Introducing - Supplement King's "Black Out" (not controlled labs)

[ddawg91]

ships tomorrow and should be here next monday!! WOO HOO

Vey nice!

[Controlled Labs]

ships tomorrow and should be here next monday!! WOO HOO

yeeeeehahhhhhh

[theking]

actually Tank just informed me i will have it on thursday. WOO HOO.

[Controlled Labs]

actually Tank just informed me i will have it on thursday. WOO HOO.

always trying to help a brother in need

[jiritt0]

I joined a new board, new meltatonin info

http://www.synergymuscle.com/forums/...read.php?t=459

melatonin--Decreases Testosterone?

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Popular supplement melatonin found to have broader effects in brain than once thought

By Robert Sanders, Media Relations | 07 February 2005

BERKELEY – Shift workers and travelers who pop melatonin pills to stave off drowsiness or jetlag have another reason to be cautious about taking the supplement, say Japanese and University of California, Berkeley, researchers.

A new study shows that melatonin, a hormone available without prescription, has broader effects in the brain than once thought. In experiments on the Japanese quail, the researchers found that melatonin switches on a recently discovered hormone called gonadotropin inhibitory hormone (GnIH), which has been found to have the opposite effect to the key hormone priming the body for sex -- gonadotropin releasing hormone (GnRH). In birds, switching off GnRH causes the gonads -- testes and ovary -- to shrink as part of the birds' yearly cycle.

Though the role of melatonin is likely to be more complex in humans, the fact that the hormone has such a big effect on birds suggests it could have significant though unnoticed effects in humans, said George E. Bentley, an assistant professor of integrative biology at UC Berkeley. In humans, GnRH -- one of various short protein or peptide hormones referred to as neuropeptides -- brings on puberty.

"This is quite exciting in terms of potential effects of melatonin on the reproductive axis, that is, the link between the brain, the pituitary gland and the gonads," said Bentley, who is finishing post-doctoral work at the University of Washington, Seattle, before a planned move this summer to UC Berkeley. "Melatonin has
not been considered to have an effect on any neuropeptide in the brain of any vertebrate. If melatonin can do this on one neuropeptide system, it has the potential to do it on any other neuropeptide system."

Bentley noted that melatonin could have good as well as bad effects, but that the current lack of knowledge of the hormone's function in the human brain is troubling.

"It really amazes me that melatonin is available in any pharmacy," Bentley said. "It is a powerful hormone, and yet people don't realize that it's as 'powerful' as any steroid. I'm sure that many people who take it wouldn't take steroids so glibly. It could have a multitude of effects on the underlying physiology of an organism, but we know so little about how it interacts with other hormone systems."

Bentley, along with graduate student Takayoshi Ubuka, senior endocrinologist Kazuyoshi Tsutsui, a professor on the faculty of integrated arts and sciences, and their colleagues at Hiroshima University, report their findings this week in the Online Early Edition of the Proceedings of the National Academy of Sciences.

Melatonin regulates the sleep-wake cycle, or circadian rhythms, in many animals, including humans. Produced at night by the pineal gland at the base of the brain, it makes us drowsy at night and, when levels drop in the morning, brings us back to alertness. As an over-the-counter supplement, it is used widely to prevent jetlag from long airline flights, and is popped daily by many nightshift workers to reset their biological clock so that they're alert at night.

Despite claims by supplement manufacturers, however, melatonin has shown mixed results as a treatment for disease, whether insomnia, Alzheimer's disease or cancer. It is not recommended for children, for women trying to get pregnant or breast-feeding mothers.

Bentley got interested in melatonin's effects in the brain through his work with Tsutsui on a new brain hormone, GnIH, that Tsutsui discovered in 2000. GnIH's discovery got a lot of attention at the time because it was one of the last remaining pieces of the brain's hormone system that controls reproduction. While most hormones produced by the brain have both agonists, called "releasing hormones," to switch them on and antagonists to switch them off, GnRH was missing an antagonist. GnIH seemed to be that missing antagonist, and work by Tsutsui and Bentley confirmed its role in turning down production of GnRH and thus switching off the gonads. Though most of these studies were conducted on the Japanese quail or the white-crowned sparrow, a search of the human genome shows that humans have a gene for the same hormone.

"This is a way in which puberty could be regulated, for example," Bentley said. "It adds a whole new dimension to reproductive biology, because there are a lot of clinical issues with reproduction and puberty. One side of the picture was missing (until) this new hormone came into play."

"Reproduction is something that has been studied very rigorously, and to identify a new peptide in that arena that seems to be playing such an important role is pretty phenomenal at this time," added Lance Kriegsfeld, an assistant professor of psychology at UC Berkeley who is collaborating with Tsutsui and Bentley on similar research.

In an effort to find out what regulates GnIH, Bentley again teamed up with Tsutsui and his laboratory colleagues to look at the effects of melatonin. Though birds make melatonin in the same way humans do, and the melatonin cycles through the day and through the year with changes in the length of the day, it's unclear the role it plays in the brain.

Ubuka in Japan removed all the organs in the Japanese quail, Coturnix japonica, that are known to produce melatonin and found that GnIH levels dropped significantly. When melatonin levels were increased with injections, however, GnIH levels more than tripled. Afterward, the bird brains were sent to Bentley to test for the presence and location of melatonin binding sites.

"We found that melatonin actually increases production of the messenger RNA and the mature peptide, GnIH, and it appeared to be a direct effect. The melatonin is binding to the GnIH neurons in the hypothalamus of quail," he said.

To look more closely at the role melatonin plays in the reproductive cycle of quail, the researchers also raised male birds under different lighting conditions. Quail raised in simulated short days, which would be expected to produce high levels of melatonin in the brain, had correspondingly higher levels of GnIH than did quail raised with longer periods of light, which would be expected to produce less melatonin. In addition, the short-day males had larger testicles than the long-day males.

Further support for the importance of melatonin in the reproductive cycle of males came from biologist John Wingfield's University of Washington lab, where Bentley looked for sites where melatonin binds (and therefore has physiological effects) in the quail brain. He found it bound to the same areas that produce GnIH, which are located in the periventricular nucleus.

"There are a lot of unknowns in terms of potential effects of melatonin," Bentley said. "We know that GnIH affects the reproductive axis, but the GnIH neurons in the hypothalamus have fibers branching from them that transport the peptide around the brain to multiple brain areas -- areas involved in basically every physiological and behavioral process you could imagine. So melatonin could affect a multitude of physiological systems via the GnIH system."

In birds, the melatonin is clearly mediating a seasonal reproductive process already known to occur, the researchers said. For mammals, however, the implications are still unclear, since human reproduction seems only slightly affected by seasonal changes.

"GnIH likely has implications for regulating the human reproductive axis, but the mechanisms by which melatonin may act on this population of cells to regulate the changes in seasonal reproduction that we see in humans remains to be determined," Kriegsfeld said.

Bentley and Kriegsfeld, in collaboration with Tsutsui, plan to look at melatonin's role in the brain and reproductive cycle of a photoperiodic mammal, the Siberian hamster, which they've shown contains GnIH.

In addition to Ubuka, who will follow Bentley to UC Berkeley this summer, the paper's other coauthors are Hiroshima University post-doctoral fellow Kazuyoshi Ukena, who was instrumental in the initial discovery of GnIH, and Wingfield, Bentley's University of Washington advisor and a professor of biology. Tsutsui, Ubuka and Ukena also are affiliated with the Core Research for Evolutional Science and Technology at Tokyo's Japan Science and Technology Corporation.

The work was funded in part by the Japanese Ministry of Education, Culture, Sports, Science and Technology, and by the National Institutes of Health (USA).



tho the study is in birds, it is an interesting find which can hopefully be cross studied on humans sometime... to provide more knowledge

[browndustin]

Despite the controversy, and very, very interesting studies dug up by jdirrito (damn, brother, GOOD job!!) I have just placed an order for BLACK OUT. Tank, Pu, I won’t take this until you guys give me the green light or until I’m past 60 days of my log… etc. I’ll flip one of you a PM if need be

[Controlled Labs]

yeah, birds are very different than humans they aren’t even mammals and should thus have very different effects.

there are a ton of studies that show melatonin is not harmful, but is indeed helpful for many different needs. With almost any compound you will find studies that are completely contradictory, here are some showing merits of melatonin for many health related benefits:


Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats.
· Pan M,
· Song YL,
· Xu JM,
· Gan HZ.
Department of Geriatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end-stage liver disease, which ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Oxidative stress and lipid peroxidation are key pathophysiological mechanisms in NAFLD. We investigate the preventive effects of intraperitoneal administration of melatonin (2.5, 5, 10 mg/kg, daily, respectively) in NAFLD rats induced by high-fat diets for 12 wk. Liver damage was evaluated by serological analysis, serum and hepatic lipid assay as well as hematoxylin-eosin staining in liver sections. Oxidative stress and lipid peroxidation were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver. The results showed that high-fat diet induced oxidative stress with extensive liver steatosis in rats. Melatonin (5 or 10 mg/kg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase, aspartate aminotransferase, and levels liver total cholesterol and triglycerides in high-fat diet rats. Moreover, melatonin (2.5, 5, 10 mg/kg) increased SOD and GSH-Px activities and the 10 mg/kg dose of melatonin reduced MDA levels in liver. This study shows that melatonin exerts protective effects against fatty liver in rats induced by high-fat diet possibly through its antioxidant actions.

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Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in CC murine skeletal muscle cells.
· Ha E,
· Yim SV,
· Chung JH,
· Yoon KS,
· Kang I,
· Cho YH,
· Baik HH.
Department of Biochemisty and Molecular Biology, College of Medicine, Kyung Hee University, Seoul, Korea.
The prevalence of diabetes has exponentially increased in recent decades due to environmental factors such as nocturnal lifestyle and aging, both of which influence the amount of melatonin produced in the pineal gland. The present study investigated the effect of melatonin on signaling pathways of glucose transport in C(2)C(12) mouse skeletal muscle cells. Intriguingly, treatment of C(2)C(12) cells with melatonin (1 nm) stimulated glucose uptake twofold increase. Melatonin-stimulated glucose transport was inhibited with co-treatment with the melatonin receptor antagonist luzindole. Furthermore, treatment of stably over-expressed melatonin receptor type 2B containing C(2)C(12) myotubes with melatonin amplified glucose transport c. 13-fold. Melatonin also increased the phosphorylation level of insulin receptor substrate-1 (IRS-1) and the activity of phosphoinositide 3-kinase (PI-3-kinase). However, 3',5'-cyclic adenosine monophosphate-activated protein kinase (AMPK), another important glucose transport stimulatory mediator via an insulin-independent pathway, was not influenced by melatonin treatment. Activity of p38 mitogen-activated protein kinase (MAPK), a downstream mediator of AMPK, was also not changed by melatonin. In addition, melatonin increased the expression level of forkhead box A2, which was recently discovered to regulate fatty acid oxidation and to be inhibited by insulin. In summary, melatonin stimulates glucose transport to skeletal muscle cells via IRS-1/PI-3-kinase pathway, which implies, at the molecular level, its role in glucose homeostasis and possibly in diabetes. Additionally, exposure to light at night and aging, both of which lower endogenous melatonin levels may contribute to the incidence and/or development of diabetes.
PMID: 16842543 [PubMed - in process]
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· Pandi-Perumal SR,
· Srinivasan V,
· Maestroni GJ,
· Cardinali DP,
· Poeggeler B,
· Hardeland R.
Comprehensive Center for Sleep Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai School of Medicine, New York, USA.
Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin's cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immune-enhancing and oncostatic properties. Its 'chronobiotic' properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder. Melatonin acting as an 'internal sleep facilitator' promotes sleep, and melatonin's sleep-facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin's role as a 'photoperiodic molecule' in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body's physiological functions.
PMID: 16817850 [PubMed - in process]
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Reactive oxygen species-induced gastric ulceration: protection by melatonin.
· Bandyopadhyay D,
· Chattopadhyay A.
Center for Biotechnology, School of Life Sciences, Visva-Bharati, Santiniketan 731 235, India. dbandyo_5@yahoo.com
Gastric hyperacidity and ulceration of the stomach mucosa due to various factors are serious health problems of global concern. Although the mechanism of acid secretion from the parietal cells is now well understood, the processes involved in gastric ulceration are still not clear. Among the various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori and due to use of non-steroidal anti-inflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species, especially the hydroxyl radical. A number of excellent drugs, developed over the decades, have proven useful in controlling hyperacidity and ulceration although their long-term use is reported to be associated with various side effects. Hence the investigations continue with an objective to find a compound possessing anti-secretory, anti-ulcer and antioxidant properties which will serve as a therapeutic agent to reduce gastric hyperacidity and ulcers. This article describes the role of reactive oxygen species in gastric ulceration, briefly presents a note on the currently available drugs controlling them, and focuses on the role of melatonin, a pineal secretory product, in protecting against gastric lesions. In experimental studies, melatonin has been shown to be effective in reducing mucosal breakdown and ulcer formation in a wide variety of situations. Additionally, the low toxicity of melatonin supports further investigation of this molecule as a promising gastro-protective agent. Finally, we include a commentary on how melatonin research with respect to gastric pathophysiology can move forward with a view to eventually using this indole as a therapeutic agent alone or in combination with the existing drugs to control gastric ulceration in humans in order to increase their efficacy and/or to reduce their side effects.

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Melatonin directly scavenges free radicals generated in red blood cells and a cell-free system: chemiluminescence measurements and theoretical calculations.

* Zavodnik IB,
* Domanski AV,
* Lapshina EA,
* Bryszewska M,
* Reiter RJ.

Department of Membrane Biochemistry, Institute of Biochemistry, National Academy of Sciences of Belarus, Blvd. Leninskogo Komsomola 50, 230017 Grodno, Belarus. hepato@biochem.unibel

Melatonin, a pineal secretory product, has properties of both direct and indirect powerful antioxidant. The aim of the present study was to compare the radical-scavenging, structural and electronic properties of melatonin and tryptophan, precursor of melatonin. Using the alkoxyl- and peroxyl radical-generating systems [the organic peroxide-treated human erythrocytes and a cell-free system containing the azo-initiator 2,2'-azobis(2-amidinopropane)dihydrochloride], we evaluated the radical-scavenging effects of melatonin and tryptophan. Melatonin rather than tryptophan at concentrations of 100-2000 microM markedly inhibited membrane lipid peroxidation in human erythrocytes treated with organic hydroperoxide as well as radical-induced generation of luminol-dependent chemiluminescence. The apparent Stern-Volmer constants for inhibition of membrane lipid peroxidation by melatonin and tryptophan were estimated to be (0.23+/-0.05) x 10(4) M(-1) and (0.02+/-0.005) x 10(4) M(-1), respectively. The apparent Stern-Volmer constants for inhibition of azo-initiator-derived peroxyl radical generation by melatonin and tryptophan were determined to be (0.42+/-0.05) x 10(4) M(-1) and (0.04+/-0.01) x 10(4) M(-1), respectively. The structural and electronic properties of melatonin and its precursor, tryptophan, were determined theoretically by performing semi-empirical and ab initio calculations. The high radical-scavenging properties of melatonin may be explained by the high surface area value and high dipole moment value. From the thermodynamic standpoint, based on our calculations, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), was the most stable end oxidative product of melatonin.

PMID: 16698043 [PubMed - indexed for MEDLINE]

[LancerV]

BUt on another note nothing can put me to sleep, so maybe I will buy it. The only thing that can put me to sleep is ambien but it makes me feel like **** the next day.

[browndustin]

Heh, Ambien, sleep aids and anxiety medication is good for nothing but recreational use, imo…. And I don’t even think they’re worth using as recreational drugs.

I use lorazepam when I’m having an emergency crisis and absolutely can’t fall asleep. Otherwise they leave me feeling like dog CRAP as well.

I’ve be sure to post my best, non-bias review once I get the chance to try things out.

[LancerV]

Heh, Ambien, sleep aids and anxiety medication is good for nothing but recreational use, imo…. And I don’t even think they’re worth using as recreational drugs.

I use lorazepam when I’m having an emergency crisis and absolutely can’t fall asleep. Otherwise they leave me feeling like dog CRAP as well.

I’ve be sure to post my best, non-bias review once I get the chance to try things out.

Yea I only take them when its like 4am and I still cant sleep. Because the next day I know its going to be impossblie to do anything

[browndustin]

It's a bitch eh

My mom's the one who actually has all this stuff. She works at the hospital, nights for 4 days, off, and then mornings for 4 days or something like that. Loooooots of sleeping pills. My medicine cabinet's a pill popper's paradise. lol

[Krueger]

so did black out come in today? .... i orderd mine last week ... just wanting to know when i will get it....

[Controlled Labs]

so did black out come in today? .... i orderd mine last week ... just wanting to know when i will get it....

he should be getting most of them today (enough to cover all of the preorders) and the rest of them next week.

[theking]

In Stock

Black Out is NOW IN STOCK WOO HOO.

[House72]

Black Out is NOW IN STOCK WOO HOO.

Hell yea. Its about time..