Can melatonin control AR amplification and therefore help mCRPC drugs work better and longer?

[JLS1]

Patrick brought this up about a year ago:

healthunlocked.com/advanced....

Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy

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

Another interesting article in the European Journal of Anatomy, although it's a bit dated:

Effect of melatonin on androgen receptor and catalase mRNA

eurjanat.com/web/paper.php?...

I'm not sure how to interpret this:

Nuclear exclusion of the androgen receptor by melatonin

researchgate.net/publicatio...

fwiw, I spoke with an oncologist (not our MO) earlier today and asked about melatonin helping inhibit the AR, and he said it was brought up at an ASCO meeting not too long ago, but no really took it any further. He did say it can't hurt to take it.

[Hidden]

Hi JLS1.

Thanks for bringing this up. I read with interest Patrick's posts concerning Melatonin and am curious as to whether the following:

'Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation"

implies that, just as ADT eventually 'selects' castrate resistant prostate cancer cells, Melatonin will 'select' neuroendocrine cells?

For those on, or contemplating taking Melatonin, I hope I'm wrong. It wouldn't be the first time.

Peter

[pjoshea13 in reply to Hidden]

Peter,

Where precisely did you find that quote?

Thanks, -Patrick

[JLS1 in reply to Hidden]

I had the same concerns, and hoping that's not correct! But perhaps that's only with mega doses? If so, then what level = mega doses vs. safer doses?

[Hidden in reply to JLS1]

I'm wondering if the dosage of Melatonin required to inhibit prostate cancer cell growth correlates with the amount required to induce the neuroendocrine differentiation. If so, it would seem that any benefit is ultimately offset by ending up with the more aggressive cells?

[JLS1 in reply to Hidden]

I've read recommendations of 10 - 20 mg for cancer patients.

My husband just started at 12mg (4 of the 3mg pills from Trader Joes) and hopes to work up to 20mg (2 of the 10mg pills from Walgreens). I don't know what the difference is in brands?

fwiw, after reading of all the health benefits, I decided to try taking the melatonin too. I started with 3 mg, then upped to 12 mg, and started feeling dizzy about 30 minutes later. The next day I was worse, I woke up with my face all puffy and had slight vertigo/dizziness ALL day. It was horrible! So I stopped. I wonder if you need to slowly increase the dose to avoid this kind of side effect? I can't imagine taking 40mg!! !

[Michalbaner]

Hi,

If you are looking to reduce sensitivity of androgen receptors especially (I presume) receptors for dihydrotestosterone, look into Saw Palmetto and Stinging Nettle. Both have been proven to reduce Testosteron -> DHT converssion.

It will probably also be helpful to reduce Insulin -> RAS - > AMPK signalling as this stimulates cell growth. This could potentially be reduced by including periods of not eating such as only eating 3 times a day.

Finallyt, reducing aromatase function could be useful by eating natural Aromatase Inhibitors. think isoflavonoids such as flax and tofu may have this function and so can the vegetables of brassica family as they are turned into isothyocyanates.

Perhaps have a chat with the oncologist about this and see what they think?

All the best in your fight !!

[j-o-h-n in reply to Michalbaner]

to Michalbane,

Thanks for the info... Can you tell us about yourself? Age? Location? Stage? PSA score? Treatment center(s)? Treatments to date? Doctor's name(s)? Your expertise/background? All info is voluntary and it helps us help you and helps us too. Thank you...

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 02/07/2020 6:12 PM EST

[Michalbaner in reply to j-o-h-n]

Hi John,

I am not a prostate cancer patient, I am just a naturopathy student who has been looking for some answers on the forum and over the time I have been using my knowledge to advice people when I though I had something to contribute. I am 30 and live in London UK

[j-o-h-n in reply to Michalbaner]

Thank you for your response.... Thank goodness you're not afflicted with this terrible disease. Thank you for your expertise and advice and keep on keeping on here. It would be helpful and best to identify your background every time you post. Note: Check your PSA at age 45 and pass the word on to all the male adults you know.

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 02/09/2020 2:51 PM EST

[Michalbaner in reply to j-o-h-n]

thanks, I will keep that advice in mind. I have the condition in family and am very cautios of my increased risk for it.

[pjoshea13]

You asked about "Nuclear exclusion of the androgen receptor by melatonin".

Most of us are on therapies that target the androgen receptor [AR] axis. One way of doing this is to prevent AR activation, part of which involves the AR going to the nucleus of the cell. Melatonin has been reported to prevent this. In fact, one study found that AR which had already moved to the nucleus was booted out.

One thing that appealed to me about high-dose melatonin, was the idea that the AR might be sleeping while I was. Daytime is another matter.

-Patrick

[Hidden]

Hi Patrick

"Melatonin, at pharmacological concentrations, inhibits cell growth and induces neuroendocrine differentiation in prostate cancer cells"

doi.org/10.1111/j.1600-079X...

I suppose the crux of the matter is what's meant by 'pharmacological levels'

Peter

[tango65 in reply to Hidden]

Interesting finding. This is one of the article explaining the mechanisms:

sci-hub.tw/https://onlineli...

[snoraste in reply to Hidden]

I've read numbers from 40-60mg range. I've been taking 40mg. I don't know much about the bioavailability, but the dosage is not consistent across different brands.

[JLS1 in reply to snoraste]

Did you notice any unpleasant side effects? My husband just started taking 12 mg and hopes to work up to 20mg. I tried 3mg (for other health benefits) and when I tried increasing to 12mg I started feeling dizzy and the next day was horrible - my face was all puffy when I woke up and I had terrible dizziness/slight vertigo all day. So I stopped. I can't imagine taking 40mg!

[snoraste in reply to JLS1]

Not really. Maybe a little drowsy for the first day or two. But nothing else.

[Hidden]

Melatonin is good for me!