melatonin at Amazon.com.
  • Chemotherapy pain could be eased by jetlag drug, study suggests - Science Daily, 9/15/17 - "melatonin given prior to chemotherapy limited the damaging effect on nerve cells and the development of pain symptoms ... In this study, melatonin did not alleviate pain when CINP had already developed, suggesting that its potential benefits could be as prevention rather than cure ... melatonin treatment did not interfere with the beneficial anticancer effects of chemotherapy in human breast and ovarian cancer cells ... Findings also showed that melatonin reduced damage caused by chemotherapy to vital parts of nerve cells known as mitochondria" - See melatonin at Amazon.com.
  • Reduced Fat Mass and Increased Lean Mass in Response to 1 Year of Melatonin Treatment in Postmenopausal Women - Medscape, 4/4/16 - "Our results suggest a possibly beneficial effect of melatonin on body composition and lipid metabolism as 1 year of treatment reduces fat mass, increases lean mass and is associated with a trend towards an increase in adiponectin"
  • iPads, tablets, smartphones disrupt good sleep, study finds - The Washington Post, 12/22/14 - "During a two-week inpatient experiment involving a dozen adults, some participants were asked to read on an iPad for four hours each night before bedtime, for five consecutive nights. Others read printed books in dim light. After a week, the groups switched ... participants using iPads displayed reduced levels of melatonin, a hormone that typically increases in the evening and helps induce sleepiness. They took longer to fall asleep, and spent less time in restorative REM, or rapid-eye movement, sleep ... the iPad readers reported being sleepier and less alert the following morning, even after eight hours of sleep. They also displayed delayed circadian rhythms ... although the study used only iPads, the effect isn't unique to that device. Other products produce similar blue-light emissions, including tablets, e-readers, smartphones, laptops and LED monitors"
  • New Study Shows Melatonin Makes Old Bones Stronger - Dr. Michael Murray, 6/3/14 - "One of the underlying causes of low melatonin levels as a person ages may be low vitamin B12 levels. Vitamin B12 is a necessary cofactor in the manufacture of melatonin ... Methylcobalamin is the body’s active form of vitamin B12. Methylcobalamin has been shown to help some people suffering from what is referred to as sleep-wake disorder ... In people with sleep wake disorders, taking methylcobalamin (3 mg daily first thing in the morning) has often led to improved sleep quality, increased daytime alertness and concentration, and improved mood. Much of the benefit appears to be a result of methylcobalamin influencing melatonin secretion" - See vitamin B12 at Amazon.com.
  • Melatonin makes old bones stronger, research shows - Science Daily, 5/26/14 - "gave twenty 22-month-old male rats (the equivalent of 60 year-old humans) melatonin supplements diluted in water for 10 weeks (the equivalent of six years in human years) ... there was a significant increase in both bone volume and density among the rats that had received melatonin supplements"
  • Melatonin Agonist Cuts Delirium Risk - Medscape, 2/19/14 - "ramelteon was associated with a lower risk for delirium ― 3% vs 32% ― compared with placebo ... One previous randomized controlled trial suggested that melatonin, a pineal gland hormone that regulates the sleep-wake rhythm, is associated with a lower risk for delirium. In addition, case series have suggested that ramelteon, which was approved in 2005 by the FDA for the treatment of insomnia, may help prevent delirium in elderly patients" - Note:  Why use the over-the-counter melatonin when you can make a drug that increases melatonin and charge a hundred times as much?  I'm just being factitious.
  • Melatonin shows potential to slow tumor growth in certain breast cancers - Science Daily, 1/28/14 - "These early stage research results with the melatonin drug in a triple-negative breast cancer animal models achieved in our lab has not been seen anywhere else ... The mice were randomly assigned to either the melatonin or control groups. The melatonin group received treatment each night for 21 days ... Those treated showed significantly smaller tumors after 21 days while the mean tumor volume increased significantly in the control group. And, there was less vascular growth in the tumors of the treated group"
  • Melatonin may lower prostate cancer risk - Science Daily, 1/20/14 - "conducted a case-cohort study of 928 Icelandic men from the AGES-Reykjavik cohort between 2002 and 2009. They collected first morning void urine samples at recruitment, and asked the participants to answer a questionnaire about sleep patterns ... men whose 6-sulfatoxymelatonin levels were higher than the median value had a 75 percent decreased risk for advanced prostate cancer. A 31 percent decreased risk for prostate cancer overall was observed as well, but this finding was not statistically significant"
  • Melatonin Helps Control Weight Gain as It Stimulates the Appearance of ‘beige Fat’ That Can Burn Calories Instead of Storing Them, Study Suggests - Science Daily, 9/25/13 - "chronic administration of melatonin sensitizes the thermogenic effect of exposure to cold, heightens the thermogenic effect of exercise and, therefore, constitutes excellent therapy against obesity. The fact is that one of the key differences between 'beige fat', which appears when administering melatonin, and 'white fat', is that 'beige fat' cell mitochondria express levels of UCP1 protein, responsible for burning calories and generating heat"
  • Topical Agents for Hair Growth Promotion - Medscape, 7/22/13 - "androgenetic alopecia (AGA), i.e., male pattern hair loss and female pattern hair loss ... Melantonin has long been known to modulate hair growth. Animal testing has shown that melatonin stimulates the anagen phase of hair growth.[23] In a double-blind, randomized, placebocontrolled study 40 women with diffuse alopecia (n=28) or AGA (n=12) were treated topically for 6 months with 1 ml daily of 0.1% melatonin-alcohol solution versus vehicle. Trichograms were used to determine efficacy in the frontal and occipital scalp areas. At the end of the study, the AGA group demonstrated a statistically significant increase in anagen hairs in the occiput region compared to placebo (mean 78 to 82 hairs), but no difference was shown with placebo in the frontal area.[24] The group with diffuse alopecia showed a substantial increase in frontal hair. Plasma melatonin levels were elevated under treatment with melatonin, but did not exceed the physiological night peak"
  • Melatonin for Migraine? - Medscape, 5/21/13 - "Participants were randomly assigned to 3 mg of melatonin, 25 mg of amitriptyline, or placebo for 3 months ... The mean reduction in headache frequency was 2.7 in the melatonin group, 2.18 in the amitriptyline group, and 1.18 in the placebo group. The proportion of responders was greatest in the melatonin group at 54% vs 39% for amitriptyline and 20% for placebo ... Patients gained weight in both the amitriptyline and placebo groups, but melatonin was associated with weight loss" - See melatonin at Amazon.com.
  • Therapeutic Applications of Melatonin - Medscape, 4/25/13 - "Melatonin is a hormone with multiple actions. It is involved in the regulation of biological rhythms, in sleep regulation, it has potent antioxidant action and protects the organism from carcinogenesis and neurodegenerative disorders. The hormone possesses immune-enhancing activity. Therapeutically, it may be used for the management of insomnia, jet lag, the resynchronization of circadian rhythms, as an adjuvant in cancer therapy and in the inhibition of disease progression in Alzheimer's disease and other neurodegenerative disorders"
  • Melatonin Delays ALS Symptom Onset and Death in Mice - Science Daily, 4/25/13 - "Melatonin is a naturally occurring hormone that is best known for its role in sleep regulation. After screening more than a thousand FDA-approved drugs several years ago, the research team determined that melatonin is a powerful antioxidant that blocks the release of enzymes that activate apoptosis, or programmed cell death ... Our experiments show for the first time that a lack of melatonin and melatonin receptor 1, or MT1, is associated with the progression of ALS ... We saw similar results in a Huntington's disease model in an earlier project, suggesting similar biochemical pathways are disrupted in these challenging neurologic diseases"
  • Decreased melatonin secretion associated with higher risk of developing type 2 diabetes - Science Daily, 4/2/13 - "The analysis consisted of a case-control study nested within the Nurses' Health Study cohort ... participants in the lowest category of urinary ratio of 6-sulfatoxymelatonin to creatinine had a 2.2 times higher odds of developing type 2 diabetes compared to participants in the highest category" - [Abstract]
  • OTC Supplement May Aid in Migraine Prevention - Medscape, 3/26/13 - "3 mg of melatonin was more effective than placebo and had efficacy similar to that of 25 mg of amitriptyline. Furthermore, it was better tolerated than amitriptyline, with lower rates of daytime sleepiness and no weight gain ... The mean reduction in headache frequency was 2.7 in the melatonin group, 2.18 in the amitriptyline group, and 1.18 in the placebo group ... Although patients gained weight in both the amitriptyline (n = 3) and placebo (n = 1) groups, melatonin was associated with weight loss ... melatonin should be taken between 10 pm and 11 pm to mimic the physiologic peak. In addition, a fast-acting rather than a slow-release formula should be used"
  • Impaired Melatonin Secretion May Play a Role in Premenstrual Syndrome - Science Daily, 12/20/12 - "PMDD sufferers can experience depression, tension, and irritability of sufficient intensity to interfere with daily activities and relationships. Disturbed sleep is also a common symptom of the disorder, with up to 70% of patients frequently reporting either poor sleep quality with increased awakenings or excessive sleepiness during the symptomatic phase ... compared to healthy controls, PMDD women had significantly decreased melatonin secretion levels during the night-time hours ... Clinical implications of reduced melatonin in PMDD The prevalence of insomnia and depression are both about twice as high in women than in me"
  • Night-Shift Work Ups the Risk for Various Cancers in Men - Medscape, 10/31/12 - "The study compared 3137 men with cancer and 512 matched control subjects who completed a detailed questionnaire about occupational work and lifestyle from 1979 to 1985 ... Compared with men who never worked at night, men who worked night shifts had an increased risk for prostate cancer (odds ratio [OR], 2.77), non-Hodgkin's lymphoma (OR, 2.31), pancreatic cancer (OR, 2.27), rectal cancer (OR, 2.09), colon cancer (OR, 2.03), bladder cancer (OR, 1.74), and lung cancer (OR, 1.76) ... "When I first proposed the light-at-night hypothesis, it linked circadian disturbance to hormone disruption and breast cancer," Dr. Stevens explained. Since then, circadian disruption has been linked to many other adverse effects, it has been demonstrated that melatonin has a direct effect on tumor growth, and some of the latest research he has been involved with has shown that circadian disruption has an epigenetic impact"
  • Melatonin and exercise work against Alzheimer's in mice - Science Daily, 9/26/12 - "The mice were divided into one control group and three other groups which would undergo different treatments: exercise -unrestricted use of a running wheel-, melatonin -a dose equivalent to 10 mg per kg of body weight-, and a combination of melatonin and voluntary physical exercise ... After six months, the state of the mice undergoing treatment was closer to that of the mice with no mutations than to their own initial pathological state. From this we can say that the disease has significantly regressed ... The results, which were published in the journal Neurobiology of Aging, show a general improvement in behaviour, learning, and memory with the three treatments ... These procedures also protected the brain tissue from oxidative stress and provided good levels of protection from excesses of amyloid beta peptide and hyperphosphorylated TAU protein caused by the mutations" - Note:  That's a huge amount of melatonin though but then on the other hand it was a short six month period but on the third hand, mice have a much shorter life span so it might interpolate to a much longer time span for humans.
  • Light from self-luminous tablet computers can affect evening melatonin, delaying sleep - Science Daily, 8/27/12 - "To produce white light, these electronic devices must emit light at short wavelengths, which makes them potential sources for suppressing or delaying the onset of melatonin in the evening, reducing sleep duration and disrupting sleep. This is particularly worrisome in populations such as young adults and adolescents, who already tend to be night owls ... Melatonin suppression after a one-hour exposure to the tablet was not significantly affected. However, after a two-hour exposure there was significant suppression"
  • Melatonin might help in controlling weight gain and preventing heart diseases associated to obesity - Science Daily, 4/28/11 - "melatonin -a natural hormone produced by the body- helps in controlling weight gain -even without reducing the intake of food-, improves blood lipid profile -as it reduces triglicerids-, increases HDL cholesterol and reduces LDL cholesterol ... analyzed in young Zucker diabetic obese rats the effects of melatonin on obesity, dyslipidemia and high blood pressure associated to obesity. Melatonin was found to be beneficial for young rats that had not still developed any methabolic or heart disease"
  • Room light before bedtime may impact sleep quality, blood pressure and diabetes risk - Science Daily, 1/13/11 - "exposure to electrical light between dusk and bedtime strongly suppresses melatonin levels and may impact physiologic processes regulated by melatonin signaling, such as sleepiness, thermoregulation, blood pressure and glucose homeostasis ... researchers evaluated 116 healthy volunteers aged 18-30 years who were exposed to room light or dim light in the eight hours preceding bedtime for five consecutive days. An intravenous catheter was inserted into the forearms of study participants for continuous collection of blood plasma every 30-60 minutes for melatonin measurements. Results showed exposure to room light before bedtime shortened melatonin duration by about 90 minutes when compared to dim light exposure. Furthermore, exposure to room light during the usual hours of sleep suppressed melatonin by greater than 50 percent"
  • Too much light at night at night may lead to obesity, study finds - Science Daily, 10/11/10 - "mice exposed to a relatively dim light at night over eight weeks had a body mass gain that was about 50 percent more than other mice that lived in a standard light-dark cycle ... Something about light at night was making the mice in our study want to eat at the wrong times to properly metabolize their food ... So how does light at night lead to changes in metabolism? The researchers believe the light could disrupt levels of the hormone melatonin, which is involved in metabolism. In addition, it may disrupt the expression of clock genes, which help control when animals feed and when they are active"
  • Melatonin: The Fountain Of Youth? - Science Daily, 6/22/09 - "Melatonin can slow down the effects of aging. A team at laboratoire Arago in Banyuls sur Mer (CNRS / Université Pierre et Marie Curie) has found that a treatment based on melatonin can delay the first signs of aging in a small mammal ... studied the long-term effects of melatonin on the Greater White-toothed shrew, a small nocturnal insectivorous mammal. Under normal conditions, this animal shows the first signs of aging after reaching 12 months, mainly through the loss of circadian rhythm in its activities. By continuously administering melatonin, starting a little before 12 months, the appearance of these first signs was delayed by at least 3 months, which is a considerable period in relation to the lifespan of this shrew ... Melatonin is now known to play several beneficial roles. These include being an antioxidant, an anti-depressant, and helping to remediate sleep problems"
  • Melatonin May Save Eyesight In Inflammatory Disease, Study Suggests - Science Daily, 11/23/08
  • Low Melatonin Associated with Increased Risk of Breast Cancer in Postmenopausal Women - Science Daily, 6/15/08 - "women with the lowest levels of melatonin had a statistically significantly higher incidence of breast cancer than those with the highest levels"
  • Night Shift Work May Cause Cancer - WebMD, 11/30/07 - "They note that shift work may raise cancer risk by suppressing production of melatonin, a chemical involved in the circadian rhythm"
  • High Melatonin Content Can Help Delay Aging, Mouse Study Suggests - Science Daily, 4/24/07 - "Therefore, the researcher asserts, daily melatonin intake in humans from the age of 30 or 40 could prevent – or, at least, delay – illnesses related to aging, free radicals and inflammatory processes, such as many neurodegenerative disorders (e.g. Parkinson's disease) and complications linked to other illnesses, like diabetes"
  • Salivary Melatonin May Help Fight Gum Disease - Science Daily, 9/13/06 - "the melatonin may fight against infection and inflammation possibly due to its antioxidant, anti-aging and immunoenhancing ability"
  • Grapes May Help With Sleep - WebMD, 6/19/06 - "The juicy fruit might be packing melatonin, a sleep hormone"
  • Another Grape Excuse To Hit The Bottle - Science Daily, 6/16/06 - "the grapes used to make some of the most popular red wines contain high levels of the sleep hormone melatonin"
  • Best Time to Take Melatonin? - WebMD, 5/3/06
  • Melatonin Improves Mood In Winter Depression - Science Daily, 5/2/06 - "melatonin, a naturally occurring brain substance, can relieve the doldrums of winter depression, also known as seasonal affective disorder, or SAD"
  • Melatonin Most Effective For Sleep When Taken For Off-hour Sleeping - Science Daily, 5/1/06 - "sleep efficiency during the six hour, 40 minute episodes was significantly higher in the groups that took melatonin during times when the body was not producing melatonin. At those times, participants taking 5.0mg of melatonin had a sleep efficiency of 83 percent and those taking 0.3mg melatonin had a sleep efficiency of 84 percent"
  • Melatonin Supplements review - ConsumerLab.com, 4/5/06
  • Melatonin Pills May Help Ease Tinnitus - WebMD, 2/24/06
  • Melatonin could help tinnitus, improve sleep - Nutra USA, 2/23/06
  • Melatonin for Travelers' Sleep Woes? - WebMD, 2/9/06
  • Melatonin may cut hypertension - Nutra USA, 2/2/06 - "A 10 per cent decline of BP over daytime values is considered appropriate to reduce the cardiovascular risk ... During placebo use only 39 per cent of the subjects reached this value, but this rate surged to 84 per cent during melatonin administration"
  • Study Demonstrates Role Of Exercise In Modifying Melatonin Levels; Increase Believed To Offer Breast Cancer Protection - Science Daily, 12/3/05
  • Stopping Jet Lag Before It Starts - WebMD, 11/2/05 - "The body clocks of those who took melatonin adapted better to the new schedule. The higher dose of melatonin fared best in that regard, but not by much. Plus, people who took the higher dose were sleepier in the evenings after taking the pill"
  • Travelers Can Avoid Jet Lag By Resetting Their Body Clocks - Science Daily, 11/2/05
  • Melatonin to Fight Insomnia: Timing Is Key - WebMD, 10/25/05 - "melatonin was most effective in resetting the body's internal, or circadian, clock when it was timed to the individual's sleep patterns ... If you only want to induce sleep you can take it about two hours before you want to go to sleep"
  • Melatonin May Reduce the Pain of Irritable Bowel Syndrome - Medscape, 10/14/05 - "Use of 3 mg of melatonin once daily for two weeks in IBS patients is associated with improvement in bowel pain and rectal distension thresholds for urgency and pain but not with a change in stool frequency, type, or quality of life"
  • Add-On Melatonin Improves Sleep Behavior in Children With Epilepsy: Randomized, Double-Blind, Placebo-Controlled Trial - Medscape, 5/24/05
  • Melatonin Modestly Effective for Sleep - WebMD, 3/3/05
  • Melatonin study could 'jump-start' interest in supplement - Nutra USA, 3/2/05
  • Popular Supplement Melatonin Found To Have Broader Effects In Brain Than Once Thought - Science Daily, 2/11/05 - "In experiments on the Japanese quail, the researchers found that melatonin switches on a recently discovered hormone called gonadotropin inhibitory hormone (GnIH), which has been found to have the opposite effect to the key hormone priming the body for sex – gonadotropin releasing hormone (GnRH). In birds, switching off GnRH causes the gonads – testes and ovary – to shrink as part of the birds' yearly cycle"
  • U.S. Study Sees Little Benefit From Melatonin - HealthDay, 12/22/04 - "The one area where melatonin did seem to work was with a group of people with a condition called "delayed sleep phase syndrome," which means that otherwise healthy people have a biological quirk that prevents a normal sleep cycle"
  • Melatonin Supplements May Not Help Sleep - WebMD, 12/10/04
  • Melatonin May Improve Sleep Quality in Patients With Asthma - Medscape, 11/1/04
  • Melatonin Effective in Relieving Pain But Not Sleep Disturbance Related to Irritable Bowel Syndrome - Doctor's Guide, 9/30/04
  • Melatonin May Help Prevent Migraines - WebMD, 9/9/04
  • Melatonin Decreases Migraine Frequency and Intensity - Medscape, 9/9/04 - "Of 32 patients who completed the study, 25 patients (78.1%) had at least a 50% reduction in headache frequency from baseline, eight patients (25%) had no headaches, and none of the patients had increased headaches after three months of therapy"
  • Melatonin Relieves Stabbing Headaches - Healthwell Exchange Daily News, 2/26/04
  • Melatonin to Lower Blood Pressure? - Dr. Weil, 2/24/04
  • Caffeine, Melatonin May Ease Jet Lag - WebMD, 2/6/04
  • Nightime Melatonin Supplementation May Be Useful in the Treatment of Essential Hypertension - Doctor's Guide, 2/4/04 - "2.5 mg/day ... mean sleep systolic blood pressure decreased by 6 mm Hg and mean sleep diastolic blood pressure decreased by 4 mm Hg ... Repeated melatonin significantly increased sleep efficiency from 80% to 85% and increased actual sleep time from 5.6 to 6.1 hours. Melatonin therapy also reduced sleep latency from 33 to 22 minutes"
  • Jet Lag Hormone Lowers Blood Pressure - WebMD, 1/20/04
  • Melatonin May Cut Hypertension Risk - HealthDay, 1/19/04 - "The men were randomly assigned to receive either a placebo, a single dose of melatonin or 2.5 milligrams of melatonin one hour before bedtime for three weeks ... those taking the hormone each night throughout the three weeks had lower nighttime systolic and diastolic blood pressure. Systolic blood pressure (the top number in the reading) decreased by an average of six millimeters of mercury while the diastolic blood pressure (the bottom number) decreased by an average of four millimeters of mercury" - See melatonin at Amazon.com.
  • Melatonin and Cancer Treatment - Life Extension Magazine, 1/04
  • Melatonin Helpful for Delayed Sleep Onset in Children With ADHD - Medscape, 10/21/03
  • People With Asthma Cautioned About Melatonin Use - Doctor's Guide, 9/8/03
  • Hormone Melatonin Slows Breast Cancer - WebMD, 7/14/03 - "The nighttime hormone melatonin puts breast cancer cells to sleep. It also slows breast cancer growth by 70%"
  • Nighttime Computer Users May Lose Sleep - WebMD, 6/20/03 - "the bright light of a computer screen may alter the body's biological clock and suppress the natural production of melatonin that's critical to the normal sleep-wake cycle"
  • Night Shifts May Raise Cancer Risk - WebMD, 6/3/03 - "Data from an ongoing study of almost 80,000 nurses already suggest that working nights increases a woman's risk of breast cancer ... a new analysis points to a similar association for colorectal cancer ... "The peak production of melatonin occurs at about 1 or 2 a.m." Exposure to light at night stops the production of melatonin" - See iHerb melatonin products.
  • Melatonin Effective Treatment for Chronic Insomnia in Children - New Hope Natural Media, 5/15/03
  • Melatonin Appears Safe for Child Insomniacs - Clinical Psychiatry News, 3/03 - "Melatonin appears to be a safe and effective treatment for children with insomnia ... The average age of the patients was 9.6 years ... Dr. Ivanenko, who is a child psychiatrist at the University of Louisville (Ky.), said she typically starts children at 1-5 mg of melatonin and titrates up to as much as 8-10 mg in adolescents" -  See melatonin at Amazon.com.
  • Melatonin: What Is the Scoop? - Dr. Weil, 1/28/03
  • Melatonin May Worsen Asthma - WebMD, 10/9/02
  • Melatonin Helps Shorten Recovery Time from Jet Lag - New Hope Natural Media, 7/11/02
  • Neuroprotective Effects of Melatonin Assessed - Doctor's Guide, 4/30/02 - "The neuroprotective effects of melatonin appear to be related to antioxidant and antiamyloidogenic features of the hormone, not to the involvement of melatonin receptors"
  • Can Melatonin Put Tumors to Sleep? - Nutrition Science News, 12/01
  • Melatonin Helps Children Sleep Through Magnetic Resonance Studies - Doctor's Guide, 11/26/01
  • Study: Power Lines May Aid Cancer Cells - Intelihealth, 10/29/01 - "electromagnetic fields disrupted the functioning of the hormone melatonin in individual cells ... Scientists have accepted since 1987 that the substance suppresses the multiplication of cancer cells ... They exposed two batches of the [breast cancer] cell to two different levels of electromagnetic field ... In both cases, the ability of melatonin to suppress the growth of the cancer cells was found to have declined. In some cells with smaller concentrations of melatonin, the suppressive effect was entirely absent"


  • Neuroprotective effects of melatonin-mediated mitophagy through nucleotide-binding oligomerization domain and leucine-rich repeat-containing protein X1 in neonatal hypoxic-ischemic brain damage - FASEB J 2023 Feb;37 - "Hypoxia-ischemia (HI) is a major cause of brain damage in neonates. Mitochondrial dysfunction acts as a hub for a broad spectrum of signaling events, culminating in cell death triggered by HI. A neuroprotective role of melatonin (MT) has been proposed, and mitophagy regulation seems to be important for cell survival ... This study aimed to clarify whether NLRX1 participates in the regulation of mitophagy during MT treatment for hypoxic-ischemic brain damage (HIBD) ... In summary, MT modulates mitophagy induction through NLRX1 and plays a protective role in HIBD, providing insight into potential therapeutic targets for MT to exert neuroprotection" - See melatonin at Amazon.com.
  • New Insights into How Melatonin Ameliorates Bisphenol A-Induced Colon Damage: Inhibition of NADPH Oxidase - J Agric Food Chem 2023 Jan 12 - "Conclusively, our finding suggested that MT can ameliorate BPA-induced colonic DNA damage by scavenging NOX-derived ROS, which further attenuates G2/M cell cycle arrest dependent on the ATM-Chk1/2-p53 axis"
  • Melatonin promotes the restoration of bone defects via enhancement of miR-335-5p combined with inhibition of TNFα/NF-κB signaling - FASEB J 2023 Jan;37(1) - "Accelerating the repair of a bone defect is crucial clinically due to the increased prevalence of trauma, tumor, and infections in bone. Studies have found that excess acute and chronic inflammation attenuate osteogenic differentiation of BMSCs (bone marrow mesenchymal stem cells). Moreover, TNF-α and NF-κB could inhibit osteoblasts differentiation of BMSCs and promote osteoclastogenesis via multiple mechanisms, such as increasing osteoclast precursor cells and acting synergistically with cell cytokines. However, melatonin could inhibit the expression of TNFα/NF-κB and promote bone formation by activating the Wnt/β-catenin signaling pathway ... In conclusion, melatonin facilitates osteogenesis in bone defect healing by enhancing miR-335-5p expression and inhibiting the TNFα/NF-κB pathway." - See melatonin at Amazon.com.
  • Several Supplements May Give the Heart a Boost - WebMD, 12/8/22 - "Omega-3 fatty acids, found in fish, vegetable oils, nuts (especially walnuts), flax seeds, flaxseed oil, and leafy vegetables ... Omega-6 fatty acids, polyunsaturated fats found in vegetable oils, nuts, and seeds ... L-arginine, an amino acid that helps the body build protein. It can be found in protein-rich foods like fish, red meat, poultry, soy, whole grains, beans, and dairy products ... L-citrulline, a nonessential amino acid found in watermelon ... Folic acid, a form of vitamin B9 used for deficiency and to prevent pregnancy complications. It is added to cold cereals, flour, breads, pasta, bakery items, cookies, and crackers, as required by federal law. Foods that are naturally high in folate include leafy vegetables, okra, asparagus, certain fruits, beans, yeast, mushrooms, animal liver and kidney, orange juice, and tomato juice ... Vitamin D, a fat-soluble vitamin that is naturally present in a few foods, added to others, and available as a dietary supplement. Fatty fish (such as trout, salmon, tuna, and mackerel) and fish liver oils are among the best sources ... Magnesium, which keeps blood pressure normal, bones strong, and your heart rhythm steady. In addition to supplements, magnesium can be found in green leafy vegetables like spinach, nuts, beans, peas, and soybeans, as well as whole-grain cereals ... Zinc, found in chicken, red meat, and fortified breakfast cereals ... Alpha-lipoic acid, an antioxidant made naturally in the body and also found in foods. It is in red meat, carrots, beets, spinach, broccoli, and potatoes ... Coenzyme Q10, an antioxidant found in cold-water fish like tuna, salmon, mackerel, and sardines; vegetable oils; and meats ... Melatonin ... Plant-based polyphenols such as catechin, curcumin, flavanol, genistein, and quercetin"
  • Melatonin Prevents against Ethanol-Induced Liver Injury by Mitigating Ferroptosis via Targeting Brain and Muscle ARNT-like 1 in Mice Liver and HepG2 Cells - J Agric Food Chem 2022 Sep 27 - "The circadian clock acts a pivotal part in human daily physiology and metabolism. Excess alcohol consumption disturbs the circadian rhythm of several metabolism-related genes of the liver. Melatonin is a member of the foremost hormones secreted by the pineal gland with numerous pharmacological properties in quite a number of diseases ... Altogether, this study revealed that melatonin could alleviate ethanol-induced liver injury by impeding ferroptosis via reprogramming the circadian protein BMAL1 and subsequently activating the Nrf2-ARE anti-ferroptosis pathway. The emergence of novel liver protective effects and mechanism of melatonin on ethanol-induced ferroptosis may provide a new dimension for prevention or intervention against liver injury associated with ethanol" - See melatonin at Amazon.com.
  • Overview of biological effects of melatonin on testis: A review - Andrologia 2022 Sep 28 - "Several studies demonstrated that melatonin acts as an anti-apoptotic, anti-inflammatory, anticancer and antioxidant agent. Melatonin can also protect testicles and spermatogonia against oxidative damage, chemotherapy drugs, environmental radiation, toxic substances, hyperthermia, ischemia/reperfusion, diabetes-induced testicular damage, metal-induced testicular toxicity, improve sperm quality and it affects the testosterone secretion pathway by affecting Leydig cells"
  • Effects of melatonin supplementation on BDNF concentrations and depression: A systematic review and meta-analysis of randomized controlled trials - Behav Brain Res 2022 Aug 29 - "The aim of this comprehensive systematic review and meta-analysis was to evaluate the beneficial effects of melatonin supplementation on brain-derived neurotrophic factor (BDNF) concentration and clinical depressive disorder ... Melatonin supplementation yielded no significant effect on BDNF concentration (WMD: -5.61; 95% CI: -14.10, 2.88; I-square: 85.6%), but improved depression by decreasing the score (WMD: -0.76 ... The subgroup analysis showed that melatonin supplementation had a significant decreasing effect on BDNF levels in doses ≤ 10mg/day, with more than 4 weeks of duration, and in men"
  • Melatonin attenuates MPP +-induced apoptosis via heat shock protein in a Parkinson's disease model - Biochem Biophys Res Commun 2022 Jul 1 - "Heat shock proteins (HSPs) play an essential role as molecular chaperones to prevent abnormal protein aggregation and misfolding. Moreover, they protect dopamine neurons from oxidative stress, inflammation, and apoptosis, all well-known pathomechanisms of Parkinson's disease (PD). Melatonin is a potent antioxidant that has the beneficial ability to prevent neurodegenerative diseases like PD ... Our findings revealed the protective roles of melatonin in an in vitro PD model. Melatonin can hinder the toxic effects of MPP + on dopaminergic neuronal cells via upregulation of the HSF1/HSP70 pathway" - See melatonin at Amazon.com.
  • Controlled-release oral melatonin supplementation for hypertension and nocturnal hypertension: A systematic review and meta-analysis - J Clin Hypertens (Greenwich) 2022 Apr 7 - "Oral melatonin is a potential alternative treatment for hypertension and nocturnal hypertension. However, high-quality and relevant meta-analyses are lacking. This meta-analysis aimed to investigate whether oral melatonin supplementation reduces daytime/asleep blood pressure and cardiovascular risk, improves sleep quality, and is well-tolerated compared with placebo ... Only controlled-release melatonin (not an immediate-release preparation) reduced asleep systolic blood pressure by 3.57 mm Hg (95% confidence interval: -7.88 to .73; I2 = 0%). It also reduced asleep and awake diastolic blood pressure, but these differences were not statistically significant. Melatonin improves sleep efficacy and total sleep time and is safe and well-tolerated"
  • Melatonin in ventricular and subarachnoid cerebrospinal fluid: Its function in the neural glymphatic network and biological significance for neurocognitive health - Biochem Biophys Res Commun 2022 Mar 17 - "After the ventricular melatonin enters the subarachnoid and Virchow-Robin spaces it is taken into the neural tissue where it functions as a potent antioxidant and anti-inflammatory agent. Experimental evidence indicates that it removes pathogenic toxins, e.g., amyloid-β and others, from the brain to protect against neurocognitive decline. Melatonin levels drop markedly during aging, coincident with the development of several neurodegenerative diseases and the accumulation of the associated neurotoxins" - See melatonin at Amazon.com.
  • Melatonin induces fat browning by transdifferentiation of white adipocytes and de novo differentiation of mesenchymal stem cells - Food Funct 2022 Mar 11 - "The role of melatonin in obesity control is extensively accepted, but its mechanism of action is still unclear. Previously we demonstrated that chronic oral melatonin acts as a brown-fat inducer, driving subcutaneous white adipose tissue (sWAT) into a brown-fat-like function (beige) in obese diabetic rats ... Mesenchymal stem cells (MSCs) ... melatonin increases brown fat in obese diabetic rats by both adipocyte transdifferentiation and de novo differentiation. Furthermore, it promotes beige MSC adipogenesis in humans. This may contribute to the control of body weight attributed to melatonin and its metabolic benefits in human diabesity"
  • Melatonin epigenetic potential on testicular functions and fertility profile in varicocele rat model is mediated by Silent information regulator1 - Br J Pharmacol 2022 Jan 21 - "Melatonin treatment of varicocele rats displayed antioxidant/anti-apoptotic efficacy, improved reproductive hormones axis, Catsper expression, fertility parameters. MiR-34a/SIRT1/FOXO1 epigenetic axis integrates testicular melatonin mediated intracellular transduction cascades in varicocele"
  • Antidepressant actions of melatonin and melatonin receptor agonist: Focus on pathophysiology and treatment - Behav Brain Res 2021 Dec 17 - "Depression has become one of the most commonly prevalent neuropsychiatric disorders, and the main characteristics of depression are sleep disorders and melatonin secretion disorders caused by circadian rhythm disorders. Abnormal endogenous melatonin alterations can contribute to the occurrence and development of depression ... The present review summarizes the mechanisms underlying the antidepressant effects of melatonin, which is related to its functions in the regulation of the hypothalamic-pituitary-adrenal axis, inhibition of neuroinflammation, inhibition of oxidative stress, alleviation of autophagy, and upregulation of neurotrophic, promotion of neuroplasticity and upregulation of the levels of neurotransmitters, etc. Also, melatonin receptor agonists, such as agomelatine, ramelteon, piromelatine, tasimelteon, and GW117, have received considerable critical attention and are highly implicated in treating depression and comorbid disorders. This review focuses on melatonin and various melatonin receptor agonists in the pathophysiology and treatment of depression, aiming to provide further insight into the pathogenesis of depression and explore potential targets for novel agent development"
  • The role of melatonin in the molecular mechanisms underlying metaflammation and infections in obesity: A narrative review - Obes Rev 2021 Dec 3 - "The tight connection between adipose tissue and the immune system has been demonstrated to play a crucial role in inflammation, and melatonin is important for circadian rhythm regulation and metabolic homeostasis, in which it orchestrates several molecular mechanisms involved in obesity and associated inflammation. Melatonin also regulates innate and adaptive immunity; its antioxidant properties are linked to reduced predisposition to infection and weight gain in patients with obesity through the modulation of the immune response, which has a significant beneficial effect on inflammation and, consequently, on the metabolic state. Low melatonin levels have been linked to obesity, and melatonin supplementation can reduce body weight, improve metabolic profile, and ameliorate immune responses and pro-inflammatory stimuli. The role of melatonin in obesity is mainly related to improved oxidative stress signaling, modulation of adipokine secretion, and a switching from white-to-brown adipose tissue phenotype and activity. Moreover, the role of melatonin in obesity modulation by controlling circadian rhythm has recently emerged as a pivotal mechanism for lipid and glucose metabolism dysfunction in adipose, muscle, and liver tissues. Melatonin may also regulate the immune system by acting directly on thymus morphology and activity as well as by modulating oxidative stress and inflammatory states during infections. The tight association between melatonin and immune response regulation is coordinated by Toll-like receptors, which are rhythmically expressed during the day. Their expression may be strongly modulated by melatonin as their signaling is highly inhibited by melatonin"
  • Melatonin ameliorates cerebral ischemia-reperfusion injury in diabetic mice by enhancing autophagy via the SIRT1-BMAL1 pathway - FASEB J 2021 Dec - "Diabetic brains are more vulnerable to ischemia-reperfusion injury. Previous studies have proved that melatonin could protect against cerebral ischemia-reperfusion (CIR) injury in non-diabetic stroke models; however, its roles and the underlying mechanisms against CIR injury in diabetic mice remain unknown ... these results indicate that melatonin treatment can protect against CIR-induced brain damage in diabetic mice, which may be achieved by the autophagy enhancement mediated by the SIRT1-BMAL1 pathway"
  • Protective Effects of Melatonin against Obesity-Induced by Leptin Resistance - Behav Brain Res 2021 Sep 23 - "Leptin resistance is due to excess leptin, a saturation of its transporters, and deficiency in either the receptor level or signalling in the hypothalamus. Leptin resistance leads to obesity due to excess food intake and less energy expenditure. Normal leptin secretion follows a rhythm, and alteration in the lifestyle leads to hormonal imbalances and increases ROS generation leading to oxidative stress. The sleep disturbance causes obesity with increased lipid accumulation in adipose tissue. Melatonin is the master regulator of the sleep-wake cycle secreted by the pineal gland during the night. It is a potent antioxidant with anti-inflammatory properties. Melatonin is secreted in a pattern called the circadian rhythm in humans as well. Research indicates that melatonin plays a vital role in hormonal regulation and energy metabolism, including leptin signalling and secretion"
  • Melatonin ameliorates endocrine dysfunction and defective sperm integrity associated with high-fat diet-induced obesity in male Wistar rats - Andrologia 2021 Sep 7 - "Taken together, these results indicate that HFD exposure causes endocrine dysfunction and disrupted sperm parameters in obese animals, which are accompanied by lipid peroxidation/defective antioxidant capacity. In addition, the present results suggest that melatonin supplementation restores endocrine function and sperm integrity in obese rat model by suppression of oxidative stress-dependent mechanism"
  • Melatonin induces Nrf2-HO-1 reprogramming and corrections in hepatic core clock oscillations in Non-alcoholic fatty liver disease - FASEB J 2021 Sep;35(9):e21803 - "Melatonin pleiotropically regulates physiological events and has a putative regulatory role in the circadian clock desynchrony-mediated Non-alcoholic fatty liver disease (NAFLD) ... high-fat high fructose (HFHF) diet ... C57BL/6J mice subjected to HFHF and/or JL, and treated with melatonin showed an improvement in the profile of lipid regulatory genes (CPT-1, PPARa, and SREBP-1c), liver function (AST and ALT) and histomorphology of fatty liver ... Melatonin induced changes in oscillations of anti-oxidant genes (Nrf2, HO-1, and Keap1) subtly contributed in the overall improvement in NAFLD recorded herein. Taken together, melatonin induced reprograming of hepatic core clock and Nrf2-HO-1 genes leads to an improvement in HFHF/JL-induced NAFLD"
  • Effects of melatonin supplementation on diabetes: A systematic review and meta-analysis of randomized clinical trials - Clin Nutr 2021 Jun 16 - "Our results showed that melatonin supplementation was useful for reducing diabetes parameters when compared to placebo"
  • Inhibition of TMPRSS4 mediated epithelial-mesenchymal transition is critically involved in antimetastatic effect of melatonin in colorectal cancers - Phytother Res 2021 Jun 11 - "transmembrane protease serine 4 (TMPRSS4) ... epithelial-mesenchymal transition (EMT) signaling ... these findings provide evidence that melatonin suppresses metastasis in colon cancer cells via inhibition of TMPRSS4 mediated EMT" - See melatonin at Amazon.com.
  • Effects of Melatonin Supplementation on Serum Oxidative Stress Markers and Disease Activity in Systemic Lupus Erythematosus Patients: A Randomized, Double-Blind, Placebo-Controlled Trial - Int J Clin Pract 2021 Apr 20 - "This study demonstrated affirmative effects of melatonin in decreasing oxidative stress in SLE patients without any effect on disease activity" - See melatonin at Amazon.com.
  • Melatonin prevents diabetes-associated cognitive dysfunction from microglia-mediated neuroinflammation by activating autophagy via TLR4/Akt/mTOR pathway - FASEB J 2021 Apr - "Cognitive dysfunction often occurs in diabetes mellitus patients. This study aimed to investigate the efficacy of melatonin (MLT) in improving diabetes-associated cognitive decline and the underlying mechanism involved. Type 2 diabetic mice and palmitic acid (PA)-stimulated BV-2 cells were treated by MLT, and the potential mechanisms among MLT, cognition, and autophagy were explored. The results showed that type 2 diabetic mice showed obvious learning and memory impairments in the Morris water maze test compared with normal controls, which could be ameliorated by MLT treatment. Meanwhile, MLT administration significantly improved neuroinflammation and regulated microglial apoptosis. Furthermore, autophagy inhibitor 3-methyladenine (3-MA) increased the microglial inflammation and apoptosis, indicating that the treatment effect of MLT was mediated by autophagy. Lastly, MLT treatment significantly decreased the levels of toll-like receptors 4 (TLR4), phosphorylated-protein kinase B (Akt), and phosphorylated-mechanistic target of rapamycin (mTOR), indicating that blocking TLR4/Akt/mTOR pathway might be an underlying basis for the anti-inflammatory and anti-apoptosis effects of MLT. Collectively, our study suggested that MLT could improve learning and memory in type 2 diabetic mice by activating autophagy via the TLR4/Akt/mTOR pathway, thereby inhibiting neuroinflammation and microglial apoptosis"
  • Role and Therapeutic Potential of Melatonin in Various Type of Cancers - Onco Targets Ther 2021 Mar 18 - "Cancer is a large group of diseases and the second leading cause of death worldwide. Lung, prostate, colorectal, stomach, and liver cancers are the most common types of cancer in men, whereas breast, colorectal, lung, cervical, and thyroid cancers are the most common among women. Presently, various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, nanotherapy, and immunotherapy, have been used as conventional treatments for patients with cancer. However, the clinical outcomes of advanced-stage disease remain relatively unfavorable owing to the emergence of chemoresistance, toxicity, and other undesired detrimental side effects. Therefore, new therapies to overcome these limitations are indispensable. Recently, there has been considerable evidence from experimental and clinical studies suggesting that melatonin can be used to prevent and treat cancer. Studies have confirmed that melatonin mitigates the pathogenesis of cancer by directly affecting carcinogenesis and indirectly disrupting the circadian cycle. Melatonin (MLT) is nontoxic and exhibits a range of beneficial effects against cancer via apoptotic, antiangiogenic, antiproliferative, and metastasis-inhibitory pathways. The combination of melatonin with conventional drugs improves the drug sensitivity of cancers, including solid and liquid tumors"
  • Melatonin pretreatment alleviates renal ischemia-reperfusion injury by promoting autophagic flux via TLR4/MyD88/MEK/ERK/mTORC1 signaling - FASEB J 2020 Jul 14 - "Autophagy is an important mechanism for cellular homeostasis and survival during pathologic stress conditions in the kidney, such as ischemia-reperfusion (IR) injury. In this study, renal IR was induced in female C57BL/6 mice after melatonin administration ... The administration of melatonin resulted in significantly preserved renal function, and the protective effect was associated with ameliorated oxidative stress, limited pro-inflammatory cytokine production, and neutrophil and macrophage infiltration. Moreover, autophagic flux was increased after melatonin administration while the apoptosis levels were decreased in the melatonin-pretreated mice. Using TAK-242 and CRX-527, we confirmed that MyD88-dependent TLR4 and MEK/ERK/mTORC1 signaling participated in melatonin-induced autophagy in IR mice. Collectively, our results provide novel evidence that antecedent melatonin treatment provides protection for the kidney against IR injury by enhancing autophagy, as regulated by the TLR4/MyD88/MEK/ERK/mTORC1 signaling pathway. Therefore, melatonin preconditioning offers a potential therapeutic approach to prevent renal IR injury related to various clinical conditions"
  • Melatonin Prevents Deterioration of Erectile Function in Streptozotocin-Induced Diabetic Rats via sirtuin-1 Expression - Andrologia 2020 Jun 1 - "The objective of this study was to evaluate the protective effects of melatonin for erectile function with sirtuin-1 protein expression in type 1 diabetic rat models. Fifty male Sprague Dawley rats were placed into five groups. Except for those in the control group (C), each animal received a single dose (60 mg/kg) of streptozotocin to induce diabetes. The animals were placed into the diabetes (D) group, insulin (I) group (6 U/kg/day), melatonin (Mel) group (10 mg kg-1 day-1 ) and combined treatment (I + Mel) group. Ten weeks later, the serum testosterone levels, intracavernosal pressure (ICP), mean arterial pressure (MAP), malondialdehyde (MDA), cyclic guanosine monophosphate (c-GMP), 8-hydroxydeoxyguanosine (8-OHdG), nitric oxide synthase (NOS), caspase-3 activity, sirtuin-1 and endothelial nitric oxide synthase (eNOS) protein expression and histological findings were assessed. The mean ICP/MAP ratio for the D group was lower than the mean ratios for the other groups. The treatment groups, particularly the I + Mel group, exhibited lower 8-OHdG and MDA levels and caspase-3 activity than the D group. The sirtuin-1 and eNOS expression and cavernosal tissue (CT) histology seemed to have been preserved by the melatonin and/or insulin therapy. These results were indicative of a profound protective effect of melatonin by the activation of sirtuin-1 protein expression against hyperglycemia-induced oxidative CT injury" - See melatonin at Amazon.com and iHerb.
  • Melatonin as a rational alternative in the conservative treatment of resistant hypertension - Hypertens Res. 2019 Sep 13 - "Since the BP threshold for starting antihypertensive therapy was reduced to ≥130/80 mmHg in the AHA guidelines, the prevalence of patients with treatment-resistant hypertension is likely to increase. Thus, finding a novel therapeutic option is a challenging issue. Commonly used therapeutic regimes involve volume reducing agents, inhibitors of the formation or effects of Ang II, and calcium channel blockers [1]. While the treatment-resistant hypertension often contains a central neurogenic pathomechanical component, the above postulated mechanisms of action of melatonin could find their application in its treatment. Based on the 2K1C model and other models of hypertension, melatonin triggers sympatholytic and bradycardic effects [9] and, due to its apparent antiproliferative action [13], this hormone even offers nephro- and cardioprotection beyond BP reduction. Therefore, melatonin becomes an essential candidate to be investigated for the treatment of resistant hypertension."
  • The effects of melatonin supplementation on blood pressure in patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials - J Hum Hypertens. 2019 Jan 15 - "In summary, the current meta-analysis demonstrated that melatonin supplementation significantly decreased SBP and DBP in patients with metabolic disorders"
  • Melatonin inhibits MLL-rearranged leukemia via RBFOX3/hTERT and NF-κB/COX-2 signaling pathways - Cancer Lett. 2018 Dec 11;443:167-178 - "MLL-rearranged leukemia is an aggressive malignancy associated with poor outcome, which is refractory to conventional treatment. Melatonin has been proven to exert anti-tumor activity ... Collectively, these results suggest that melatonin inhibits MLL-rearranged leukemia through suppressing the RBFOX3/hTERT and NF-κB/COX-2 signaling pathways. Our findings provide new insights into the role of melatonin for MLL-r leukemia treatment" - See melatonin at Amazon.com.
  • The protective role of melatonin and curcumin in the testis of young and aged rats - Andrologia. 2018 Nov 22:e13203 - "Aged Melatonin (MLT; n = 6, 10 mg/kg, s.c.); (d) Aged Curcumin (CUR; n = 6, 30 mg/kg, i.p.). At the end of 21 days, the rats were sacrificed, and testicular tissues were removed. Malondialdehyde (MDA) in the testicular tissue was determined with thiobarbituric acid reactive substances formation, and glutathione (GSH) was determined with modified Ellman method; testosterone level was determined with chemiluminescence method and histologic changes were determined with Haematoxylin-Eosin and Johnsen's scoring; Apoptotic cell counts were made with TUNEL staining of seminiferous tubule in testis. With ageing, MDA level increased in testicular tissue, but GSH and blood testosterone levels decreased. Melatonin treatment for aged rats significantly decreased Paired total testicular/body weight ratio compared to aged control group (p < 0.05). Curcumin treatment for aged rats significantly increased GSH level compared to the aged control group (p < 0.05). Besides, melatonin and curcumin treatment significantly decreased the number of apoptotic cells and significantly increased Johnsen's score"
  • Melatonin Upregulates Nuclear Factor Erythroid-2 Related Factor 2 (Nrf2) and Mediates Mitophagy to Protect Against Early Brain Injury After Subarachnoid Hemorrhage - Med Sci Monit. 2018 Sep 13 - "Our study indicated that, by increasing the expression of NRF2, the mitophagy induced by melatonin provided protection against brain injury post-SAH"
  • Melatonin Secretion and Muscle Strength in Elderly Individuals: A Cross-Sectional Study of the HEIJO-KYO Cohort - J Gerontol A Biol Sci Med Sci. 2016 Mar 1 - "Recently, oxidative stress and inflammation have been shown to contribute to the loss of muscle strength, and although melatonin has antioxidative and anti-inflammatory properties, the association between melatonin secretion and muscle strength remains unclear ... elderly individuals (mean age, 71.0 years), we measured overnight urinary 6-sulfatoxymelatonin excretion (UME) and grip strength and quadriceps strength ... On dividing participants into quartiles by their UME level (lowest-highest UME, Q1-Q4), higher quartiles were significantly associated with increased grip strength and quadriceps strength"
  • Melatonin Prevents Mitochondrial Damage Induced by Doxorubicin in Mouse Fibroblasts Through Ampk-Ppar Gamma-Dependent Mechanisms - Med Sci Monit. 2016 Feb 10;22:438-46 - "Melatonin given with doxorubicin succesfully countered apoptosis generated by doxorubicin alone, which points to its potential as a protective agent against cell death in doxorubicin chemotherapy. This also implies that patients should be receiving doxorubicin treatment when their physiological level of melatonin is at its highest, which is early in the morning"
  • The effect of melatonin on sleep and quality of life in patients with advanced breast cancer - Support Care Cancer. 2015 Aug 11 - "Thirty-two patients with metastatic breast cancer, receiving hormonal or trastuzumab therapy, took 5 mg of melatonin at bedtime for 2 months ... Bedtime melatonin was associated with a significant improvement in a marker of objective sleep quality, sleep fragmentation and quantity, subjective sleep, fatigue severity, global quality of life, and social and cognitive functioning scales. Morning clock gene expression was increased following bedtime melatonin intake"
  • Melatonin can help you get a good night's sleep in a noisy environment - Science Daily, 3/19/15 - "intensive care unit (ICU) ... participants were randomly divided into four equal groups but continued to sleep in the simulated ICU. The first group did not receive any sleep aid. The second were provided with eye masks and earplugs. The third group took 1mg of fast-release oral melatonin when going to bed. The final group of participants was given a placebo ... all sleep patterns were disturbed by exposure to the simulated ICU environment. This resulted in feelings of anxiety and reduced quality of sleep ... Those who took melatonin were found to have decreased awakenings during the night even compared to the eye mask and earplugs group. The quality of the sleep was also found to be much improved for those taking melatonin, with reported lower anxiety levels and increased REM sleep -- thought to be linked to improved cognitive restoration"
  • The protective effect of melatonin against brain oxidative stress and hyperlocomotion in a rat model of mania induced by ouabain - Behav Brain Res. 2014 Jun 21 - "Our study showed that Melatonin, similarly to lithium, protected against OUA-induced brain oxidative stress and hyperlocomotion in rats. Thus, our findings reinforce the notion that oxidative stress may play an important role in the manic-like behavioural. Therefore, we indicate that Melatonin has antimanic-like action, suggesting a potential role for this substance in the pharmacological management of Bipolar disorder"
  • Resveratrol- and melatonin-abated ovariectomy and fructose diet-induced obesity and metabolic alterations in female rats - Menopause. 2014 Jan 27 - "Ovariectomy caused an increase in body weight, body mass index, feed efficiency, serum glucose, cholesterol, triglycerides, and free fatty acids, which was further exacerbated by fructose diet. These parameters were significantly decreased by resveratrol, alone and in combination with melatonin. Histopathological examination revealed reduced hypertrophy of adipocytes in adipose tissue and reduced macrophage infiltration in the liver" - See resveratrol products at Amazon.com and melatonin at Amazon.com.
  • Melatonin prevents gentamicin-induced testicular toxicity and oxidative stress in rats - Andrologia. 2013 Nov 4 - "This study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced testicular toxicity and oxidative damage in rats ... These results indicate that MT prevents testicular toxicity induced by GM in rats, presumably due to its potent antioxidant activity, and its ability to inhibit lipid peroxidation, and restore antioxidant enzyme activity"
  • Melatonin modulates microsomal prostaglandin E synthase 1 and nuclear factor-E2-related factor-2-regulated antioxidant enzyme expressions in LPS-induced murine peritoneal macrophages - Br J Pharmacol. 2013 Sep 30 - "Increasing evidences demonstrate that melatonin regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses ... melatonin might be a promising target for diseases associated with overactivation of macrophages"
  • Shiftwork and Prostate-Specific Antigen in the National Health and Nutrition Examination Survey - J Natl Cancer Inst. 2013 Aug 13 - "Shiftwork has been implicated as a risk factor for prostate cancer. Results from prior studies have been mixed but generally support an association between circadian disruption and prostate cancer ... We combined three NHANES surveys (2005-2010) to obtain current work schedule among employed men aged 40 to 65 years with no prior history of cancer (except nonmelanoma skin cancer) ... We found a statistically significant, age-adjusted association between current shiftwork and elevated PSA at the 4.0ng/mL or greater level (odds ratio = 2.48, 95% confidence interval [CI] = 1.08 to 5.70; P = .03)" - Note:  Many believe that the increased risk of breast cancer in shift workers is attributed to melatonin.  Maybe it's the same for prostate cancer.
  • Urine melatonin levels are inversely associated with sarcopenia in postmenopausal women - Menopause. 2013 Jun 10 - "Seventy-eight Korean postmenopausal women participated ... Our study shows an inverse association between urine melatonin and sarcopenia, suggesting that melatonin may have a protective role in the pathophysiology of sarcopenia"
  • Night Shift Work and Levels of 6-Sulfatoxymelatonin and Cortisol in Men - Cancer Epidemiol Biomarkers Prev. 2013 Apr 5 - "We investigated whether male nightshift workers demonstrated changes in levels of melatonin and cortisol, potential biomarkers of cancer risk ... Nightshift workers had significantly lower 6-sulfatoxymelatonin levels during daytime sleep, nighttime work, and nighttime sleep on off-nights (57%, 62% and 40% lower, respectively), relative to the dayshift workers during nighttime sleep (p<0.0001); urinary cortisol in nightshift workers was 16% higher during daytime sleep and 13% lower during nighttime sleep on off-nights (p<0.05). Morning serum cortisol post-work and post-sleep in nightshift workers were 24% and 43% lower, respectively, than post-sleep levels among dayshift workers (p<0.0001). Within-subject comparisons among the nightshift workers revealed significantly lower melatonin levels and significantly higher urinary cortisol levels during daytime sleep and nighttime work, relative to nighttime sleep (p<0.01); morning serum cortisol levels post-work were lower than those post-sleep ... Shiftwork could be an important risk factor for many types of cancer"
  • Melatonin as a free radical scavengr in the ovarian follicle [Review] - Endocr J. 2012 Nov 22 - "Melatonin reduces oxidative stress as an antioxidant, and contribute to oocyte maturation, embryo development and luteinization of granulosa cells. Our clinical study demonstrated that melatonin treatment for infertile women increases intra-follicular melatonin concentrations, reduces intra-follicular oxidative damage, and elevates fertilization and pregnancy rates. Melatonin treatment also improves progesterone production by corpus luteum in infertile women with luteal phase defect. Melatonin treatment could become a new cure for improving oocyte quality and luteal function in infertile women"
  • Protective effects of melatonin against oxidative injury in rat testis induced by wireless (2.45 GHz) devices - Andrologia. 2012 Nov 12 - "In conclusion, wireless (2.45 GHz) EMR caused oxidative damage in testis by increasing the levels of lipid peroxidation and decreasing in vitamin A and E levels. Melatonin supplementation prevented oxidative damage induced by EMR and also supported the antioxidant redox system in the testis"
  • Melatonin Prolonged Release : In the Treatment of Insomnia in Patients Aged ≥55 years - Drugs Aging. 2012 Oct 9 - "Melatonin prolonged release (PR) 2 mg is approved for the treatment of primary insomnia characterized by poor sleep quality in patients aged ≥55 years in the EU and elsewhere ... Administration of melatonin PR 2 mg 1-2 h before bedtime mimics the natural secretion pattern of melatonin, thereby leading to improvements in the circadian regulation of the sleep-wake cycle. In older adults, melatonin PR 2 mg had no effect on psychomotor functions, memory recall or driving skills during the night or the next morning relative to placebo, and was associated with significantly less impairment on many of these tasks relative to zolpidem 10 mg alone or in combination with melatonin PR 2 mg. In 3-week and 6-month, randomized, double-blind clinical trials in patients with primary insomnia aged ≥55 years, melatonin PR 2 mg 1-2 h before bedtime was associated with significant improvements relative to placebo in many sleep and daytime parameters, including sleep quality and latency, morning alertness and health-related quality of life. Melatonin PR 2 mg was very well tolerated in clinical trials in older patients, with a tolerability profile that was similar to that of placebo. Short- or longer-term treatment with melatonin PR 2 mg was not associated with dependence, tolerance, rebound insomnia or withdrawal symptoms"
  • Melatonin prevents testicular damage in hyperlipidaemic mice - Andrologia. 2012 Jan 20 - "Hyperlipidaemia was induced in ApoE-knockout C57BL/6J male mice fed with high-fat diet alone (group A), or with high-fat diet and melatonin (group B) ... The results suggest that melatonin may be potential to attenuate testicular damage by improving histopathological changes and reducing germ cell apoptosis in hyperlipidaemic mice"
  • Melatonin improves the restoration of endothelium-derived constricting factor signalling and inner diameter in the rat femoral artery after cessation of L-NAME treatment - J Hypertens. 2010 Sep;28 Suppl 1:S19-2 - "Although melatonin did not accelerate blood pressure reduction, it attenuated EDCF-contractions and oxidative load and enlarged arterial diameter. These effects may be beneficial for cardiovascular protection"
  • Continuous light and L-NAME-induced left ventricular remodelling: different protection with melatonin and captopril - J Hypertens. 2010 Sep;28 Suppl 1:S13-8 - "In hypertension induced by a combination of continuous light and L-NAME treatment, melatonin and captopril protect the heart against pathological left ventricular remodelling differently"
  • Cardiac hypertrophy and remodelling: pathophysiological consequences and protective effects of melatonin - J Hypertens. 2010 Sep;28 Suppl 1:S7-12 - "Whereas melatonin did not reduce left ventricular hypertrophy in spontaneously hypertensive rats or in nitric oxide-deficient hypertension, it did have other beneficial effects, e.g. it curtailed oxidative damage to the heart that resulted in an attenuation of left ventricular fibrosis. In contrast to the findings in hypertensive rats, melatonin administration was effective in overcoming cardiac enlargement resulting from induced hyperthyroidism or chronic hypoxia exposure. In addition, in these situations, melatonin also conferred protection against free radical-mediated damage at the level of cardiomyocytes. Collectively, the results of the publications summarized herein along with numerous other published reports on other aspects of cardiovascular physiology indicate that, when damage to the heart is a result of free radicals, melatonin is clearly protective. This is not unexpected considering the now well documented potent antioxidative actions of both melatonin and its metabolites. In general, melatonin improves cardiovascular physiology and heart function"
  • Urinary melatonin and risk of incident hypertension among young women J Hypertens. 2010 Jan 19 - "During 8 years of follow-up, a total of 125 women developed hypertension. The relative risk for incident hypertension among women in the highest quartile of urinary melatonin (>27.0 ng/mg creatinine) as compared with the lowest quartile (<10.1 ng/mg creatinine) was 0.49 (95% confidence interval 0.28-0.85, P < 0.001). CONCLUSION: First morning melatonin levels are independently and inversely associated with incident hypertension; low melatonin production may be a pathophysiologic factor in the development of hypertension"
  • Melatonin Treatment for Insomnia in Pediatric Patients with Attention-Deficit/Hyperactivity Disorder (January) - Ann Pharmacother. 2009 Dec 22 - "Available data suggest that melatonin is a well-tolerated and efficacious treatment option for pediatric patients with chronic SOI and ADHD"
  • Dietary correlates of urinary 6-sulfatoxymelatonin concentrations in the Nurses' Health Study cohorts2 - Am J Clin Nutr. 2009 Aug 12 - "In multivariate analyses, we found no significant associations between the intake of various nutrients, including tryptophan and urinary melatonin concentrations. A higher intake of meat, particularly red meat, was associated with lower concentrations of aMT6s (adjusted mean concentrations of aMT6s across increasing quartiles of red meat intake were 17.9, 17.0, 18.1, and 15.3 ng/mg creatinine; P for trend = 0.02). In contrast, neither intake of poultry (including turkey) nor fish was associated with aMT6s concentrations ... Although no specific nutrients were associated with altered concentrations of melatonin, our findings raise the possibility that several specific foods, including red meat, could affect cancer risk through the lowering of melatonin concentrations"
  • The circadian melatonin rhythm and its modulation: possible impact on hypertension - J Hypertens. 2009 Aug;27 Suppl 6:S17-20 - "The chronic administration of melatonin to individuals with hypertension induces a measurable drop in night time systolic and diastolic blood pressure. Moreover, the higher the night time level of endogenous melatonin (estimated from urinary metabolite of melatonin, 6-hydroxymelatonin sulphate), the greater the reduction in arterial blood pressure at night. The implication of these findings is that melatonin may have utility as an antihypertensive agent"
  • Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats - J Hypertens. 2009 Aug;27 Suppl 6:S5-10 - "It is concluded that although melatonin, in comparison with captopril, did not reverse left ventricle hypertrophy, it reversed left ventricular fibrosis. This protection by melatonin may be caused by its prominent antioxidative effect"
  • Urinary melatonin levels and postmenopausal breast cancer risk in the nurses' health study cohort - Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):74-9 - "An increased concentration of urinary aMT6s was statistically significantly associated with a lower risk of breast cancer (odds ratio for the highest versus lowest quartile of morning urinary aMT6s, 0.62 ... Results from this prospective study add substantially to the growing literature that supports an inverse association between melatonin levels and breast cancer risk"
  • Endocrine regulation of the course of menopause by oral melatonin: first case report - Menopause. 2007 Nov 8 - "The data obtained in this case report show that melatonin administration was able to delay the characteristic endocrine changes that occur during the course of menopause"
  • Night Shift Work and the Risk of Endometrial Cancer - Cancer Res. 2007 Nov 1;67(21):10618-10622 - "Women who worked 20+ years of rotating night shifts had a significantly increased risk of endometrial cancer [MVRR, 1.47 ... obese women working rotating night shifts doubled their baseline risk of endometrial cancer (MVRR, 2.09; 95% CI, 1.24-3.52) compared with obese women who did no night work ... Women working rotating night shifts for a long duration have a significantly increased risk of endometrial cancer, particularly if they are obese. We speculate that this increased risk is attributable to the effects of melatonin on hormonal and metabolic factors"
  • Acute effect of metformin on exercise capacity in active males - Diabetes Obes Metab. 2007 Oct 29 - "A single dose of metformin does not acutely influence maximal oxygen consumption or ventilatory threshold in healthy active males. The lower lactate concentration observed during continuous exercise with metformin was an unexpected finding considering that, in the resting state, metformin has been previously associated with a modest increase in lactate concentrations"
  • Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes - Curr Med Res Opin. 2007 Sep 14 - "PR-melatonin results in significant and clinically meaningful improvements in sleep quality, morning alertness, sleep onset latency and quality of life in primary insomnia patients aged 55 years and over"
  • Effects of melatonin and rilmazafone on nocturia in the elderly - J Int Med Res. 2007 Sep-Oct;35(5):685-91 - "melatonin (2 mg/day; n = 20) or rilmazafone (2 mg/day; n = 22) for 4 weeks ... After 4 weeks' treatment, the number of nocturnal urinations was significantly decreased and the QoL score was significantly improved in both groups. There was no significant difference between the patient-reported effectiveness ratings between the two groups" - See melatonin at Amazon.com.
  • Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension - Hypertension. 2004 Feb;43(2):192-7 - "In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure"-  See melatonin at Amazon.com.
  • Melatonin-induced reduction in age-related accumulation of oxidative damage in mice - Biogerontology. 2003;4(3):133-9 - "The findings indicate that low-dose chronic administration of melatonin acts as a free radical scavenger and anti-aging agent"
  • Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled, crossover study - Arch Gen Psychiatry 2001 Nov;58(11):1049-52
  • Melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary-gonadal axis in the rat - Neuroendocrinol Lett 2000;21(4):301-306
  • Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation - Proc Soc Exp Biol Med. 2000 Oct;225(1):9-22 - "The radioprotective effects of melatonin against cellular damage caused by oxidative stress and its low toxicity make this molecule a potential supplement in the treatment or co-treatment in situations where the effects of ionizing radiation are to be minimized."
  • Evidence for a local action of melatonin on the rat prostate - J Urol 1998 Mar;159(3):1069-73 - "The results demonstrate putative melatonin receptors in the rat prostate and suggest a direct suppression by melatonin of testosterone-dependent prostate growth"
  • Bioavailability of oral melatonin in humans - Neuroendocrinology 1984 Oct;39(4):307-13 (shows that melatonin has a short half-life)