Subject: Re: Melatonin

My son has been taking Melatonin for almost 2 years. I can't say that it makes him sleep longer but he does seem to go into a deeper sleep and is less restless than normal. His neurologist recommended it and we use just a commercial brand 3 mg tablet before bed. I can't say that I've seen anything with him that would indicate he was having nightmares or bad dreams and he's always pleasant when he wakes (as long as his breakfast is ready for him). Apparently, the melatonin would have different results with people based on what their normal production of it is. I wouldn't want people not to try it based on someone else's stories. And as with most products there will always be varying results. If your Doctor/neurologist is monitoring whats being taken and there's potential for good results, I recommend trying it. As an AS parent I know I want my kid to get as much sleep as he can so I can get some benefit and get some sleep!

Regards.

Tammy (Kolade, age 10)

Subject: Melatonin "Article in Washington Post Health Magazine

Hi Everyone:

Here are some selected highlights from an article in the Tuesday, August 20, 1996, Washington Post Health Magazine. The article is titled: " Researchers Urge Skepticism on Melatonin". Subtitled: "At NIH-Sponsored Meeting, Scientists Say Claims for Hormone Are Largely Unfounded." The article was written by Caryle Murphy a Post Staff Writer.

"Meltonin is one miracle that still awaits proof. In recent years, this hormone has been touted in the popular media as a 'natural' cure for insomnia and jet lag, an enhancer of sex dirves, a preventer of cancer, even a rival to Ponce de Leon's fountain for its alleged anti-aging properties.

But scientists gathered in Washington last week rained on the parade of claims. 'Where,' these laboratory Poirots demanded 'is the evidence?".

"the unregulated sale of melatonin--the only hormone available over the counter without a prescription and without Food and Drug Administration approval--means that millions of consumers are engaged in a vast, uncontrolled experiment, as one resercher put it, whose outcome is unknown."

"One of the major concerns of health officials is that melatonin is sold over-the-counter without having been tested by the Food and Drug Administration's strict standards. The Dietary Supplement Health and Education Act of 1994 permits the sale of natural dietary suplement products, such as herbs, vitamins, amino acids and minerals, without prescription as long as their labels do not make "health" or "drug" claims. Such claims, which say a product can cure, treat or lower the risk of a disease, require FDA approval."

"The FDA is concerned because the public is looking for assurance that products like melatonin are safe and work as promised, said Mitch Zeller, FDA deputy associate commissioner for policy. And the only thing we can say on melatonin is, 'We can't tell you it's going to work as promised. And we can't tell you it's not going to work as promised. We simply don't know. Because all science is ongoing. People should be very careful."

"The scientists at last week's meeting said one of their concerns is that the over-the-counter melatonin, which is a synthetic version of the hormone, is often sold in dosages 10 times higher than what is needed to induce sleep. The higher doses raise melatonin levels in the blood to 3,000 times the normal nighttime level and can produce side effects such as hangovers, headaches, nightmares, hypothermia and the release of prolactin from the pituitary gland, which dampens sex drive in males, Wurtman said.

Most ongoing melatonin experiements use small doses of 0.1 and 0.3 milligrams. Four health food stores in the Washington area called at random reported that they sold melatonin in doeses ranging from 1 to 5 milligrams."

"Another concern raised by the NIH workshop was that the synthetic melaton being sold could have impurities. The scientists said, however, that they had not heard of any specific problems."

"A key research question involves how melatonin works. sic The Jury is still out, with differences of opinion. sic Somehow, even a low dose 'tricks the body clock into thinking dusk is earlier'"

"a paper given at the workshop by Fred W. Turek and Charles A. Czeisler was more cautious. Many of the human studies reporting that melatonin can induce sleep and/or phase shifts in circadian rhythms...have methodological problems that limit the conclusions that can be drawn."

"Carefully controlled clinical trials ...are urgently needed... and the chronic use of melatonin cannot be justified for any sleep disorder at this time, since neither the therapeutic or potential toxic effects of long-term use of this hormone--which has profound effects on the reproductive system of other mammals--are known."

Hope this doesn't confuse those interested. We haven't been "web searchers' and haven't seen an address for the Washington Post in the paper but it would seem likely to us that the Post is on the Net. If so, and anyone has the web site address they might share it so those interested might be able to read the whole article.

Carolyn & Fred Windbeck (David 28)

Subject: Re: Melatonin "Article in Washington Post Health Magazine

There was a posted article about melatonin-about a month ago-at either: http://www.nih.gov/nichd/news.html or http://www.med.jhu.edu/peds/pedspage.html The first is the National Institute for Child Health and Development, and the second is Johns Hopkins University Pediatrics Page. Deanna

Subject: Melatonin

Hi Heikki,

My friends tthat took melatonin took about 1/3 of a 3 mg. tablet. I have two female friends that have had wierd dreams every time they take it, but one male friend took it for the first time the other night and slept great with no side effects.

Corinne

Subject: Re: Melatonin

I work with two women who have taken Melatonin many times and they both say how wierd and wild their dreams are. One woman had a dream about a few friends from school and they were married and had a child ( they aren't married in real life.) anyways, in her dream they were all three murdered and she said it was as if she were really there, the blood and the bodies were so real to her that she woke up feeling as though she had just experienced that in real life. The other lady I work with has had very real sick dreams as well when taking Melatonin. Both woman take a 1.0 mg tablet and break it into thirds and take just that small piece. So I quit giving it to Coralynn as it wasn't helping her sleep and I don't want her to start getting nightmares.

Corinne

Subject: Re: Melatonin

More information please on Melatonin. How much, how often, what time??? Big article in Washington Post today and how nothing has been proven.

Anne ( mom to Susan)

Subject: Re: Melatonin

Hi-our daughter Stephanie takes 3.0mg of Melatonin about 1 hour before her bedtime every night. She has been on it for over a year and it has helped ALOT! She still has occasional weeks of waking up every night but they are less frequent since she has been on the Melatonin. My husband also takes it every night and he has not had any problems with any side effects. Recently, we went through a period of Stephanie waking up every night for about 2 weeks. I read about the Telia tea on-line and went to the natural health food store to buy it. I was not able to get the bulk herb but was able to buy a tea that included the telia flower along with other natural herbs used for sleep. Well, I am almost afraid to say it because as soon as I do she will start waking up again, but in two weeks she has only woken up two nights!! We give her the tea with ice in it about 30 mins before bed and she has been sleeping great! We still give her the Melatonin and the combination seem to be working wonders. She sleeps until 7am! I keep crossing my fingers that this works because weeks of little to none sleep makes everyone grumpy!

Sally

Subject: Re: Melatonin

Hi Anne,

Dr. Wagstaff gave 0.3 mg pure melatonin at 7.30 p.m. every night during his study. There were no apparent adverse effects, but he mentioned some possible side effects, with the anti-aging one being the most likely, yet still questionable. Another puzzle he mentioned was that it appeared as if some AS children might become resistant to melatonin. He doesn't recommend any of the preparations available in health food stores, because they include other ingredients, the effects of which may be unknown and even harmful. Melzone is 0.3 mg and pure melatonin.

Corinne - did your friends initially take a dose that was too high for them, as it is suspected that very high levels of melatonin may induce, among other things, nightmares. Do they still have nightmares ? There are huge differences between individuals as regards their natural levels of melatonin, and probably only a small addition to that would lead to adverse effects.

I've just read that Washington Post article (online). There are in fact three articles at http://www.washingtonpost.com/cgi-bin/search. To me, the main thrust seemed to be that researchers disagree on a number of issues, especially the long-term effects, and that much more research is needed. As regards Dr. Wagstaff's study, I think there is no doubt that melatonin helps most AS children. Maybe many of you would like to see his recommendations in writing, but, of course, the ultimate responsibility would rest with your Dr. (if prescription) or with yourselves (if over-the-counter).

Our experience is that the abnormal sleep pattern is also a behavioral problem, that is, it matters a lot what the previous day was like, how Liisa was treated at bedtime, and how we reacted to her awakenings at night. In a private conversation, Dr. Wagstaff said he hadn't tried to take this into account. Also, there is evidence that seizure medication and age play a role.

Here in Finland, the 1.0 mg preparation is produced and distributed by the University Pharmacy of Helsinki, which, according to our family Dr., should guarantee its safety. Still, we have another doctor who is in the process of finding out more details. It became available soon after the publication of a dissertation which showed the benefits of melatonin to aircraft crew, who suffer from jet lag, and to old people.

Heikki Taimio, dad to Liisa (6, del-) Finland

Subject: melatonin for sleep

Several of you have E-Mailed us reguarding melatonin for sleeping problems. No doctors that i have discussed this with have any suggestions for a dosage. Our son is three years old and weighs 31 pounds. Can anyone help me?

Thanks, Michelle and Ken Martin

Subject: Re: melatonin for sleep

I give Juli 2 mg of it and she's 42 lbs. It's not a prescription, but you can buy it at a health food store and I know Walgreen's here in CT has it. Try it and good luck.

Carley - mom of Juliette (9)

Subject: melatonin for sleep

Dear Michelle and Ken,

We started using health-food store melatonin (3 mg.) about a year ago, on the suggestion of Sara's neurologist. He had reports from other parents that it helped, and it did help Sara, too. His suggestion for dosage was one 3 mg tablet (we crushed them in applesauce or yogurt) about a half-hour before bedtime. If she did not fall asleep or at least get drowsy to the point where we could put her in her bed when the half-hour was up, give her another tablet. After 20 minutes or so, if she still were alert, another tablet. No more than three was his prescription.

In January, Sara joined Dr. Wagstaff's melatonin study at Childrens Hospital in Boston. In conjunction with MIT, Dr. Wagstaff's research has found that in normal children, the pineal gland begins to secrete melatonin (a sleep-inducing hormone) at the onset of darkness. The younger the child, the more melatonin is secreted. His studies of melatonin blood levels in AS kids showed much later start of secretion, some at 1 or 2 a.m. I know that if Sara had her way, she wouldn't fall asleep before midnight.

He provides us with .3 mg pure melatonin, which is the only dose Sara gets before bedtime. His theory is that this small dose will "prime" her pineal gland to get busy.

Because there is no way of knowing how much melatonin is actually in over-the-counter melatonin, you probably do need a larger dose to get the same effect. Melatonin currently on the market is not regulated by the FDA because it is considered a food supplement, not a drug. This is, again, a political issue, with a powerful lobby successfully keeping substances with unproven benefits readily available to the gullible, but also blocking availability of genuinely useful drugs in a pure form, simply because they would have to be prescribed by a physician.

The melatonin Dr. Wagstaff provides is made by Interneuron Pharmaceuticals and he says it will be made available at drug stores, not health-food or grocery stores, over the counter in the near future. The study is still going on, and the ASF recently gave Dr. Wagstaff a $10,000 grant to support this work.

I asked him about giving Sara the melatonin, not at bedtime, but when she wakens in the wee hours and has such trouble getting back to sleep. He strongly advised against this because he said it would confuse her pineal gland-secretion cycle and could really lead to a more serious problem.

And that's all I know.

Martha Sprowles

Subject: melatonin

Just wanted to thank everyone for their advice concerning melatonin for assistance in sleep. I fowarded all of this advice to my pediatrician and that prompted him to do something for us. The nurse from his office just called me and said that Dr. Davison checked with a few other doctors and now has decided that Schayne can use 1mg of melatonin 1 hour before bedtime. We are supposed to try this for a few nights and report any progress to them. Anyway, I just wanted to thank everyone!!!!

Michelle and Ken Martin (parents of Schayne age 3 del. +)

Subject: melatonin

Tonight we tried melatonin to help schayne sleep. It didn't seem to help him at all. 1mg 1 hour brfore bedtime was what we were told to give him. It took him an hour to go to sleep and he only slept for only half an hour. Then finally now at 11:00 he is just asleep. Does this sound familiar to anyone? Is there hope for us, or do we need to move on to something esls?

Michelle and Ken(Parents of Schayne 3 del.+)

Subject: Re: melatonin

Michelle and Ken, How did Schayne do through the night? Did he sleep all the way through? My daughter Taylor never goes to sleep before 11:00 - even if she is very tired. I can handle the late bedtime if she would only sleep through the night. On her bad nights, which have been every night for the past 2 1/2 weeks, she gets up between 2:00 - 4:00 for the day. We started taking Klonopin this week at bedtime (0.25 mg) and it seems to have helped. The Klonopin was also prescribed to help calm her tremoring, which has gotten worse over the last month or so (she is also on Depakene). I hope you have some success with the melatonin!

Robbin

Subject: melatonin

Dear Michelle and Ken,

Our Sara is in Dr. Wagstaff's study and doing well at getting to sleep (this is a change). Before we used Dr. Wagstaff's melatonin, Sara's neurologist suggested using it like so: one 3 mg tablet about 1/2 hr. before bedtime, then another 20 min after bedtime if child is still alert, then one final one 20 min later. I think you may have been told to give Schayne too little. Maybe whoever advised you was relying on Dr. Wagstaff's study. The problem with that is that Wagstaff uses pure melatonin, which is much more potent than what is available outside his study. Probably the three 3mg doses together have a pure melatonin content approaching the .3mg Dr. Wagstaff gives us. Because over the counter melatonin is not regulated by the FDA (it is a food supplement legally), actual melatonin content is not subject to a standard measure and probably varies widely from brand to brand and even within a brand from batch to batch.

I think you ought to give it another try, only with more melatonin. The difference in Sara's ability to fall asleep and stay asleep for about five hours is remarkable. I spent years lying on the floor next to her bed waiting for her to fall asleep, so I know about this. I hope this stuff will help you.

Martha Sprowles

Subject: Re: melatonin

In a message dated 96-09-12 00:57:48 EDT, you write:

<< do we need to move on to something esls? >>

I would like to suggest that you try the melatonin for at least a week. From my reading about it at various websites, it seems to be needed for the body to get into its natural circadian rhythm (day-night cycle). I would also suggest that you give it to him at the same time each evening, trying to create a bedtime routine. These kids seem to thrive on routines anyway.

Deanna

Subject: melantonin article

I have been reading the numerous enthusiastic reports on melantonin and I was considering trying it if Liselotte's sleeping problems were to get as bad as those of some other angels.

I stopped considering this morning when I read that melantonin has been banned by the Dutch FDA. The ban was a result of objections by a professor in fysiology on the grounds that the long term effects of the drug have not yet been investigated. The professor himself has used melantonin as an anti jetlag medicine, it was sold as such over here, and reported great results, i.e. no jetlag. The professor thinks the drug is safe as such, but perhaps not if used on a daily basis.

The article continues with the question as to why no research is being done while there obviously is a huge market for a drug that regulates one's biological rhythm. The answer is that melantonin is a hormone that is part of the human fysiology and therefore cannot be licensed. That seems straightforward enough, the results of treatment with a promising drug are not investigated because the pharmaceutical industry won't make a buck because of it.

However, according to the same fysiologist, manufacturers are trying to fabricate the hormone synthetically and then try to turn it into a derivate which can be patented and hence profitable.

This is making me a little ill, something is definitely wrong about this story.

The article also states that melantonin is regarded as a wonderdug in the U.S., that there is a melantonin hype going on and that it is supposed to do wonders against sleep disorders, cancer and even the ageing process. The professor remarks:"Everybody wants to have a good night's sleep, everybody wants to live forever, and everybody is afraid of cancer, but melantonin also regulates fertility and nobody knows what the side effects of prolonged treatment are."

This will end my contribution to the melantonin discussion until the mentioned derivates are available and provided that Liselotte will have a need for them.

I am going to put my wooden shoes on and pick some tulips in the field next to the windmill near the dike. Frank van Hof, father of Liselotte, 11 months, del+. http://www.zeelandnet.nl/people/fhof/

Subject: melantonin article

Dear Frank,

I'm just in from punching some cows, and as soon as I get my spurs off, I will give some information about melatonin.

It IS being studied in the US. The ASF just gave Dr. Joseph Wagstaff, a geneticist at Childrens Hospital in Boston, a $10,000 grant to continue his study of (guess what?) melatonin as a sleep aid in AS children. Dr. Wagstaff's address is Enders 5, Dept. of Genetics, Children's Hospital, 300 Longwood Ave., Boston, Mass. 02115. I'm sure he would send you some information on his study if you wrote him a note.

There IS a pharmaceutical company involved in commercial production of pure melatonin. It is Interneuron Pharmaceuticals, the same lab that developed Redux, the new obesity drug, and the new drug whose name I don't know which if administered soon after a stroke reduces damage from the stroke.

Obviously, I don't believe melatonin will help everyone, but it has helped Sara. I enrolled her in the study specifically because I was concerned about the purity of melatonin now available over the counter (although I would certainly go back to it in a minute if we were dropped from the study). There have been many books and magazine articles touting melatonin as a cure for everything from hangnails to impotence, but according to Dr. Wagstaff the only proven effects are to do with jetlag and sleep inducement.

Melatonin is sold in the US as a food supplement and as such is not regulated by our FDA. I don't understand how there could be any adverse side effects from a substance secreted by the pineal gland and administered in tiny amounts.

Dr. Wagstaff's study found that people with AS secrete melatonin much later in the circadian cycle than his normal subjects. This probably accounts for the terrible sleep disorders many of our children (and we the parents) suffer from. If Liselotte is sleeping relatively well, you are very, very lucky.

I also don't understand the Dutch position that because melatonin is part of human physiology it can't be licensed. There are all kinds of human by-products (so to speak) on the market, including blood derivatives like the clotting factor and insulin. The urine from Italian nuns is used to make fertility drugs--I know, I took them.

In short, a lot of this story doesn't make sense to me. I suggest that anyone concerned about safety of melatonin write to Dr. Wagstaff, and you might also want to ask the ASF executive committee why they are funding such a potentially dangerous project.

Actually, Frank, I just noticed that your daughter is only 11 months old. Sara slept through the night once, when she was six years old. Every other night of her life, and it's almost eleven years now, I have not slept more than six hours at a shot, usually more like four. I can certainly understand your concern for the safety of any substance you might give your daughter, but I believe that the information you are spreading is unduly alarmist.

Yours for a good night's sleep,

Crabby Martha Sprowles (mother of Sara 10 upd and non-sleeper)

Subject: Re: melatonin article

Hi Martha,

I was just quoting what was said in the article. Also it isn't the Dutch position that melatonin can't be patented, it just is not patentable simply because it is not a new product, but an existing human hormone. Anyone is free to make pills from it it and sell it, so pharmaceutical companies are generally unwilling to do expensive research on a drug that they can't monopolize. Says the article.

Obviously the reporter isn't aware of Dr. Wagstaff's research on the effects of melatonin on A.S. kids. I didn't mean to be alarmist about something I know very little about, and I am sure that Dr. Wagstaff can give answers to people who have questions, I just thought I'd share what my newspaper has to say about melatonin. Didn't see any harm in that, especially because it isn't said in the article that melatonin can be harmful, the professor who is quoted just says that there hasn't been enough investigation on the long term effects.

I hope nobody quits on melatonin just on the basis of an article in a Dutch paper probably written by a reporter who knows no more of melantonin than I do.

I do still think that I was right in sharing the information that melatonin can no longer be sold over here because a Dutch professor is concerned that too little is known about the long term effects of melatonin.

I understand how you feel Martha, when I asked questions about phenobarbital a couple of months ago I also got alarmist replies that turned out to be unfounded...

No hard feelings Martha? Frank van Hof, father of Liselotte, 11 months, del+.

Subject: Re: melatonin article

Dear Frank,

Of course you were right to share the information you had. I do apologize for jumping on you as I did. I think what I was really reacting to was the tulips crack; I felt there was a European conspiracy to make sure I never forgot that Heikki didn't appreciate my stupid skating Finns joke.

As I've said before, the immediacy and uncensored nature of these proceedings allow us to exchange remarks that on consideration might be left unsaid, and I think overall that's a good thing. But it does also permit me to behave very rudely to people I can't see.

No hard feelings on my part, Frank, and I hope none on yours. Chalk my nastiness up to sleep deprivation.

Martha

Subject: Melatonin

Hello everyone,

As many of you already know, the production of melatonin in the pineal gland seems to be disturbed in children with AS, and this appears to contribute to the sleep disorder. Dr. Joseph Wagstaff of the Children's Hospital in Boston has been studying the effects of a 0.3 mg dose of melatonin given to 13 AS children at bedtime. According to his presentation at the Calgary Conference, 12 of these children showed improved sleep during study, the average increase in the amount of sleep being ca. 50 % and the average time to sleep being shortened by more than 50 %. There were no apparent adverse effects, but probably seizure control improved as well.

Dr. Wagstaff will need to clear some puzzles before he can publish the study. One major problem remaining is how to get the level of melatonin elevated for longer periods of time, for it now tends to return to its normal level by 3-4 a.m..

Earlier on this list I, and someone else, had transmitted Dr. Wagstaff's news that the pure 0.3 mg preparation he was using and recommending, under the name Melzone, would have been available in the U.S. in April this year. However, it hasn't been introduced as yet, but that should happen any time now. Whoever spots it first, would do a great favor to others by announcing its arrival on-line.

Here in Finland, a 1.0 mg melatonin preparation has been available since May. (The size of the dose at these levels doesn't matter much.) We regret that it was introduced only just after Liisa had started to sleep much better. It hasn't really made any big difference - maybe it has improved her sleep somewhat, but she still tends to wake up at 4-5 a.m. for a short period. Of course, to children who normally get only a few hours of solid sleep, as well as to their parents, melatonin could work wonders.

I also heard that there would be another report by Dr. Wagstaff in the Newsletter. If it's not already in the Summer issue, could you, Kathy (Vogelsang) please try to get some of Dr. Wagstaff's enlightening graphs printed, too ?

Heikki Taimio, dad to Liisa (6, del-) Finland

Subject: Re: Melatonin

Corinne, how old is your daughter? Did the neurologist say to only do it for 4 days? What if she goes back to not sleeping? Are supposed to repeat it for 4 days again? I would like to try this and my son is 40 lbs, should I try 1/2 also?

Hilda (mother of Raffi 4.9 del -)

Subject: Melatonin

Stephanie weighs 40 lbs and takes 3 mg. of Melatonin from the natural health food store every night Also for eating, putting ketchup on things always helped her eat!

Sally

Subject: AS and melatonin

Hi everyone,

In the following are Dr. Wagstaff's replies to some questions I posted to him a few days ago.

>Dear Dr. Taimio: Thank you for your message of 17 September. I apologize for the delay in >answering- I am preparing a grant application on AS that is due October 1.

#1 Why was the number of AS children involved in your study 9 in the ASF Newsletter article, whereas it was 13 in your presentation at the Calgary Conference ?

>1. Nine children were enrolled in the study as of March 15, 1996, when the AS application >was submitted. Four additional children (including a set of identical twins) were enrolled after >March 15.

#2 We're talking here about a pure melatonin preparation and not about the health food stuff which you don't recommend. Does it matter in any way if the size of the dose varies between, say 0.3 mg and 3 mg ? For example, if the dose is too large, could the person get horrendous nightmares ?

>2. We have not compared 0.3 mg with higher doses of the melatonin preparation that we are >using, so I can not answer the question based on studies that we have done. The parents of 2 >children in the study had previously used higher doses (2.5-3.0 mg) and had discontinued the >melatonin because they did not feel that it was effective; in both cases, they felt that 0.3 mg >was much more effective than the higher doses. Whether this is dose-related or is related to >other differences in the melatonin preparations is not clear.

#3 Recently, there have been several newspaper articles, where many scientists have objected to the use of melatonin, at least on a daily basis, because its benefits have not been proven and/or its long-term effects are still unknown. How would you answer to these criticisms ?

>3. By measuring the blood levels of melatonin after giving 0.3 mg to AS>children and >comparing the peak blood levels to normal melatonin peak blood levels in children of >comparable age (from the literature), it appears that the blood levels after 0.3 mg in AS >children are in the high normal range. That is, there are some normal children whose melatonin >levels (without taking melatonin) are as high as the melatonin levels in the AS children after >taking 0.3 mg melatonin. Therefore, this dose is unlikely to have adverse effects, even with >longterm use. However, larger doses (e.g., 3.0 mg) are likely to give levels much higher than >the normal range; whether this could have adverse effects over a prolonged period is >unknown.

#4 In your study, you found that, with the 0.3 mg preparation, melatonin levels could not be kept up for the whole night. Also, at the Calgary Conference, you showed some very illuminating graphs. Could you explain this in some detail ?

>4. With the preparation of melatonin that we use, blood levels are significantly higher than >baseline (pre-treatment) blood levels for approximately 6-7 hours after administration of >melatonin. This is because of destruction of melatonin by the liver. In principle, it should be >possible to prolong the elevated blood levels by special coating of the melatonin pills, but we >do not have a preparation like that.

#5 The layman's solution to the difficulty mentioned in #4 is to give the pill later at night (e.g., at 11 p.m., rather than at 7.30 p.m. as you did) and/or increase the dose. What are the dangers in this ?

>5. The normal pattern of melatonin secretion is very low levels during the day, with an increase >starting at about 7-8 PM, reaching a peak level at 1-2 AM, decreasing to very low levels by >6-7 AM. If melatonin is administered at 11 PM, it is likely that the peak level will be delayed >and there may even be 2 peaks, the peak occurring at the normal time then a second peak >from the exogenous melatonin. This would be an unnatural situation, and I don't know if it >would have adverse effects. Administering the melatonin at 11 PM might also affect the >timing of the patient's own melatonin secretion. Giving a higher dose of melatonin might >prolong the activity, but it would also give higher peak levels; in order to prolong the activity >significantly, I suspect that the doses would need to be quite large. I have discussed the >possibility of a timed-release 0.3 mg melatonin preparation with my colleagues at MIT, and I >hope that the company with which Dr. Wurtman is associated will try to do something in that >regard.

#6 A neurotransmitter called serotonin is involved in the production of melatonin. Do you think that AS children have a more fundamental problem with serotonin, and if so, could you envisage any treatment of that ?

>6. We do not yet know the basic defect in AS, although we are making some progress in that >direction. At this point, I do not think that the sleep disorder in AS is due to melatonin >deficiency, but giving additional melatonin is able to partially overcome whatever the cause or >causes of the sleep disorder may be. Melatonin is synthesized from serotonin, but only a very >very small fraction of the body's serotonin is used to make melatonin in the pineal gland. >Impaired serotonin function is possibly associated with depression, which is not a problem for >most AS children. Please feel free to foreward this information to the online list.I hope that this >information will be helpful to the parents who subscribe to the list. If any additional questions >come up, please send them to me and I will answer- after October 1.

>Sincerely, Joseph Wagstaff, MD, PhD

As is evident from Dr. Wagstaff's answers, there still are a number of puzzles to be resolved. For U.S. onliners' information, a pure 0.3 mg preparation under the name Melzone, manufactured by Intraneuron Pharmaceuticals, should be available already, or in the very near future.

Heikki Taimio, dad to Liisa (6, del-) Finland