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Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined hormone radiation treatment

pjoshea13 profile image
37 Replies

New study below [1].

"A retrospective study included 955 patients of various stages of prostate cancer (PCa) who received combined hormone radiation treatment from 2000 to 2019. Comprehensive statistical methods were used to analyze the overall survival rate of PCa patients treated with melatonin in various prognosis groups."

"The overall survival rate of PCa patients with favorable and intermediate prognoses treated or not treated with melatonin was not statistically significantly different. In the poor prognosis group, the median overall survival in patients taking the drug was 153.5 months versus 64.0 months in patients not using it (p < 0.0001). The 5-year overall survival rates in the research and control groups were 66.8 ± 1.9 and 53.7 ± 2.6 (p < 0.0001) respectively. In a multivariate analysis, melatonin administration proved to be an independent prognostic factor and reduced the risk of death of PCa patients by more than twice (p < 0.0001)."

I have been using high-dose melatonin for 16 years. I take 50 mg before bed.

From 4 years ago:

healthunlocked.com/advanced...

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/331...

Oncotarget

. 2020 Oct 13;11(41):3723-3729. doi: 10.18632/oncotarget.27757.

Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined hormone radiation treatment

Gennady M Zharinov 1 , Oleg A Bogomolov 1 , Irina V Chepurnaya 1 , Natalia Yu Neklasova 1 , Vladimir N Anisimov 2

Affiliations collapse

Affiliations

1 A.M. Granov Russian Research Center for Radiology and Surgical Technologies of the Ministry of Health of the Russian Federation, Pesochny, St. Petersburg 197758, Russia.

2 N.N. Petrov National Medical Research Center of Oncology, Pesochny, St. Petersburg 197758, Russia.

PMID: 33110479 PMCID: PMC7566809 DOI: 10.18632/oncotarget.27757

Abstract

Background: The antitumor and immunomodulating activities of melatonin are widely known. These activities are based upon the multifactorial mechanism of action on various links of carcinogenesis. In the present paper, the long-term results of the clinical use of melatonin in the combined treatment of patients with prostate cancer of various risk groups were evaluated.

Materials and methods: A retrospective study included 955 patients of various stages of prostate cancer (PCa) who received combined hormone radiation treatment from 2000 to 2019. Comprehensive statistical methods were used to analyze the overall survival rate of PCa patients treated with melatonin in various prognosis groups.

Results: The overall survival rate of PCa patients with favorable and intermediate prognoses treated or not treated with melatonin was not statistically significantly different. In the poor prognosis group, the median overall survival in patients taking the drug was 153.5 months versus 64.0 months in patients not using it (p < 0.0001). The 5-year overall survival rates in the research and control groups were 66.8 ± 1.9 and 53.7 ± 2.6 (p < 0.0001) respectively. In a multivariate analysis, melatonin administration proved to be an independent prognostic factor and reduced the risk of death of PCa patients by more than twice (p < 0.0001).

Conclusions: The multicomponent antitumor effect of melatonin is fully realized and clearly demonstrated in treatment of PCa patients with poor prognosis with a set of unfavorable factors of the tumor progression.

Keywords: melatonin; overall survival; poor prognosis; prostate cancer.

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37 Replies
snoraste profile image
snoraste

Patrick,

I read somewhere that even higher doses are generally well tolerated. I've increased my dosage from 40mg to 180mg now over the past year. No side effects that I can detect, and blood works are fine.

LearnAll profile image
LearnAll in reply tosnoraste

Wow...you can tolerate that high dose of Melatonin. I can only take up to 10 mg a night. Higher dose makes me too sleepish during day and less alert at work.

snoraste profile image
snoraste in reply toLearnAll

I am sure your body learns how to counteract. That's why it becomes ineffective as a sleeping aid after a short period of time. Have you tried increasing the dosage gradually? But the real problem is that the actual dosage is unclear, not to mention the quality of the manufactured melatonin and accuracy of the dosage. There was a Canadian study done and found wide discrepancy on the actual level of melatonin against the advertised levels by different manufacturers (I don't have the link, but you should be able to search it online).

pjoshea13 profile image
pjoshea13 in reply tosnoraste

180 mg? That's aggressive! So far, I haven't seen any suggestion that there might be benefit above 50 mg.

Of course, there are various non-PCa rat studies that used 10mg/kg, which would get me to ~80mg.

Unknown territory. Good luck. -Patrick

snoraste profile image
snoraste in reply topjoshea13

Indeed!

I was reading the full text you posted:

ncbi.nlm.nih.gov/pmc/articl...

It's interesting how little the dosage was:

" Melatonin was prescribed in tablet form, in a dosage of 3 mg, to be taken 30 minutes before sleep daily. Patients did not receive melatonin during the winter season (December-February)"

I may need to rethink my dosage!

PhilipSZacarias profile image
PhilipSZacarias in reply topjoshea13

Hello Patrick, I use the equation in Shannon Reagan-Shaw, FASEB J. 22, 659–661 (2007) to calculate equivalent dosage rates (based on comparative surface areas). 10 mg/kg in a rate translates to 1.62 mg/kg or approximately 118 mg for a 160 lb person. Cheers, Phil

pjoshea13 profile image
pjoshea13 in reply toPhilipSZacarias

Thanks Phil! -Patrick

Ralph1966 profile image
Ralph1966

Hi Patrick,

What is the minimum dosage to take?

I am taking 30 mg each night.

I taught that 20 mg is enough to increase our survival rate?

pjoshea13 profile image
pjoshea13 in reply toRalph1966

Hi Ralph,

Well, it seems from the general literature that researchers feel happy with 20mg as perhaps being an effective minimum & safe. Here is a recent paper:

ncbi.nlm.nih.gov/pmc/articl...

"This study extended data that use of 20mg of melatonin prior to the first cycle of ACBC has a neuroprotective effect on cognitive functions evaluated by a set of tests that measures several dimensions of cognitive flexibility allied to attention. However, a study that used 6mg of melatonin prior and post ACBC did not find a similar benefit in cognitive function. In fact, our results are in the sense of most clinical studies that demonstrated a benefit of 20mg of melatonin use in cancer patients on clinical outcomes (i.e. mortality, tumor remission, etc.)"

-Patrick

6357axbz profile image
6357axbz

What are the characteristics of the poor prognosis group?

pjoshea13 profile image
pjoshea13 in reply to6357axbz

see full: oncotarget.com/article/2775...

treedown profile image
treedown

What specifically defines "In the poor prognosis group"? Seems this is the only group that shows a benefit if I am reading this right.

pjoshea13 profile image
pjoshea13 in reply totreedown

see full: oncotarget.com/article/2775...

treedown profile image
treedown in reply topjoshea13

Thanks can Melatonin levels be determined by blood tests?

Shanti1 profile image
Shanti1 in reply totreedown

Not sure about blood as you would have to have a night time blood draw, but you can test it in saliva with a home test kit, such as offered by Doctors Data and other labs. Once people are taking it, it will always test high on these tests, especially at doses used for cancer.

treedown profile image
treedown in reply toShanti1

Thank you

sedgley profile image
sedgley

Hi Patrick.

They are not defining what constitutes 'Combined Hormone Radiation Treatment'.

Any idea of examples of the treatments to which they are referring?

Thanks.

pjoshea13 profile image
pjoshea13 in reply tosedgley

see full: oncotarget.com/article/2775...

Shooter1 profile image
Shooter1 in reply topjoshea13

Interesting. Looks like melatonin really helps--taking 24 mg nightly--is this a realistic dose or should I change it??

pjoshea13 profile image
pjoshea13 in reply toShooter1

I'm not qualified to recommend a dose, but the smart money seems to be on a minimum of 20 mg for cancer. LEF says as much as 50 mg for cancer. So 20-50 mg appears to be the ballpark for those wanting to use it.

-Patrick

Shooter1 profile image
Shooter1 in reply topjoshea13

Thanks--on the low edge of good. May up to 30.

It's a very interesting hormone. It supposedly has antioxidant properties at low doses and pro-oxidant properties at high doses. Lots of studies to this effect. I worked it out one time as around <3mg is antiox, >3mg is pro-ox. To be safe I'm guessing <1mg for antiox and >20mg for pro-ox. I take 500mcg a night for about 2 weeks each month and then 50mg a night for the other 2 weeks.

pubmed.ncbi.nlm.nih.gov/250...

Seems like most of the PCa benefits are for pro-ox doses. thomashealthblog.com/wp-con...

I read somewhere that melatonin should be taken only in the evening or at night. Otherwise, it messes up your circadian rhythm and its use was associated with increased mortality risk (unfortunately I did not save the link).

pjoshea13 profile image
pjoshea13 in reply to

Hormones produced within the endocrine system usually have a feedback mechanism. With melatonin, this is light. What happens if you sleep 16 hours in a dark room? No problem. The receptors become insensitive to nelatonin well before dawn. They need some downtime to regain sensitivity for the next night.

Taking melatonin during the day would ensure the continued insensitivity of the receptors.

Good intentions triggering the law of unitended consequences.

-Patrick

donovan0932 profile image
donovan0932

I am on Docetaxel and supplemented by Melatonin .I have been taking 20 mgs a night for many years and now started to up it to 240gs a day .60mgs x 4 times a day .about 3 months ago .No side affects and absolutely minimal side affects from the Chemo .Bloods fine for me also .

pjoshea13 profile image
pjoshea13 in reply todonovan0932

see my response to RSH1 re daytime use

maley2711 profile image
maley2711

Has anyone's MO suggested the use of melatonin?

Concerned-wife profile image
Concerned-wife in reply tomaley2711

My husband’s MO and RO ( in separate practices) said he could take it but were ambivalent about it

RonnyBaby profile image
RonnyBaby

I have been taking about 30 mg. of melatonin for years - I can keep this post' and study in mind, moving forward.

Thanks for sharing - this could be of benefit to many PCa patients.

The 'only' side effect I've ever heard of was that some dreams were more vivid - I could think of a lot of worse situations.

I recall many years ago - on '60 Minutes' when melatonin was the topic of one of the segments.

The 'drug' was rolled out as a kind of miracle drug - anti-ageing and much more.

Eventually, the 'debunkers' made snake oil out of it.

Go figure .....

MateoBeach profile image
MateoBeach

Hate to question this amazing result but ...

Looking at the clinical differences between the melatonin treatment vs non treatment groups in the high risk comparison where the survival benefit was demonstrated. That is in Table 3 in the article. It appears clear that the non melatonin treated patients much more advanced disease than the treated cohort. At baseline. This is in PSA, PSADT, Gleason score groups, positive nodes and number of mets etc. they are clearly not comparable groups for comparison.

It makes me think there may have been selection bias going on. That that those with the worst disease or their doctors may have chosen for whatever reason, not to have started them on melatonin?

Table 3: Clinical and morphological characteristics of poor prognosis prostate cancer patients (n = 655)

Alternatively, were the melatonin patients already taking melatonin for a long time prior to intake and may have changed the development of their PC in favorable ways? That would be a sunny view but I don’t see that supported in this analysis. They suggest “long term” melatonin was prescribed at diagnosis or after the R + HT.

“All patients were divided into two groups depending on their melatonin intake: research group (n-396, took melatonin per os, according to the scheme, for a long time); and control group (n-559, did not take melatonin). Melatonin was prescribed at the end of the course of remote radiotherapy or immediately after the diagnosis in the case of hormone therapy or chemotherapy. Melatonin was prescribed in tablet form, in a dosage of 3 mg, to be taken 30 minutes before sleep daily. Patients did not receive melatonin during the winter season (December-February). It is well known that in the winter season the melatonin level is at its maximum and in the spring–summer season the melatonin level is at its minimum. “

Still may consider adding melatonin to my routine based upon the overall body of evidence on it. Paul

GeorgeGlass profile image
GeorgeGlass in reply toMateoBeach

I just asked the same basic questions below, then I saw your post here. I was wondering if they all started the melatonin after radiation treatments. I also asked this - there is a much bigger % of men in the non-melatonin group, who were gleason 9-10, or had 2-3 metastatic sites, in comparison to the melatonin group. Wouldn't this explain why the melatonin group lived much longer? Am I missing something? It seems like scientists would check all their Ps and Qs. Am I not factoring in part of the equation?George

Rod98168 profile image
Rod98168

I have the tendency to believe that it's not the melatonin that's making it seem like it's the cause of I better outcome for people with poor prognosis for prostate cancer progression but that it's actually because they're able to get a very good night's sleep, that is actually causing the better prognosis. I have several painful disabilitys other than my prostate cancer that I take cyclobenzaprine 5 mg at night when I'm unable to sleep because of my pain. And that always gives me a very good night of sleep.

Thanks! I ve taken 20 mgs before bed for over five years now ...

Manilo profile image
Manilo

Hello, I started with 1 mg, then 2, ... now I take 5 mg and thought it was a lot !!

really made me sleep fast at the beginning, but is less effective now. I will keep rising the dose up to 20 mg

Shooter1 profile image
Shooter1 in reply toManilo

I'm now up to 35 mg and notice no difference. Hope it will give my g 9/10 w/mets a kick in the ass and give me more than the 10 yrs (now 8 to go on 10 yr plan) that I have been aiming for.

Manilo profile image
Manilo in reply toShooter1

Great number those 8 years. Hope many more to come and soon have some drugs to cure or make stable disease.

Are you 8 years on ADT alone, or also abiraterone or enzalutamide ?

My PSA has risen from 0.05 to 0.10-0.15. Above 0.20 will probably have to add abi or enza. I am at 25 mg melatonin already. I will increase also some more

Shooter1 profile image
Shooter1 in reply toManilo

Misspoke------3 1/2 years in....when Dr's told me I had 12 mo. to live after prostatectomy, I had chemo and started Xtandi when PSA started back up. I told them I was on the 10 yr plan after chemo and had thumb rebuilt and Orchiectomy. Now little finger repaired and wrist worked on 2 yrs later. So 8 yrs left on 10 yr plan. Latest PSA 0.12. Still hoping for 10 yrs of good QOL before decline Dr's assure me I will see.

GeorgeGlass profile image
GeorgeGlass

From the Russian study chart below, there is a much bigger % of men in the non-melatonin group, who were gleason 9-10, or had 2-3 metastatic sites, in comparison to the melatonin group. Wouldn't this explain why the melatonin group lived much longer?

Clinical and morphological characteristics of poor prognosis prostate cancer patients (n = 655)

Parameters Patients treated with Melatonin Patients treated without Melatonin p

Number 259 396

Age at diagnosis, years, Me (IQR) 65.0 (58.8–71.7) 64.5 (59.6–69.4) > 0.05

PSA at diagnosis, ng/ml, Me (IQR) 33.5 (19.0–53.0) 43.9 (29.9–85.6) < 0.01

Pretreatment PSADT, mo, Me (IQR) 21.7 (8.2–48.8) 16.0 (4.6–38.7) < 0.05

Biopsy Gleason score, n (%)

6–7 126 (48.6) vs. 180 (45.5) > 0.05

8 - 112 (43.2) vs. 153 (38.6) > 0.05

9–10 21 (8.1) vs. 63 (15.9) < 0.01

Clinical positive lymphnodes, n (%) 69 (26.6) 141 (35.6) < 0.05

Number of metastatic sites, n (%)

1 (M1a or 1b or 1c) 110 (42.5) vs. 196 (49.5) > 0.05

2 (M1a+b or 1a+c or 1b+c) 9 (3.5) vs. 24 (6.1) < 0.01

3 (M1a+b+c) 6 (2.3) vs. 12 (3.0) > 0.05

5-Y Overall survival, % 66.8 ± 1.9 vs. 53.7 ± 2.6 < 0.0001

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