Melatonin and Breast Cancer

Fallleaves

(Edited on 10/6/16 to add: A new review of three large studies found NO link between night shift work and breast cancer. I added an article about this research under review articles.)

There are several topics that have already been created about light at night (LAN) affecting breast cancer, and melatonin suppressing breast cancer stem cells, as well as much discussion on many threads of melatonin as a sleep aid.

I thought I would try and put most of the studies related to melatonin and breast cancer in one spot, incorporating studies previously posted by Bestbird, cp148 and JohnSmith

To summarize, melatonin is a hormone secreted by the pineal gland at night, but is also produced by the immune system and is a metabolite of the amino acid tryptophan, found in many different foods (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC364576...). Melatonin levels drop with age (starting as early as 30), and seem to be lower in relation to increased BMI (http://www.ncbi.nlm.nih.gov/pubmed/25943349). Levels of melatonin are also reduced by exposure to light at night (LAN), and there have been many epidemiological studies linking increased rates of breast cancer to shift work, and exposure to outside and interior light during sleeping hours. Melatonin helps protect normal tissues from radiation therapy and may help reverse resistance to tamoxifen and various chemotherapy drugs. It may also have a use in the surgical setting to reduce anxiety and pain. Most importantly, Melatonin may itself be a treatment for breast cancer by reducing the production of estrogen in various ways, by modulating the immune system, and by anti-angiogenic and anti-metastatic actions. Not all studies have shown a benefit, but there is some research showing it may synergize with various breast cancer treatments and reduce side effects. Finally, there is evidence it helps improve sleep in some people.

Review Articles

Working night shifts unlikely to increase breast cancer risk

"The researchers found that the incidence of breast cancer was essentially the same whether someone did no night shift work at all or did night shift work for several decades -- the combined relative risks taking all 10 studies together were 0.99 for any night shift work, 1.01 for 20 or more years of night shift work, and 1.00 for 30 or more years night shift work."

https://www.sciencedaily.com/releases/2016/10/1610...

(10/6/2016)

Circadian disruption and breast cancer: An epigenetic link?

"In 2007, the International Agency for Research on Cancer (IARC) concluded "shift work that involves circadian disruption is probably carcinogenic to humans" [13]. Although this statement refers to shift work as a potential carcinogen, shift work is not the only potential cause of circadian disruption (CD). Time zone changes, jet lag, space travel, psychiatric disorders, and even light exposure from lamps and electronics during the evening hours can cause circadian disruption [14–18]. Furthermore, studies have shown that CD can promote the spontaneous development of a variety of tumours in a rodent model, and that CD may be linked to a higher risk of prostate cancer in men [19–21]. However, the most prominent link established thus far between CD and carcinogenesis has been in breast cancer, and recent case studies have supported the 2007 IARC claim by providing indirect evidence that shift workers are at a higher risk of developing breast cancer. Specifically, studies found that work after midnight significantly increased the risk of breast cancer in women when compared to day work, that the risk increased with the duration and accumulation of overnight shifts, and that rotating shifts between day and night is more disruptive than permanent night work "

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627279/
(Kochan, 2015)

Melatonin: an Inhibitor of Breast Cancer

"In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin, via the MT1 receptor, suppresses ERα mRNA expression and ERα transcriptional activity. As well, melatonin regulates the transactivation of other members of the nuclear receptor super-family, estrogen metabolizing enzymes, and the expression of core clock and clock-related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism (Warburg effect), and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways including inhibition of p38 MAPK and repression of epithelial-to-mesenchymal transition... Finally, research in animal and human models indicate that LEN (light at night) induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer to drive breast tumors to endocrine and chemotherapeutic resistance. "
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457700/
(Hill, 2015)

Breast cancer cell studies

Membrane-bound melatonin receptor MT1 down-regulates estrogen responsive genes in breast cancer cells (ER+)

"Expression of BRCA-1, p53, p21(WAF) and c-myc were up-regulated by estradiol. Treatment of the stimulated cells with melatonin counteracted the increase induced by estradiol almost completely. The more MT1 a cell line expressed, the stronger was the reduction of the expression of the estradiol-induced genes."

http://www.ncbi.nlm.nih.gov/pubmed/19522736

(Girgert, 2009)

Melatonin Represses Metastasis in Her2-Postive Human Breast Cancer Cells by Suppressing RSK2 Expression. (ER-, HER2+ and ER+, HER2+)

"In the present study, the anti-metastatic actions of melatonin were evaluated and compared on the ERa-negative, Her2-positive SKBR-3 breast tumor cell line and ERa-positive MCF-7 cells overexpressing a constitutively active HER2.1 construct (MCF-7Her2.1 cells). Melatonin inhibition of Rsk2 represses the metastatic phenotype in breast cancer cells suppressing EMT or inhibiting other mechanisms that promote metastasis; disruption of the melatonin signal may promote metastatic progression in breast cancer."

http://www.ncbi.nlm.nih.gov/pubmed/27535706

(Mao, 2016)

Melatonin Regulates Angiogenic Factors under Hypoxia in Breast Cancer Cell Lines. (TN and ER+)

The results showed that 1 mM of melatonin reduced the viability of MCF-7 and MDA-MB-231 cells (p < .05). This treatment also decreased both gene and protein expression of HIF-1α and VEGF-A under hypoxic conditions (p < .05). Among the proteins evaluated by protein array, melatonin treatment during hypoxia reduced VEGF-C, VEGFR receptors (VEGFR2 and VEGFR3), matrix metalloproteinase 9 (MMP9) and Angiogenin in MCF-7 cells. In MDA-MB-231 cells, a significant decrease was observed in VEGFR2, epidermal growth factor receptor (EGFR) and Angiogenin (p < .05). Taken together, these results showed that melatonin acts in the regulation of angiogenic factors in breast tumor cells and suggests an anti-angiogenic activity, particularly under hypoxic conditions.

https://www.ncbi.nlm.nih.gov/pubmed/25963143

(Jardim-Perassi, 2016)

Melatonin decreases estrogen receptor binding to estrogen response elements sites on the OCT4 gene in human breast cancer stem cells.

Here, we evaluated the effect of melatonin on the regulation of the transcription factor OCT4 (Octamer Binding 4) by estrogen receptor alpha (ERα) in breastcancer stem cells (BCSCs). The cells were grown as a cell suspension or as anchorage independent growth, for the mammospheres growth, representing the CSCs population and treated with 10 nM estrogen (E2) or 10 μM of the environmental estrogen Bisphenol A (BPA) and 1 mM ofmelatonin. At the end, the cell growth as well as OCT4 and ERα expression and the binding activity of ERα to the OCT4 was assessed. The increase in number and size of mammospheres induced by E2 or BPA was reduced by melatonin treatment. Furthermore, binding of the ERα to OCT4 was reduced, accompanied by a reduction of OCT4 and ERα expression. Thus, melatonin treatment is effective against proliferation of BCSCs in vitro and impacts the ER pathway, demonstrating its potential therapeutic use in breast cancer.

http://www.ncbi.nlm.nih.gov/pubmed/27551335

(Lopes, 2016)

Use in Cancer Therapy for solid tumors

Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. (study of 250 patients, 77 of them with breast cancer)

The 1-year survival rate and the objective tumour regression rate were significantly higher in patients concomitantly treated with MLT than in those who received chemotherapy (CT) alone (tumour response rate: 42/124 CT + MLT versus 19/126 CT only, P < 0.001; 1-year survival: 63/124 CT + MLT versus 29/126 CT only, P < 0.001). Moreover, the concomitant administration of MLT significantly reduced the frequency of thrombocytopenia, neurotoxicity, cardiotoxicity, stomatitis and asthenia. This study indicates that the pineal hormone MLT may enhance the efficacy of chemotherapy and reduce its toxicity, at least in advanced cancer patients of poor clinical status.

http://www.ncbi.nlm.nih.gov/pubmed/10674014

(Lissoni, 1999)

Chemoneuroendocrine therapy of metastatic breast cancer with persistent thrombocytopenia with weekly low-dose epirubicin plus melatonin: a phase II study.

"The study was performed in 14 metastaticbreast cancer women treated by weekly epirubicin. Each cycle consisted of epirubicin at 25 mg/m2 i.v. at weekly intervals. Melatonin was given orally at 20 mg/day in the evening every day, starting 7 days prior to chemotherapy. Patients were considered as evaluable when they received at least four cycles of chemotherapy. Evaluable patients were 12/14. The induction phase with melatonin induced a normalization of platelet number in 9/12 evaluable patients, and no further platelet decline occurred in chemotherapy. Objective tumor regression was achieved in 5/12 (41%) patients. This preliminary study would suggest that melatonin may be effective in the treatment of cancer-related thrombocytopenia and to prevent chemotherapy-induced platelet decline. Until now, melatonin therapy of cancer has been generally considered as an alternative treatment to chemotherapy. In contrast, this study would suggest that melatonin may contribute to the realization of chemotherapy in metastatic cancer patients unable to tolerate the chemotherapeutic approach because of persistent thrombocytopenia."

http://www.ncbi.nlm.nih.gov/pubmed/10231730

(Lissoni, 1999)

The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials.

"The search strategy identified 8 eligible RCTs (n = 761), all of which studied solid tumor cancers. The dosage of melatonin used in the 8 included RCTs was 20 mg orally, once a day. Melatonin significantly improved the complete and partial remission (16.5 vs. 32.6%; RR = 1.95, 95% CI, 1.49-2.54; P < 0.00001) as well as 1-year survival rate (28.4 vs. 52.2%; RR = 1.90; 95% CI, 1.28-2.83; P = 0.001), and dramatically decreased radiochemotherapy-related side effects including thrombocytopenia (19.7 vs. 2.2%; RR = 0.13; 95% CI, 0.06-0.28; P < 0.00001), neurotoxicity (15.2 vs. 2.5%; RR = 0.19; 95% CI, 0.09-0.40; P < 0.0001), and fatigue (49.1 vs. 17.2%; RR = 0.37; 95% CI, 0.28-0.48; P < 0.00001). Effects were consistent across different types of cancer. No severe adverse events were reported. Melatonin as an adjuvant therapy for cancer led to substantial improvements in tumor remission, 1-year survival, and alleviation of radiochemotherapy-related side effects."

http://www.ncbi.nlm.nih.gov/pubmed/22271210

(Wang, 2012)

Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials.

"The authors included data from 21 clinical trials, all of which dealt with solid tumors. The pooled relative risk (RR) for 1-year mortality was 0.63 (95% confidence interval [CI] = 0.53-0.74; P < .001). Improved effect was found for complete response, partial response, and stable disease with RRs of 2.33 (95% CI = 1.29-4.20), 1.90 (1.43-2.51), and 1.51 (1.08-2.12), respectively. In trials combining MLT with chemotherapy, adjuvant MLT decreased 1-year mortality (RR = 0.60; 95% CI = 0.54-0.67) and improved outcomes of complete response, partial response, and stable disease; pooled RRs were 2.53 (1.36-4.71), 1.70 (1.37-2.12), and 1.15 (1.00-1.33), respectively. In these studies, MLT also significantly reduced asthenia, leucopenia, nausea and vomiting, hypotension, and thrombocytopenia. MLT may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy."

http://www.ncbi.nlm.nih.gov/pubmed/22019490

(Seely, 2012)

Treatment Resistance and Melatonin

Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer.

"In this study, we used a rat model of estrogen receptor (ERα(+)) MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characteristics were not observed in animals in which the circadian melatonin rhythm was not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression."

http://www.ncbi.nlm.nih.gov/pubmed/25062775
(Dauchy, 2014)

Doxorubin resistance driven by light at night/melatonin disruption

"We demonstrate in tissue-isolated estrogen receptor alpha-positive (ERα+) MCF-7 human breast cancer xenografts, grown in nude rats maintained on a light/dark cycle of LD 12:12 in which dLEN is present during the dark phase (suppressed endogenous nocturnal melatonin), a significant shortening of tumor latency-to-onset, increased tumor metabolism and growth, and complete intrinsic resistance to Dox therapy. Conversely, a LD 12:12 dLEN environment incorporating nocturnal melatonin replacement resulted in significantly lengthened tumor latency-to-onset, tumor regression, suppression of nighttime tumor metabolism, and kinase and transcription factor phosphorylation, while Dox sensitivity was completely restored.Melatonin acts as both a tumor metabolic inhibitor and circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to Dox and drive tumor regression, indicating that dLEN-induced circadian disruption of nocturnal melatonin production contributes to a complete loss of tumor sensitivity to Dox chemotherapy."
http://www.ncbi.nlm.nih.gov/pubmed/25857269

(Xiang, 2015)

Synergic Effects of Doxorubicin and Melatonin on Apoptosis and Mitochondrial Oxidative Stress in MCF-7Breast Cancer Cells: Involvement of TRPV1 Channels.

"The intracellular production of reactive oxygen species, mitochondrial membrane depolarization, apoptosis level, procaspase 9 and PARP activities, and caspase 3 and caspase 9 activities were higher in the DOX and MEL groups than in the control. Apoptosis and the activity of caspase 9 were further increased in the DOX plus MEL groups. Taken together, the findings indicate that MEL supported the effects of DOX by activation of TRPV1 and apoptosis, as well as by inducing MCF-7 cell death. As the apoptosis and caspase activity of cancer cells increase because of their elevated metabolism, MEL may be useful in supporting their apoptotic capacity."

http://www.ncbi.nlm.nih.gov/pubmed/26525975

(Kosar, 2016)

Radiation Therapy

Can Melatonin Help Us in Radiation Oncology Treatments?

"Ionizing radiation interacts with biological systems to produce free radicals, which attack various cellular components. Radioprotectors act as prophylactic agents that are administered to shield normal cells and tissues from the harmful effects of radiation. Melatonin has been shown to be both a direct free radical scavenger and an indirect antioxidant by stimulating antioxidant enzymes and suppressing prooxidative enzymes activity. In addition to its antioxidant property, there have also been reports implicating antiapoptotic function for melatonin in normal cells. Furthermore, through its antitumor and radiosensitizing properties, treatment with melatonin may prevent tumor progression."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037598/

(Mihandoost, 2014)

Melatonin for Prevention of Breast Radiation Dermatitis: A Phase II, Prospective, Double-Blind Randomized Trial.

"The occurrence of grade 1/2 acute radiation dermatitis was significantly lower (59% vs. 90%, P = 0.038) in the melatonin group. Women older than 50 had significantly less dermatitis than younger patients (56% vs. 100%, P = 0.021). The maximal radiation dermatitis in the study group was grade 2 in 15% of the treated patients."

http://www.ncbi.nlm.nih.gov/pubmed/27228641

(Ben-David, 2016)

Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double-strand DNA break repair.

Pretreatment of breast cancer cells with melatonin 1 wk before radiation led to a significantly greater decrease of MCF-7 cell proliferation compared with radiation alone. Melatonin pretreatment before radiation also decreased G2 -M phase arrest compared with irradiation alone, with a higher percentage of cells in the G0 -G1 phase and a lower percentage of cells in S phase. Radiation alone diminished RAD51 and DNA-protein kinase (PKcs) mRNA expression, two main proteins involved in double-strand DNA break repair. Treatment with melatonin for 7 days before radiation led to a significantly greater decrease in RAD51 and DNA-PKcs mRNA expression compared with radiation alone. Our findings suggest that melatonin pretreatment before radiation sensitizes breast cancer cells to the ionizing effects of radiation by decreasing cell proliferation, inducing cell cycle arrest and downregulating proteins involved in double-strand DNA break repair.

http://www.ncbi.nlm.nih.gov/pubmed/25623566

(Alonzo-Gonzalez, 2015)

Melatonin enhancement of the radiosensitivity of human breast cancer cells is associated with the modulation of proteins involved in estrogen biosynthesis.

We demonstrated a role of melatonin in mediating the sensitization of human breast cancer cells to the ionizing radiation by decreasing around 50% the activity and expression of proteins involved in the synthesis of estrogens in these cells. Thus, melatonin pretreatment before radiation reduces the amount of active estrogens at cancer cell level. Melatonin 1 nM induced a 2-fold change in p53 expression as compared to radiation alone. The regulatory action of melatonin on p53 could be a link between melatonin and its modulatory action on the sensitivity of breast cancer cells to ionizing radiation.

http://www.ncbi.nlm.nih.gov/pubmed/26497762

(Alonzo-Gonzalez, 2016)

Surgical/Sleep benefits

Melatonin for preop and postoperative anxiety in adults (Cochrane review)
"When compared to placebo, melatonin given as premedication (tablets or sublingually) can reduce preoperative anxiety in adults (measured 50 to 100 minutes after administration). Melatonin may be equally as effective as standard treatment with midazolam in reducing preoperative anxiety in adults (measured 50 to 100 minutes after administration). The effect of melatonin on postoperative anxiety (measured 90 minutes and 6 hours after surgery) in adults is mixed but suggests an overall attenuation of the effect compared to preoperatively."
http://www.ncbi.nlm.nih.gov/pubmed/25856551

A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects. (As an analgesic agent)

"The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent."
http://www.ncbi.nlm.nih.gov/pubmed/25947930

A randomized, placebo-controlled trial of melatonin on breast cancer survivors: impact on sleep, mood, and hot flashes.

"Compared to subjects on placebo, subjects randomized to melatonin experienced significantly greater improvements in subjective sleep quality as measured by the PSQI, including domains on sleep quality, daytime dysfunction and total score. For example, the mean change in PSQI score was -0.1 in the placebo group compared to -1.9 in the melatonin group. There were no significant differences in measures of depression or hot flashes."
http://www.ncbi.nlm.nih.gov/pubmed/24718775

(Chen, 2014)

Effect of Melatonin on Cognitive Function and Sleep in relation to Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

"The total sleep period was significantly longer in the melatonin group; mean difference was 37.0 min. Melatonin increased sleep efficiency and total sleep time but did not affect cognitive function."

http://www.ncbi.nlm.nih.gov/pubmed/25328711

(Hansen, 2014)

Effect of Melatonin on Sleep in the Perioperative Period after Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

"Administration of 6 mg oral melatonin approximately 1 hour before bedtime resulted in significantly increased sleep efficiency and reduced wake after sleep onset for the entire 2-week postoperative period."

http://www.ncbi.nlm.nih.gov/pubmed/26414973

(Madsen, 2016)

Fallleaves

Thanks, Kayb! Please let me know if there's anything I should add---I know you are familiar with the research on melatonin.

geewhiz

Thank you SO much for keeping this in the forefront of our minds! I read so many studies and rotate through supplements accordingly...and had fallen off the melatonin bandwagon for a bit. Back on it I will go!!

Fallleaves

Geewhiz, you raise a good point, that occurred to me when I was looking at all the different substances that show promise. It's hard to keep track of all the supplements that could help with breast cancer. And it's hard to determine which ones are the best to take. I cycle through stuff, too, because I lose track. I wish there was an entity that would keep track of all the different studies on natural substances and sort of give us a running scorecard on how effective they are, and which ones show the greatest promise. Foodforbreastcancer.com is really good site, that keeps track of a lot of studies (I go there a lot to see if I'm missing anything!) But I really feel like this is something that should be under the auspices of the NCCIH (National Center for Complementary and Integrative Health) They do have some things of value like this clinical practice guide for BC: http://jncimono.oxfordjournals.org/content/2014/50..., and this guide for patients: https://www.cancer.gov/publications/patient-educat...

But there doesn't seem to be anyone evaluating the research that has been done to identify the most promising areas for further research, and the integrative treatments and supplements that are currently best supported. I realize the NCCIH is operating with a small budget, but I would love to see them try and direct research being done by other institutions so it could be more collaborative and effective. Or if not them, another organization, that is just focused on cancer research. (There probably is, and I'm just not aware of it!)

ClarkBlue

I bought some Melatonin today! Thank you!

-Keely

tgtg

Fallleaves--

In response to your observation, "...there doesn't seem to be anyone evaluating the research that has been done to identify the most promising areas for further research...," I would suggest a reason other than government funding or lack thereof as a reason. Melatonin is an over-the-counter supplement, and relatively inexpensive at that, and is not produced by big Pharma, which funds an overwhelming number of studies.. But there is no percentage to the pharma industry in funding a study that might cut into their huge profits!

pupmom

Tgtg, then why is low dose aspirin now routinely recommended to prevent heart attack and cancer by physicians? That OTC med is about as cheap as it gets.

KathyL624

I just bought some today too! Are you supposed to take it at night? Do you feel results quickly or does it takes a few weeks

pupmom

KathyL624, what do you mean by "results?" Melotonin is typically taken to help one sleep. It should work the first time you take it. If you mean cancer prevention, who knows! I guess if you don't get a recurrence you can praise Melatonin, or any number of other factors. I took Melatonin for 10 years before I got breast cancer, so I'm not so sure.

KathyL624

I actually meant, does it work like a sleeping pill to immediately help you sleep? Since it is a supplement/vitamin I didn't know if it worked slowly, like Vitamin D or Calcium pills, to build up melatonin levels. So, do I take it in the evening to help me sleep that night? Sorry if I wasn't clear.

pupmom

In my experience, it worked the first time. But there are many different dosage levels for Melatonin. You might want to get a lower dose and move to higher dosages if the first, lower, one does not work. I currently take 3 mg. for sleep. Best wishes to you Kathy!

ChiSandy

I think supplements would be more highly regarded, respected and taken more seriously by the medical community if the FDA were allowed to regulate them the way it does OTC drugs and even food! The problem is not that the pharm industry can't make money off them--it's that there's no enforceable and truly reliable way to tell that consumers are getting exactly what the label says: no more, no less, nothing but. It isn't even a matter of testing for efficacy--there is no verifiable measure of quantity, purity and safety. The supplement lobby is deep-pocketed and notoriously anti-government libertarian, and it contributes heavily to like-minded conservatives in Congress who make the laws and confirm or deny the appointment of FDA commissioners and staffers who make the administrative regs & policies. "Big Pharma" may have bigger money, but it by-and-large lacks within its own ranks the rabidly anti-regulation supporters and sympathetic gov't officials that the supplement lobby does. Money + passion are a very difficult combination to breach.

And if supplements could be so regulated, the pharm industry would be onboard and join the money-making bandwagon (and we could be assured that at least we're getting what we pay for). Nothing wrong with wanting to make money per se--if there were, everyone who succeeds financially or even makes a decent living would be on the road to perdition. The profit motive is evil only if unaccompanied by a motive to do good. If all Big Pharma wanted to do was turn a profit, they'd abandon the drug business and become private equity venture capitalists and hedge fund managers.

And I say this as someone who does take several supplements.

Fallleaves

Kayb, I'm glad to hear there's more of a collaborative environment among cancer researchers than I was aware of. My experience with science is limited to the period my mom worked at Johns Hopkins University in the Biophysics department, when I was in high school! It was pretty cutthroat among scientists back then. But I imagine things have changed a lot, and with cancer research there's a much greater sense of something bigger at stake than making one's mark.

Yorkiemom, I hope you don't think I'm putting melatonin out there as a panacea. I don't think anything is a panacea. You can take tamoxifen and AI's and still get a recurrence, but I also think those drugs are of great value. There are a lot of factors at play when any of us get breast cancer. I ran 3 miles a day almost every day before I got cancer. Do I feel like exercise was of no value in preventing breast cancer? No. Maybe it meant I got a more favorable type of breast cancer, and maybe it kept it in check longer. Even now I consider it a form of medicine. I just think there were other factors promoting the breast cancer that overwhelmed the good things I was doing, including the exercise. So, I figure the more things we do to tip the scales, the better.

ChiSandy, I have mixed feelings about increasing regulation on supplements. You raise some good points about the supplement lobby, which is, after all, driven by money, too. A few years ago I read a book that was critical of the industry and illustrated how hard it was for the FDA to take a supplement off the market (they talked about ephedra and a few others), but by the same token there are millions of people taking supplements every day and very few instances of harm. I would think the gov't could use existing laws to ensure that supplements are what they say they are. Isn't it considered fraud to market something as other than what it is purported to be? I also have a hard time wanting to increase regulation on supplements, when chemical regulation is still so weak, even with the newly revised Toxic Substances Control Act. In the meantime, consumerlab.com seems like a pretty good watchdog organization.

pupmom

Falleaves, I don't disagree! I still take Melatonin. It helps me sleep, and if it can help prevent a recurrence, so much the better!

ChiSandy

Actually, Fallleaves, without a specific statute, protecting the public from unsafe drugs is at best tough and at worst meaningless. Watchdog organizations are toothless. Just because other substances are insufficiently regulated, it doesn’t mean we should throw in the towel and give supplement manufacturers a free pass. Fraud prosecutions, even via civil suits, can take years, even a decade--with overburdened gov’t lawyers outmatched by white-shoe law firms whose ticking meters are being paid for by some very, very deep pockets. (I ought to know--I’ve worked as a lawyer on both sides). And by your logic, the gov’t shouldn’t regulate the purity and safety of food, either. Think of that the next time you visit the grocer, butcher or fishmonger--or eat in a restaurant.

We need to stop putting all our faith in private enterprise. It doesn’t work, precisely because it is motivated purely by profit. I shudder to think what might happen if we end up divesting our governments of every function on which somebody gets to make a buck. We’ve seen this happen when private equity companies take over public utilities--most recently, EMS and fire services. (The N.Y. Times had a frightening and depressing series of articles on this). No, we shouldn’t have to rely on gov’t for everything. But I don’t trust the free-market system any further than I can throw it.

pupmom

What ChiSandy just said!

Fallleaves

ChiSandy, I agree that we shouldn't be putting our trust in private industry (I am a Democrat!) However, I think the FDA does have some oversight over the supplements industry

What is FDA's oversight responsibility for dietary supplements?

Because dietary supplements are under the "umbrella" of foods, FDA's Center for Food Safety and Applied Nutrition (CFSAN) is responsible for the agency's oversight of these products. FDA's efforts to monitor the marketplace for potential illegal products (that is, products that may be unsafe or make false or misleading claims) include obtaining information from inspections of dietary supplement manufacturers and distributors, the Internet, consumer and trade complaints, occasional laboratory analyses of selected products, and adverse events associated with the use of supplements that are reported to the agency.

http://www.fda.gov/Food/DietarySupplements/UsingDi...

I would definitely be in favor of increasing funding for more than "occasional" lab tests, and to ensure purity and clarity of sourcing. I just wouldn't treat supplements like drugs, because there is a long history of human consumption of almost all supplements, whereas drugs are newly created compounds. I don't think supplements are all harmless by any means, and we should definitely keep track of studies that indicate potential harm to human health, publicize any possible health threats, and if the evidence is strong enough ban them. I would also track adverse reactions, as the FDA does, and make sure there is clear communication between health care providers and the agency. The FDA's budget should be increased for EVERYTHING they have to do. I don't feel very confident in food safety in general at this point (E. Coli, salmonella, antibiotic resistant bacteria, etc). Supplements are the least of my worries.

wallycat

For those using melatonin for sleep, take it 30 to 45 minutes BEFORE you plan to go to bed.

Melatonin is a hormone and it works right away. I will say that some people experience zero sleep benefit from it and I often wonder if it is a genetic variant/pathway, as can happen with so many other drugs we take.

I also think that dosage matters. For sleep, 3mg can be enough for some people. For off-label hope that it can stave off a recurrence, a higher dosage may be required. The same has been found with Vitamin D. At "recommended" levels, some of the benefits that are seen in high doses are simply never experienced at the lower dose.

Anonymous

Does anyone know how long you can you can take it? I have been taking it for 9 years.

wallycat

Melatonin is non toxic and naturally made in the body, so I don't believe there is a cut-off.

I'm on year 9-1/2 at 20mg. I don't know if it will help with the cancer part, but it helps me sleep.

MelissaDallas

I am concerned about the possibility of blood sugar elevation. My weight has really zoomed up recently and I think it started about the time I consistently started taking melatonin. I need to try taking my bs levels for a few days with and without to see if it is upping my blood glucose level. I already know that if I take more than 3mg that it makes me extremely irritable and anxious.

From WebMD

Melatonin is LIKELY SAFE for most adults when taken by mouth or injected into the body in the short-term, or when applied to the skin.

Melatonin is POSSIBLY SAFE when used by mouth appropriately, long-term. Melatonin has been used safely for up to 2 years in some people. However, it can cause some side effects including headache, short-term feelings of depression, daytime sleepiness, dizziness, stomach cramps, and irritability. Do not drive or use machinery for four to five hours after taking melatonin.

Special Precautions & Warnings:

Pregnancy and breast-feeding: Melatonin is POSSIBLY UNSAFE when taken by mouth or injected into the body during pregnancy. Do not use it. Melatonin might also interfere with ovulation, making it more difficult to become pregnant.

Not enough is known about the safety of using melatonin when breast-feeding. It is best not to use it.

Children: Melatonin is POSSIBLY SAFE when taken by mouth as a single dose. It is POSSIBLY UNSAFE when taken by mouth or injected into the body in multiple doses in the short-term. Because of its effects on other hormones, melatonin might interfere with development during adolescence.

Bleeding disorders: Melatonin might make bleeding worse in people with bleeding disorders.

Depression: Melatonin can make symptoms of depression worse.

Diabetes: Melatonin might increase blood sugar in people with diabetes. Monitor your blood sugar carefully, if you have diabetes and take melatonin.

High blood pressure: Melatonin can raise blood pressure in people who are taking certain medications to control blood pressure. Avoid using it.

Seizure disorders: Using melatonin might increase the risk of having a seizure.

Transplant recipients: Melatonin can increase immune function and might interfere with immunosuppressive therapy used by people receiving transplants.

Do not take this combination

• Sedative medications (CNS depressants) interacts with MELATONIN
  Melatonin might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking melatonin along with sedative medications might cause too much sleepiness.
  Some sedative medications include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.

Moderate Interaction Be cautious with this combination

• Birth control pills (Contraceptive drugs) interacts with MELATONIN
  The body makes melatonin. Birth control pills seem to increase how much melatonin the body makes. Taking melatonin along with birth control pills might cause too much melatonin to be in the body.
  Some birth control pills include ethinyl estradiol and levonorgestrel (Triphasil), ethinyl estradiol and norethindrone (Ortho-Novum 1/35, Ortho-Novum 7/7/7), and others.
• Caffeine interacts with MELATONIN
  Caffeine might decrease melatonin levels in the body. Taking melatonin along with caffeine might decrease the effectiveness of melatonin supplements.
• Fluvoxamine (Luvox) interacts with MELATONIN
  Taking fluvoxamine (Luvox) can increase the amount of melatonin that the body absorbs. Taking melatonin along with fluvoxamine (Luvox) might increase the effects and side effects of melatonin.
• Medications for diabetes (Antidiabetes drugs) interacts with MELATONIN
  Melatonin might increase blood sugar. Diabetes medications are used to lower blood sugar. By increasing blood sugar, melatonin might decrease the effectiveness of diabetes medications. Monitor your blood sugar closely. The dose of your diabetes medication might need to be changed.
  Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others.
• Medications that decrease the immune system (Immunosuppressants) interacts with MELATONIN
  Melatonin might increase the immune system. Taking melatonin along with medications that decrease the immune system might decrease the effectiveness of medications that decrease the immune system.
  Some medications that decrease the immune system include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), corticosteroids (glucocorticoids), and others.
• Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs) interacts with MELATONIN
  Melatonin might slow blood clotting. Taking melatonin along with medications that also slow clotting might increase the chances of bruising and bleeding.
  Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
• Nifedipine GITS (Procardia XL) interacts with MELATONIN
  Nifedipine GITS (Procardia XL) is used to lower blood pressure. Taking melatonin might decrease the effectiveness of nifedipine GITS for lowering blood pressure.
• Sedative medications (Benzodiazepines) interacts with MELATONIN
  Melatonin might cause sleepiness and drowsiness. Drugs that cause sleepiness and drowsiness are called sedatives. Taking melatonin along with sedative medications might cause too much sleepiness.
  Some of these sedative medications include clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), and others.
• Verapamil (Calan, Covera, Isoptin, Verelan) interacts with MELATONIN
  The body breaks down melatonin to get rid of it. Verapamil (Calan, Covera, Isoptin, Verelan) can increase how quickly the body gets rid of melatonin. Taking melatonin along with verapamil (Calan, Covera, Isoptin, Verelan) might decrease the effectiveness of melatonin.

Minor Interaction Be watchful with this combination

• Flumazenil (Romazicon) interacts with MELATONIN
  Flumazenil (Romazicon) might decrease the effects of melatonin. It is not yet clear why this interaction occurs yet. Taking flumazenil (Romazicon) along with melatonin might decrease the effectiveness of melatonin supplements.

wallycat

Melissa,

That is interesting. Many of the diabetes/glucose studies have been done on rats and I see very little on humans, so I am wondering where they are getting their information for this specific topic.

I know my fasting glucose actually went down when I started low-carbing, and I was able to lose some of the weight I gained from the tamoxifen and AI regime. I'm starting to add back some carbs so I will see what happens with my labs.

Some of the peer reviewed journals using rats indicated that special genetic alleles influence getting diabetes from the outstart. My first higher fasting glucose was pre-cancer when I was doing the low-fat/high carb craze and I still had a bmi of 19 or 20.

Fallleaves

MelissaDallas,

The research on melatonin and diabetes indicates there may be different effects on type 1 and type 2 diabetes http://www.ncbi.nlm.nih.gov/pubmed/21929683

Some research indicates that melatonin levels are lower in women at risk of type 2 diabetes http://www.webmd.com/diabetes/news/20130402/study-...

This explains some of the relationship between melatonin and insulin: "Melatonin may be involved in the genesis of diabetes as a reduction in melatonin levels and a functional interrelationship between melatonin and insulin was observed in diabetic patients. Evidences from experimental studies proved that melatonin induces production of insulin growth factor and promotes insulin receptor tyrosine phosphorylation. The disturbance of internal circadian system induces glucose intolerance and insulin resistance, which could be restored by melatonin supplementation." http://www.ncbi.nlm.nih.gov/pubmed/26331226

However, this study indicates that certain polymorphisms for melatonin receptors may lead to increased risk of type 2 diabetes: https://www.sciencedaily.com/releases/2016/05/1605...

Makes me think this may be another reason having a longer fasting cycle at night is probably beneficial in reducing breast cancer recurrence, because this is when insulin levels are naturally lowest. So if you are not eating during that time you would not be creating a glucose load at a point that your body is least able to handle it. https://community.breastcancer.org/forum/73/topics...

wallycat

Fallleaves, I cannot open the scielo link.

I also found this: https://www.ncbi.nlm.nih.gov/pubmed/21298562
Interestingly, some of the rat studies show that melatonin can maintain the glycogen in liver-stores. People with high fasting glucose can be experiencing something similar to the "dawn phenomenon" in diabetics..

pupmom

Wallycat, can you give me the layperson's definition of "maintain the glycogen in liver-stores?" Thanks!

Jiffrig

Everyone thinks all kinds of things cause them to gain weight and raise glucose. Usually it's eating too much

pupmom

Jiffrig, that made me lol! I know that once I passed age 40 it became harder for me to lose weight, although I am still well within my BMI. But, that's only because I watch my carbs religiously.

MelissaDallas

Gee, it never dawned on me that eating too much makes me fat

I haven't changed my eating habits or the amount I eat or exercise. I just started gaining weight fast all of a sudden the last couple of months. I am not diabetic, but I am skating dangerously close to getting there.

ChiSandy

Jiffrig, that is extremely simplistic. It is a statement that has led to damaging misconceptions, harmful dietary advice (e.g., the low-fat craze that caused an obesity epidemic), and devastating prejudice against the obese, the one prejudice that remains socially acceptable.

Yes, it all comes down to “calories in vs. calories out" but there are so many factors that affect not only the “calories out" (including the slowed metabolism that comes from estrogen reduction) but also the “calories in," because our bodies process the various macronutrients (carb, protein, fat) very differently and therefore drastically affect the potential energy (calories) in those macronutrients as well as how our bodies use them. Throw into the mix that not everyone processes a given amount of a given macronutrient the same way (nor even that a given individual processes it the same way at various stages of life or altered medical condition), and you can see that “fat people eat too much" is a grossly inaccurate statement--regardless of the intent behind it.

Fallleaves

Wallycat, thanks for the heads up on the scielo link. I changed it to the pubmed link to the study.

Jiffrig

Sorry, didn't mean to have that statement taken so seriously! Where's those emojis when you need them