49 replies to this topic

[Guinevere]

What is the range for normal melatonin blood levels in a human (at its peak)?

[SieAn]

Define normal...

[Guinevere]

The normal levels in youth. The melatonin levels of a person before age-related decline.

[SieAn]

You could make an argument that that's still not normal, because of internet, TV, youth, etc, their melatonin levels might be higher than when you age, but they still might not be high enough.

I've seen a study give melatonin to kids in HS and they did better with paying attention and waking up fresh. So whatever numbers are out there, they are probably still too low to be *optimal* for your health.

With as many SSRIs that seem to fix certain problems, you'd think we have a chronic melatonin deficiency in the Western culture.

I also think that time released is better than instant. I've tried both, and do better on timed release, and not just for sleeping.

I'll keep an eye out for average levels, but can't do any digging right now.

[SeekingSerenity]

Maybe you can try eating some walnuts.

Just found out that it's a natural source of melatonin.

[hippocampus]

Well, your body is also a natural source of melatonin, so why not just sleep in a dark quiet place (darkness is very important!) and take care for sleep hygiene and healthy lifestyle, so your body can make enough melatonin. Supplementation may be needed in elderly because their bodies produce less melatonin, though.

[garcia]

Back to the study I referenced .... I managed to find the full paper here in case anyone wants to know more details:

girish_et_al_2013_melatonin_study

Melatonin elevates apoptosis in human platelets via ROS mediated mitochondrial damage.

Melatonin is a pineal hormone that regulates circadian and seasonal rhythms. The chronobiotic role of melatonin corresponds with a repertoire of pharmacological properties. Besides, it has a wide range of therapeutic applications. However, recent studies have demonstrated its direct interaction with platelets: at physiological concentration it promotes platelet aggregation; on the other hand, at pharmacological doses it raises intracellular Ca²⁺ leading to platelet activation, thrombus formation and cardiovascular disorders. In order to further probe its effects on platelets, the current study targeted platelet apoptosis and melatonin was found to stimulate apoptosis. The mitochondrial pathway of apoptosis was mainly investigated because of its susceptibility to oxidative stress-inducing factors including therapeutic and dietary elements. Melatonin significantly increased the generation of intracellular ROS and Ca²⁺, facilitating mitochondrial membrane depolarization, cytochrome c release, caspase activation, protein phosphorylation and phosphatidylserine externalization. Further, the overall toxicity of melatonin on platelets was confirmed by MTT and lactate dehydrogenase assays. The elevated rate of platelet apoptosis has far reaching consequences including thrombocytopenia. Besides, platelets undergoing apoptosis release microparticles, which fuel thrombus formation and play a significant role in the pathophysiology of a number of diseases. In many parts of the world melatonin is an over-the-counter dietary supplement and alternative medicine. Since, melatonin displays platelet proapoptotic effect at a concentration attainable through therapeutic dosage, the present study sends a warning signal to the chronic use of melatonin as a therapeutic drug and questions its availability without a medical prescription.

Edited by garcia, 03 September 2013 - 09:38 AM.

[blood]

Back to the study I referenced .... I managed to find the full paper here in case anyone wants to know more details:

girish_et_al_2013_melatonin_study

Melatonin elevates apoptosis in human platelets via ROS mediated mitochondrial damage.

Melatonin is a pineal hormone that regulates circadian and seasonal rhythms. The chronobiotic role of melatonin corresponds with a repertoire of pharmacological properties. Besides, it has a wide range of therapeutic applications. However, recent studies have demonstrated its direct interaction with platelets: at physiological concentration it promotes platelet aggregation; on the other hand, at pharmacological doses it raises intracellular Ca²⁺ leading to platelet activation, thrombus formation and cardiovascular disorders. In order to further probe its effects on platelets, the current study targeted platelet apoptosis and melatonin was found to stimulate apoptosis. The mitochondrial pathway of apoptosis was mainly investigated because of its susceptibility to oxidative stress-inducing factors including therapeutic and dietary elements. Melatonin significantly increased the generation of intracellular ROS and Ca²⁺, facilitating mitochondrial membrane depolarization, cytochrome c release, caspase activation, protein phosphorylation and phosphatidylserine externalization. Further, the overall toxicity of melatonin on platelets was confirmed by MTT and lactate dehydrogenase assays. The elevated rate of platelet apoptosis has far reaching consequences including thrombocytopenia. Besides, platelets undergoing apoptosis release microparticles, which fuel thrombus formation and play a significant role in the pathophysiology of a number of diseases. In many parts of the world melatonin is an over-the-counter dietary supplement and alternative medicine. Since, melatonin displays platelet proapoptotic effect at a concentration attainable through therapeutic dosage, the present study sends a warning signal to the chronic use of melatonin as a therapeutic drug and questions its availability without a medical prescription.

I'm having some problems downloading that file - the linked page appears to require a log in.

What concentrations/ levels of melatonin were used in the study to get the toxic effects?

[SieAn]

That's an in vitro study. Just because it can do that in vitro doesn't mean it does it in vivo.

You can't attach a .pdf in the post? Or pick a file sharing service that doesn't include spyware in its apps?

[filo74]

I have noticed that people take WAAAYY TOOO much of Melatonin. There is clinically studied patented dosage of only 300 mcg that does wonders for most people. Try it !

[Zaul]

 girish_et_al_2013.pdf   1.28MB   9 downloads

Here's the pdf, in case someone wonder Virustotal says it's clean.

oh and in similar situations Bugmenot is your friend.

[xks201]

Anyone else wake up dizzy during the next day when they take too much?

[bobz1lla]

300mcg 6hr timed release gets the job done here. I get sleepy/drowsy within the hour.

I try to only take it when my hours need adjusting back to baseline.

Edited by bobz1lla, 15 September 2013 - 04:04 PM.

[SieAn]

You have an obviously biased paper from India, that performs only in-vitro testing. No one has confirmed his results. His bias drips through the abstract and the preface. He draws conclusions based on flimsy data and words things in ways that take things out of context.

Then you have things like this, from Harvard, that actually specifically mention mitochondria, and seems to contradict the paper previously mentioned in this thread:

http://www.ncbi.nlm....les/PMC2846661/

Then you have a "human" trial in ALS patients for *two years* at 300mg/day rectally...where they actually tested for oxidation and adverse effects, and found lowered oxidation levels and no adverse effects. If the paper talking about mitochondrial damage has as much merit as the author gives himself, then these results should be especially confusing.

http://www.ncbi.nlm....pubmed/17014688

And let us not forget all the other human trials that have been found to not have any side effects.

There's a reason in-vitro is not the gold standard. Now, if multiple universities can reproduce the mitochondrial platlet damage research, and also verify it in vivo, then you have an argument.

Also, am I the only one concerned that the Indian paper only had 22 references? I read a lot of papers, and that's pretty flimsy...

Edited by lymeblood, 15 September 2013 - 07:41 PM.

[blood]

New study - melatonin can turn white fat "beige", in rats at least:

Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats

Article first published online: 6 SEP 2013
Journal of Pineal Research

Keywords:
beige/brite adipose tissue;melatonin;mitochondria;nonshivering thermogenesis;obesity;white adipose tissue;ZDF rats

Abstract

Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Identification of brown fat (beige/brite) in white adipose tissue (WAT) prompted us to investigate whether melatonin is a brown-fat inducer. We used Zücker diabetic fatty (ZDF) rats, a model of obesity-related type 2 diabetes and a strain in which melatonin reduces obesity and improves their metabolic profiles. At 5 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control and those treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk. Melatonin induced browning of inguinal WAT in both ZDF and ZL rats. Hematoxylin–eosin staining showed patches of brown-like adipocytes in inguinal WAT in ZDF rats and also increased the amounts in ZL animals. Inguinal skin temperature was similar in untreated lean and obese rats. Melatonin increased inguinal temperature by 1.36 ± 0.02°C in ZL and by 0.55 ± 0.04°C in ZDF rats and sensitized the thermogenic effect of acute cold exposure in both groups. Melatonin increased the amounts of thermogenic proteins, uncoupling protein 1 (UCP1) (by ~2-fold, P < 0.01) and PGC-1α (by 25%, P < 0.05) in extracts from beige inguinal areas in ZL rats. Melatonin also induced measurable amounts of UCP1 and stimulated by ~2-fold the levels of PGC-1α in ZDF animals. Locomotor activity and circulating irisin levels were not affected by melatonin. These results demonstrate that chronic oral melatonin drives WAT into a brown-fat-like function in ZDF rats. This may contribute to melatonin′s control of body weight and its metabolic benefits.

Interview with the researchers by Nutra Ingredients (the researchers state that melatonin could be "a potentially useful tool for a stand-alone or adjunct therapy for obesity” and hope to perform human studies):

http://www.nutraingredients.com/Research/Melatonin-may-offer-weight-management-potential-Animal-data

Consumption of melatonin could help control weight gain by stimulating the development of ‘beige fat’ cells that burn - rather than store - calories, say researchers.

The new study, published in the Journal of Pineal Research, noted that recent research has suggested that melatonin limits obesity in rodents without affecting food intake and activity – something that therefore indicates that the hormone may have a thermogenic effect.

Coupled with previous work that identified brown fat (or beige fat) in white adipose tissue (WAT) “prompted us to investigate whether melatonin is a brown-fat inducer,” explained the research team.

Led by senior author Ahmad Agil from the University of Granada, Spain, the team used a rat model to reveal that melatonin consumption is associated with the induction of beige fat that is known to help regulate body weight control, and offer metabolic benefits.

“We report, for the first time, that oral melatonin supplementation induces browning of the inguinal WAT,” the authors said.

Agil and his colleagues suggested that their results may also offer an insight in to the previously unsolved puzzle of why melatonin consumption has metabolic benefits for people with diabetes and hyperlipidaemia.

“We have demonstrated that chronic melatonin treatment in rats behaves as a white fat browning inducer with thermogenic properties. This may be one of the mechanisms that underlies the antiobesity effect of melatonin and thereby explains its metabolic benefits, that is, antidiabetic and lipid-lowering properties,” wrote the researchers.

“Because melatonin treatment does not modify rat physical activity, it is presumed that it can potentiate the thermogenic effect of exercise,” they said – adding that such an observation, coupled with the hormone’s high pharmacological safety profile make melatonin “a potentially useful tool for a stand-alone or adjunct therapy for obesity.”

Study details

The team used Zücker diabetic fatty (ZDF) rats - a model of obesity-related type 2 diabetes and a strain in which melatonin reduces obesity and improves their metabolic profiles.

At five weeks of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control and those supplemented with oral melatonin in the drinking water (10 mg/kg/day) for six weeks.

Melatonin supplementation was found to induce the browning of WAT in both ZDF and ZL rats.

The study also showed that chronic administration of melatonin sensitised the thermogenic effect of exposure to cold, heightened the thermogenic effect of exercise. Therefore, the team suggested that melatonin supplementation may be an ‘excellent’ therapy against obesity.

Given the importance of this discovery, Agil said that he is confident the team will obtain the funding needed to continue their work and be able to achieve their final objective: “to confirm these findings in humans, by administering melatonin to help combat obesity and diabetes.”

Source: Journal of Pineal Research
Published online ahead of print, doi: 10.1111/jpi.12089
“Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats”
Authors: Aroa Jiménez-Aranda, Gumersindo Fernández-Vázquez, Daniel Campos, et al

Edited by blood, 29 September 2013 - 09:21 AM.

[SieAn]

Sure, if you want to consume about 500mg per day if you only weight 115lbs. 10mg/kg/per day is a LOT of melatonin. The highest chronic dose was in ALS patients at 300mg per day, rectally. I'm not sure if I'm comfortable quadrupling that dosage to lose weight. That's Star Trek territory right there.

Then, if it's not time released, it only lasts about 40 minutes in the system, and it's gone. So you'd have to source a time released melatonin, which almost all come with B6, the kind that you can overdose on (not P5P). Or you'd have to dose throughout the day. Fun.

So, while interesting, this study shows that you can't ingest a theraputic dose easily.

10mg melatonin time release for 120 pills, at the cheapest, is around $10 a bottle. 1.2 grams...if you weight 200lbs, you're looking at a bottle a day...assuming you can find something with no additives.

Now, you can buy it bulk from Purebulk, but it's not going to be time released. It's going to be fun to take 500mg or more at one time of that stuff.

If you go the bulk route, you might be able to do it, assuming no side effects from dumping that much in your system at once. It looks like it would be less than $50 a month the bulk way.

http://purebulk.com/...nin-powder.html

Then they say this on the page:

Because of the extremely small recommended serving size for this product, and the potential for TOXICITY reactions from excess use, do not purchase this product unless you are a compounding pharmacist or other health practice professional. We request that you contact us via email at support@purebulk.com prior to purchasing this product to let us know why you are qualified to purchase, handle and measure this product safely. Please observe extreme caution when measuring and handling this product.

Now, I only know of the albino rat studies in terms of toxicity, and while I favor higher doses than most, 1.2 GRAMS a day, IMO, is too damn risky when you can just...

Put. The. Cookie. Down.

[david ellis]

Sure, if you want to consume about 500mg per day if you only weight 115lbs. 10mg/kg/per day is a

http://purebulk.com/...nin-powder.html

Then they say this on the page:

Because of the extremely small recommended serving size for this product, and the potential for TOXICITY reactions from excess use, do not purchase this product unless you are a compounding pharmacist or other health practice professional. We request that you contact us via email at support@purebulk.com prior to purchasing this product to let us know why you are qualified to purchase, handle and measure this product safely. Please observe extreme caution when measuring and handling this product.

Now, I only know of the albino rat studies in terms of toxicity, and while I favor higher doses than most, 1.2 GRAMS a day, IMO, is too damn risky when you can just...

Put. The. Cookie. Down.

That CYA statement from PureBulk doesn't convince me. Try again please.

[blood]

Sure, if you want to consume about 500mg per day if you only weight 115lbs. 10mg/kg/per day is a LOT of melatonin. The highest chronic dose was in ALS patients at 300mg per day, rectally. I'm not sure if I'm comfortable quadrupling that dosage to lose weight. That's Star Trek territory right there.

The human equivalent dose would be around 0.8 mg/kg, I think.

There is other research showing that melatonin prevents weight gain and opposes development of visceral fat in mice at lower doses (than those used in this study). I recall reading a LEF article in which a human dose of 50 mg/ day was suggested as being required to match the mouse studies. (They weren't suggesting people take such doses).

I experimented with doses of 50 to 100 mg/ night for a few months earlier this year. (Powder, obtained from purebulk). I didn't notice much of an effect on my abdominal fat and reverted back to my usual 8 mg/ night. But, I wasn't exercising at the time.

Edited by blood, 30 September 2013 - 01:59 PM.

[SieAn]

I assume you are using this method for conversion?

http://www.fasebj.or...9.full.pdf html

Curious how the more obese you are, the less you would need, with this calculation. If you plug in numbers for a 250lb man, the Km value goes to 60 over their suggested 37 (37 is waaay to low for an average American)...you'd also have to assume that an obese man would have more surface area, but there's not a good way to calculate that easily. That number doesn't seem to matter much, as it's in square meters, so it won't move much.

I have my reservations on the bigger you are, the less you need trend of this equation.

Also, I know you've contributed to this thread, and I appreciate you doing the conversion, but you could have linked the study for others and not let me find it and leave the others to take your numbers by faith.

One of the reasons most of us get the conversion wrong is that not enough people talk about the BSA method. It's a free paper, it should be stickied and thrown around constantly, considering the whole point of this forum is supposed to be education.

[blood]

I know you've contributed to this thread, and I appreciate you doing the conversion, but you could have linked the study for others and not let me find it and leave the others to take your numbers by faith.

Agreed, we should all endeavour to include links. In this instance I was posting from bed on my ipad making running down links more inconvenient.