Melatonin 3 mg and Melatonin 1 mg Source Naturals

Melatonin is a hormone secreted by the pineal gland that aids biorhythm regulation. Biorhythm is disturbed by stress, crossing time zones and changing work shifts. Melatonin production declines with age. The sustained release form of melatonin provides a slower, more physiological absorption. There are two popular Source Naturals melatonin products, 1 mg sublingual and 3 mg sustained release.


 

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Subscribe to a FREE Supplement Research Update newsletter. Twice a month you will receive an email with a review of several studies on various supplements and natural medicine topics, and their practical interpretation by Ray Sahelian, M.D. We will cover research updates on melatonin and sleep as they become available.

Good Night Rx with Melatonin for Sleep Aid
Developed by Ray Sahelian, M.D.

Good-Night-Rx with melatonin and more than a dozen herbs and nutrients for sedation helps you fall asleep and stay asleep without the side effects common to prescription sleeping pills.

Suggested Use: For restful sleep, take one capsule of Good Night Rx half an hour to three hours before sleep, preferably on an empty stomach.

High Quality products formulated by a medical doctor
Consider highly popular all natural products. These top quality products include Mind Power Rx for better mental focus and mood; Diet Rx which helps you eat less. It really does curb appetite; Good Night Rx with melatonin for better sleep; MultiVit Rx a daily comprehensive multivitamin for more energy and vitality; Joint Power Rx for healthy joints; Prostate Power Rx for a healthy prostate gland.

Functions of Melatonin hormone besides sleep aid:
1. Jet lag. Nightly doses of melatonin hormone, at 1 to 3 mg, taken one to three hours before bedtime at the new destination for a few nights may be helpful in reducing symptoms of jet lag, especially if the travel is in an Eastern direction and several time zones have been crossed. It's very difficult to know exactly the dosage of melatonin that would be effective. There is a wide range of individual response to melatonin. As a rule, a higher dose of melatonin would be taken the more time zones are crossed while traveling eastward.

2. Is a strong antioxidant. Evidence continues to accumulate regarding the antioxidant benefits of melatonin hormone. In laboratory studies, melatonin has been found to stimulate natural antioxidant systems in addition to offering protection to the DNA present within cells. While these effects have been observed primarily using pharmacological (very large) doses of melatonin, in a small number of experiments melatonin has been found to have antioxidant properties in small, physiological doses as well. The ability of melatonin in inhibiting oxidative damage has been tested in a variety of neurological diseases where free radicals have been suspected as being in part causative of the condition. Thus, melatonin has been shown to reduce amyloid protein toxicity of Alzheimer's disease, to reduce oxidative damage in some types of Parkinson's disease, to reduce brain injury when exposed to low blood or oxygen flow, and to lower brain damage due to a variety of toxins.
        Low dose melatonin treatment in mice enhances the body's natural anti-oxidant system, and this may have anti-aging properties. This study has convinced me to take 0.1 or 0.5 mg of melatonin a couple of nights a week. I have a melatonin pill of 1 mg and I take a portion of it about an hour to three hours before bed.

3. Immune system. The details are fuzzy in humans, but in cell culture and animal studies melatonin hormone has immune stimulating capabilities.

4. May have anti-tumor abilities. There's been quite a few studies with melatonin and cancer, most of them done in Italy. Most of the cancer studies have shown benefits using 10 to 40 mg of melatonin nightly. However, much is yet to be learned about this approach, and hardly any oncologists in the US are familiar with the use of melatonin as an anti cancer agent. Therefore, at this point, the use of melatonin for cancer is still experimental. However, since certain forms of cancer are ultimately fatal in many cases, it may be worthwhile to try melatonin. Your physician can easily access all the research on Medline.

5. Melatonin may have anti-aging potential due to its anti-oxidant properties. We won't know for sure for many years to come if melatonin hormone increases longevity, nor will we know in the near future the ideal dosage, timing, and frequency. In the meantime, a low dose of melatonin taken a couple of nights a week seems reasonable.

6. Dream enhancement. This could lead to vivid, enjoyable and memorable dreams or, on the flip side, vivid nightmares. Melatonin enhances REM sleep. Any dose over 0.5 or 1 mg is likely to make dreams very intense. People report nightmares on high doses of 2 to 5 mg.

7. Melatonin hormone reduces body temperature which helps with sleep.

Additional Melatonin Benefits
Melatonin reduces the frequency of nighttime visits to the bathroom in men with enlarged prostate (see study below). The melatonin dose used was 2 mg of sustained release.
May reduce blood pressure if used regularly at night.
Melatonin may prevent migraine headaches.
May improve sleep in patients with asthma symptoms.
Patients with irritable bowel syndrome were found to have fewer symptoms after taking 3 mg melatonin nightly for 2 weeks.
Children with autism may sleep better if they use this natural sleep aid.

Melatonin side effects
Melatonin has side effects, but much less so that pharmaceutical sleeping pills. A common melatonin side effect is a nightmare. Another melatonin side effect is morning grogginess. Long-term safety is not known, however melatonin thus far appears to be very safe in the short term. Vivid dreams and next day morning grogginess are common melatonin side effects on dosages greater than 0.5 mg. Prolonged use may have an influence on sex organs (see study below) and reduce libido in some users. Most pharmaceutical sleeping pills are associated with memory loss, but this does not happen to be a melatonin side effect. Overdose of melatonin is not likely to be dangerous since research shows extremely high amounts of melatonin are not fatal as pharmaceutical sleep drugs would be. Extreme grogginess would be a melatonin overdose side effect. Those with high blood pressure can use melatonin without a major contraindication since melatonin may slightly lower blood pressure.

Q. I am concerned about a long term melatonin side effect. My step daughter is 15 years old and has been taking melatonin for 7 years a few times a week. She takes 2.5mg every night. Her mother took her to a sleep physician who prescribed melatonin supplement. She sometimes has trouble getting to sleep, usually because of her imagination and the number of "stories" going around in her head. We find that when she has written the stories down, or had a lot of exercise outside, and adequate food during the day, she sleeps well. Her mother wants her to go to sleep every night at 8pm the same as her 5 and 7 year old half siblings, so gives her the melatonin pill. I am concerned about the long term side effects of high dose melatonin, especially after reading your website. She is small for her age, about 44 kg. She is almost always very groggy in the mornings, has vivid dreams, irregular periods (even after 18 months), and recurrent thrush. She is an intrinsically happy child, but increasingly has low moods and low self esteem.
   A. It's difficult to say whether the long term use of melatonin supplement is causing these problems, but it is possible.

Melatonin Dosage and Frequency guidelines
It's best not to take high dose melatonin product on a nightly basis. The following are some of my concerns:

1) Tolerance develops in some people when melatonin is used every night. After a few weeks some find that melatonin is not inducing or maintaining sleep as well as it did in the past. To avoid the creeping up of tolerance, melatonin should be used at most every other night, or preferably every third night. The dose should be the lowest amount that works, such as 1 mg or less. Some users find that a dose as little as 0.3 mg taken around 8 pm can induce sleep. It is ok to occasionally take a high dose such as 3 to 5 mg if needed, for instance jet lag or shift work changes. Melatonin is not toxic at high doses when used infrequently. New research suggests a low dose of melatonin at 0.3 mg taken earlier in the evening may be as effective as a higher dose taken closer to bedtime.
2) Tiredness, low mood, or fatigue can develop when people use melatonin every night, especially in doses more than 2 or 3 mg. Some people feel sleepy or groggy the next day with the urge to take naps.
3) We still don't know the long-term effects on the immune and hormonal systems of chronic melatonin use. Also, high doses of melatonin used nightly without breaks could possibly interfere with optimal sex drive and have an untoward influence on gonads (see study below).

Should one take the regular melatonin pills, sublingual melatonin or the time release version?
Most of the melatonin presently on the market is the regular 3 mg pill. You may want to cut this pill into a fifth or even a tenth and use this dose your first night, about an hour or two before bed. Alternatively, you can also purchase melatonin pills at 1 mg or sometimes even lower dosages are sold. If this low dose is effective, then you may keep using it as needed for sleep. If you don't feel any effect, then take a little more the following nights.
   If your main problem is falling asleep, then try the sublingual form (also available in liquid form), in the range of 0.3 to 1.0 mg, about an hour or two before bed. However, some people wake up in the middle of the night, or early morning, feeling alert. Most of these people would want to sleep a couple of hours longer. Melatonin has a short half-life and therefore is metabolized very fast and will be out of the body soon. This explains why many people wake up early.
   In order to stay asleep longer, a good option is slow-release melatonin, which is released consistently throughout the night. Slow-release (also known as sustained, time or controlled-release) melatonin will likely become more popular in the future. Another form that is useful is melatonin tea. The tea is drunk about an hour before bed. One company has added half a mg of melatonin to their tea bag.

Melatonin and Children -- Melatonin for children
The use of melatonin for a child appears to be safe as long as melatonin use is kept to no more than 2 times a week and a dose of 0.5 mg or less. Further research with melatonin and children will tell us if more frequent use is appropriate or safe.

Are Melatonin supplements over the counter reliable?
ConsumerLab.com announced in march, 2006 results from its new Product Review of Melatonin Supplements covering 29 products. Among the products selected for testing, only one failed for not properly breaking apart, not implying that it did not contain melatonin. Therefore, it appears that melatonin supplements sold in stores or on the internet appear to be true to their label. Sales of melatonin supplements in the U.S. rose 7% in 2004 to $67 million, according to Nutrition Business Journal.

Melatonin and Blood Pressure
Prolonged melatonin administration decreases nocturnal blood pressure in women.
Am J Hypertens. 2005 Dec;18(12 Pt 1):1614-8. Cagnacci A, Cannoletta M, Renzi A, Baldassari F, Arangino S, Volpe A. Department of Obstetrics Gynecology and Pediatrics, Policlinico di Modena, Modena, Italy.
The nocturnal decline of blood pressure (BP) is almost coincident with the elevation of melatonin, which may exert vasodilatating and hypotensive effects. In this study we investigated whether prolonged nocturnal administration of melatonin could influence the daily rhythm of BP in women. In a randomized double-blind study, 18 women, 47 to 63 years of age and with normal BP (N = 9) or treated essential hypertension (N = 9), received a 3-week course of a slow-release melatonin pill (3 mg) or placebo 1 h before going to bed. They were then crossed over to the other treatment for another 3 weeks. In each woman ambulatory BP was recorded for 41 h at baseline at the end of each treatment period. In comparison with placebo, melatonin administration did not influence diurnal BP but did significantly decrease nocturnal systolic (-3.77 +/- 1.7 mm Hg), diastolic (-3.63 +/- 1.3 mm Hg, and mean (-3.71) BP without modifying heart rate. The effect was inversely related to the day-night difference in BP. These data indicate that prolonged administration of melatonin may improve the day-night rhythm of blood pressure, particularly in women with a blunted nocturnal decline.

Melatonin and morning sun exposure for Alzheimer's patients
Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease.
J Am Geriatr Soc. 2008 February. Dowling GA, Burr RL, Van Someren EJ, Hubbard EM, Luxenberg JS, Mastick J, Cooper BA. Department of Physiological Nursing, University of California at San Francisco, San Francisco, California 94143, USA.
Fifty subjects (mean age 86) with Alzheimer's disease were divided in three. One group received 1 hour of natural morning light exposure (> or = 2,500 lux in gaze direction) Monday to Friday for 10 weeks and 5 mg melatonin, anther group had natural light therapy alone. Control subjects received usual indoor light (150-200 lux). Light treatment alone did not improve nighttime sleep, daytime wake, or rest-activity rhythm. Light treatment plus melatonin increased daytime wake time and activity levels and strengthened the rest-activity rhythm.

Melatonin Sleep Research Update - Melatonin Research
MIT scientists confirm that melatonin is an effective sleep aid for older insomniacs and it appears that only a small dose of melatonin (about 0.3 milligrams) is necessary for a restful effect. Taken in that quantity, melatonin not only helps people fall asleep, but also makes it easier for them to return to sleep after waking up during the night. However, most melatonin products on the market range between 1 to 5 mg. At this high dose, tolerance can develop and the melatonin receptors in the brain become unresponsive. Thereafter, melatonin becomes less effective.
     Dr Sahelian says: When I first wrote my book Melatonin: Nature's Sleeping Pill back in 1995, I cautioned users to keep at a low dose. I recommended that people not take more than 1 mg on a regular basis even though the most common dosage on the market at that time was 3 mg. It appears now that a third of a mg works better in the long run.  Back in 1995 I had personally noticed tolerance within a few days of taking 3 mg nightly. I also experienced some of the side effects of high dose melatonin, which include wonderful psychedelic dreams, but also nightmares. In addition, I felt tired and sleepy in the mornings. I know feel comfortable recommending 0.2 to 0.5 mg a few nights a week. Melatonin is best absorbed on an empty stomach. If you can only find the 1 mg product, just take about a third of it. As to the ideal time of use, it can range from 3 to 4 hours before bed to 1 hour before bed. The higher dosages of 1 to 5 mg may be used occasionally for jet lag.

Melatonin research shows it may affect the sex glands. Tests on Japanese quail showed the hormone regulates a sexual pathway believed to be involved in seasonal breeding patterns. It is likely to affect human gonads as well. Writing in the Proceedings of the National Academy of Sciences, Bentley and colleagues at Hiroshima University in Japan said they were studying melatonin's effects on a brain hormone called gonadotropin-inhibitory hormone, or GnIH. They removed all melatonin-producing organs from the birds -- the eyes and the pineal glands - and found GnIH levels fell. When they gave the birds melatonin, levels of GnIH went back up. This is important because GnIH has been found to have the opposite effect to the key hormone that primes the body for sex -- gonadotropin releasing hormone, or GnRH. In birds, switching off GnRH causes the gonads -- the testes and ovary -- to shrink as part of the birds' yearly cycle. In humans, GnRH brings on puberty.

5-Hydroxytryptophan is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C.
J Pineal Res. 2005 Jan;38(1):62-6.
Hydroxyl radicals are involved in direct damage of important biomolecules. Potent radical scavengers such as vitamin C and indoles of the tryptophan family can avert the potential damage. Melatonin and its precursor 5-hydroxytryptophan (5-HTP) were compared with water-soluble vitamin C. 5-HTP showed highest hydroxyl radical scavenging effects with a 50% inhibition concentration (IC(50)) of 1.8 mum. For vitamin C an IC(50) of 12.7 mum was measured, whereas melatonin in pure demineralized water was much less efficient (IC(50) = 724 mum). A comparison between melatonin in aqueous solution and melatonin in ethanol solution revealed that melatonin was significantly more effective in pure demineralized water.

Melatonin improves bowel symptoms in irritable bowel syndrome patients who have sleep disturbances.
Gut 2004; 53 (Suppl VI) A69
Melatonin, a sleep-promoting agent, is involved in the regulation of gastrointestinal motility and sensation. We aimed to determine if melatonin was effective in improving bowel symptoms and sleep disturbances in irritable bowel syndrome (IBS) patients. A total of 30 IBS patients (females = 17; ages, 20­64 years; constipation-predominant : diarrhea-predominant : alternating = 11:13:6) with sleep disturbances were randomly assigned to two groups receiving either melatonin 3 mg each night (n=15) or identical appearing placebo 1 tablet at night (n=15) for two weeks. Compared with patients who received placebo, those who were treated with melatonin had significantly decreased mean abdominal pain score, reduced mean bloating score, and enhanced rectal pain threshold. There was no difference in stool type, frequency of defecation, and anxiety and depression scores between the treatment groups. Data from sleep questionnaire and PSG showed that the 2-week course of melatonin did not influence sleep parameters including total sleep time, sleep latency, sleep efficiency, sleep onset latency, number of awakenings, duration of stage 1­4, REM sleep and REM onset latency. Administration of melatonin 3 mg for two weeks significantly attenuated abdominal pain and bloating, while reducing rectal pain sensitivity. These changes occurred despite the absence of improvements in sleep disturbance and psychological distress. The findings suggested that the beneficial effects of melatonin on bowel symptoms in IBS patients were independent of its action on sleep disturbances and psychological profile.

Melatonin, 3 mg, is effective for migraine prevention.
Neurology. 2004 Aug 24;63(4):757. More research is needed to determine whether melatonin is useful for migraine treatment and to find the appropriate melatonin dose and timing. Those with migraine in the meantime can use a mg of melatonin 2 or 3 nights a week.

Melatonin Improves Sleep in Asthma: A Randomized, Double-blind, Placebo-controlled Study.
Am J Respir Crit Care Med. 2004 Aug 11
Disturbed sleep is common in asthma. Melatonin has sleep-inducing activity and reportedly affects smooth muscle tone and inflammation. The aim of this study was to evaluate the effect of melatonin on sleep in patients with mild and moderate asthma. This was a randomized, double-blind, placebo-controlled study. Twenty-two consecutive asthmatic women were randomized to receive melatonin 3 mg (n= 12) or placebo (n= 10) for four weeks. Sleep quality and daytime somnolence were assessed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, respectively. Pulmonary function was assessed by spirometry. Use of relief medication, asthma symptoms and morning and evening peak expiratory flow rate (PEFR) were recorded daily. Melatonin treatment significantly improved subjective sleep quality, as compared to placebo. No significant difference in asthma symptoms, use of relief medication and daily PEFR was found between groups. We conclude that melatonin can improve sleep in patients with asthma. Further studies looking into long-term effects of melatonin on airway inflammation and bronchial hyperresponsiveness are needed before melatonin can be recommended in asthmatic patients.

Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension.
Hypertension. 2004 Feb;43(2):192-7.
Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function. Recently, the biological clock was shown to be involved in autonomic cardiovascular regulation. Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension. We conducted a randomized, double-blind, placebo-controlled, crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute (single) and repeated (daily for 3 weeks) oral melatonin (2.5 mg) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality. Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg, respectively. The treatment did not affect heart rate. The day-night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15% and 25%, respectively. A single dose of melatonin had no effect on blood pressure. Repeated (but not acute) melatonin also improved sleep. Improvements in blood pressure and sleep were statistically unrelated. In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure. Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake. The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension.

Melatonin: An Anti-Aging Hormone Supplement?
Ever since melatonin became available over the counter in 1994, it has created a lot of controversy. The medical establishment has been quite uneasy with this hormone being available without a doctor's prescription, and I remember back in the mid 1990s quite a number of articles were published in journals read by doctors warning them of potential serious side effects. This surprised me since my evaluation of the research did not indicate that melatonin was dangerous. It has been a decade since melatonin has been freely sold to the public, and to my knowledge there have not been any published studies to indicate that this hormone has caused any serious harm. In fact, more research continues to be published regarding its benefits. Numerous studies now indicate that melatonin has powerful antioxidant properties, in addition to its known hormonal activities which includes sleep inducement . A recent study published at the University of Rajasthan in Jaipur, India investigated the influence of low-dose chronic administration (0.10 mg/kg body weight/day for 3 months) of melatonin against age-induced oxidative stress in mice tissues, namely brain, liver, spleen and kidney. Sixteen-month-old mice were supplemented with melatonin for three months and then autopsied (at the age of 19 months). The results indicated that melatonin was able to significantly reduce the age-induced decline in the body's natural antioxidant system. The researchers state, "These findings indicate that low-dose chronic administration of melatonin acts as a free radical scavenger and anti-aging agent."
     Dr. Sahelian says: Research thus far is convincing that melatonin has many beneficial properties. However, it is difficult to determine the ideal dosage and frequency of melatonin use in humans. At this time it would seem safe and prudent to take a low dose, such as 0.1 to 0.5 mg of melatonin a few nights a week, particularly for those who suffer from insomnia. Melatonin is best taken on an empty stomach about 1 to 3 hours before bedtime. Since most pills come in dosages ranging from 0.5 to 3 mg, you could bite off a small portion of the pill.

Melatonin Pharmacotherapy for Nocturia in Men With Benign Prostatic Enlargement.
Drake MJ, Mills IW, Noble JG. J Urol. 2004;171:1199-1202.
Nocturia is a common condition often attributed in aging men to benign prostatic enlargement. Older adults are prone to nocturnal sleep disturbance, of which disturbed circadian rhythm may be a component since it improves with nighttime administration of melatonin. This study was designed to investigate melatonin as a potential treatment for nocturia associated with bladder outflow obstruction in older men. A total of 20 men with urodynamically confirmed bladder outflow obstruction and nocturia were entered into a randomized, double blind, placebo controlled crossover study assessing the effect of 2 mg controlled release melatonin at night on nocturia. Symptoms were assessed at baseline and after each 4-week treatment period using a frequency volume chart, the International Prostate Symptom Score and symptom problem index. Maximum urinary flow rate and post-void residual urine volume were also assessed. Baseline frequency of nocturia was 3.1 episodes per night. There were 7 men (35%) with detrusor overactivity and 10 (50%) had nocturnal polyuria. Melatonin and placebo caused a decrease in nocturia of 0.32 and 0.05 episodes per night (p = 0.07) and a decrease in the nocturia bother score of 0.51 and 0.05, respectively (p = 0.008). Nocturia responder rates (a reduction from baseline of at least -0.5 episodes per night) differed between the active medication and placebo groups (p = 0.04). Daytime urinary frequency, International Prostate Symptom Score, relative nocturnal urine volume, maximum urinary flow rate and post-void residual were unaffected by melatonin treatment. Melatonin treatment is associated with a significant nocturia response rate, improvement in nocturia related bother and a good adverse effect profile. However, it is uncertain whether the observed changes in this study are clinically significant.

Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial.
Friedrich-Schiller-University, Erfurter Strasse 35, D-07740 Jena, Germany.
Br J Dermatol. 2004 Feb;150(2):341-5.
In addition to the well-known hormonal influences of testosterone and dihydrotestosterone on the hair cycle, melatonin has been reported to have a beneficial effect on hair growth in animals. The effect of melatonin on hair growth in humans has not been investigated so far. To examine whether topically applied melatonin influences anagen and telogen hair rate in women with androgenetic or diffuse hair loss. A double-blind, randomized, placebo-controlled study was conducted in 40 women suffering from diffuse alopecia or androgenetic alopecia. A 0.1% melatonin or a placebo solution was applied on the scalp once daily for 6 months and trichograms were performed to assess anagen and telogen hair rate. To monitor effects of treatment on physiological melatonin levels, blood samples were taken over the whole study period. Melatonin led to a significantly increased anagen hair rate in occipital hair in women with androgenetic hair loss compared with placebo. For frontal hair, melatonin gave a significant increase in the group with diffuse alopecia. The occipital hair samples of patients with diffuse alopecia and the frontal hair counts of those with androgenetic alopecia also showed an increase of anagen hair, but differences were not significant. Plasma melatonin levels increased under treatment with melatonin, but did not exceed the physiological night peak. To the authors' knowledge, this pilot study is the first to show that topically applied melatonin might influence hair growth in humans in vivo. The mode of action is not known, but the effect might result from an induction of anagen phase.

Melatonin Safe in 6 Month Study
Melatonin has been recommended for the treatment of insomnia and jet lag, yet little is known about its long term effects on the body, and some in the medical community have questioned its safety. Researchers at the University of Lodz in Poland. evaluated the effects of melatonin administration on sleep and routine blood chemistry in elderly women. The study was performed on 14 women aged from 64 to 80 years. Melatonin 2 mg was given at 7 pm nightly for 6 months. Before and after melatonin treatment blood samples were taken in the morning after an overnight fast. The total blood count, glucose, total cholesterol, LDL, HDL, and triglycerides were measured by routine laboratory methods. Thirty-six percent of those on melatonin had an improvement in general sleep quality. Melatonin treatment did not influence significantly either total blood count, glucose or blood lipids levels. The researchers conclude that on the basis of this preliminary open study it seems that melatonin administration may be safe for elderly subjects.
     Dr. Sahelian says: It’s reassuring to know that blood chemistry was not affected in any significant adverse way by 6 months therapy with melatonin. On the basis of this preliminary study, it seems that elderly individuals should be quite safe if they use melatonin one to three times a week at a dose of 0.1 or 0.5 mg.

Melatonin in patients with reduced REM sleep duration: two randomized controlled trials.
Charite Campus Mitte-Universitatsmedizin Berlin, Germany.
J Clin Endocrinol Metab. 2004 Jan;89(1):128-34.
Recent data suggest that melatonin may influence human physiology, including the sleep-wake cycle, in a time-dependent manner via the body's internal clock. Rapid-eye-movement (REM) sleep expression is strongly circadian modulated, and the impact of REM sleep on primary brain functions, metabolic processes, and immune system function has become increasingly clear over the past decade. In our study, we evaluated the effects of exogenous melatonin on disturbed REM sleep in humans. Fourteen consecutive outpatients (five women, nine men; mean age, 50 yr) with unselected neuropsychiatric sleep disorders and reduced REM sleep duration (25% or more below age norm according to diagnostic polysomnography) were included in two consecutive, randomized, double-blind, placebo-controlled, parallel design clinical trials. Patients received 3 mg melatonin daily, administered between 2200 and 2300 h for 4 wk. The results of the study show that melatonin was significantly more effective than placebo: patients on melatonin experienced significant increases in REM sleep percentage (baseline/melatonin, 14.7/17.8 vs. baseline/placebo, 14.3/12.0) and improvements in subjective measures of daytime dysfunction as well as clinical global impression score. Melatonin did not shift circadian phase or suppress temperature but did increase REM sleep continuity and promote decline in rectal temperature during sleep. These results were confirmed in patients who received melatonin in the second study (REM sleep percentage baseline/placebo/melatonin, 14.3/12.0/17.9). In patients who received melatonin in the first study and placebo in the second, the above mentioned effects outlasted the period of melatonin administration and diminished only slowly over time (REM sleep percentage baseline/melatonin/placebo, 14.7/17.8/16.2). Our findings show that exogenous melatonin, when administered at the appropriate time, seems to normalize circadian variation in human physiology. Melatonin may, therefore, have a strong impact on general health, especially in the elderly and in shift workers.

Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance.
Aviat Space Environ Med. 2003 Dec;74(12):1263-70.
Modern military operations may require pharmaceutical methods to sustain alertness and facilitate sleep in order to maintain operational readiness. In operations with very limited sleep windows, hypnotics with very short half-lives (e.g., zaleplon, t(1/2) 1 h) are of interest, while with longer sleep opportunities, longer acting agents (e.g., zopiclone, temazepam (t(1/2) 4-6 hours) may be used. This study was designed to compare the effect of a single dose of zaleplon, zopiclone, temazepam, and melatonin on psychomotor performance and to quantify the post-ingestion time required for return to normal performance. METHOD: There were 23 subjects (9 men, 14 women), 21-53 yr of age, assessed for psychomotor performance on 2 test batteries (4 tasks) that included a sleepiness questionnaire. Psychomotor testing was conducted prior to, and for 7 h after, ingestion of a single dose of each of placebo, zaleplon 10 mg, zopiclone 7.5 mg, temazepam 15 mg, and time-released melatonin 6 mg. The experimental design was a double-blind cross-over with counter-balanced treatment order. Zaleplon, zopiclone, and temazepam impaired performance on all four tasks: serial reaction time (SRT), logical reasoning (LRT), serial subtraction (SST), and multitask (MT). Melatonin did not impair performance on any task. The time to recovery of normal performance for SRT during the zaleplon, zopiclone and temazepam conditions were 3.25, 6.25, and 5.25 h respectively; for LRT were 3.25, >6.25, and 4.25 h; for SST were 2.25, >6.25, and 4.25 h, and for MT were 2.25, 4.25, and 3.25 h. The recovery time to baseline subjective sleepiness levels for zaleplon, zopiclone, temazepam, and melatonin were 4.25, >6.25, 5.25, and >4.25 h, respectively. In spite of a prolonged period of perceived sleepiness, melatonin was superior to zaleplon in causing no impact on performance. The remaining drugs listed in increasing order of performance impact duration are zaleplon, temazepam, and zopiclone.

Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial.
J Am Acad Child Adolesc Psychiatry. 2003 Nov;42(11):1286-93.
To investigate the effect of melatonin treatment on health status and sleep in children with idiopathic sleep-onset insomnia. A randomized, double-blind, placebo-controlled trial was conducted in a Dutch sleep center, involving 62 children, 6 to 12 years of age, who suffered more than 1 year from idiopathic chronic sleep-onset insomnia. Patients received either 5 mg melatonin or placebo at 7 pm. The study consisted of a 1-week baseline period, followed by a 4-week treatment. Health status was measured with the RAND General Health Rating Index (RAND-GHRI) and Functional Status II (FS-II) questionnaires. Lights-off time, sleep onset, and wake-up time were recorded in a diary, and endogenous dim light melatonin onset was measured in saliva. The total scores of the RAND-GHRI and FS-II improved significantly more during melatonin treatment compared to placebo. The magnitude of change was much higher in the melatonin group than in the placebo group, with standardized response means for the RAND-GHRI of 0.69 versus 0.07 and for the FS-II of 1.61 versus 0.64. Melatonin treatment also significantly advanced sleep onset by 57 minutes, sleep offset by 9 minutes, and melatonin onset by 82 minutes, and decreased sleep latency by 17 minutes. Lights-off time and total sleep time did not change. Melatonin improves health status and advances the sleep-wake rhythm in children with idiopathic chronic sleep-onset insomnia.

Melatonin treatment for sleep disorders in children with neurodevelopmental disorders: an observational study.
Dev Med Child Neurol. 2002 May;44(5):339-44.
The study aim was to quantify melatonin -associated improvement in sleep by means of a parent-completed sleep diary during routine outpatient activity. An investigation into sleep disturbance was made at neurology outpatient appointments. Those parents who identified a problem were asked to complete a sleep diary, after which melatonin treatment was initiated. The first week of the diary was completed before melatonin treatment, the second when established on the maximum dose of melatonin required. Forty-nine patients (26 males, 23 females) aged from one to 13 years, were treated between 1997 and 1998: 28 of these returned interpretable diaries. In a further 18 patients, an assessment could be made of the usefulness of the melatonin treatment. Patients were fairly typical of those attending a tertiary centre, the most common primary diagnosis being epilepsy (n=26). Only seven patients were visually impaired. Of the 46 patients who were assessed, 34 showed an improvement with melatonin. No adverse effects were attributed to the melatonin treatment.

Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag.
University of Zurich Travel Clinic, Switzerland.
Aviat Space Environ Med. 2001 Jul;72(7):638-46.
The aim of this study was to compare the effectiveness and tolerability of a chronobiotic (melatonin) with a hypnotic (zolpidem) and the combination of both substances to alleviate jet lag symptoms associated with eastward travel. This double-blind, randomized, placebo-controlled study is based on 137 volunteers flying from Switzerland to the American continent and back (6-9 time zones). The participants either received melatonin 5 mg (n = 35), zolpidem 10 mg (n = 34), a combination thereof or placebo on the eastbound flight back to Switzerland and once daily at bedtime on 4 consecutive days after the flight. RESULTS: The self-rated sleep quality was significantly improved by zolpidem, especially during the night flight. Subjects taking zolpidem reported significantly less jet lag and zolpidem was rated as the most effective jet lag medication. However, zolpidem and the combination melatonin/zolpidem were less well tolerated than melatonin alone; adverse event reports included nausea, vomiting, amnesia and somnambulia to the point of incapacitation. Confusion, morning sleepiness and nausea were highest in the combination group. All active treatments led to a decrease of jet lag severity with zolpidem being the most effective treatment, particularly in facilitating sleep on night flights. Potential individual adverse reactions to this hypnotic have to be considered.

Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study.
Andrade C. National Institute of Mental Health and Neurosciences, Bangalore, India. andrade@nimhans.kar.nic.in
J Clin Psychiatry 2001 Jan;62(1):41-5
It has been suggested that melatonin improves sleep functioning, but this possibility has not been studied in medical populations. 33 medically ill persons with initial insomnia were randomly assigned to receive either melatonin (N = 18) or placebo (N = 15) in a flexible-dose regimen. Double-blind assessments of aspects of sleep functioning were obtained daily across the next 8 to 16 days. The mean stable dose of melatonin was found to be 5.4 mg. Relative to placebo, melatonin significantly hastened sleep onset, improved quality and depth of sleep, and increased sleep duration without producing drowsiness, early-morning "hangover" symptoms, or daytime adverse effects. Melatonin also contributed to freshness in the morning and during the day and improved overall daytime functioning. Benefits were most apparent during the first week of treatment. Melatonin may be a useful hypnotic for medically ill patients with initial insomnia, particularly those for whom conventional hypnotic drug therapy may be problematic.

Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment.
J Pineal Res. 2000 Nov;29(4):193-200.
The objective of the present study was to assess the toxicology of melatonin (10 mg), administered for 28 days to 40 volunteers randomly assigned to groups receiving either melatonin (N = 30) or placebo (N = 10) in a double-blind fashion. The following measurements were performed: polysomnography (PSG), laboratory examinations, including complete blood count, urinalysis, sodium, potassium and calcium levels, total protein levels, albumin, blood glucose, triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), urea, creatinine, uric acid, glutamic-oxalacetic transaminase (GOT), glutamic-pyruvate transaminase (GPT), bilirubin, alkaline phosphatase, gama-glutamic transaminase (GGT), T3, T4, TSH, LH/FSH, cortisol, and melatonin serum concentrations. The study was carried out according to the following timetable: Visit 0, filling out the term of consent and inclusion criteria; Visit 1, PSG, laboratory examinations, ESS, SD, melatonin serum concentrations; Visit 2, SD, melatonin serum concentrations, SE; Visit 3, melatonin serum concentrations, PSG, ESS, SE; Visit 4, laboratory examinations, SE, melatonin serum concentrations, SD; and Visit 5, PSG, ESS, SE. Analysis of the PSG showed a statistically significant reduction of stage 1 of sleep in the melatonin group. No other differences between the placebo and melatonin groups were obtained. In the present study we did not observe, according to the parameters analyzed, any toxicological effect that might compromise the use of melatonin at a dose of 10 mg for the period of time utilized in this study.

Melatonin and Cancer
Patients with advanced primary hepatocellular carcinoma treated by melatonin and transcatheter arterial chemoembolization: a prospective study.
Hepatobiliary Pancreat Dis Int. 2002 May;1(2):183-6.
To observe the clinical efficacy of transcatheter arterial chemoembolization (TACE) and TACE + Melatonin (melatonin) on inoperable advanced primary hepatocellular carcinoma. From January 1997 to January 1998, one hundred patients with inoperable advanced primary hepatocellular carcinoma were treated separately by TACE (50) and TACE+Melatonin (20 mg/d at 8:00 PM orally, 7 days before TACE)(50). The effective rates (WHO standards) of TACE and TACE + Melatonin were 16% and 28% respectively. After TACE or TACE+Melatonin, the resection rate at two-stage of TACE was 4% or 14%. The 0.5-, 1- and 2-year survival rates in the TACE group were 82%, 54% and 26% respectively; in the TACE+Melatonin group 100%, 68% and 40% respectively. The results were significantly better in the TACE + Melatonin group than in the TACE group. Melatonin could protect liver function from the damage caused by TACE.The IL-2 levels of all patients significantly increased, whereas sIL-2R expressions decreased after TACE+Melatonin as compared with the TACE group. With definite protection and treatment effect on the liver function damage caused by TACE, Melatonin can enhance the immunological activities of patients. It also can improve the effect of TACE by increasing the survival and resection rate after two-stage operation.

Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial.
J Pineal Res. 2003 Aug;35(1):12-5.
Numerous experimental data have documented the oncostatic properties of melatonin. In addition to its potential direct antitumor activity, melatonin has proved to modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity. The increase in chemotherapeutic efficacy by melatonin may depend on two main mechanisms, namely prevention of chemotherapy-induced lymphocyte damage and its antioxidant effect, which has been proved to amplify cytotoxic actions of the chemotherapeutic agents against cancer cells. However, the clinical results available at present with melatonin and chemotherapy in the treatment of human neoplasms are generally limited to the evaluation of 1-year survival in patients with very advanced disease. Thus, the present study was performed to assess the 5-year survival results in metastatic non-small cell lung cancer patients obtained with a chemotherapeutic regimen consisting of cisplatin and etoposide, with or without the concomitant administration of melatonin (20 mg/day orally in the evening). The study included 100 consecutive patients who were randomized to receive chemotherapy alone or chemotherapy and melatonin. Both the overall tumor regression rate and the 5-year survival results were significantly higher in patients concomitantly treated with melatonin. In particular, no patient treated with chemotherapy alone was alive after 2 years, whereas a 5-year survival was achieved in three of 49 (6%) patients treated with chemotherapy and melatonin. Moreover, chemotherapy was better tolerated in patients treated with melatonin. This study confirms, in a considerable number of patients and for a long follow-up period, the possibility to improve the efficacy of chemotherapy in terms of both survival and quality of life by a concomitant administration of melatonin. This suggests a new biochemotherapeutic strategy in the treatment of human neoplasms.

Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations.
Anticancer Res. 2003 Mar-Apr;23(2C):1951-4.
Recent advances in immunobiological knowledge have suggested the possibility of enhancing the therapeutic activity of various chemotherapeutic agents by a concomitant administration of anti-oxidant drugs and/or immunomodulating neurohormones. In particular, the pineal neurohormone melatonin (Melatonin), which is able to exert both antioxidant and immunomodulating effects, has been proven to enhance the efficacy of various chemotherapeutic drugs, namely cisplatin, anthracyclines and 5-fluorouracil, whereas at present there are no data about its possible influence on cytotoxic drugs effective in the treatment of colon cancer other than 5-fluorouracil, such as irinotecan (CPT-11). The present study was performed to evaluate the influence of a concomitant administration of Melatonin on CPT-11 therapeutic activity in metastatic colorectal cancer. The study included 30 metastatic colorectal cancer patients progressing after at least one previous chemotherapeutic line containing 5-fluorouracil, who were randomized to be treated with CPT-11 alone or CPT-11 plus Melatonin. According to a weekly low-dose schedule, CPT-11 was given i.v. at 125 mg/m2/week for 9 consecutive weeks. Melatonin was administered orally at 20 mg/day during the dark period of the day. No complete response was observed. A partial response (PR) was achieved in 2 out of 16 patients treated with CPT-11 alone and in 5 out of 14 patients concomitantly treated with Melatonin. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with CPT-11 alone and in 7 out of 14 patients treated with CPT-11 plus Melatonin. Therefore, the percent of disease-control achieved in patients concomitantly treated with Melatonin was significantly higher than that observed in those treated with chemotherapy alone (12 out of 14 vs 7 out of 16, p < 0.05). The only important toxicity was diarrhoea grade 3-4, which occurred in 6 out of 16 patients treated with CPT-11 alone and in 4 out of 14 patients treated with CPT-11 plus Melatonin, which required a 50% dose reduction. However, taken together, patients treated with CPT-11 at 50% of the planned dose showed a percent of disease control comparable to that achieved in patients who had no dose reduction (6 out of 10 vs 13 out of 20). This preliminary study shows that the efficacy of weekly low-dose CPT-11 in pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily administration of the pineal hormone Melatonin, according to the results previously reported for other chemotherapeutic agents. Moreover, since the dose reduction of CPT-11 does not influence its efficacy, the dose of CPT-11 for successive studies might be not greater than 70 mg/m2.

Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms.
Nat Immun. 1998;16(1):27-33.
The possibility of natural cancer therapy has been recently suggested by advances in the knowledge of tumor immunobiology. Either cytokines such as IL-2, or neurohormones, such as the pineal indole melatonin (Melatonin), may activate anticancer immunity. In addition, immunomodulating substances have also been isolated from plants, particularly from Aloe vera. Preliminary clinical studies had already shown that Melatonin may induce some benefits in untreatable metastatic solid tumor patients, whereas, for the time being, no clinical trial has been performed with aloe products. We have carried out a clinical study to evaluate whether the concomitant administration of aloe may enhance the therapeutic results of Melatonin in patients with advanced solid tumors for whom no effective standard anticancer therapies are available. The study included 50 patients suffering from lung cancer, gastrointestinal tract tumors, breast cancer or brain glioblastoma, who were treated with Melatonin alone (20 mg/day orally in the dark period) or Melatonin plus A. vera tincture (1 ml twice/day). A partial response (PR) was achieved in 2/24 patients treated with Melatonin plus aloe and in none of the patients treated with Melatonin alone. Stable disease (SD) was achieved in 12/24 and in 7/26 patients treated with Melatonin plus aloe or Melatonin alone, respectively. Therefore, the percentage of nonprogressing patients (PR + SD) was significantly higher in the group treated with Melatonin plus aloe than in the Melatonin gorup. The percent 1-year survival was significantly higher in patients treated with Melatonin plus aloe. Both treatments were well tolerated. This preliminary study would suggest that natural cancer therapy with Melatonin plus A. vera extracts may produce some therapeutic benefits, at least in terms of stabilization of disease and survival, in patients with advanced solid tumors, for whom no other standard effective therapy is available.

Melatonin Questions & Answers
I've been taking melatonin for about 6 weeks with great success. I take a combination of the lozenge type and the time released. I've found that I can take it every 4 days because of the carry over effect. The results have been wonderful. Then suddenly last week, out of the blue, it seemed like the melatonin just stopped working. It seemed to have the opposite effect upon me, rather than putting me to sleep, I was awake all night. Now I'm back where I was at the beginning with my sleep problems. What happened? Things were going so well. Do I just need a break from the melatonin for a couple of weeks? On the night that I'd been taking the melatonin, I take a total of up to 20 milligrams throughout the night. I've tried a lower dosage, but it had no effect.
     A. Tolerance could have developed. Taking a break for 2 or 3 weeks followed by using it less frequently is an option.

Q. I have read with interest some of your articles on melatonin for insomnia. I can lie awake most of the night and never fall asleep. I will eventually fall asleep sometime after 4 a.m., but awaken around 8:30 a.m. and not be able to sleep anymore. I'm trying to find the correct time and dosage for taking the meltonin. I started out with a 1 mg. of the regular type of melatonin and found it didn't do anything. I increased it to 3 mg. and found I do fall asleep, but it's usually around 2 a.m. I've been taking it at different times of try and figure out what the best time to take it. I've taken it between an hour to an hour and a half before going to bed with the same results. Sometimes I don't realize I've been asleep until I wake up and remember some of the dreams I've had. Is that normal with melatonin? If I fall asleep, say around 2 a.m., I'll sleep until 7:00 or so, then am able to fall asleep until about 8:30, when I get up. I would like to be able to fall asleep earlier. I've read about the different types of melatonin; sublingual, time released, and the regular (which I take). Should I try a different type of melatonin or try taking it earlier in the evening, say around 7 or 8 at night, then more closer to bedtime?
     A. Melatonin, unlike pharmaceutical sleeping pills, is not consistent in providing sleep. You have to try by trial and error which dosage of melatonin works for you and how many hours before bed is best. For instance, in some people, a third of a mg taken 3 to 4 hours before bed works better, whereas for others, 1 to 3 mg taken an hour or two before bed is best. The problem with the higher amount of melatonin is that it causes vivid dreams. Also, I prefer to use melatonin no more than 2 or 3 times a week in order to avoid potential tolerance. I prefer the sustained release, others prefer sublingual melatonin.

Q. You have a very informative newsletter. I am a scientist so appreciate the objectivity in reporting and interpretting results of scientific studyies. Perhaps you could provide links to some of the articles, or at least references? My question relates to melatonin. I have sometimes problems falling asleep at night sometimes. I've read your webpage and you provide good advice, but unfortunately, alot of the suggestions you make only work if you do them well before bedtime and also with some conisistency. I've found that I often start thinking late at night and have a hard time settling down sometimes (or else I will wake up bcs of a noise or some distrubance and can't fall back to sleep). I have found that melatonin is very effective for me, but was wondering about dosage and side-effects. I read somewhere (perhaps on your website?) to limit dosage to 1mg and also not take more than a couple time a week at most. I once had a doctor who said he was a sleep specialist make a remark about melatonin affecting sterility (and sexual arousal)? I wasn't sure if he was serious or not, but am concerned about any such side effects. Can you shed some light on this?
     A. Each person is unique in their response to melatonin, dosage, frequency of use, hours before bedtime for best effect, etc. it is possible that high doses over prolonged periods could cause the side effects you mention, but occasional use 2 times a week should not be a problem at all.

Q. I am currently taking an average of 1mg of melatonin almost every night and have been for nearly 5 years. I am 45 years old. I realize that long term use of melatonin is not conclusive. I'm afraid I have been making a potentially very bad mistake taking it as much as I have. Given the information we have to work with, would you recommend I reduce melatonin or even discontinue my use? What, if any, health risk have I subjected myself to with this prolonged use? I have not noticed any side effects from melatonin use of 1 mg for 5 years.
     A. We have not seen any human melatonin studies longer than a few months so we do not know the 5 year melatonin side effects, if any. There are some positive effects from melatonin use, such as antioxidant protection and perhaps anti-tumor activity, but we do not know the long term effects on the immune system, reproductive system, or effects on other hormones and glands. We are not in a position to make any individual recommendations as to what you should do. That is your decision in consultation with your health care provider..

Q. I have been taking melatonin for several years before bedtime (usually a 3mg dose a couple times a week).  First, I’ve noticed that I’ve had to increase the dosage initially from 1 mg to 3mg over the course of about a year to maintain its effectiveness.  I’ve read you website and you recommend not taking more than 3mg – which I generally do not.  I have a question regarding negative side-effects of melatonin on sex-drive and fertility (for males).  I once asked a doctor (who said he was a specialist in sleep disorders) about the side effects of taking melatonin.  He made some off-the-cuff comments about melatonin being fine to take if you don’t mind going sterile after a few years.  I thought he was joking, but noticed in your website that you mention reduced sex-drive and some other ambiguous effects on reproduction/fertility.  Is there any evidence to back this up?  I have noticed a correlation with reduced sex-drive (including intensity of orgasm) when I take high or frequent doses of melatonin but am not sure this is not just related to general aging (I’m 39 now and have been taking melatonin since about my early 30’s).  Are things like sperm count and sperm viability affected?
     A. We have not come across any specific long-term studies regarding the role of melatonin in male sexuality or fertility. Anecdotal reports have suggested that there may be a libido decrease in some users with long term melatonin use but this is difficult to confirm. The dose of melatonin may influence each person's response. A few rodent studies indicate that low dose melatonin actually enhances sexuality.
         Since we don't have a full understanding of chronic melatonin use and libido in men, a good option is to stop melatonin use for a month or two in order to see if libido returns. Please keep us up to date on your response.

Q. I have read your statements about the use of melatonin. You say it should only be used maybe once or twice a week. What I don't understand is if your own body produces (or tries to produce) melatonin daily on its own, how can it be harmful if you help it along on a regular basis, like even daily? Is the melatonin taken by mouth different from that which your own body produces? For that matter, why do you recommend taking a "vitamin supplement holiday" periodically? After all, we continue to take in vitamins daily from our food without apparent harm? 'Tis a puzzlement.
     A. The body usually produces only a small fraction of the melatonin that may be ingested by pill. Also, the body produces it gradually   throughout the evening and night as opposed to a sudden ingestion of a 3 mg pill. Although the body produces a number of different hormones and substances, this does not mean that indiscriminate use of high doses of these hormones is safe, the body usually has developed a fine balance and upsetting the balance can sometimes get us into trouble.
    As to multivits, we ingest quite a variety of vitamins and minerals through our diet, often in small, well balanced proportions. Many multivits have high amounts of certain vitamins and minerals and not necessarily in the same balance the body is used to through foods. Hence, to be cautious, I find a reasonable approach is to take breaks. Other doctors or scientists certainly have different opinions.

Q. Are there any side effects to mixing alcohol and melatonin? Sometimes I may have a beer or two and then later take a melatonin when bed time approaches. Does alcohol lessen the effectiveness? Strengthen it?
     A. Alcohol helps induce sleep, however, there is often a rebound effect a few hours later with waking up in the middle of the night with difficulty falling back asleep. I think one drink of alcohol combined with one mg of melatonin should be safe, but two or more drinks along with more than 1 mg of melatonin may interfere with clarity of thinking or induce vivid dreams. However different people respond differently.

Q. Will taking melatonin help me live longer?
     A. Maybe, maybe not. There are some theoretical reasons why this could happen, but we don't know for certain.
1) Melatonin often provides for a deeper sleep. The positive influence of melatonin on deep, restorative sleep could alone account for a longer life span.
2) It's probably a good antioxidant. The advantage of melatonin over other antioxidants is that it is both water and fat soluble, meaning it goes into almost all cells and all parts of the body. Melatonin's disadvantage is that it has a short half-life and it's antioxidant benefits may only last overnight, as opposed to vitamin E, which is stored in tissues and protects all day long.
3) Perhaps immune system improvement. Interestingly, some people report that since they've been on melatonin, they don't catch colds and infections as much as they used to. These stories are, of course, anecdotal, and we don't have any published human studies on the influence of melatonin on the immune system in the long-term.

Q. I suffer from chronic insomnia, yet when I had my melatonin levels checked, the levels were normal throughout the day and very HIGH (almost off the charts) at night. My doctor is very puzzled by this and I am wondering if you have ever heard  of an occurrence of HIGH melatonin levels associated with chronic insomnia.
     A. Melatonin is only one of the factors involved with sleep. Daytime physical activity is one of the most important things you can do to help you sleep. I don't find melatonin levels to be that helpful in assessing causes of insomnia.

Q. A number of years ago i purchased your excellent book on melatonin. What is unclear to me is that some forms of arthritis are indicated to be the result of an auto-immune condition. Melatonin is indicated that it is not To be taken in the case of auto-immune conditions. Would a low dose of say 1 mg per day with a person with arthritis be the wrong thing to do because It might aggravate the condition?
     A. When I wrote the melatonin book in 1995, some studies had mentioned that melatonin enhanced immune function and thus this required that a caution be placed in the book that those with autoimmune conditions should be careful about the use of this hormone. However, since then, there haven't been any significant mentions of melatonin's influence on autoimmune conditions. It would appear at this point that the use of 1 mg of melatonin a couple of times a week should be fine for those with rheumatoid arthritis, and more frequent use should not interfere in those who have osteoarthritis.

Q. My children are very hyperactive and have trouble falling asleep. I tried Melatonin and it worked great. Now I hear it has negative long term effects.
     A. Melatonin appears to be very safe when used occasionally such as once or twice a week. I would recommend limiting the dose in children to no more than 0.3 mg and no more than once or twice a week until additional information is available regarding safety of melatonin in children.

Q. When is the best time to take the time released melatonin?
     A. Each person is unique in their melatonin requirement, for some melatonin taken an hour before sleep works, for others it could be 3 hours before bedtime. Best way to find out the ideal melatonin dose and time of use is through trial and error.

Q. n l998 Walter Pierpaoli and William Regelson's book 'The Melatonin Miracle' persuaded me to take Melatonin for eye protection. They advocate increasing dosage with age and at 75 3.5 to 5mg which I was then. I had been taking 6mg daily until five years years ago when my Opthalmologist said I had cataracts forming so I increased the dose to 9mg daily. At 82 I enjoy a full sex life and sleep well with dreams but no vivid ones or nightmares or cataracts. The salient point in your Melatonin question and answers is 'melatonin affects different people differently' After eight years daily dosage I am enjoying still a full and healthy life.

Q. I take 100 milligrams of 5-htp daily. How safe is it to also take milligrams of melatonin at night? I am going through menopause and the
melatonin helps with the night sweats and sleeping and the 5-htp helps throughout the day. Thank you for your website, very informative.
     A. Thank you for your email, but this is a personal type question that we can't say if it is safe or not for you. We do suggest reading the cautions on each of these supplements as presented on the website. See 5-HTP on cautions and usage.

Q.  Do you have a herbal (vegetarian) melatonin? I understand from one of my colleagues that black cherries, for example, have either melatonin or an analogue.
     A. As far as they know, it is difficult to extract enough melatonin from fruits or other sources. It is much easier to make it synthetically, and it is not difficult to make melatonin in the laboratory.

Q.  I would like to give you feedback to the usage of melatonin. What I have noticed about melatonin, since I have been taking it, is that the higher the dosage the greater the benefits. I have initially taken 3mg, but with no real results. I decided to increase the dosage cautiously every week and after 30mg daily I noticed a REMARKABLE improvement in my physical conditions and mood. I decided to do that after reading your interview with Dr. Walter Pierpaoli in the final section of your book called: "Melatonin Nature's Sleeping Pill". I have not since then increased the dosage. But this small incident "proved" to me that the key lies in the dosage ! I got the same kind of benefits with vitamin C after increasing the dosage considerably. This may be a very important information or not. I"ll leave it to you and your colleagues in the scientific field, "the brains", to decide what to do with this information. Thank you very much for writing the book "Melatonin Nature`s sleeping Pill"
   A. There may be certain benefits with supplements that occur at higher dosages, but the potential side effects can increase dramatically when these high dosages are continued.

Q. I have chronic lymphocytic leukemia and Type 2 diabetes. Would it hurt me to take melatonin for one week to get my sleeping habits corrected? I would start with a low dose.
   A. Short term use of melatonin for sleep should be fine but I don't know what kind of effect, beneficial or harmful, melatonin use would have with long term use.