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Old 07-04-2010, 05:54 PM
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Lightbulb Melatonin Benefits - sleep +

LE Magazine June 2007
Melatonin

New Research Shows Impressive Health Benefits By Debra Fulghum Bruce, PhD

New research indicates that melatonin does much more than help some people sleep better. Exciting studies show that melatonin’s multifaceted effects may improve treatment outcomes in cancer patients and extend their lives. Additional applications of melatonin include guarding the nervous system against degenerative diseases—such as Alzheimer’s disease and stroke—and preventing debilitating migraines.

Melatonin is secreted from the pineal gland deep inside the brain. For more than a quarter-century, scientists have been intrigued by melatonin’s ability to coordinate the body’s physiological rhythms that help set the brain’s biological clock.

The principal factor affecting melatonin is light, which inhibits the secretion of this hormone. Darkness has the opposite effect from light, resulting in signaling to the pineal gland to increase melatonin secretion. The normal cycles of melatonin production are altered due to factors including aging, medications, and light exposure at night. While the long-term health effects of disrupted melatonin secretion are not yet fully known, some scientists have suggested that years of working nights could lead to adverse effects—even cancer.

Fortunately, melatonin supplements can safely and effectively restore balance to the body’s circadian rhythm of this important hormone—helping achieve a restful night’s sleep and keeping your biological clock ticking throughout a long, healthy life span.

Neuroprotective Benefits

Melatonin is a powerful and versatile antioxidant produced within the body. Melatonin protects both lipids and proteins against damage, and can scavenge some of the most dangerous free radicals in the body—including hydroxyl radicals and hydrogen peroxide. Unlike other antioxidants, melatonin easily diffuses into all cells, and even crosses the blood-brain barrier to protect the delicate brain.1

Unfortunately, levels of naturally produced melatonin decline with advancing age, leaving older adults with limited antioxidant protection against conditions associated with oxidative stress, particularly neurodegenerative diseases.1 Supplementing with melatonin may thus help older adults enhance their antioxidant protection against some of the most ravaging diseases of aging, such as Alzheimer’s disease, Parkinson’s disease, and stroke.

Melatonin levels are particularly low in patients with Alzheimer’s disease. Nearly half of affected individuals suffer from sleep disturbances and “sundowning”—increased confusion, agitation, and other symptoms in the afternoon and evening.2 Not surprisingly, melatonin supplementation benefits patients with Alzheimer’s disease by improving sleep and reducing late-day aggravation of symptoms. Melatonin has also been found to decrease cognitive deterioration in individuals with Alzheimer’s disease, possibly by protecting brain cells from the toxic protein, beta-amyloid.2

Melatonin may likewise play an important role in assisting patients suffering from Parkinson’s disease. Parkinson’s disease is associated with disrupted melatonin secretion in the brain, and supplemental melatonin may help improve sleep efficiency in affected adults.3

The brain can suffer dramatic, irreparable damage when an individual suffers a stroke. Utilizing animal models of stroke, scientists have found that melatonin may offer important protection against stroke-related damage and deterioration. When administered at the time of stroke, melatonin limited the area of brain tissue damage, decreased brain cell death, lessened behavioral deficits, and reduced the rate of stroke-related death. These investigators believe that melatonin’s protective actions stem from its free-radical-scavenging and antioxidant activities, and suggest that melatonin may hold promise in improving stroke outcomes in humans.4

Melatonin may help manage one of the leading risk factors for stroke—elevated blood pressure. While an earlier study reported that hypertensive men taking melatonin experienced reduced nighttime blood pressure, a newer study confirms the same benefit for women.5 In a randomized, double-blind study, 18 women
(aged 47 to 63) with either normal blood pressure or treated high blood pressure received a three-week course of slow-release melatonin (3 mg) or placebo, one hour before bedtime. Researchers recorded blood pressure readings for 41 hours at the end of the trial. While the daytime blood pressure readings remained unchanged com-pared to placebo, the melatonin treatment significantly decreased nighttime blood pressure, without modifying heart rate.6

Fighting Cancer

One of melatonin’s most important applications is in fighting a wide array of cancers, including breast and liver cancers, non-small-cell lung cancer, and brain metastases from solid tumors.7

When women with metastatic breast cancer who had failed to respond to tamoxifen received melatonin supplements (20 mg every evening), they demonstrated an improved response to the chemotherapy drug. More than one quarter of the subjects—whose disease otherwise was expected to progress rapidly—began responding to the chemotherapy treatment. Most of the women also experienced anxiety relief from the melatonin supplementation.8 Laboratory studies suggest that melatonin may help fight hormone-responsive breast cancers by inhibiting the aromatase enzyme, which is responsible for the local synthesis of estrogens.9,10

Emerging research suggests that melatonin may help fight one of the most common malignancies in aging men—prostate cancer. In the laboratory, scientists treated androgen-sensitive and androgen-insensitive prostate cancer cells with pharmacological concentrations of melatonin. Treatment with melatonin dramatically reduced the number of prostate cancer cells, while the remaining cells displayed signs of slowed replication and increased differentiation—characteristics of healthy, non-cancerous cells. Melatonin may thus hold promise against prostate cancers, whether they are hormone-sensitive or hormone-insensitive.11

Scientists conducted a meta-analysis of 10 randomized, controlled trials examining melatonin’s effects (alone or as an adjuvant treatment) on patients with various types of cancer. Supplementation with melatonin reduced the relative risk of death at one year by an impressive 34%—regardless of the type of cancer or the melatonin dosage. Importantly, no adverse effects were reported.12

In addition to its benefits for cancer survival, melatonin may also help counteract the toxicity of chemotherapy treatment. Two-hundred-fifty individuals undergoing chemotherapy for advanced cancers of the lung, breast, gastrointestinal tract, or head and neck received chemotherapy, either alone or in combination with melatonin (20 mg/day). After one year, the melatonin-supplemented individuals demonstrated a higher rate of survival, and were significantly protected against many of the side effects associated with chemotherapy, including decreased platelet count, neurotoxicity, heart damage, mouth sores, and fatigue.13

Migraine Prevention

A promising study suggests that migraine sufferers may be able to reduce the frequency and severity of their headaches by using melatonin. Researchers gave 34 migraine sufferers (29 women and 5 men) a 3-mg dose of melatonin, 30 minutes before bedtime, for three months. Of the 32 patients who finished the study, more than two thirds experienced at least a 50% reduction in number of headaches per month. Additionally, the intensity and duration of headaches decreased. The scientists believe that melatonin’s anti-inflammatory effect and free-radical-scavenging effects contribute to its headache-relieving benefits.14

Promoting Healthy Sleep

Obtaining sufficient amounts of quality sleep is an absolute necessity for good health, yet many of us experience sleep difficulties on occasion. Insomnia occurs due to a variety of factors—ranging from long hours of work or travel to sleep-disruptive conditions, such as urinary frequency and stressful events. Elderly adults may be particularly susceptible to difficulty sleeping and nighttime awakenings, due to the decline in melatonin levels associated with aging.15 Melatonin can help promote healthy sleep patterns in some people, regardless of the cause of insomnia.

A large analysis revealed several of melatonin’s sleep-enhancing benefits. Reviewing 15 studies of sleep in healthy adults, scientists noted that melatonin administration significantly reduced sleep latency (the amount of time needed to fall asleep), while boosting sleep efficiency (the percentage of time in bed spent asleep) and increasing total sleep duration.16

Men with benign prostatic enlargement often experience poor sleep due to nighttime urinary frequency. Scientists from the United Kingdom found that melatonin may offer an effective solution. When 20 older men were treated with 2 mg of melatonin each day for one month, they experienced a significant decrease in nighttime urination, and reported that their condition was less bothersome than before treatment.15

Individuals who work the night shift are often chronically tired due to difficulty falling asleep during the daytime. Supplementing with melatonin has helped improve the length and quality of daytime sleep in these individuals. These findings demonstrate an important characteristic of melatonin: the hormone exerts its hypnotic (sleep-inducing) and sedative (anxiety-relieving) effects, regardless of dosage time.7



Traveling to different time zones often leads to the fatigue and insomnia known as jet lag. Supplementing with melatonin can help prevent or reduce jet lag, particularly when traveling across several time zones. Melatonin works by helping re-synchronize the body’s circadian rhythms, helping the traveler adapt to the local time.7

Dosage and Interactions

Melatonin is used in doses ranging from 0.3-5.0 mg to promote sleep, with doses of 1-3 mg most common.17 Studies examining melatonin’s effects on cancer have utilized doses of 3-50 mg/day.7
Melatonin has a sedating effect, which may be magnified by the use of benzodiazepines or other sedating drugs such as antihistamines or antidepressants. Similarly, the use of melatonin with valerian, 5-hydroxytryptophan, or alcohol may increase sedation.17
The bioavailability of oral melatonin is increased by co-administration of the antidepressant drug fluvoxamine (Luvox®).17 Beta blockers, as well as aspirin and other non-steroidal anti-inflammatory drugs, may decrease melatonin production in the body.17

Conclusion

A factor in restorative sleep, melatonin’s benefits extend to neuroprotection and fighting cancer. Its powerful antioxidant effect offers important enhancements to the brain and nervous system, helping protect against age-related damage. Most exciting are melatonin’s benefits for cancer patients—relieving anxiety and improving survival from an array of cancers. Finally, migraine sufferers using melatonin may enjoy a vast decline in the frequency and severity of their headaches—leading to a tremendously improved quality of life.

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Old 07-05-2010, 01:56 AM
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There is a lot more to melatonin that most people realise.

Not just it's proven role in sleep disorders

Seems also to work as an anti inflammatory agent

Regulating circadian rhythm, Bright light early morning and during the day to switch OFF melatonin production and SUBDUED light evenings and AS DARK AS POSSIBLE throughout the night (to start and continue melatonin production) is the NATURAL situation our DNA evolved with.

It may indeed be contributing to (bright nightlights in kids bedrooms) why we have an obesity epidemic
Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity.
Quote:
Summary
A worldwide increase in the incidence of obesity indicates the unsuccessful battle against this disorder.
Obesity and the associated health problems urgently require effective strategies of treatment.
The new discovery that a substantial amount of functional brown adipose tissue (BAT) is retained in adult humans provides a potential target for treatment of human obesity.
BAT is active metabolically and disposes of extra energy via generation of heat through uncoupling oxidative phosphorylation in mitochondria.
The physiology of BAT is readily regulated by melatonin, which not only increases recruitment of brown adipocytes but also elevates their metabolic activity in mammals.
It is speculated that the hypertrophic effect and functional activation of BAT induced by melatonin may likely apply to the human.
Thus, melatonin, a naturally occurring substance with no reported toxicity, may serve as a novel approach for treatment of obesity.
Conversely, because of the availability of artificial light sources, excessive light exposure after darkness onset in modern societies should be considered a potential contributory factor to human obesity as light at night dramatically reduces endogenous melatonin production.

In the current article, the potential associations of melatonin, BAT, obesity and the medical implications are discussed.
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Old 07-05-2010, 03:26 AM
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Melatonin in traditional Mediterranean diets
Quote:
Compared with other industrialized countries, the lower incidence of chronic-degenerative disorders in Mediterranean populations has been emphasized in recent decades.
The health-promoting effects arising from Mediterranean dietary habits have been attributed to the large intake of plant foodstuffs rich in bioactive phytochemicals, such as melatonin.
Recently, it has been suggested that melatonin present in edible plants may improve human health, by virtue of its biological activities and its good bioavailability.
Plant melatonin, besides contributing to optimize the physiological functions regulated, in humans, by endogenous melatonin, may be involved in nutritional therapy to reduce the risk of cancer, cardiovascular and neurodegenerative diseases in western populations.
In this view, the presence of melatonin in some Mediterranean foods and beverages adds a new element to the hypothesis of health benefits associated to Mediterranean dietary patterns, although the available data are still preliminary and incomplete.
It may explain why eating a Mediterranean diet in the Mediterranean climate using foods/wine grown in that climate may not be as effective when using the same diets but with food grown under polythene in soil less compounds in more northerly latitudes.

Sun ripened outdoor grown fruit/veg/herbs may have higher anti oxidant status than those never directly exposed to natural sunlight
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Old 07-05-2010, 04:07 AM
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I would be concerned with regular use. I'm aware of precautions when supplementing with glandulars. They can cause the glands to weaken; because the glands are no longer required to produce. I know that melatonin is not a glandular; but has similar effects of substituting the activity of the pineal gland.

Melatonin is a hormone produced in the brain by the pineal gland from the amino acid tryptophan. Supplementing with tryptophan might be an alternative; or might be used on a rotating basis with melatonin.

Here are some precautions:

Quote:
Precautions:

Because of the potential for side effects and interactions with medications, people should take dietary supplements only under the supervision of a knowledgeable health care provider.
Some people may have vivid dreams or nightmares when they take melatonin. Taking too much melatonin may disrupt circadian rhythms (your “body clock”).
Melatonin can cause drowsiness if taken during the day. If you are drowsy the morning after taking melatonin, try taking a lower dose.
Additional side effects include stomach cramps, dizziness, headache, irritability, decreased libido, breast enlargement in men (called gynecomastia), and decreased sperm count.
Pregnant or nursing women should not take melatonin because it could interfere with fertility.
Some studies show that melatonin supplements worsened symptoms of depression. For this reason, people with depression should consult their doctor before using melatonin supplements.
Although many researchers believe that melatonin levels go down with age, newer evidence has brought this theory into question. People older than 65 should ask their doctor before taking melatonin supplements, so blood levels of this hormone can be monitored.

Possible Interactions:

If you are being treated with any of the following medications, you should not use melatonin without first discussing it with your health care provider.
Antidepressant medications -- In an animal study, melatonin supplements reduced the antidepressant effects of desipramine and fluoxetine (Prozac). More research is needed to know if the same thing would happen in people. In addition, fluoxetine (a member of a class of drugs called selective serotonin reuptake inhibitors, or SSRIs) can cause low levels of melatonin in people.
Antipsychotic medications -- A common side effect of antipsychotic medications used to treat schizophrenia is a condition called tardive dyskinesia, which causes involuntary movements. In a study of 22 people with schizophrenia and tardive dyskinesia caused by antipsychotic medications, those who took melatonin supplements had fewer symptoms compared to those who did not take the supplements.
Benzodiazepines -- The combination of melatonin and triazolam (Halcion) improved sleep quality in one study. In addition, a few reports have suggested that melatonin supplements may help people stop using long-term benzodiazepine therapy. (Benzodiazepines are habit-forming.)
Blood pressure medications -- Melatonin may make blood pressure medications like methoxamine (Vasoxyl) and clonidine (Catopres) less effective. In addition, medications in a class called calcium channel blockers may lower melatonin levels. Calcium channel blockers include:
  • Nifedipine (Procardia)
  • Amlodipine (Norvasc)
  • Verapamil (Calan, Isoptin)
  • Diltiazem (Cardizem)
  • Felodipine (Plendil)
  • Nisoldipine (Sular)
  • Bepridil (Vascor)
Beta-blockers -- Use of beta-blockers may lower melatonin levels in the body. Beta-blockers include:
  • Acebutolol (Sectral)
  • Atenolol (Tenormin)
  • Bisoprolol (Zebeta)
  • Carteolol (Cartrol)
  • Metoprolol (Lopressor, Toprol XL)
  • Nadolol (Corgard)
  • Propranolol (Inderal)
Blood-thinning medications (anticoagulants) -- Melatonin may increase the risk of bleeding from anticoagulant medications such as warfarin (Coumadin).
Interleukin-2 -- In one study of 80 cancer patients, use of melatonin along with interleukin-2 led to more tumor regression and better survival rates than treatment with interleukin-2 alone.
Nonsteroidal anti-inflammatory drugs (NSAIDs) -- NSAIDs such as ibuprofen (Advil, Motrin) may lower levels of melatonin in the blood.
Steroids and immunosuppressant medications -- Melatonin may cause these medication to lose their effectiveness. Do not take melatonin with corticosteroids or other medications used to suppress the immune system.
Tamoxifen -- Preliminary research suggests that the combination of tamoxifen (a chemotherapy drug) and melatonin may benefit some people with breast and other cancers. More research is needed to confirm these results.
Other -- Caffeine, tobacco, and alcohol can all lower levels of melatonin in the body.


References can be found here:
http://www.umm.edu/altmed/articles/melatonin-000315.htm
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Old 07-05-2010, 09:06 AM
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Quote:
Taking too much melatonin may disrupt circadian rhythms (your “body clock”).
Indeed it MAY also, if used sensibly at the right time of day do the opposite
Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells.

Interesting to speculate if the health benefits from drinking red wine come in part from the extra time the grapes spend in sunshine and higher melatonin content.

It's a pity they don't link the claims with direct links to the references they are relying on.
I'd like to know why they suggest melatonin production may not decline with age.
In humans, melatonin production not only diminishes with age but is also significantly lower in many age-related diseases, including cardiovascular disease
Quote:
Individuals with hypertension have lower melatonin levels than those with normal blood pressure, and the administration of melatonin reduces
blood pressure. It has been shown that melatonin reduces blood pressure in both normo- and hypertensive subjects. Melatonin has been shown to reduce the resistance of the large arteries to blood flow in adult men and young women.
See also Dr Davis Heartscanblog melatonin blood pressure
I think it is generally the case that taking endogenous nutritional supplements better is generally better than taking pharmaceutical drugs to do the same end points.

Improving sleep hygiene is clearly the place to start, knowing caffeine, tobacco, and alcohol all lower levels of melatonin in the body are obvious starting points to improve matters. I agree it's likely improving your bodies own ability to make melatonin and control melatonin as required will be more effective than the use of supplemental melatonin.
I haven't found any good evidence that worries me about melatonin's toxicity, even at high pharmacological levels.
It seems to me, at the minimal levels most people would use melatonin to improve sleep (1 to 3 mg 1 hour before bedtime), it is absolutely safe.

Long-term melatonin administration protects brain mitochondria from aging.
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