Melatonin - what do you think?

Flalady, I use it.  I usually take 6mg/nightly (one 3mg timed release to keep me asleep and one 3mg regular tab to put me asleep).  On the weekends I can take 8 (3mg TR and 5mg reg). I take it about 30 minutes before I want to be asleep and I sleep very well.  It is also supposed to be good for your bones.  Best wishes

Althea, here is a little blurb on how it acts against bc:

 Breast Cancer

"Several studies indicate that melatonin levels may be linked with breast cancer risk. For example, women with breast cancer tend to have lower levels of melatonin than those without the disease. In addition, laboratory experiments have found that low levels of melatonin stimulate the growth of certain types of breast cancer cells, while adding melatonin to these cells inhibits their growth. Preliminary laboratory and clinical evidence also suggests that melatonin may enhance the effects of some chemotherapy drugs used to treat breast cancer. In a study that included a small number of women with breast cancer, melatonin (administered 7 days before beginning chemotherapy) prevented the lowering of platelets in the blood. This is a common complication of chemotherapy, known as thrombocytopenia that can lead to bleeding.

In another study of a small group of women whose breast cancer was not improving with tamoxifen (a commonly used chemotherapy medication), adding melatonin caused tumors to modestly shrink in over 28% of the women."

I take Schiff's knock out which is a combination of Melatonin, l-theanine

and Valerian which Constantine suggested for me to help my insomnia.

They also have a formulation which only contains the Melatonin an l-theanine.

Swanson vitamins put out a 10mg melatonin.

Swanson also has a 3 mg dual release---have the tab releases immediately

and the other half releases later to keep you asleep.

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Here is info on the benefits of melatonin from Constantine's site.

Melatonin Antitumor Activity
Taking the protective role for melatonin further, Kim et al. (J Cardiovasc Pharmacol (2005): Modulation by Melatonin of the Cardiotoxic and Antitumor Activities of Adriamycin) have shown that given melatonin's oncolytic activity, the combination of adriamycin and melatonin improved the antitumor activity of adriamycin, as indicated by an increase in the number of long-term survivors as well as decreases in body-weight losses resulting from adriamycin treatment, suggesting that melatonin not only protects against adriamycin-induced cardiotoxicity but also enhances its antitumor activity and further suggesting that a melatonin and adriamycin combination represents a potentially useful regimen for the treatment of human neoplasms, by virtue of the fact that it allows the use of lower doses of adriamycin, thereby avoiding the toxic side effects associated with this drug.

Furthermore, the research findings of Cos et al. J Pineal Res (2005): Melatonin modulates aromatase activity in MCF-7 human breast cancer cells) have demonstrated that melatonin, at physiological concentrations, decreases aromatase activity and expression in MCF-7 cells, and that this aromatase inhibitory effect of melatonin, together with its already known antiestrogenic properties interacting with the estrogen-receptor,strongly suggests a role in the prevention and treatment of hormone-dependent mammary neoplasias; see also the study of COs et al. (Int J Cancer (2005): Melatonin inhibits the growth of DMBA-induced mammary tumors by decreasing the local biosynthesis of estrogens through the modulation of aromatase activity), which investigated the in vivo aromatase-inhibitory properties of melatonin, noting that melatonin inhibits the growth of breast cancer cells by interacting with estrogen-responsive pathways, thus behaving as an antiestrogenic hormone, and concluding from their in vivo study that melatonin could exert its antitumoral effects on hormone-dependent mammary tumors by inhibiting the aromatase activity of the tumoral tissue, and phase II studies report an increase of objective responses in cancer patients using melatonin. Partially on the basis of this and related findings, Abrial et al. (Pathol Biol (Paris) (2005): Potentiel thérapeutique de la mélatonine dans la prise en charge de la pathologie cancéreuse [Therapeutic potential of melatonin in cancer treatment]) initiated a phase II randomised study of melatonin versus placebo in metastatic breast cancer patients after two lines of treatment. And Y. Touitou (Bull Acad Natl Med (2005): Melatonin: what for?) concluded that melatonin has both strong antioxidant properties - stronger than those of vitamin E - and oncostatic action. Furthermore, according to the research of Martinez-Campa et al. (Breast Cancer Res Treat (2005): Melatonin enhances the inhibitory effect of aminoglutethimide on aromatase activity in MCF-7 human breast cancer cells), melatonin may be a novel means to increase the efficacy of competitive aromatase inhibitors used in treating breast cancer.





Melatonin as a SERM, Aromatase Inhibitor, and Anti-Estrogen
Melatonin demonstrates an an oncostatic role on hormone-dependent mammary tumors, interacting with estrogen-signaling pathways via three antiestrogenic mechanisms:
(1) acting through the estrogen receptor to interfere with the effects of endogenous estrogens (in keeping with selective estrogen receptor modulator (SERM) activity); and
(2) interfering with estrogen synthesis by inhibiting the enzymes that control the interconversion from their androgenic precursors (in keeping with anti-aromatase / inhibitory activity);. and
(3) decreasing circulating levels of estradiol (anti-estrogen activity)
(on these melatonin mechanism, see the review of Sánchez-Barceló and colleagues (J Pineal Res (2005): Melatonin–estrogen interactions in breast cancer) who conclude that melatonin fulfills all the requirements to be considered as a true antiestrogenic agent. This is reinforced by the findings of Cos et al. (Cancer Detect Prev (2006): Estrogen-signaling pathway: A link between breast cancer and melatonin oncostatic actions) who conclude that "melatonin's direct effect on mammary tumor cells is that it interferes with the activation of the estrogen receptor, thus behaving as a selective estrogen receptor modulator", and citing the multiple activities on distinct endocrine pathways, adds "It is these action mechanisms that collectively make melatonin an interesting anticancer drug in the prevention and treatment of estrogen-dependent tumors, since it has the advantage of acting at different levels of the estrogen-signaling pathways".

The antiestrogen activity of melatonin is further documented in the discussion of "Melatonin as an oncostatic substance" in Pandi-Perumal et al.'s review (FEBS (2006): Melatonin: Nature's most versatile biological signal?) who observe that (1) melatonin exhibits a growth inhibitory effect in estrogen-positive, MCF human breast cancer cell lines, (2) melatonin inhibits the growth of estrogen-responsive breast cancer by modulating the cell's estrogen signaling pathway, and (3) can exert its action on cell growth by modulation of estradiol receptor transcriptional activity in breast cancer cells.

For further clarification of the complex and multiple pathways melatonin exerts activity over, see Bartsch & Bartsch, Pineal Gland and Cancer–An Epigenetic Approach to the Control of Malignancy: Evaluation of the Role of Melatonin (Chapter 7 in Pandi-Perumal & Cardinali (Ed.), Melatonin: Biological Basis of its Function in Health and Disease (Landes Bioscience (2005)) who observe that fresh tumors are“sensed” by the pineal gland via neuroimmunoendocrine changes, leading to a stimulation of melatonin secretion which in turn activates endogenous defense processes, and they further document the mobilization of endogenous defense mechanisms against malignant processes by melatonin, thus improving survival, suggesting that melatonin via indirect systemic mechanisms is able to favorable affect even advanced forms of malignancy, although a caution is that melatonin also exerts stimulatory effects on the hematopoietic system, thus potential aggravating a bone marrow cancer like leukemia.


Circadian Disruption and Breast Cancer
A new hypothesis has been postulated about the relation of melatonin, light at night, and breast cancer, known as circadian disruption. Thus there appears to be an inverse association between sleep duration and breast cancer risk, possibly due to greater overall melatonin production in longer sleepers, according to a recent population-based study (Verkasalo et al., Cancer Res (2005): Sleep Duration and Breast Cancer: A Prospective Cohort Study), and this is consonant with the recent findings of Blask et al. (Endocrine (2005): Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal) who found in their animal study that nocturnal dietary supplementation with melatonin, at levels contained in a melatonin-rich diet inhibits tumorogenesis, possibly by multiple activities: via inhibition of cell proliferation, a stimulation of differentiation and apoptosis, and melatonin-induced suppression of tumor linoleic acid (LA) uptake (note that light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of human breast cancer). These findings are the first demonstrating that tumor growth response to exposure to light-during-darkness is (1) intensity dependent and (2) that the human nocturnal circadian melatonin signal both inhibits human breast cancer growth, but also is an effect nullified by short-term ocular exposure to bright white light at night.

And cross-confirmation exists from the animal research of Saez et al. (Mol Cell Biochem (2005): Melatonin increases the survival time of animals with untreated mammary tumours: neuroendocrine stabilization) who found that strongly suggest that melatonin per se is beneficial during advanced breast cancer, by increasing survival time, perhaps by improving the homeostatic and neuroendocrine equilibrium which is imbalanced during advanced breast cancer. And light and lighting during typical periods of darkness, as at night, of sufficient intensity can disrupt circadian rhythms, including reduction of circulating melatonin levels and resetting of the circadian pacemaker, and this reduced melatonin may increase breast cancer risk through several mechanisms, including increased estrogen production and altered estrogen receptor function (RG Stevens, Epidemiology (2005): Circadian Disruption and Breast Cancer: From Melatonin to Clock Genes). See also Mahmoud et al. (Am J Hosp Palliat Care (2005): The therapeutic application of melatonin in supportive care and palliative medicine) who concluded that circadian disruption is linked to increased cancer risk, and that the chronobiotic capacity of melatonin to reset circadian clocks may provide a verifiable strategy to reduce cancer risk and enhance quality of life by diminishing cancer-induced circadian disruption.

And related to this, it appears that although shorter sleep duration (< 7 hours nightly) is not associated with breast cancer risk reduction, it was the case that increasing sleep duration (9 or more hours nightly) is modestly associated with an increased breast cancer risk (McElroy et al., J Sleep Res (2006): Duration of sleep and breast cancer risk in a large population-based case–control study), a finding the may hinge on melatonin and cortisol activity.

And in addition, melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state such as cancer disease and the immunocompromised state induced by various oncotherapies (including chemotherapy, endocrine/hormonal therapy, biological therapy and radiotherapy (Srinivasan et al., Immune Ageing (2005): Melatonin, immune function and aging).

And the recent systematic review of randomized controlled trials and meta analysis reported the efficacy of melatonin in solid tumor cancer patient (Mills et al., J Pineal Res (21005): Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis), with the presence of melatonin prolonging both disease progression-free and overall 1-year survival in many randomized controlled trials (Indian J Med Sci (2006): Melatonin in pathogenesis and therapy of cancer). See also Paula Witt-Enderby and her colleagues at Duquesne University (J Pineal Res (2006): Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy).


Night-shift Breast Cancer
These findings are in keeping with what is known about so-called night-shift breast cancer phenomenon: an increased risk of breast cancer is seen among subjects not sleeping during the period of the night when nocturnal melatonin levels are typically at their highest, and hence with graveyard shiftwork, with even some indication of an increased risk among subjects with the brightest bedrooms (Davis et al, J Natl Cancer Inst: Night Shift Work, Light at Night, and Risk of Breast Cancer, where it was concluded that "to the extent that graveyard shiftwork and nonpeak sleep reflect exposure to light at night, the results of this study add to a growing body of evidence that such exposure, for whatever reason, may be linked to breast cancer risk", speculated to be due to the fact that light at night exposure reduces nocturnal melatonin levels, which can result in increased circulating estradiol concentrations in the blood). (See also Schernhammer et al, J Natl Cancer Inst: Rotating Night Shifts and Risk of Breast Cancer in Women Participating in the Nurses' Health Study and Schernhammer et al, Cancer Epidemiol Biomarkers Prev: Epidemiology of urinary melatonin in women and its relation to other hormones and night work).

Evidencewatch Commentary
Although a recent study (Travis et al, J Natl Cancer Inst: Melatonin and Breast Cancer: A Prospective Study) found no evidence that the level of melatonin is strongly associated with the risk for breast cancer, this study measured the level of 24-hour melatonin excretion despite the fact, as pointed out by Hrushesky & Black (J Natl Cancer Inst (2004): Re: Melatonin and Breast Cancer: A Prospective Study) in their commentary that differences in the nocturnal duration of melatonin secretion and thus its distribution across the night cannot be accounted for by measuring 24-hour excretion levels, and it may be necessary to examine whether instead cancer risk is conferred not by average 24-hour melatonin exposure, but by the circadian temporal organization of melatonin availability. Hrushesky & Black also correctly point out that in those studies which have evidenced a relationship between cancer risk and melatonin excretion, have discovered the relationship based on circadian amplitude or phase (time of melatonin upswing), not on the 24-hour average amount of melatonin metabolite excreted.

Nor did the Travis study (above) control for the potentially confounding factor of the relative nighttime light exposure of case patients and control subjects, given the well-established fact light exposure and especially nocturnal light exposure may confer cancer risk through modulation of the melatonin circadian pattern: see Schernhammer & Hankinson (J Natl Cancer Inst (2005): Urinary Melatonin Levels and Breast Cancer Risk) who used a prospective case–control study nested within the Nurses' Health Study II cohort, finding the prospective data supporting the hypothesis that higher melatonin levels are associated with a lower risk of breast cancer; also Schernhammer et al. (Cancer Epidemiol Biomarkers Prev (2004): Epidemiology of Urinary Melatonin in Women and Its Relation to Other Hormones and Night Work) who also concluded that women working on rotating night shifts appear to experience changes in hormone levels, as measured by urinary melatonin, that may be associated with the increased cancer risk observed among night-shift workers; and similar findings have emerged with respect to colorectal cancer (see Schernhammer et al., J Natl Cancer Inst (2003): Night-Shift Work and Risk of Colorectal Cancer in the Nurses’ Health Study who found that working a rotating night shift at least three nights per month for 15 or more years may increase the risk of colorectal cancer in women. (Although the exact mechanisms involved in noctural light, decreased melatonin levels, and increased cancer risk are still being study, the molecular mechanisms are beginning to be defined: the recent animal research of Flipski et al. (J Natl Cancer Inst (2005): Effects of Light and Food Schedules on Liver and Tumor Molecular Clocks in Mice) has found that altered light-dark modifies the expression of molecular clock genes and genes involved in carcinogenesis and tumor progression).

In addition, Megdal et al. (Eur J Cancer (205): Night work and breast cancer risk: A systematic review and meta-analysis) conducted a systematic review and meta-analysis of 13 qualifying observational studies between January 1960 to January 2005 in order to assess the effects of night work on breast cancer risk, concluding that the studies to date collectively show an increased breast cancer risk among women, with publication bias unlikely to have influenced the results.

In conclusion, therefore, Evidencewatch finds that numerous systematic reviews and meta-analyses, and their underlying research, provide in the balance compelling evidence of an increased risk of breast cancer consequent to night shift work and its known adverse impact on melatonin production.

 

I have taken melatonin every night for 15 years.  Sublingual works best for me, 3 mg is my dose though I may investigate to see if I should take a higher one with regard to the BC dx. 

Melatonin did not keep me from getting BC but one could not ask for a better histiological tumor (well-differentiated, which is said to be only 9% of all BCs, with most being moderately well-differentiated), so maybe the melatonin helps somewhat. 

have we determined that is it ok to take melatonin if one is unable to be sure that one will get a full 8 hours of darkness and sleep?  I'm a single mom, and not a great sleeper, and get scared that the melatonin, in teh presence of light and disturbances, could be deleterious to me.

Does it work for Triple Negative BC???

Hi

Im taking 20mg of melatonin, my doc who is a natural healer as well as a main stream doc said that this is the first thing that I want to get you started on as it has many benefits for women with breast cancer.

Ive had no side effects and enjoy a good nights sleep, Ive also seen a study that suggests that high doses of melatonin actually work well with Tamoxifen and helpe to enhance tamoxifens effects.