Melatonin

For those who do now or have considered supplementing with melatonin to fight advanced PCa, how concerned are you about the association between it and bone fracture? Also, how concerned are you about the relatively high dose implications (20-50 mg daily) for use in advanced PCa compared to the dose of 1-3 mg (and often even less) that authorities generally say is safer and tends to be more effective when used to treat sleep disturbances? Did anyone titrate their dose upward when starting and did that seem to help minimize side effects?

[pjoshea13]

Manatee,

I began following the LEF PCa protocol for metatonin 13.5 years ago. It was 40mg then - 50mg now. I have had no side effects. I can't say that it has affected my sleep in any way. As for bones, I have no idea.

It would help if you could provide a link to a human study. I have come across a British insomnia study [1] where all prescriptions, including melatonin, increased the risk of fracture.

I suppose that anything used to promote sleep might make people less steady on their feet during a nighttime bathroom visit. The mechanisms are not explored in the Abstract. However, risks were based on a comparison with "unexposed controls". Were the controls untreated insomniacs? Perhaps not. Non-insomniacs then?

With melatonin: "Only patients with three or more melatonin prescriptions had elevated risk." I don't know how long a prescription is good for, but risk was immediate for "hypnotic benzodiazepines (temazepam, nitrazepam) or Z-drugs (zolpidem, zopiclone)".

There is no mention of dosage, but if Circadin is prescribed: "The dose is one 2 mg tablet daily, taken 1-2 hours before bedtime." [2] "it is designed to release melatonin slowly over a few hours."

50mg is a pharmaceutical dose (as is 2mg, of course), but high enough that I would think only cancer patients would consider it. If I were healthy, the idea of 50mg would seem crazy. With metastatic PCa, the standard treatment - castration - causes a long list of morbid changes that reduce QOL in many men & increase the risk of CVD. Compared to that, melatonin is not at all scary, but I would like to see the data for high doses of at least 20mg & fractures - or any other condition.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/?te...

[2] patient.info/medicine/melat...

[Hidden in reply to pjoshea13]

Hi Patrick, and thanks for the kind reply. I highly value your presence and contributions here.

The study you cited is indeed the one that shows this apparent fracture risk. I believe it was the 2 mg timed-release melatonin that was used. This prescription-only formula melatonin is apparently all that is available to UK residents.

I must admit that I'm not very good at digesting scientific papers. I tend to more readily rely on various commentaries on studies rather than the studies themselves. I know I would be better served by learning how to adequately read and interpret study papers. Do you by chance have any recommendations of learning aids for this?

I am a paid subscriber to Consumer Labs and I can't reference their subscribers only melatonin supplement article or I would. Right or wrong, I have assessed Consumer Labs to be generally quite reliable. However, after reading your response and taking a closer look at the study, I am wondering if maybe they are playing up the significance of it more than is reasonable. They use it to justify a seemingly rather stern suggestion that melatonin not be used long term. I had some uncertainty about that advice even initially, especially with regard to using it for prostste cancer which they don't specifically mention. That was my reason for inquiring here. I did realize the study only showed correlative association. I honestly was thinking more along the lines of how taking melatonin might cause changes in the bones that could lead to fracture risk rather than it increasing risk of falls by way of sedating side effects. Clearly, the study can't conclude causation. The same Consumer Labs article cites another study

ncbi.nlm.nih.gov/m/pubmed/2...

that showed melatonin use impaired bone fracture healing. Consumer Labs goes on to state that this result is in spite of melatonin seeming to increase bone density.

My concerns about dose are mostly separate from those about bone fracture, but if 2 mg a day showed significance, then whether higher doses increased that risk would be something to question. However, I know of no studies that assess that.

Certainly it is always wise to weigh risks and potential benefits of anything we do to fight our diseases in the context of our own predicaments. My current goals differ from yours and presumably most others here in that I am trying my best to prevent advanced PCa. My risk of advancement seems to be somewhat high and there is also evidence that my initial diagnosis was too conservative. Still, my risk tolerance now would naturally be lower than yours and others here. Both my parents suffered from osteoporosis and that caused me extra pause when I saw Consumer Lab's cautionary section on melatonin and bone fracture.

I am day three into taking a bedtime dose of 3 mg of the Life Extension branded melatonin. Barring any adverse events or a change of heart, I plan to work my way up to at least 20 and maybe 50 mg. So far, there are no recognizable issues and I believe I am already experiencing some relief from what is most probably a longstanding delayed-onset sleep disorder (undiagnosed). Until PCa, my general and admittedly not well substantiated concerns about melatonin kept me from trying it. This could be an unfair question and feel free not to answer it if you think so: I'm wondering if you'd think taking 50 mg of melatonin a day was crazy if you were at high risk of PCa advancing from localized rather than currently having advanced PCa.

[pjoshea13 in reply to Hidden]

Hi Manatee,

I did see the other study, but ignored it since it involved micw:

"Thirty CD-1 mice received 50 mg/kg body weight melatonin i.p. daily during the entire 2-wk or 5-wk observation period."

For me, that would be 4,000 mg. & the length of the study was very short.

...

Sometimes a commentary on a study can provide more details than found in the Abstract, but I always go back to the study paper.

I find that papers tend to be well-written. & why wouldn't the team want to clearly communicate their findings? The issue for me was the accumulation of common terms, such as "apoptosis". Wikipedia is extraordinarily useful in this regard:

"Apoptosis ... is a process of programmed cell death that occurs in multicellular organisms."

There is a lot more on the Wiki site, but "programmed cell death" gets one past that hurdle. That first sentence allows one to get back to the paper. & so it goes. Learn one new term a day & you will be speed reading in a few months. If you get bogged down with a paper, move on.

...

My situation 13 years ago was that both RP & salvage radiation had failed. There was a good possibility of distant cells. I had no problem making the decision to take the LEF 40mg dose.

...

Regarding concerns about osteoporosis risk, a vitamin K deficiency is common. & vitamin K2 seems to be useful against PCa. Vitamin D insufficiency is also common, & D is also good for PCa. People throw calcium at the problem, but calcium intake should be limited in PCa cases. A good magnesium:calcium ratio appears to be of benefit in PCa - & bones need magnesium too. Boron is good for bones & against PCa. Etc.

When my wife was ~50, she had the start of osteoporosis. She was over 60 when she started taking K2. She is 70 now. At her last bone density test, there was no loss at all. & a scan 5? years ago showed no arterial calcification in & out of the heart.

-Patrick

[wifeofvet in reply to pjoshea13]

my husband's cancer was and remains soooooooo aggressive that even with casodex and zoladex back in the beginning, followed by 42 IMRT treatments, they still only gave him a 1% chance of surviving three years. i took to the net and found every supplement that killed even one pca cell in ''in vivo'' experimentation and put him on massive doses...he took 50mgs for 10 years without any adverse effects that, as no medical person, i could see...other than the constant whining when he had to swallow dozens of supplements three times a day. the list was an arm's length long, but melatonin in high dosage was one of the supplements. he suffered no bone breaks. just prior to his cancer diagnosis he snapped his fibula backwards in an accident with a shrub that was firmly planted in the ground while skidding into home plate on an ATV... and for years they watched it for adverse signs of healing...at least two years...because it was such a nasty break. even IT healed just fine without the bone surgery they feared they might ultimately have to do.

as far as it helping with Pca, i suppose i will never know, but i DO know that all of his doctors were absolutely surprised as hell that his PSA dropped to almost 0.5. OF COURSE, then they said, some people respond better than others to their drugs...no one willing to lend any credence to supplements.

[curt504 in reply to wifeofvet]

What was the list of stuff you got him to take? tnx!

[MelaniePaul]

Hi.

As you may have read, my husband got Melatonin last week because of his difficulty with sleep. Unfortunately, he can't take it. He threw up three times after he had taken it, an hour or so later. Since his weight is already very low, we don't want to risk this happening and have therefore stopped it for now.

Mel.

[Hidden]

Thank you all for your very helpful replies.