Blood Clots, Heart Disease, and How Melatonin Can Help

250 mg per day???

Why so much? For how long?

I'm having insomnia again Art and want to try Melatonin but I was reading that there is a synthetic, FDA approved, and also a pure that is non-FDA approved. Synthetic anything worries me, but what do you think? Thanks much and I am still weaning off my Clonazepam, doing good, but when I get bad insomnia I have to updose so it slows the process. So the melatonin which was 3 mg was doing fine for me except for something I read scared me off it.

It's hard when every good review has a bad one and I can't find the "bad" one now that I had read. The brain-fog from the long-time use of clonazepam is lifting, so many things are better for me already at between 3-4 months weaning tiny amounts. I've gone down from .171 pill weight, to .127 pill weight which is around 25% of the pill, very slow taper. I need to update the thread/topic that EC was so gracious in adding for me,

denise

Gary,

The nature of melatonin studies these days is that they are pushing dosing levels to new highs to try and determine if more is better and in this case, more was better. The toxic dose of melatonin in humans has not been found yet and in this case, they showed that 250 mg/day is not only not toxic, but very helpful for the heart! The 10 mg study was also beneficial, but not as much as the 250 mg study. This study was only for 12 weeks, but there was an ALS study that used 300 mg/day for up to 2 years.

Part of the issue with melatonin is that most people are mainly aware of it as a sleep aid at a very low dosing of 1/3 mg to 5 mg, so automatically 250 mg sounds like a huge amount of melatonin. If a study used 250 mg of vitamin C per day, most people would say that is so low of a dose that it isn't going to do anything.

There are other ways to get melatonin than supplementing with pills and I have previously written about two of those ways on EC here and I will soon be adding a third way:

https://www.earthclinic.com/supplements/how-to-increase-melatonin-naturally.html

The advantage of getting melatonin naturally is that it has no side effects, only health effects.

Art

Thank You Art for this extraordinary research re: melatonin. Question I have is that some claim that high dosages of melatonin over long periods of time slow down ones metabolic rate and causes obesity as well as depletes testosterone.

What are you thoughts or research on this.

Cheers

Fibonaci,

On the contrary recent studies suggest that melatonin may increase metabolism and improve our ability to lose weight as discussed here :

https://www.centerforinternalmed.com/blog/low-dose-melatonin-weight-loss#:~:text=Research now shows that melatonin, thermogenic capacity of the mitochondria.

A relevant article quote :

' Research now shows that melatonin may increase metabolism and improve our ability to lose weight. Melatonin fights fat in two major ways: it has the ability to assist in turning fat into energy rather than storing it and it improves thermogenic capacity of the mitochondria. '

And here :

https://joe.bioscientifica.com/view/journals/joe/251/1/JOE-20-0462.xml

Here is a relevant quote :

' In the present study, we demonstrated that long-term melatonin treatment (from 10 weeks to 43 weeks of age) attenuated body weight gain during aging in female mice. We also revealed, using micro-CT, that melatonin treatment decreased the deposition of both visceral fat and s.c. fat. Furthermore, metabolome analysis revealed that melatonin treatment downregulated a number of metabolites involved in lipogenesis.'

Similarly, regarding studies related to melatonin and testosterone, they show that melatonin dose not reduce testosterone levels as discussed here :

https://www.nature.com/articles/pr19842381#:~:text=Published: November 1984-, Melatonin does not alter human serum gondotropin and testosterone, but it increases prolactin levels

This is the title of the study :

Melatonin does not alter human serum gondotropin and testosterone levels, but it increases prolactin levels

Art

How can I shop for Melatonin, Art, I need to know what to look for as the last bottle I got was very cheap, bought it at a Grocery Outlet. I was taking just 3 mg and that put me to sleep but no hangover type feeling next morning. I can't imagine how someone taking 250mg could even stay upright after taking that much?

One time I took a 10mg tablet and I was so woozy the next morning I didn't want to do anything but lay around. Is there a trick or secret how to take the supplementation? I'm 70 btw, very high cholesterol from my Ketogenic diet, but information I've been studying says that it's only Trigs divided by HDL is the ratio a person needs to watch and mine is 1.5 which is pretty good even though my total Chol. is 511. I've had tests on my heart arteries, and carotoid artery and nothing significant as far as calcium build-up.

I still get concerned but not willing to take a 'statin, thanks for any feedback, Denise

Thank You Art.

FYI I've been on 10mg of Melatonin for over 5 years now and since then I have not caught the flu/cold nor covid. And I'm unvaxxed.

I believe this is due to the melatonin.

Hi Denise,

Some people adjust to the next day tiredness after 1 week to a month and then it is not a problem anymore, but some people don't adjust and can not tolerate regular use of higher dose melatonin. For those who can't tolerate melatonin in supplement form, I wrote the following :

https://www.earthclinic.com/supplements/how-to-increase-melatonin-naturally.html

Art

Thank you Art, just remembered I posted this, thanks so much and I'll look at the link. I'm doing much better not using anything for sleep, although I take have my dose of Magnesium at bedtime and I think it helps me too. I also am keeping up on my exercise (walking, and gym weight resistance). Thank you again, Denise!!

Thank you for the feedback on your use of melatonin, Fibonacci!

Art

Hi Art,

I would like to ask if you have any experience with the sleep aid DOXYLAMINE or know any facts about it's use or long term use.

My brother has been uses it long term and he sleeps like a baby and has lost 20 kgs. Note he has changed nothing else about his lifestyle other than using doyxlamine to sleep well and long. He swears it is 10x better then melatonin.

Your feedback is appreciated.

Fibonacci,

I have no personal experience with the antihistamine Doxylamine, but it has a very good side effect profile as listed here :

https://www.drugs.com/mtm/doxylamine.html#side-effects

Clearly it is working well for your brother and antihistamines like Benadryl(diphenhydramine) are often quite effective for sleep. I have tried diphenhydramine and found it effective for that purpose, but have avoided it because of a potential risk in its use.

The following article suggests there may be an increased risk potential between these antihistamines and dementia :

https://www.healthline.com/health/healthy-sleep/antihistamine-for-sleep#when-to-talk-with-a-pro

Here is a relevant quote from the article :

' People sometimes use antihistamines, such as diphenhydramine and doxylamine succinate, to combat insomnia.

These over-the-counter medications are OK for occasional use in most people. However, they may increase the risk for dementia and Alzheimer's disease if taken long term. '

Art

Thanks for that Art,

Another question. Although melatonin (i use Natrol advanced 2x 10mg slow release I.e. 20mg each night) has been great at getting me to sleep. However it seems majority of times if I get up in the night for whatever reason I have difficulty getting back to sleep.

Have you had this problem or have any suggestions?

Cheers

Fibonacci,

From what I have seen, it seems to be hit or miss with melatonin alone for sleep. Melatonin does not help everyone with sleep, but for those that it helps, it seems to help very well.

In your case, adding other things might be helpful since melatonin alone seems to help you get to sleep initially, but not so helpful later in the night if you get up. I previously wrote about such a combination here :

https://www.earthclinic.com/cures/art-solbrig-insomnia-protocol.html

The melatonin 123 approach would be the simplest addition and if that is insufficient then the 3 supplement regimen would be the next choice.

Art

Hi Art,

Thank you for your suggestions. Since then, I did the following and it has been a miracle change in my sleep.

I now sleep like a baby (well a week so far so not proof yet). I don't get up during the night and if I get up to pee I go back to sleep. Here's what I did on top of the melatonin.

After dinner, I take Ashwaghanda

1 hour before bed, I take

* 10mg melatonin

* 1gram of cinnamon

* 4 grams of glycine

then as I am about to hit the pillow I take another * 10mg of melatonin.

I am sleeping like a baby.

Thank you for all your help.

Fibonacci,

Glad to hear it helped you to get good sleep! Please update after you have been on it longer.

Art

Hi Art, need your help!

I asked you about the my wife's kidney protein is high. since tgen, my wife have been taking 5 mg melatonin with 10mg of B6 in each pill (3pills total a day) for kidney problem for 6 weeks . Should she just taking more melatonin without the B6? Would there be problem with too much B6? I want to increase her dosage of melatonin per your suggestion . I forgot to mentioned to you on last email her 5 mg melatonin has 10 mg of b6. I hope I did not cause her any harm.

Peter,

I don't know what tgen is?

Too much B6 can be deleterious to the kidneys and her health!!! As discussed here :

https://www.miamikidney.com/single-post/can-taking-a-lot-of-supplements-really-damage-the-kidneys#:~:text=In diabetes patients with advanced, Vitamins Review for more information).

Here is a relevant quote :

' In diabetes patients with advanced kidney disease, high daily doses of B vitamins (folate, B6 and B12) were found in one study to worsen kidney function and double the risk of heart attack stroke and death (see the Cautions section of the B Vitamins Review for more information). '

Some manufacturers add B6 to melatonin to make it more effective and I don't really like this, but they do. It is good to read the label to know exactly what you are taking, especially in your wife's case.

If there is a reason she is wanting to take extra B6, and her doctor approves it, she should be taking B6 in the form referred to as P5P. The type of B6 found in a few melatonin supplements is not this type. Here is a link to typical P5P products :

https://www.amazon.com/s?k=P5P&crid=897VJDFKK4V2&sprefix=p5p,aps,211&ref=nb_sb_noss_1

Again, since she is a transplant recipient, every supplement she takes should be approved by her doctor and or transplant doctor and or team to make sure it will not cause her harm!

Art

Peter,

Here is the RDA for vitamin B6 to give you an idea for comparison to what your wife is taking in total :

https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/#h2

Art

Hi Denise E,

I think most melatonin is synthetically made. If you look on Amazon, I see that they have a natural version, but it is fairly pricey at $50 for 120 three mg capsules.

I have only used the synthetic version, so that is the only one I am familiar with.

If you don't want to use the synthetic version then you do have the option for the natural one, but give some consideration to the very good safety profile that the synthetic version has accrued over decades.

Another option, if you want to avoid the synthetic version, is to increase your melatonin naturally via earlier morning and later afternoon sun exposure as I wrote about here :

https://www.earthclinic.com/supplements/how-to-increase-melatonin-naturally.html

It is also worth noting that most studies of melatonin use the synthetic version. Another point worth considering is that melatonin is non addictive and you can stop cold turkey at anytime without any withdrawal symptoms.

Lastly, you will be hard pressed to find a bad study about melatonin. I hope that answers your questions.

Art

Thank you for your reply. I plan to ask my doctor about this at my next appointment. I seem to have more heartburn since I have been on the additional aspirin. If he agrees to DC the aspirin, what dosage is considered high for the melatonin? I can't tell you how I appreciate your wisdom.

Sheila,

Talking to your doctor about melatonin, he will likely want to see a study or two suggesting it has useful benefit at higher dosing. The following randomized, double-blind clinical trial used only 10 mg/day in humans and saw minimal improvement :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427988/

Here is a relevant quote from the RCT :

Melatonin supplementation in HFrEF might improve endothelial function; however, this beneficial effect might not be seen in diabetic patients.

This meta-analysis of multiple studies(31 studies actually used) using melatonin to lower inflammation, while not giving individual study dosing, determined that melatonin has statistically significant anti-inflammatory effects :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979486/

Here is a relevant quote from the meta analysis :

This systematic review and meta-analysis of 31 clinical trials involving 1517 participants in diverse populations of different ages and health conditions demonstrated significant anti-inflammatory effects of melatonin.

Melatonin had a large anti-inflammatory effect on IL-1, IL-6, and IL-8, which remained large and statistically significant even after trimming outlier studies with large effect sizes to eliminate publication bias. Usually, SMD of 0.8 is considered a large effect size (Faraone, 2008; Zlowodzki et al., 2007), and in this meta-analysis, all the SMDs for IL-1, IL-6, and IL-8 were above 1 before and after excluding outlier studies. The SMD for TNF was also above 1 but became non-significant after excluding outlier studies with large effect sizes. Although a direct comparison with other putatively anti-inflammatory agents is difficult, based on existing meta-analyses, melatonin generally had an effect that is comparable to that reported for statins (SMDs ranging from 1.3 to 4.3 for various inflammatory markers) and a larger effect than that reported for curcumin (SMDs ranging from non-significant to 2.1 for various inflammatory markers), fish oil (SMDs ranging from non-significant to 1.2 for various inflammatory markers), probiotics (SMDs ranging from non-significant to 0.5 for various inflammatory markers), and vitamin D (SMDs ranging from non-significant to 0.5 for various inflammatory markers) (Li et al., 2018; Lv et al., 2015; Milajerdi et al., 2020; Mousa et al., 2018; Tabrizi et al., 2019; Xin et al., 2012).

This last randomized, double blind placebo controlled trial (RCT) used 50 mg per day of melatonin in people with Parkinson's disease (PD), a disease noted for highly elevated oxidative stress levels and perturbed mitochondrial function and often seen in cardiovascular disease also and melatonin was shown to return elevated oxidative stress levels to healthy control levels and significantly improve mitochondrial function :

https://www.hindawi.com/journals/omcl/2021/5577541/

Here is a relevant quote from the RCT :

At the end of the trial, in patients who received melatonin, we detected a significant diminution of lipoperoxides, nitric oxide metabolites, and carbonyl groups in plasma samples from PD patients compared with the placebo group. Conversely, catalase activity was increased significantly in comparison with the placebo group. Compared with the placebo group, the melatonin group showed significant increases of mitochondrial complex 1 activity and respiratory control ratio. The fluidity of the membranes was similar in the melatonin group and the placebo group at baseline and after three months of treatment. In conclusion, melatonin administration was effective in reducing the levels of oxidative stress markers and restoring the rate of complex I activity and respiratory control ratio without modifying membrane fluidity. This suggests that melatonin could play a role in the treatment of PD.

If your doctor approves the 50 mg dose, I suggest slowly working up to that dose for a gradual transition up to 50 mg/day to be taken at night. If not, maybe your doctor will approve the GSPE at the label recommended dose that I previously pointed out to you.

Art

Sheila,

I forgot to include this melatonin study in CABG participants at 10 mg melatonin per day and its effects on cognitive function :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098135/

Here is a relevant quote :

' The MMSE and WAIS-R tests revealed that melatonin might have prophylactic effects against postoperative cognitive disturbance in patients undergoing elective CABG.'

Art