17 replies to this topic

[dumbdumb]

Hi!

My goal in using melatonin is just to help me ease into sleep, and then to make the most of my time spent sleeping, so as to feel well-refreshed upon waking. So - which kind of melatonin pill makes more sense? Sustained release or non?

I can't really figure how they would play out differently in the course of the body's melatonin roller-coaster rebounding system that swings us from drowsiness to wakefulness...

So which is the better, and why?

Thanks much!

[krillin]

I regularly use time release, since it more closely mimics the natural secretion. But when I used to have insomnia, I'd need to hit it with a sledgehammer made of 3 mg instant release. I also found that I could take the instant release in the middle of the night and not be groggy the next morning.

[LIB]

I've had much better success with time release Jarrow brand.

[Ben]

NOW Foods 1mg instant and sustained release. Half of the tablet is made to digest and enter the blood stream immediately and the other, well, you get the idea.

Has worked for me so far. I get a good nights sleep and I've always had problems in that area. I can't pin it down to the melatonin though, my sleep cycle is better as well as my sleep hygiene.

[dumbdumb]

Thanks very much for the great replies, much appreciated!

[mustardseed41]

The August edition of Life Extension magazine (not online yet) has a really great article on some newly found benefits of melatonin. Great stuff.

[pycnogenol]

Timed-release works well for me. A mere 300 micrograms 2-3 hours prior to bedtime usually does the trick. I take the Life Extension brand.

[kenj]

I take a time-released also, continually. 750mcg-1mg. Some days I get up at 4.45 so I take it rather early in the evening ~9PM to make sure I avoid any grogginess upon waking. But, don't know if it really makes a diff. now that I've taken it for a while.

[tintinet]

According to his posting at Morelife.org, Paul Wakfer is taking 30 mg of melatonin QHS.

Edited by tintinet, 20 July 2008 - 11:18 PM.

[tintinet]

According to his posting at Morelife.org, Paul Wakfer is taking 30 mg of melatonin QHS

"Increased Melatonin over several weeks from 10 mg at night to total intake of 40 mg daily spread over the day - following results of studies including recent study and correspondence with author reported at sci.life-extension."

[edward]

Wow, 30 mg, 40 mg thats a lot. Though I am having a hard time finding the amount produced daily by the pineal gland I am sure that is much more as some more major hormones are produced at a daily amount of 10-20 mg.

I currently take 3 mg timed release and 3 mg immediate release.

edit: As I have mentioned before melatonin doesn't do a whole lot to make me sleep by itself (I am definitely sleeping impaired) but I take it for its other benefits and the fact that I do feel it enhances the sleep that I get just doesn't put me to sleep.

Edited by edward, 22 July 2008 - 03:37 AM.

[krillin]

Here's some endogenous secretion and exogenous bioavailability data. A male full replacement dose would be about 415 mcg, or less than half of what I'm taking now. I may have to rethink this, since I don't need it to sleep.

Am J Physiol Endocrinol Metab. 2001 Jan;280(1):E11-22.
Melatonin secretion occurs at a constant rate in both young and older men and women.
Fourtillan JB, Brisson AM, Fourtillan M, Ingrand I, Decourt JP, Girault J.
CEMAF s.a., 86000 Poitiers, France.

The magnitude and duration of melatonin (MLT) secretion were measured over a period of 25 h with pharmacokinetic studies employing administration of D(7) MLT at midday and at midnight in two separate studies and two groups of subjects, 12 young and 11 older men and women. Plasma levels of endogenous MLT and D(7) MLT were quantified separately by use of a specific and sensitive method (gas chromatography-mass spectrometry) previously developed in our laboratory, enabling us to measure endogenous and exogenous MLT levels down to 0.5 pg/ml in plasma. In the two groups of subjects, MLT secretion occurred only at night: onset time of secretion was from 1915 to 2205 (Greenwich mean time), and offset was from 0305 to 0545. No MLT peak was observed in individual nocturnal MLT profiles that were similar to curves obtained for a rate-constant infusion. Modelization demonstrated the superimposition of observed data and simulated curves. MLT concentrations decreasing from the offset of secretion might correspond to the elimination of MLT present in the body at the end of nocturnal secretion. By use of the MLT clearance given by pharmacokinetics, the amount of secreted MLT was found to be 35.7 and 21.6 microg for men and women, respectively, and the rate of secretion was 4.6 and 2.8 microg/h, respectively. No significant gender difference was observed for these two parameters when normalized to body weight. No significant gender difference was observed for onset times of secretion or duration of secretion (7.6-8.6 h) within the two groups, or between young and older subjects.

PMID: 11120654

Biopharm Drug Dispos. 2000 Jan;21(1):15-22.
Bioavailability of melatonin in humans after day-time administration of D(7) melatonin.
Fourtillan JB, Brisson AM, Gobin P, Ingrand I, Decourt JP, Girault J.
CEMAF, 6 Avenue Mozart, 86000 Poitiers, France. labocemaf@cemaf.com

Absolute bioavailability of the neurohormone melatonin (MLT) was studied in 12 young healthy volunteers (six males, six females) after administration at midday, on two separate occasions, of 23 microg by intravenous (i.v.) infusion and 250 microg by oral solution of D(7) MLT, a molecule in which seven deuterium atoms replace seven hydrogen atoms. Exogenous (D(7)) and endogenous (D(0)) MLT were quantified simultaneously but separately by a highly specific assay: gas chromatography/negative ion chemical ionization mass spectrometry, developed in our laboratory, which enabled us to go down to 0.5 pg/mL in plasma samples. After i.v. administration, the maximum plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC) values were significantly different in male and female subjects, but there was no significant gender difference in total body clearance normalized to body weight: 1.27+/-0.20 L/h/kg and 1.18+/-0.22 L/h/kg for males and females, respectively. The apparent terminal half-life (t(1/2(z))) values were 36+/-2 and 41+/-10 min, respectively. After oral administration, pharmacokinetic parameters used to quantify bioavailability were near three-fold greater in female subjects than in males, with large inter-individual variations. The maximum plasma MLT concentration C(max)+/-S.D. was found at 243.7+/-124.6 pg/mL and 623.6+/-575.1 pg/mL for male and female subjects respectively, while the mean values for AUCs were 236+/-107 pg.h/mL and 701+/-645 pg.h/mL. The absolute bioavailability of MLT was from 1 to 37%: mean=8.6+/-3.9% and 16.8+/-12.7% for male and female subjects, respectively. Copyright 2000 John Wiley & Sons, Ltd.

PMID: 11038434

[edward]

So basically we all are taking "unnatural" amounts, which may or may not be good.

If Paul talked to the researchers who did this this study http://www.ncbi.nlm....pt=AbstractPlus which from this http://groups.google...dc693dc9b?hl=en shows he did. Then his rationale for increasing melatonin to 30 mg is hopefully based on a human scaled dosage of what the rats got. In that case we might just throw out "natural levels" and go with the science. Unnatural levels increase lifespan and decrease mitochondrial aging. I've always thought melatonin was a pretty amazing supplement. I don't know though about taking it during the day. Fine for lab animals who dont have to function but for humans I dont know.

Here's some endogenous secretion and exogenous bioavailability data. A male full replacement dose would be about 415 mcg, or less than half of what I'm taking now. I may have to rethink this, since I don't need it to sleep.

Am J Physiol Endocrinol Metab. 2001 Jan;280(1):E11-22.
Melatonin secretion occurs at a constant rate in both young and older men and women.
Fourtillan JB, Brisson AM, Fourtillan M, Ingrand I, Decourt JP, Girault J.
CEMAF s.a., 86000 Poitiers, France.

The magnitude and duration of melatonin (MLT) secretion were measured over a period of 25 h with pharmacokinetic studies employing administration of D(7) MLT at midday and at midnight in two separate studies and two groups of subjects, 12 young and 11 older men and women. Plasma levels of endogenous MLT and D(7) MLT were quantified separately by use of a specific and sensitive method (gas chromatography-mass spectrometry) previously developed in our laboratory, enabling us to measure endogenous and exogenous MLT levels down to 0.5 pg/ml in plasma. In the two groups of subjects, MLT secretion occurred only at night: onset time of secretion was from 1915 to 2205 (Greenwich mean time), and offset was from 0305 to 0545. No MLT peak was observed in individual nocturnal MLT profiles that were similar to curves obtained for a rate-constant infusion. Modelization demonstrated the superimposition of observed data and simulated curves. MLT concentrations decreasing from the offset of secretion might correspond to the elimination of MLT present in the body at the end of nocturnal secretion. By use of the MLT clearance given by pharmacokinetics, the amount of secreted MLT was found to be 35.7 and 21.6 microg for men and women, respectively, and the rate of secretion was 4.6 and 2.8 microg/h, respectively. No significant gender difference was observed for these two parameters when normalized to body weight. No significant gender difference was observed for onset times of secretion or duration of secretion (7.6-8.6 h) within the two groups, or between young and older subjects.

PMID: 11120654

Biopharm Drug Dispos. 2000 Jan;21(1):15-22.
Bioavailability of melatonin in humans after day-time administration of D(7) melatonin.
Fourtillan JB, Brisson AM, Gobin P, Ingrand I, Decourt JP, Girault J.
CEMAF, 6 Avenue Mozart, 86000 Poitiers, France. labocemaf@cemaf.com

Absolute bioavailability of the neurohormone melatonin (MLT) was studied in 12 young healthy volunteers (six males, six females) after administration at midday, on two separate occasions, of 23 microg by intravenous (i.v.) infusion and 250 microg by oral solution of D(7) MLT, a molecule in which seven deuterium atoms replace seven hydrogen atoms. Exogenous (D(7)) and endogenous (D(0)) MLT were quantified simultaneously but separately by a highly specific assay: gas chromatography/negative ion chemical ionization mass spectrometry, developed in our laboratory, which enabled us to go down to 0.5 pg/mL in plasma samples. After i.v. administration, the maximum plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC) values were significantly different in male and female subjects, but there was no significant gender difference in total body clearance normalized to body weight: 1.27+/-0.20 L/h/kg and 1.18+/-0.22 L/h/kg for males and females, respectively. The apparent terminal half-life (t(1/2(z))) values were 36+/-2 and 41+/-10 min, respectively. After oral administration, pharmacokinetic parameters used to quantify bioavailability were near three-fold greater in female subjects than in males, with large inter-individual variations. The maximum plasma MLT concentration C(max)+/-S.D. was found at 243.7+/-124.6 pg/mL and 623.6+/-575.1 pg/mL for male and female subjects respectively, while the mean values for AUCs were 236+/-107 pg.h/mL and 701+/-645 pg.h/mL. The absolute bioavailability of MLT was from 1 to 37%: mean=8.6+/-3.9% and 16.8+/-12.7% for male and female subjects, respectively. Copyright 2000 John Wiley & Sons, Ltd.

PMID: 11038434

[jagged]

I'm very interested in sleep supplements too. I tried Tryptophan for awhile and had mixed results. When I first started taking it, I had very vivid dreams, but woke up feeling more refreshed than I had in a long time.

I didn't take anything for awhile, but took Tryptophan again this week. It made my heart and mind race and I couldn't fall asleep. I was exhausted the next day. Very strange.

So now I'm back to Melatonin. With sleep and the other health benefits, it may be the best option.

I'm also looking to see what people take. 3mg looks like the standard dose, but time release makes me feel sleepy at work the next day. Anyone else have lingering effects from it?

Edited by jagged, 24 July 2008 - 09:29 PM.

[FunkOdyssey]

An important piece of information: melatonin has a half-life of only 45 minutes. IMHO sustained release is definitely the way to go, although you'll have no assurance that it is being released properly like you would with a sustained release drug that has pharmacokinetic studies to back it up.

Edited by FunkOdyssey, 24 July 2008 - 10:05 PM.

[tintinet]

For years, I've taken a 1:1 combination of regular and time release melatonin QHS. I've run out of one type or the other or both at times, but I've noticed any of 'em had any effect on my sleep quality, duration, etc.

[krillin]

Melatonin has a u-curve. 0.5 mg worked for the person in the first abstract, but not 10-20 mg. The second abstract says that they determined the dose response curve in the physiological range, which they appear to have defined as up to 300 mcg. Does anyone have access to this paper so we can see what the curve looks like?

Melatonin's effects on the eye are a mixed bag. Abstract #3 found it helped with macular degeneration, but abstract #4 says that it increases photoreceptor death at doses of 50 mcg/kg and up, even in the absence of high intensity illumination in some cases. From the full text

Surprisingly, melatonin treatment early in the dark period and without exposure to HII in male Long-Evans rats caused the most photoreceptor cell death as compared to the Day and HII exposed groups.

This paper says that melatonin's lowering of dopamine and raising of prolactin may be involved. I'm going to chicken out and back down to 300 mcg.

Chronobiol Int. 2002 May;19(3):649-58.Links
Low, but not high, doses of melatonin entrained a free-running blind person with a long circadian period.
Lewy AJ, Emens JS, Sack RL, Hasler BP, Bernert RA.
Department of Psychiatry, Oregon Health & Science University, Portland, USA.

In a previous report, we were unable to entrain one out of seven totally blind people with free-running endogenous melatonin rhythms to 10 mg of exogenous melatonin. This person had the longest circadian period (24.9 h) of the group. We now find that this person can be entrained to 0.5 mg of melatonin, but not to 20 mg. These results are consistent with the idea that too much melatonin may spill over onto the wrong zone of the melatonin phase-response curve.

PMID: 12069043

Chronobiol Int. 2005;22(6):1093-106.
Melatonin entrains free-running blind people according to a physiological dose-response curve.
Lewy AJ, Emens JS, Lefler BJ, Yuhas K, Jackman AR.
Sleep and Mood Disorders Laboratory, Department of Psychiatry, Oregon Health & Science University, Portland, OR 97239-3098, USA. lewy@ohsu.edu

The specific circadian role proposed for endogenous melatonin production was based on a study of sighted people who took low pharmacological doses (500 microg) of this chemical signal for the "biological night": the magnitude and direction of the induced phase shifts were dependent on what time of day exogenous melatonin was administered and were described by a phase-response curve that turned out to be the opposite of that for light. We now report that lower (physiological) doses of up to 300 microg can entrain (synchronize) free-running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day. The resulting log-linear dose-response curve in the physiological range adds support for a circadian function of endogenous melatonin in humans. Efficacy of exogenous doses in the physiological range are of clinical significance for totally blind people who will need to take melatonin daily over their entire lifetimes in order to remain entrained to the 24 h day. Left untreated, their free-running endocrine, metabolic, behavioral, and sleep/wake cycles can be almost as burdensome as not having vision.

PMID: 16393710

Ann N Y Acad Sci. 2005 Dec;1057:384-92.
Effects of melatonin in age-related macular degeneration.
Yi C, Pan X, Yan H, Guo M, Pierpaoli W.
Department of Fundus Diseases, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 510060 Guangzhou, China. yichang@public.guangzhou.gd.cn

Age-related macular degeneration (AMD) is the leading cause of severe visual loss in aged people. Melatonin has been shown to have the capacity to control eye pigmentation and thereby regulate the amount of light reaching the photoreceptors, to scavenge hydroxyradicals and to protect retinal pigment epithelium (RPE) cells from oxidative damage. Therefore, it is reasonable to think that the physiological decrease of melatonin in aged people may be an important factor in RPE dysfunction, which is a well known cause for initiation of AMD. Our purpose is to explore a new approach to prevent or treat AMD. We began case control study with a follow-up of 6 to 24 months. One hundred patients with AMD were diagnosed and 3 mg melatonin was given orally each night at bedtime for at least 3 months. Both dry and wet forms of AMD were included. Fifty-five patients were followed for more than 6 months. At 6 months of treatment, the visual acuity had been kept stable in general. Though the follow up time is not long, this result is already better than the otherwise estimated natural course.1,2 The change of the fundus picture was remarkable. Only 8 eyes showed more retinal bleeding and 6 eyes more retinal exudates. The majority had reduced pathologic macular changes. We conclude that the daily use of 3 mg melatonin seems to protect the retina and to delay macular degeneration. No significant side effects were observed.

PMID: 16399908

Exp Eye Res. 2008 Feb;86(2):241-50.
Influence of dietary melatonin on photoreceptor survival in the rat retina: an ocular toxicity study.
Wiechmann AF, Chignell CF, Roberts JE.
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. allan-wiechmann@ouhsc.edu

Previous studies have shown that melatonin treatment increases the susceptibility of retinal photoreceptors to light-induced cell death. The purpose of this study was to evaluate under various conditions the potential toxicity of dietary melatonin on retinal photoreceptors. Male and female Fischer 344 (non-pigmented) and Long-Evans (pigmented) rats were treated with daily single doses of melatonin by gavage for a period of 14 days early in the light period or early in the dark period. In another group, rats were treated 3 times per week with melatonin early in the light period, and then exposed to high intensity illumination (1000-1500 lx; HII) for 2h, and then returned to the normal cyclic lighting regime. At the end of the treatment periods, morphometric measurements of outer nuclear layer thickness (ONL; the layer containing the photoreceptor cell nuclei) were made at specific loci throughout the retinas. In male and female non-pigmented Fischer rats, melatonin administration increased the degree of photoreceptor cell death when administered during the nighttime and during the day when followed by exposure to HII. There were some modest effects of melatonin on photoreceptor cell death when administered to Fischer rats during the day or night without exposure to HII. Melatonin treatment caused increases in the degree of photoreceptor cell death when administered in the night to male pigmented Long-Evans rats, but melatonin administration during the day, either with or without exposure to HII, had little if any effect on photoreceptor cell survival. In pigmented female Long-Evans rats, melatonin administration did not appear to have significant effects on photoreceptor cell death in any treatment group. The results of this study confirm and extend previous reports that melatonin increases the susceptibility of photoreceptors to light-induced cell death in non-pigmented rats. It further suggests that during the dark period, melatonin administration alone (i.e., no HII exposure) to pigmented male rats may have a toxic effect on retinal cells. These results suggest that dietary melatonin, in combination with a brief exposure to high intensity illumination, induces cellular disruption in a small number of photoreceptors. Chronic exposure to natural or artificial light and simultaneous intake of melatonin may potentially contribute to a significant loss of photoreceptor cells in the aging retina.

PMID: 18078931

[Harvey Newstrom]

Time released works best for me. If I take a non-time-released product, I wake up 4-5 hours later unable to sleep.