Melatonin study.

[Peter LeDrew]

Anat Rec (Hoboken). 2008 Apr;291(4):448- 55.
Melatonin is as effective as testosterone in the prevention of soleus muscle atrophy induced by castration in rats.
Oner J, Oner H, Sahin Z, Demir R, Ust?nel I.
The purpose of this experiment was to compare the weight, insulin-like growth factor-I (IGF-I) expression, and ultrastructure of the soleus muscle in growing castrated rats treated with testosterone or melatonin. In this study, adult male Wistar albino rats were used. The groups were arranged as sham, castrated, and testosterone- or melatonin-injected groups after castration. The soleus muscle samples were fixed in Bouin's solution for immunohistochemistr y, and in 2.5% gluteraldehyde in 0.1 M phosphate buffer (pH 7.4). Whereas castration reduced the soleus weight and fiber diameter, testosterone and melatonin administration increased them. IGF-I immunostaining observed in the satellite cells and periphery of the myofibers was least intense in the castrated group. Strong staining of IGF-I was observed in the testosterone- and melatonin-administe red groups. The ultrastructure of the soleus muscle in castrated animals showed the important ultrastructural modifications related to degeneration. In these groups, degenerative mitochondria, glycogen clusters under the sarcolemma, irregular Z lines, and loss of lamina externa were observed. The ultrastructure of myofibrils in the testosterone- and melatonin-injected groups was similar to that in sham groups in view of structure. In conclusion, we suggest that melatonin is as effective as testosterone in the prevention of atrophy induced by castration through the IGF-I axis. 2008 Wiley-Liss, Inc

[Rootoo]

Will keep that in mind if I lose my balls....

[Dr.Dave1]

interesting study. It would be nice to see some numbers instead of vague info regarding the treatment conditions and vague remarks about the results. Also it looks like they injected the melatonin . . . this could be very different from taking it by mouth. Unfortunately I do not have access to this journal; if anyone finds it post up some numbers if you don't mind.

[Peter LeDrew]

Will keep that in mind if I lose my balls....

Obviously you do not get the point and the science. Why waste your time in the science section then?

[leonidas300]

melatonin may be useful during PCT, which is something I had not previously considered.

[Fisher33]

Anat Rec (Hoboken). 2008 Apr;291(4):448- 55.
Melatonin is as effective as testosterone in the prevention of soleus muscle atrophy induced by castration in rats.
Oner J, Oner H, Sahin Z, Demir R, Ust?nel I.
The purpose of this experiment was to compare the weight, insulin-like growth factor-I (IGF-I) expression, and ultrastructure of the soleus muscle in growing castrated rats treated with testosterone or melatonin. In this study, adult male Wistar albino rats were used. The groups were arranged as sham, castrated, and testosterone- or melatonin-injected groups after castration. The soleus muscle samples were fixed in Bouin's solution for immunohistochemistr y, and in 2.5% gluteraldehyde in 0.1 M phosphate buffer (pH 7.4). Whereas castration reduced the soleus weight and fiber diameter, testosterone and melatonin administration increased them. IGF-I immunostaining observed in the satellite cells and periphery of the myofibers was least intense in the castrated group. Strong staining of IGF-I was observed in the testosterone- and melatonin-administe red groups. The ultrastructure of the soleus muscle in castrated animals showed the important ultrastructural modifications related to degeneration. In these groups, degenerative mitochondria, glycogen clusters under the sarcolemma, irregular Z lines, and loss of lamina externa were observed. The ultrastructure of myofibrils in the testosterone- and melatonin-injected groups was similar to that in sham groups in view of structure. In conclusion, we suggest that melatonin is as effective as testosterone in the prevention of atrophy induced by castration through the IGF-I axis. 2008 Wiley-Liss, Inc

Nice post Peter!

[Peter LeDrew]

melatonin may be useful during PCT, which is something I had not previously considered.

Great point!
Might help maintain an anabolic state even in a low testosterone environment, if this holds up in humans.

"In conclusion, we suggest that melatonin is as effective as testosterone in the prevention of atrophy induced by castration through the IGF-I axis."

Any possible benefit to increasing IGF expression is sure to raise the eyebrow of any serious bodybuilder. My personal feeling on melatonin is that a low-dose 300mcg time-released supplement is worth trying for not only improved sleep, but many other benefits.

[DRP7]

melatonin may be useful during PCT, which is something I had not previously considered.

I believe that melatonin has a plethora of benefits. But I have some doubts whether PCT would be the right situation to take melatonin:

Neuro Endocrinol Lett. 2000;21(4):301-306.

Melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary-gonadal axis in the rat.

Yilmaz B, Kutlu S, Mogulko? R, Canpolat S, Sandal S, Tarak?i B, Kelestimur H.

Firat University, Medical School, Department of Physiology, Department of Histology, 23119 Elazig, Turkey. b.yilmaz@excite.com

OBJECTIVES: We have investigated the changes in serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone levels together with testicular histology in both pinealectomized (PNX) and intact rats. MATERIAL and METHODS: Twenty-one animals were PNX and allowed to recover for two months. Group I was assigned as PNX, group II PNX+melatonin and group III PNX+Human Chorionic Gonadotropin (HCG). Rats in group IV were sham PNX (S-PNX). An intact group of animals was s.c. injected with melatonin (0.5 mg/kg/day), another group with a combination of melatonin+HCG (5000 IU/kg/day) for seven days. Controls received saline alone (1 ml/kg). At the end, all animals were decapitated and blood samples obtained. Serum LH and FSH levels were determined by Radioimmunoassay, testosterone values by Chemiluminescent Enzyme Immunassay. Testicular tissue was collected and processed for light microscopy. RESULTS: Serum LH levels were increased following PNX, but no such increases were seen in testosterone. In the PNX+melatonin group, serum LH and testosterone values were found to be similar to those of S-PNX group. HCG supplementation to PNX rats resulted in significant decreases in LH (p<0.005), but increased testosterone levels (p<0.001). Melatonin administration to intact animals significantly decreased both LH and testosterone levels (p<0.01). Co-administration of HCG+melatonin resulted in significant decreases in LH (p<0.001) and increases in testosterone levels (p<0.01). Serum FSH values did not show significant changes among groups. Only HCG administration significantly reduced FSH levels (p<0.01). CONCLUSIONS: Our results suggest that melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary axis. There is a functional relationship and feedback regulation between the pineal gland and the testes.

PMID: 11455362 [PubMed - as supplied by publisher]

Moreover, the interaction between melatonin and HPTA appears to be pretty complex, as the following article illustrates:

Int J Androl. 2005 Aug;28(4):234-40.Related Articles, Links
Altered melatonin secretion in hypogonadal men: clinical evidence.

Kumanov P, Tomova A, Isidori A, Nordio M.

Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria. phkumanov@lycos.com

The pineal gland, through the rhythmic production of melatonin, seems to play an important role in the control of the reproductive function of many vertebrate species. In contrast, the effects of the pineal gland in humans and the relationship between gonadotropins and melatonin secretion are not yet clarified. On the basis of these considerations, the aim of the present study was to clarify whether melatonin serum concentrations were altered in males with different hypothalamo-pituitary-gonadal disturbances, in comparison to normal individuals. We have studied 36 individuals divided into three groups according to their gonadotropin status: normals, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism. They were submitted to blood sample withdrawal at 03.00, 11.00 and 19.00 h for melatonin determination according to a radioimmunological method, without extraction of the sample. The results obtained in the present study suggest the existence of an interaction between the pituitary and the pineal gland. In fact, in the case of hypersecretion of gonadotropins, nocturnal melatonin release is reduced, while night melatonin secretion is increased in the opposite situation (hypogonadotropic hypogonadism). Both these endocrine pathologies are characterized by a reduced sexual steroid secretion; for that reason, this reduction cannot be regarded as responsible for the two opposite dysfunctions of melatonin release. In conclusion, our study shows that darkness-dependent release of melatonin in males with hypogonadotropic hypogonadism is significantly higher in comparison with the healthy men, while it is significantly reduced in patients with hypergonadotropic hypogonadism. A strong significant negative correlation is also found between gonadotropins and melatonin release.

Finally, you should not forget that melatonin stimulates prolactin release, which is the very last thing someone during PCT wants to have.

prolactin = lactation + suppression of testosterone!

[leonidas300]

Fine, way to burst my bubble Dr.

[DRP7]

Fine, way to burst my bubble Dr.

oh, I didn't intend this. actually, I believe that the research on melatonin shows that its interactions with HPTA are..., well, complex, to say the least.

it appears that HPTA and melatonin interact with each other at multiple levels. melatonin has anti-aromatase activity. we all know what mere AI can do: they can increase peripheral test levels.
but with melatonin, it doesn't stop at being an AI. apparently melatonin interferes with the HPTA at the brain level as well (hypthalamus/pituitary) and the final net effect on peripheral test levels is barely predictable.

but the most disturbing point is actually the stimulation pf prolactin. this is potentially a real issue (all those lactating superdrol victims know what I am speaking about) but how much of an issue it is will depend on the strength of prolactin stimulation and your individual hormonal environment. this hormonal environment is surely very bad immediately/shortly after a cycle, and any further elevation of prolactin may have unwanted effects in people prone to gyno etc.

[coolbreeze]

awesome post guys. thanks.

what do you feel about the use of supplemental melatonin on inhibition of pineal gland endogenous melatonin release?

My guess is over 40 yrs of age, it would be risk/benefit ratio.

[BabyLance]

1: J Pineal Res. 2001 Jan;30(1):34-42. Links
Lack of changes in serum prolactin, FSH, TSH, and estradiol after melatonin treatment in doses that improve sleep and reduce benzodiazepine consumption in sleep-disturbed, middle-aged, and elderly patients.Siegrist C, Benedetti C, Orlando A, Beltr?n JM, Tuchscherr L, Noseda CM, Brusco LI, Cardinali DP.
Sanatorios Los Arroyos e IPAM, Rosario, Argentina.

An open pilot study on the safety and efficacy of melatonin in the treatment of insomniac patients was conducted in 22 subjects (16 females), mean +/- S.D. age 60.1 +/- 9.5 years. All patients received 3 mg of gelatin melatonin capsules per os daily for 6 months, 30 min before expected sleep time. Twenty of 22 patients were on benzodiazepine treatment and they continued this treatment for part of or for the entire melatonin administration period. Serum concentrations of prolactin, follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), or estradiol were measured by radioimmunoassay (RIA) in morning samples at the beginning and after 6 months of melatonin administration, and standard clinical laboratory tests for blood components were performed. Urinary 6-sulphatoxymelatonin (aMT6s) excretion was measured by RIA before treatment. Serum concentrations of prolactin, FSH, TSH, or estradiol did not exhibit changes after 6 months of melatonin administration, nor were any indications of hematologic or blood biochemistry alteration found. Melatonin augmented significantly the quality and duration of sleep, and decreased sleep latency and the number of awakening episodes, as assessed from sleep logs filled by the patients (first 21 days) and from structured interviews performed by incumbent physicians (up to 6 months). Estimates of next-day function (i.e., alertness in the morning and during the day) also improved significantly during melatonin treatment. The observed effect lasted for the entire period examined (up to 6 months), with 22 out of 22 patients showing improved sleep at the end of treatment. The urinary excretion of aMT6s before starting administration of melatonin correlated negatively and significantly with age, but not with the intensity of sleep the disorder or the outcome of treatment. In 13 of 20 patients taking benzodiazepines together with melatonin, benzodiazepine use could be stopped, and in another four patients, benzodiazepine dose could be decreased to 25-66% of the initial dose. The results of this open, subacute administration trial indicate that melatonin is a safe and useful treatment for sleep disturbances in middle-aged or elderly patients, either by itself or together with benzodiazepines.

[BabyLance]

Effect of oral melatonin administration on sex hormone, prolactin, and thyroid hormone concentrations in adult dogs - Abstracts: recently published abstracts - Brief Article
Alternative Medicine Review, Sept, 2001 by PF Ashley, LA Frank, LP Schmeitzel
E-mail Print Link OBJECTIVE: To determine the effect of oral melatonin (MT) administration on serum concentrations of sex hormones, prolactin, and thyroxine in dogs. DESIGN: Prospective study. ANIMALS: 8 male and 8 female adult sexually intact dogs. PROCEDURE: 5 male and 5 female dogs were treated with MT (1.0 to 1.3 mg/kg [0.45 to 0.59 mg/lb] of body weight), PO, every 12 hours for 28 days; the other 6 dogs were used as controls. Blood samples were collected on days 0, 14, and 28, and serum concentrations of estradiol-17 beta, progesterone, testosterone, androstenedione, 17-hydroxyprogesterone (17-HP), dihydroepiandrostenedione sulfate (DHEAS), prolactin, and thyroxine were determined. On day 5, serum MT concentrations were measured before and periodically for up to 8 hours after MT administration in 4 treated dogs. RESULTS: Female dogs treated with MT had significant decreases in serum estradiol, testosterone, and DHEAS concentrations between days 0 and 28. Male dogs treated with MT had significant decreases in serum estradiol and 17-HP concentrations between days 0 and 28. Serum MT concentrations increased significantly after MT administration and remained high for at least 8 hours. Prolactin and thyroxine concentrations were unaffected by treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Melatonin is well absorbed following oral administration and may alter serum sex hormone concentrations.

[BabyLance]

the research seems to be all over the place about melatonin and prolactin...


Positive relationship between the nocturnal concentrations of melatonin and prolactin, and a stimulation of prolactin after melatonin administration in young men.
Author: Webley, G E : Bohle, A : Leidenberger, F A
Citation: J-Pineal-Res. 1988; 5(1): 19-33
Abstract: The relationship between the concentrations of melatonin and prolactin over the 24-h cycle has been investigated in a group of young men at three times in the year. Melatonin and prolactin showed a significant positive correlation (P less than 0.001) for all times during the 24-h period but with a greater contribution from concentrations during the nocturnal period, when both hormones were elevated. The positive correlation for nocturnal concentrations was evident in February and March (P less than 0.01) but was of greatest significance in June (P less than 0.001). In blood samples taken at 15-min intervals during the morning (0800-1200) and evening (2000-2400), melatonin and prolactin concentrations were not significantly correlated. Melatonin concentrations increased before prolactin during the evening and decreased before prolactin in the morning. Oral administration of 6 mg melatonin significantly stimulated prolactin release above concentrations measured after placebo administration, in both the morning (P less than 0.05) and evening (P less than 0.01) time periods; the prolactin response being greater in the evening. These results provide evidence for melatonin controlling the nocturnal increase of prolactin via its ability to stimulate prolactin release.

[Peter LeDrew]

I have no trouble sticking to my 300mcg time-released product that more closely resembles the natural endogenous nightime release than the 3-6mg doses that are all too common.

[DRP7]

@Babylance:

the first study that you cited investigated chronic effects, the third study examined acute effects of melatonin on prolactin. apparently, there is an acute and transient elevation on proalctin from melatonin, but most likely there is no chronic, outlasting effect.

[DRP7]

I have no trouble sticking to my 300mcg time-released product that more closely resembles the natural endogenous nightime release than the 3-6mg doses that are all too common.

agreed. is this a sublingual or oral preparation?

In case that it is NOT sublingual, I found interesting what a friend of mine (who works in a lab with the hypothalami and pineal glands of hamsters) told me about melatonin: he said that orally ingested melatonin gets destroyed in the intestines / liver and that only a minor fraction reaches the brain. a further problem is the stunningly low half time of melatonin.

the latter has two implications:

1. it makes melatonin suitable for acute, short interventions
2. it renders melatonin almost unusable for long-lasting effects.

this is why many people (including myself) find themselves fall asleep nicely after orally taking melatonin but waking up after a realitively short time thereafter (1-2 houtrs) and then having difficulties to fall asleep again.

[Peter LeDrew]

agreed. is this a sublingual or oral preparation?

In case that it is NOT sublingual, I found interesting what a friend of mine (who works in a lab with the hypothalami and pineal glands of hamsters) told me about melatonin: he said that orally ingested melatonin gets destroyed in the intestines / liver and that only a minor fraction reaches the brain. a further problem is the stunningly low half time of melatonin.

the latter has two implications:

1. it makes melatonin suitable for acute, short interventions
2. it renders melatonin almost unusable for long-lasting effects.

this is why many people (including myself) find themselves fall asleep nicely after orally taking melatonin but waking up after a realitively short time thereafter (1-2 houtrs) and then having difficulties to fall asleep again.

Interesting. Never heard that little melatonin would reach the brain before.

I experience that same effect from melatonin also, but I am ordering some time-released form that I have been looking to try for some time now.

[FlyingV]

agreed. is this a sublingual or oral preparation?

In case that it is NOT sublingual, I found interesting what a friend of mine (who works in a lab with the hypothalami and pineal glands of hamsters) told me about melatonin: he said that orally ingested melatonin gets destroyed in the intestines / liver and that only a minor fraction reaches the brain. a further problem is the stunningly low half time of melatonin.

the latter has two implications:

1. it makes melatonin suitable for acute, short interventions
2. it renders melatonin almost unusable for long-lasting effects.

this is why many people (including myself) find themselves fall asleep nicely after orally taking melatonin but waking up after a realitively short time thereafter (1-2 houtrs) and then having difficulties to fall asleep again.

Is the half life of supplemental melatonin any shorter than endogenous melatonin?

_____

I have a few not-really scientific observations to make, having sold and discussed melatonin with the lay public God knows how many times over the last 15 years.

Re; the sublinguals, I've read elsewhere a long time ago, I think on the LEF website, that at least in some people melatonin is mostly degraded by digestion and not very bioavailable. So, the lozenges are the way to go in all cases.

Yet, here we are in 2008, and most melatonin products are still in tablet or capsule form.

IME most users who've claimed (in so many words) "Melatonin never did anything for me at any dose" used capsule or tablet products, unaware that there might be a significant disadvantage to doing so. In fact, as soon as I heard that claim, my next question would be what kind of melatonin product?

I've noticed also that most of the I-swear-by-melatonin crowd are using sublinguals and/or time released products (usually the Source Naturals brand).

Another point about melatonin to make is that it really shouldnt be considered a "sleep aid" in the traditional sense. But because it's marketed that way, that's how people think of it, and this sets them up to be disappointed in the results.

It's primary role in terms of sleep (it has other, unrelated roles too) is not to make you drowsy and sleep soundly - although it can do that to an extent - but to help establish (or, usually, re-establish) the sleep cycle as part of the daily circadian rhythm.

As such, it's not something that is going to resolve someone's sleep problems in a night or two. It's shouldnt be considered anything at all like an ******, valerian, tryptophan, or anything like that. But it's clear that that is how and where it is marketed.

So many people will take melatonin on an occasional or casual basis, and when it doesn't make them drowsy and get them a trouble free nights sleep, they conclude that it "doesnt work", when instead, you really need to use it on a consistent daily basis to get the best results in terms of improving sleep quality.

You also have to use it over the course of a multiple consecutive nights, experimenting with different doses, to really zero in on what the most effective dose for you happens to be. It varies widely from person to person, regardless of age. Take to little and it has no noticeable effects, take too much and you wake up groggy. You just have to experiement, but you will find the sweet spot before too long. I usually suggest starting with 1 mg for each decade of life and increasing or decreasing that systematically.

I think all of these reasons contribute to why melatonin has so much potential but such a spotty track record in terms of results.

[Swarovski]

sorry if I'm posting wrong, but isn't melatonin a medicine to restore sleeping pattern/cycles?

[FlyingV]

sorry if I'm posting wrong, but isn't melatonin a medicine to restore sleeping pattern/cycles?

It's not classified as a medicine here in the US but I did hear someone say something along the lines of it helping restore sleep cycles

[Peter LeDrew]

agreed. is this a sublingual or oral preparation?

In case that it is NOT sublingual, I found interesting what a friend of mine (who works in a lab with the hypothalami and pineal glands of hamsters) told me about melatonin: he said that orally ingested melatonin gets destroyed in the intestines / liver and that only a minor fraction reaches the brain. a further problem is the stunningly low half time of melatonin.

the latter has two implications:

1. it makes melatonin suitable for acute, short interventions
2. it renders melatonin almost unusable for long-lasting effects.

this is why many people (including myself) find themselves fall asleep nicely after orally taking melatonin but waking up after a realitively short time thereafter (1-2 houtrs) and then having difficulties to fall asleep again.

Melatonin does seem to be well absorbed and there does seem to be use for time-released preparations, especially with regard to your last points.

http://www.pubmedcentral.nih.gov/art...?artid=1463812

Also from wikipedia on melatonin, supporting my views that lower doses are better. There is another study I read a couple years ago that showed 300mcg was more effective than higher doses if my memory serves me correct.

Studies from Massachusetts Institute of Technology have said that melatonin pills sold as supplements contain three to ten times the amount needed to produce the desirable physiologic nocturnal blood melatonin level for enhancement of sleep. Dosages are designed to raise melatonin levels for several hours to enhance quality of sleep, but some studies suggest that smaller doses are just as effective at improving sleep quality.[63] Large doses of melatonin can even be counterproductive: Lewy & al[64] provide support to the "idea that too much melatonin may spill over onto the wrong zone of the melatonin phase-response curve" (PRC). In one of their subjects, 0.5 mg of melatonin was effective while 20 mg was not.

[Rsurf72]

Is it killing my gains or isn't it!!! Heh
How are these studies showing contradicting results!?

I wake up several times throughout the night due to any little noise. Thus when I'm awake I'm so tired I don't feel like doing anything.. and I can't afford to move because for some reason a tiny two bedroom apartment cost triple what it did a decade ago

[Heisman2]

Is it killing my gains or isn't it!!! Heh
How are these studies showing contradicting results!?

I wake up several times throughout the night due to any little noise. Thus when I'm awake I'm so tired I don't feel like doing anything.. and I can't afford to move because for some reason a tiny two bedroom apartment cost triple what it did a decade ago

Have you considered purchasing and using ear plugs? They work very well in my experience.

[GeneralSerpant]

Yeah but what about all the other muscles?