Foods/Supplements-Vitamins: Melatonin

[pjoshea13]

Melatonin is a hormone produced by the pineal gland at night. Production is tied to the circadian cycle, but can be cut short upon exposure to certain light frequencies. It is therefore unwise to turn on a light once production begins. Night lights lacking the blue frequencies might be OK.

Melatonin receptors are found throughout the body - & notably, in the prostate. Since melatonin is produced only at night, one might wonder why its activities in the prostate need to occur during sleep, or are not needed during daylight.

Unlike other hormones in the endocrine system, there is no feedback mechanism from target tissue. With exposure to melatonin, receptors in the prostate ultimately lose sensitivity to the stimulus. Daytime use of a supplement would be self-defeating, since it would prevent the receptors from regaining sensitivity before nightfall.

The liver metabolises ~90% of an oral dose. Even so, the low doses initially available in the U.S. were too strong for some, which led to the introduction of much lower doses. Some report disturbed sleep even at the lowest dose. It seems that melatonin increases dream awareness. Not a good supplement for those who suffer from nightmares. Melatonin does not appear to affect dream content, but the dreams may appear to be more vivid.

Melatonin supplements are not sleeping pills, although many seem to think they are. There are complaints of morning grogginess, which makes no sense to me. I take 50mg each night - a dose recommended by Life Extension as part of their PCa protocol, although I haven't checked with LEF recently. I fall asleep quickly whether I take melatonin or not. I seem to sleep in two hour cycles. If I need to visit the bathroom after the first cycle, it makes no difference whether I have taken melatonin or not. I get up at 5 am feeling fully alert.

[1] Shift work & PCa.

(There are parallel BCa studies involving night nurses, etc.)

[1a] (2005 - Italy - military and civil pilots)

"Flight personnel are exposed to cosmic ionizing radiation, chemicals (fuel, jet engine exhausts, cabin air pollutants), electromagnetic fields from cockpit instruments, and disrupted sleep patterns."

"In civil pilots, {meta-standardized incidence ratio} was 1.47 ... for prostate cancer. Age (civil pilots are older than military pilots and cabin attendants) and disrupted sleep pattern (entailing hyposecretion of melatonin, which has been reported to suppress proliferative effects of androgen on prostate cancer cells) might be involved."

[1b] (2012 - Canada(

"Night work might influence cancer risk, possibly via suppression of melatonin release. In a population-based case-control study conducted in Montreal, Quebec, Canada, between 1979 and 1985, job histories, including work hours, were elicited from 3,137 males with incident cancer at one of 11 anatomic sites and from 512 controls. Compared with men who never worked at night, the adjusted odds ratios among men who ever worked at night were ... 2.77 ... for prostate cancer ..."

[2] Altered melatonin production in PCa.

[2a] First reported by Bartsch (Germany) over 30 years ago.

"Carcinoma patients showed different interhormonal correlations than all other groups. These results indicate that modulation of melatonin secretion, accompanied by changes in the pituitary hormone levels, may be related to development and growth of prostate cancer."

[2b] Bartsch again, 1992:

blah blah ... "indicating that the depression of serum melatonin in PC is due to a reduced pineal activity and is not caused by an enhanced metabolic degradation in the liver."

[2c] Bartsch, 1997:

"From a theoretical point of view substitution therapy with melatonin might be worthwhile since a progressive decline of pineal melatonin secretion is observed parallel to the growth of the primary tumor in breast and prostate cancer."

[2d] (2015 - Iceland)

"Melatonin has anticarcinogenic properties in experimental models. We undertook a case-cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa."

"We found that lower levels of aMT6s were associated with an increased risk for advanced PCa."

[3] Melatonin & resistance to GnRH analogues.

[3a] (1997 - Italy) "Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin"

(Triptorelin is a gonadotropin-releasing hormone agonist)

"Experimental and preliminary clinical studies have suggested that the pineal hormone melatonin (MLT) may stimulate hormone receptor expression on both normal and cancer cells. Moreover, MLT has appeared to inhibit the growth of some cancer cell lines, including prostate cancer, either by exerting a direct cytostatic action, or by decreasing the endogenous production of some tumor growth factors, such as prolactin (PRL) and insulin-like growth factor-1 (IGF-1). On this basis, a study was carried out to evaluate the clinical efficacy of a neuroendocrine combination consisting of the LHRH analogue triptorelin plus MLT in metastatic prostate cancer progressing on triptorelin alone."

"A decrease in PSA serum levels greater than 50% was obtained in 8/14 (57%) patients. Moreover, PSA mean concentrations significantly decreased on therapy of triptorelin plus MLT."

"Mean serum levels of both PRL and IGF-1 significantly decreased on therapy."

[4] PCa cell studies: apoptosis (cell death) or halting of the cell cycle.

[4a] (2000 - Italy)

"The pineal hormone melatonin has been shown to exert a direct oncostatic activity on neoplastic cells, particularly from breast cancer. In the present study, we evaluated the effects of melatonin on the proliferation and on the cell cycle distribution of human androgen-independent DU 145 prostate cancer cells."

"Melatonin, in physiological doses, significantly inhibited DU 145 cell proliferation and induced cell cycle withdrawal by accumulating cells in G0/G1 phase."

[4b] (2001 - Hong Kong)

"The antiproliferative action of melatonin on LNCaP tumor growth was demonstrated in vivo, and its association with mt1 receptor protein expression suggests the potential involvement of the receptor in the antitumor activity of the pineal gland hormone."

[4c] (2005 - U.S.)

"Melatonin treatment dramatically reduced the number of prostate cancer cells and stopped cell cycle progression in both LNCaP and PC3 cells. In addition, it induced cellular differentiation as indicated by obvious morphological changes and neuroendocrine biochemical parameters."

[5] Melatonin & the Androgen Receptor [AR]

[5a] (2001 - Israel - Rimler)

"The melatonin-mediated nuclear exclusion of the AR may explain the attenuation of AR activity in the prostate cancer cells. This is the first demonstration of a hormone-induced mislocalization of the AR in prostate epithelial cells and may represent a novel route for regulating AR activity."

[5b] (2002 - Israel - Rimler)

"Melatonin caused a robust exclusion of the AR from the cell nucleus to the cytoplasm. ... The exclusion was selective since melatonin had no such effect on the nuclear localization of estrogen receptors alpha (ERalpha) in these cells. Melatonin also caused nuclear exclusion of the AR in the presence of DHT. In addition, it attenuated androgen induced reporter gene activity in PC3 cells co-transfected with the human AR and AR reporter plasmids. Elevated androgen concentrations counteracted melatonin's effects. Melatonin did not decrease AR level or androgen binding in the cells. The nuclear localization of the AR is a hallmark of its cellular activity. These data point to AR nuclear exclusion as a possible mechanism to attenuate androgen responses in target tissues."

[6] PCa & visual impairment.

Light polution is ubiquitous. Men who are seriously visually impaired may be protected from its negative effects. I have no idea how the circadian rhythm operates in blind people who lack light cues, but the pineal gland seems to function well.

[6a] (2006 - Finland)

"Breast cancer risk in females decreased by degree of visual impairment, and a similar but less consistent trend was observed for prostate cancer in males. The incidence for the remaining cancers among nearly to totally blind persons was significantly higher than in average Finnish population."

"Our findings add to the suggestive epidemiological evidence for a decreased risk of hormone-related cancers in people with visual impairment and, consequently, a relationship between visible light at night and breast cancer risk. The result is strongly against the hypothesis of a systemic protective effect related lack of visible light."

[7] Melatonin & Angiogenesis.

[7a] (2009 - Korea)

"Melatonin, the main secretory product of the pineal gland, has been shown to exert an oncostatic activity in cancer cells. Recently, several studies have shown that melatonin has antiangiogenic properties. However, the mechanism by which melatonin exerts antiangiogenenic effects is not understood. Hypoxia inducible factor (HIF)-1 is a transcription factor which mediates adaptive response to changes in tissue oxygenation. ... In this study, pharmacologic concentrations of melatonin was found to inhibit expression of HIF-1 alpha protein under both normoxic and hypoxic conditions in DU145, PC-3, and LNCaP prostate cancer cells without affecting HIF-1 alpha mRNA levels. Consistent with the reduction in HIF-1 alpha protein levels, melatonin inhibited HIF-1 transcriptional activity and the release of vascular endothelial growth factor."

-Patrick

[1a] ncbi.nlm.nih.gov/pubmed/164...

[1b] ncbi.nlm.nih.gov/pubmed/230...

[2a] ncbi.nlm.nih.gov/pubmed/242...

[2b] ncbi.nlm.nih.gov/pubmed/139...

[2c] ncbi.nlm.nih.gov/pubmed/944...

[2d] ncbi.nlm.nih.gov/pubmed/251...

[3a] ncbi.nlm.nih.gov/pubmed/907...

[4a] ncbi.nlm.nih.gov/pubmed/110...

[4b] ncbi.nlm.nih.gov/pubmed/111...

[4c] ncbi.nlm.nih.gov/pubmed/153...

[5a] ncbi.nlm.nih.gov/pubmed/115...

[5b] ncbi.nlm.nih.gov/pubmed/121...

[6a] ncbi.nlm.nih.gov/pubmed/165...

[7a] ncbi.nlm.nih.gov/pubmed/195...

[bdriggers]

Do you trust the Life Extension protocol? They stand to benefit from supplement recommendations. Our nutritionalist recommended their

Super Bio-Curcumin 400mg. I do take that only. I have backed off Green Tea also.

[pjoshea13 in reply to bdriggers]

The LEF protocol is simply a list - one has to check why each item is on the list before buying in to it. (Note that there are many things not on the list.)

LEF has way more credibility than Mercola, etc., in my view.

On the other hand, Super Bio-Curcumin is not very super or bioavailable compared to some products. I favor Longvida - NOW sells it as CurcuBrain.

-Patrick

[AnnieAppleseed in reply to pjoshea13]

When I was diagnosed with breast cancer in Jan 1993, there were very few resources available or findable. Life Extension was there. They do quote studies, their products change over time with new research. Their prices are not bad. Yes, they sell stuff, but very few people or companies do things for free. That said, I founded all-volunteer nonprofit Annie Appleseed Project to provide info on (evidence-based) natural protocols and products. Active on line, on Facebook and with an e-newsletter.

[bdriggers in reply to pjoshea13]

I like the Super Bio-Curcumin but completely agree about Mercola.

[Charlean in reply to bdriggers]

Why have you backed off Green tea? Just curious because I still hear a great deal about its benefits.

Charlean

[AnnieAppleseed in reply to Charlean]

I've been taking LEF green tea capsules (lunchtime due to the light caffineation)

[bdriggers in reply to Charlean]

Charlean,

That's a good question

A few books I read and the nutritionalist at Provision Proton said you needed to drink 6-8 cups a day to get it's benefit. Depending on who you talk to or which study you read, that may or may not be too much fluoride. I cut back to one or two cups a week. Honestly, like I told Patrick, you can find 100 for and 100 against so many supplements I'm not a doctor I have just decided to minimize my supplements and maximize my meals I search for organic food and eat all in moderation it's the best I can do. Again, please realize, I'm just a guy with Prostate Cancer and my advice is not medical in any shape or fashion.

[Neal-Snyder in reply to bdriggers]

I drink 20 oz or so of white tea in the morning, instead of the Peet's French Roast I loved until I had advanced PC. White tea is made from the youngest buds & leaves of Camellia sinensis, the tree that also provides green, black & oolong teas. White tea is even more healthful than green. I get mine from Teatulia.com.

I also take 1 LEF lightly caffeinated green tea extract supplement daily. I used to take the decaf, but switched on Patrick's advice--more bioavailable, if I remember correctly, which I often don't anymore.

[bdriggers in reply to Charlean]

Charlean,

I feel horrible after my reply to you about Green tea. I want to stress again, I am not a doctor and a WHOLE LOT of people drink green tea. A WHOLE LOT of people. I have been thinking about it all day yesterday and I am going to start back. My nutritionalist is a very sharp young lady with a Masters degree and is the nutritionalist for a major college's sports programs including football, track, soccer, etc. she also is for a professional team. She firmly believes in felt even tea AT 6 CUPS A DAY. ( she said drink 3 cups and steep 2 bags if you use bags). She directed me to the teavana website. You can choose Country of origin, color, caffeine or not, etc. she believes them to be a high quality source of tea. I am sorry if I caused a disruption in your routine. I try to do all in moderation. I exercise and watch what goes in my mouth. I do purchase a lot of organic food from Walmart ( yes Walmart) and Kroger and Trader Joes. I consider eating right to mean as clean a food as I can obtain, eat mainly plant ( organic carrots, organic broccoli, organic gala apples,? organic cauliflower, organic asparagus ,organic Peanut butter ( I use Smuckers, and yes I know about the mold, but eat it in moderation and have a letter from Smuckers that the level is below the safe amount set by the Government. What do we really know about any food? Anyway. I am going to teavana today to purchase my green tea.

I will try my best to keep my weight down, exercise, eat everything in moderation and diversity, and attempt to get my supplements in food not pills, when I can. I'm considering just using Tumeric in cooking.

The one thing I truly miss is Beer. ( I know, shallow thinking, but in a hot Georgia day......)

Thank you for letting me clear my conscious and please, keep enjoying your tea!

Have a beautiful day!

[BigRich in reply to bdriggers]

Why not try non-alcoholic beer: Beck's or Brinkers. I enjoy drinking them for pure pleasure.

Rich

[Charlean]

That is definitely interesting. My husband worked nights for 25 years, with split days off. When he was off, he would try to sleep at night but on his work days, he slept during the day with great difficulty from light and noise.

Charlean

[AnnieAppleseed]

Several companies now make 'low blue light' glasses and night lights. Avoid turning lights on at night- melatonin dissipates immediately.

[Neal-Snyder]

Thanks for all of this, Patrick, including what your dosage of choice is.

Do we lose some of the benefits of melatonin at bedtime if we:

1. Turn the bathroom light on when we wake up to pee? (I often do 2 hours, like you.)

2. Have some light from street lights, etc., in the bedroom? (I assume moonlight is OK.)

3. Are night owls, doing a lot of our sleeping after dawn?

I've needed a trazodone at bedtime to sleep since I found out I had micro-metastases at the time of my RP, & I still have to listen to my music library on my iPod to get to sleep the first & subsequent times. So my biggest concern with melatonin is not with the minor help it may give me with sleeping. It's with making sure I get the full benefit of its ability to fight PC.

Again, thanks.

Neal

[Charlean]

I read a book, an entire fascinating book, on melatonin and according to the information, it is very important to all of us and as we age, we don't have enough. It really suggests that older folk take the supplements, which is why I have for a long time.

[Hidden]

Interesting. I've been taking melatonin as a sleep aid but only a 3 mg dose. Now that I know that it has a prostate cancer benefit I will look into ordering higher dose capsules.

[cesanon]

"Life Extension as part of their PCa protocol" Patrick

Life Extension has a pca protocol????

What is in their protocol?

[pjoshea13 in reply to cesanon]

T_A dismissed it as snake oil earlier this year.

-Patrick

[cesanon in reply to pjoshea13]

Apparently you don't dismiss it.

[cesanon in reply to cesanon]

I just went and posted the protocol on it's own post. Seems not unreasonable to me.

[pjoshea13 in reply to cesanon]

15 years ago there was very little to go on. I had yet to wade through PubMed. The LEF protocol was useful to me & I'm still here. They probably update it every other year, but I have not felt the need to keep up. Their advice is based on studies that they cite, but I already read everything that is added to PubMed each day.

-Patrick

[cesanon in reply to pjoshea13]

I sort of like using them as a base. I am reluctant to buy anything other than from them.

If it is in their protocol, no doubt they are selling it. LOL

Are you taking anything that is not in their protocol?

[pjoshea13 in reply to cesanon]

I haven't checked the protocol for some years. I expect that I take a lot of things that are not in it.

[cesanon in reply to pjoshea13]

TA can be a bit conservative at times.

Some here can be crazy and wild eyed.

Nothing wrong with a thoughtful and balanced approach. Even on the internet LOL