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Niacinamide Is Anti-estrogenic

Discussion in 'Scientific Studies' started by haidut, Mar 1, 2016.

  1. haidut

    haidut Member

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    Yet another strong point for niacinamide. I am beginning to wonder if there is any condition or biomarker of disease that niacinamide cannot affect.
    Peat has written many times about the sirtuin genes and their promoter resveratrol. While there is already quite a bit of evidence that SIRT1 promoters are potentialy carcinogenic, the exact mechanism is officially labelled as "unknown". This study shows that the estrogen "receptor" activity is dependent on SIRT1 activation, and inhibiting SIRT1 suppresses estrogenic activity. The first study directly shows the anti-estrogenic effects of niacinamide, while the second one notes the similarity of niacinamide to the potent pharmacological estrogen "receptor" antagonist fulvestrant (used for breast cancer). This suggests that niacinamide may be a possible treatment for estrogen-driven conditions like breast and prostate cancer, as well as heart disease and osteoporosis. This anti-estrogenic effects gives another possible explanation of the beneficial mechanism of niacinamide for "autoimmune" conditions, which are caused and driven mainly by estrogen.

    The EC50 of niacinamide for sirtuin inhibition is 11uM, which in humans is achievable with less then 100mg niacinamide. Interestingly, Hoffer apparently sent somebody recommendations for 1,500mg niacinamide daily being optimal for longevity and health. This is the same dose successfully used in humans for diabetes type II and metabolic syndrome.
    Niacinamide and SIRT - what is the minimum dose required for inhibition? - Supplements
    "...According to Pubchem, the concentration required for 50% inhibition of SIRT2 is 11uM, although I have no idea how this translates to mg/kg)."

    "...Upregulation of SIRT1 may increase lifespan in fruit flies and roundworms, but may actually have detrimental effects in strokes, some types of cancer and dementia, particularly when NAD+ levels are insufficient. The types of cancer in question apparently include prostate cancer and SCLC. The anticancer protocol which the late Abram Hoffer faxed me 16 years ago included 1,500 mg of niacinamide. Inhibition of SIRT1 is apparently one of the pathways in which niacinamide fights cancer."


    And here is the actual study showing niacinamide is anti-estrogenic through sirtuin inhbition.

    Inhibition of SIRT1 deacetylase suppresses estrogen receptor signaling. - PubMed - NCBI
    "...Estrogen receptor α (ERα) mediates estrogen-dependent gene transcription, which plays a critical role in mammary gland development, reproduction and homeostasis. Histone acetyltransferases and class I and class II histone deacetylases (HDACs) cause posttranscriptional modification of histone proteins that participate in ERα signaling. Here, we report that human SIRT1, a class III HDAC, regulates ERα expression. Inhibition of SIRT1 activity by sirtinol suppresses ERα expression through disruption of basal transcriptional complexes at the ERα promoter. This effect leads to inhibition of estrogen-responsive gene expression. Our in vitro observations were further extended that SIRT1 knockout reduces ERα protein in mouse mammary gland. Finally, ERα-mediated estrogen response genes are also decreased in mouse embryonic fibroblasts derived from SIRT1-knockout mice. These results suggest that inhibition of SIRT1 deacetylase activity by either pharmacological inhibitors or genetic depletion impairs ERα-mediated signaling pathways."

    "...To address the role of SIRT1 in ERα-mediated transcription, the ERα-positive breast cancer cells MCF-7 and T47D were used as cell culture models to monitor effect of class III HDACs on ERα expression. Cells were treated with nicotinamide, a non-specific sirtuin inhibitor for class III HDAC enzymatic activity (26,27), or sirtinol (SN), a specific inhibitor for SIRT1 without affecting the other sirtuin members (28). Reverse transcription–PCR analysis showed that the level of ERα mRNA in T47D cells was reduced after 48 h of 100 μM SN treatment (Figure 1A). The level of ERα mRNA in MCF-7 cells was also reduced after treatment with SN (100 μM) and nicotinamide (20 mM) (Figure 1B). A quantitative real-time PCR analysis confirmed the reduction of ERα mRNA. These results demonstrated that inhibition of SIRT1 deacetylase activity reduces the steady-state level of ERα mRNA. To examine if downregulation of ERα is correlated with its protein level, western blot analysis showed that the ERα protein level was completely abolished while the level of SIRT1 protein remains unchanged in T47D cells after 48 h of treatment with 100 μM SN (Figure 1C). To further investigate the effect of nicotinamide and SN treatments on ERα, MCF-7 and T47D cells were grown in the same media but in the absence of estrogen for 72 h followed by the treatment with 10 nM E2, 100 μM SN or a combination of both for 48 h (Figure 1D). Although E2 stimulation slightly reduced ERα expression, treatment with either SN alone or SN with E2 caused a significant reduction of ERα protein in both cell lines tested. These data suggest that inhibition of SIRT1, a class III HDAC, suppresses ERα expression at both mRNA and protein levels."


    http://www.hindawi.com/journals/omcl/2014/713894/
    "...Background. Sirtuin 1 (SIRT1) is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII-) induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs) to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury."
     
  2. superhuman

    superhuman Member

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    Thats awesome.
    What is the optimal frequency etc or way to take the 1500 mg niacinamide @haidut in regards to what you think and what does Hoffer used?
     
  3. vertigo

    vertigo New Member

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    Prostate cancer is driven by testosterone, not estrogen, and estrogen is a treatment for it. Taking something that inhibits estrogen would be potentially harmful in the case of prostate cancer.
     
  4. tankasnowgod

    tankasnowgod Member

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    Ha! I think you'll find a lot of members here that question that line of reasoning, even though the theory that "androgens cause prostate cancer" seems to be accepted by mainstream medicine.

    One thing I'll point out, Lupron, a drug used to treat prostate cancer, dramatically slashes both testosterone and estrogen in both males and females. That is not exactly using estrogen as a treatment. And in Europe, some doctors have been using DHT gel as a treatment for prostate cancer, specifically because it does not aromatise into estrogen.

    Also, this- Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: results from a pilot clinical study. - PubMed - NCBI
     
  5. vertigo

    vertigo New Member

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    Well, I'm not sure why people question it, since it's a well-known and proven fact that testosterone contributes to prostate cancer progression. Maybe people are confusing testosterone with causing prostate cancer vs causing it to progress, or maybe they're forgetting that testosterone is a type of androgen, so it's not necessarily androgens that are responsible for this but testosterone. In any event, it is well-documented that reduction of testosterone, as well as introduction of estrogen, slows the cancer. That said, estrogen is not a mainline treatment due to side-effects and, like testosterone reduction, the fact it is only temporary. I suspect DHT gel is used both because by not aromatizing into estrogen you don't get the side-effects of estrogen and because DHT competes with testosterone, thereby preventing it from doing what it's known for: contributing to the worsening of the cancer.

    And I'm not sure what your intention is with that link, as it seems to argue against your case. Granted, I only read the abstract and skimmed parts of the paper, as I don't have the time to read the full study, but essentially it states that testosterone-reduction therapy (via castration) is effective and is the primary treatment, which is no surprise since again, it's known to work. It then explains why the effects are temporary (upregulation of the receptors due to a low-testosterone environment which leads to the low levels being significantly more effective, to the point of negating the reduction). Finally, it discusses the effects of using cycles of supraphysiologic amounts of testosterone alternately with castration levels to prolong the effects of testosterone reduction by killing the upregulated receptors by overwhelming them. In summary, enhancing the anti-testosterone treatment.

    So again, testosterone = bad, estrogen = good but with side effects. And I'm not saying people should boost their estrogen, but based on what we know I certainly don't think taking something that inhibits it is a good idea.
     
  6. ecstatichamster

    ecstatichamster Member

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    @vertigo i think you will find that the idea that testosterone increases or worsens prostate cancer is totally wrong. It is well known like s lot of medical "facts" are well known. Wrongly.
     
  7. vertigo

    vertigo New Member

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    Yes, a lot of medical "facts" are wrong, but many, if not most, are right, or at least closer to right than many other beliefs, many of which are formed by people that seem to think they're right just because they differ from popular medical belief, as some people seem to just think that the medical community is wrong about just about everything. In any event, all I've seen is one person giving advice contrary to current, mainstream medical advice and two people stating that mainstream medicine is wrong with neither backing up these claims and one's attempt to back them up actually (accidentally?) arguing FOR current medical beliefs. Ultimately, I saw something said that I, and mainstream medicine, disagree with and I wanted to provide additional info so others reading it wouldn't just take it for truth. I've done that, and they can make up their own minds. Everyone is free to do that.
     
  8. HDD

    HDD Member

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  9. tankasnowgod

    tankasnowgod Member

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    OK, that's a fair thing to do. My question is, where is your additional info? All you did was come into a forum based on the ideas of Ray Peat, didn't bother to get familiar with his work (or the other studies that Haidut has posted in this forum), then make a claim that testosterone drives prostate cancer while estrogen can treat it, and not provide a single reference for your statement, only an appeal to authority.

    Here's a question for you- Testosterone levels in men are highest in the teens and twenties, and then decline over time. If testosterone is driving prostate cancer, how come it's mainly a problem for older men, and not young men, as they have more testosterone to drive prostate cancer?
     
  10. meatbag

    meatbag Member

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    Can you please explain how something that lowers estrogen would be harmful in regards to prostate cancer?
     
  11. meatbag

    meatbag Member

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    "In human prostate slices, several hormones (including insulin, and probably prolactin) stimulated cell division; testosterone did not, under these experimental conditions. (McKeehan, et al., 1984.) Contrary to the stereotyped ideas, there are suggestions that supplementary androgens could control prostate cancer (Umekita, et al., 1996), and that antagonists to prolactin and estrogen might be appropriately used in hormonal therapy (for example, Wennbo, et al., 1997; Lane, et al., 1997)." - Ray Peat ; Prostate Cancer


    "...simultaneous treatment of intact...rats with testosterone and estradiol-17beta for 16 weeks consistenly induced a putative precancerous lesion, termed dysplasia, in the dorsolateral prostate of all animals. Since treatment of rats with androgen alone did not elicit the same response, we concluded that estrogen played a critical role in the genesis of this proliferative lesion." Shuk-mei Ho and M. Yu, in "Selective increase in type II estrogen-binding sites in the dysplastic dorsolateral prostates of Noble rats," Cancer Research 53, 528-532, 1993.

    "Free testosterone levels were lower in men with PCa who had reclassification during AS. Men with moderately severe reductions in free testosterone level are at increased risk of disease reclassification." "For men with low-risk prostate cancer, low levels of testosterone may indicate a worsening of their disease." Ignacio F. San Francisco, Pablo A. Rojas, William C. DeWolf, Abraham Morgentaler. Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance. BJU International, 2014; DOI: 10.1111/bju.12682

    Prolactin As A Causative Agent In Prostate Cancer - Haidut
    Prolactin As A Causative Agent In Prostate Cancer
    "Just wanted to post this, given the almost perfect correlation between prolactin and expression of estrogen "receptors" in tissues. If prolactin is a causative agent in prostate cancer, than the current idea of treating prostate cancer with estrogen is laughable. I also posted a study showing that PSA is raised by estrogen, not DHT or T."

    "[Relation of prolactin with nodular hyperplasia and carcinoma of the prostate]. - PubMed - NCBI

    "...With regard to Nodular Hyperplasia, once its hormone dependency is rated, it also appears to be stimulated by high levels of prolactin. The NH cell cultures with human prostate increase their growth, cell division, as well as the DNA synthesis. The aspects of the prolactin-prostate carcinoma interaction involve considering this hormone as a possible carcinogenic agent, emphasizing the existence of high plasma levels of this hormone in individuals with prostate carcinoma, where any androgen excess is considered a major factor at the genesis of this tumour, and prolactin increases indirectly its testicular synthesis. Also, prolactin itself stimulates the growth and development of carcinomatous human cell lines, increasing its effect in the presence of testosterone. For this reason, controlling this hormone levels becomes an element to have into consideration in the treatment and follow-up of these patients; also, the reevaluation of any drug therapy that, besides the initial goal pursued, does not maintain baseline prolactin levels. The association of anti-prolactin drugs has to be understood as a co-adjuvant therapy when there is androgenic deprivation, never as a single treatment.""

    Umekita Y, Hiipakka RA, Kokontis JM, Liao S, Proc Natl Acad Sci U S A 1996 Oct 15;93(21):11802-11807 "Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride," "When the human prostate cancer cell line, LNCaP 104-S, the growth of which is stimulated by physiological levels of androgen, is cultured in androgen-depleted medium for > 100 passages, the cells, now called LNCaP 104-R2, are proliferatively repressed by low concentrations of androgens. LNCaP 104-R2 cells formed tumors in castrated male athymic nude mice. Testosterone propionate (TP) treatment prevented LNCaP 104-R2 tumor growth and caused regression of established tumors in these mice. Such a tumor-suppressive effect was not observed with tumors derived from LNCaP 104-S cells or androgen receptor-negative human prostate cancer PC-3 cells. 5 alpha-Dihydrotestosterone, but not 5 beta-dihydrotesto- sterone, 17 beta-estradiol, or medroxyprogesterone acetate, also inhibited LNCaP 104-R2 tumor growth. Removal of TP or implantation of finasteride, a 5 alpha-reductase inhibitor, in nude mice bearing TP implants resulted in the regrowth of LNCaP 104-R2 tumors. Within 1 week after TP implantation, LNCaP 104-R2 tumors exhibited massive necrosis with severe hemorrhage. Three weeks later, these tumors showed fibrosis with infiltration of chronic inflammatory cells and scattered carcinoma cells exhibiting degeneration. TP treatment of mice with LNCaP 104-R2 tumors reduced tumor androgen receptor and c-myc mRNA levels but increased prostate-specific antigen in serum- and prostate-specific antigen mRNA in tumors. Although androgen ablation has been the standard treatment for metastatic prostate cancer for > 50 years, our study shows that androgen supplementation therapy may be beneficial for treatment of certain types of human prostate cancer and that the use of 5 alpha-reductase inhibitors, such as finasteride or anti-androgens, in the general treatment of metastatic prostate cancer may require careful assessment."

    Wennbo H, Kindblom J, Isaksson OG, Tornell J., Endocrinology 1997 Oct;138(10):4410-4415. "Transgenic mice overexpressing the prolactin gene develop dramatic enlargement of the prostate gland," "An altered endocrine status of elderly men has been hypothesized to be important for development of prostate hyperplasia. The present study addresses the question whether increased PRL expression is of importance for development of prostate hyperplasia in mice. Three lines of PRL transgenic mice were generated having serum levels of PRL of approximately 15 ng/ml, 100 ng/ml, and 250 ng/ml, respectively. These mice developed dramatic enlargement of the prostate gland, approximately 20 times the normal prostate weight and they had a 4- to 5-fold increased DNA content. Histologically, the prostate glands in the transgenic mice were distended from secretion, and the amount of interstitial tissue was increased. The levels oftestosterone and IGF-I were increased in the PRL transgenic animals. In mice overexpressing the bovine GH gene, displaying elevated IGF-I levels, the prostate gland was slightly larger compared with normal mice, indicating that the effect of PRL was not primarily mediated through elevated plasma IGF-I levels. "The present study suggests that PRL is an important factor in the development of prostate hyperplasia acting directly on the prostate gland or via increased plasma levels of testosterone."

    So clearly increasing DHT and lowering prolactin are the two best things to do in regards to prostate cancer. In regards to niacinamide, consider this;

    Niacinamide Is Androgenic And Increases Dht Effects/signaling by Haidut - Niacinamide Is Androgenic And Increases Dht Effects/signaling

    "I just posted a study showing that inhibition of SIRT1 is anti-estrogenic, and SIRT1 inhibitors like niacinamide have similar effects to the estrogen receptor antagonist fulvestrant.
    Niacinamide Is Anti-estrogenic | Ray Peat Forum

    This study shows that, again through inhibition of SIRT1, niacinamide enhances AR expression and effects of the powerful androgen DHT. Given the anti-cortisol effects of niacinamide that I also posted about it seems that niacinamide is one of the most versatile substances that can stop stop the stress response and maybe even reverse the catabolic state. Also, there should be nice synergy with DHEA and glycine to potentiate the androgenic effect even more, given glycine's upregulation of 5-AR.

    Glycine Strongly Upregulates 5-alpha Reductase (5-ar) Activity | Ray Peat Forum
    Glycine Powerfully Lowers Cortisol | Ray Peat Forum

    The androgenic mechanism of action of niacinamide is inhibition of the sirtuins. The EC50 of niacinamide for sirtuin inhibition is 11uM, which in humans is achievable with less then 100mg niacinamide. Interestingly, Hoffer apparently sent somebody recommendations for 1,500mg niacinamide daily being optimal for longevity and health. This is the same dose successfully used in humans for diabetes type II and metabolic syndrome.
    Niacinamide and SIRT - what is the minimum dose required for inhibition? - Supplements
    "...According to Pubchem, the concentration required for 50% inhibition of SIRT2 is 11uM, although I have no idea how this translates to mg/kg)."

    "...Upregulation of SIRT1 may increase lifespan in fruit flies and roundworms, but may actually have detrimental effects in strokes, some types of cancer and dementia, particularly when NAD+ levels are insufficient. The types of cancer in question apparently include prostate cancer and SCLC. The anticancer protocol which the late Abram Hoffer faxed me 16 years ago included 1,500 mg of niacinamide. Inhibition of SIRT1 is apparently one of the pathways in which niacinamide fights cancer."

    In summary, the ability of both niacinamide and glycine to lower cortisol, oppose estrogen, and promote androgenic signalling may also make them potential drugs for osteoporosis, depression, PTSD, sarcopenia, stress-induced ulcers, heart disease, hair loss, and even some neurodegenerative conditions like ALS and Huntington that have been shown to benefit from androgenic therapy.


    Hormonal control of androgen receptor function through SIRT1. - PubMed - NCBI

    "...The NAD-dependent histone deacetylase Sir2 plays a key role in connecting cellular metabolism with gene silencing and aging. The androgen receptor (AR) is a ligand-regulated modular nuclear receptor governing prostate cancer cellular proliferation, differentiation, and apoptosis in response to androgens, including dihydrotestosterone (DHT). Here, SIRT1 antagonists induce endogenous AR expression and enhance DHT-mediated AR expression. SIRT1 binds and deacetylates the AR at a conserved lysine motif. Human SIRT1 (hSIRT1) repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited coactivator-induced interactions between the AR amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins."

    "...What might be the significance of the finding that AR expression and DHT signaling are regulated by nicotinamide and NAD-dependent deacetylation? The requirement for NAD in Sir2 enzymatic activity has led to suggestions that Sir2 activity may be regulated by the intracellular concentration of NAD, by the NAD/NADH ratio, or by the intracellular concentration of nicotinamide (2, 35, 36, 45). Endogenous levels of nicotinamide may limit Sir2 activity (49), suggesting that the concentration of nicotinamide in response to physiological changes could affect Sir2 function. Metabolic changes in muscle induced by pyruvate, for example, increase the NAD+/NADH ratio and inhibit muscle gene expression, whereas lactate reduces the NAD/NADH ratio and stimulates muscle gene expression (21). Androgens maintain male muscle mass (10a, 26, 50) and induce muscle cellular gene expression. During prostate cancer progression, metabolism shifts toward cytosolic glycolysis (1, 12). The increased production of lactate that occurs during prostate cancer progression (5, 46) is predicted to inhibit SIRT1 and thereby enhance AR function. A recent study also suggested that global histone modification in prostate tumor tissues, including acetylation of H3K18 and H4 K12, dimethylation of H3K4 and H4R3, and acetylation of H3K9, a target of SirT1 (54), predict a risk of prostate cancer recurrence (51)."

    "...Here, SIRT1 inhibited androgen-dependent prostate cancer cellular growth and repressed the endogenous androgen-responsive target gene, AR. AR is an androgen-responsive gene, and sirtinol, a Sir2-specific inhibitor, increased the abundance of acetylated-AR acetylation. Nicotinamide, a noncompetitive inhibitor of Sir2, induced expression of the endogenous androgen-responsive AR gene. The selective chemical inhibitor of SIRT activity, splitomycin, enhanced AR-dependent gene expression, suggesting that endogenous SirT1 contributes to maintenance of the AR in a repressed state."

     
  12. lisaferraro

    lisaferraro Member

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    Fantastic post @Meatbag - nice culling of a lot of information...
     
  13. vertigo

    vertigo New Member

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    Because, as I already stated, prostate cancer being testosterone-driven is the currently widely-accepted belief (be it true or not). I could easily provide hundreds of link stating that, but a quick Google search would provide that, and it's not really necessary because, again, it is the mainstream belief. Conversely, this thread is stating something which goes against the majority of medical knowledge, which means a) it's not so simple to do a quick search and find corroborating evidence, and (more importantly) b) it's the responsibility of the person arguing against decades of medical literature stating one thing to present evidence as to why their stated belief holds water. If somebody were to make a thread stating that smoking doesn't cause cancer, without offering any evidence, most people would ignore or question it, and rightly so. And, frankly, I have seen many cases where ridiculous arguments are being made about things, medical and otherwise, that are just absolute nonsense. And I'm not going to familiarize myself with the work of the creator of the forum to respond to a user of the forum, nor am I going to (or should I have to) read all the previous posts of said user before responding to a post I happened to run across that they posted on a public forum, thereby opening it up to responses. I came here trying to learn, as I'm sure others do, and seeing something said that goes against current medical knowledge, without any explanation or disclaimer, concerned me.

    As for your question, my answer is that correlation does not equal causation. Just because testosterone declines while incidence of prostate cancer simultaneously increases, that does not necessarily mean the two are linked or, even if they are, that it's a direct relation. Additionally, many, many things related to health occur not due to what's going on right now, but what's been going on throughout life. The majority of UV exposure for many people occurs in their youth, yet skin cancer becomes much more prevalent in older age. By your logic, it must be the decreased UV exposure that is causing the cancer. But it's actually the cumulative damage over years that finally leads to cells becoming cancerous.

    Or take glaucoma for another example. It's a disease primarily of older populations, and it's linked to intraocular pressure, yet it's not like these people suddenly develop higher pressures when they're older which then causes glaucoma. It's a combination of having pressures that are too high for years and, likely more significantly, probable physiologic changes in their later years making the nerves more susceptible. But again, your logic would argue that it must not be related to the pressure, because it's been like that their whole life. Yet, it is well-known that lowering the pressure is very often a successful treatment for the disease.

    Furthermore, it has been found through autopsies that prostate cancer is much more prevalent in younger populations than previously thought based on screenings of live patients, due to it being present in large numbers subclinically. It could be argued that this is occurring before a significant drop-off in testosterone levels, and therefore a potential link between prostate cancer and decreased testosterone is less likely. It could also be argued that, as you said, levels start dropping in the 20s to early 30s, and while not significant, perhaps you could graph the decline in testosterone levels over time and the increase in prostate cancer over time and the two would have slopes roughly inverse of one another. My point is, we don't know right now. The area, like most in medicine, still needs a lot of research. And I'll be the first to say that medicine is a field of many unknowns and, yes, many falsely held beliefs. But when presenting a belief that is so contrary to what the majority of medicine believes, it's important to validate it.

    And, sadly, many research studies are questionable. Some have been found later to be wrong due to one reason or another. Some (many?) are biased, either by who financed them or by the researchers own interests. And some make assumptions based on other, possibly invalid, studies. That's why I generally try to maintain some skepticism when reading a study. And nothing against Ray Peat or Haidut, but I don't know them, and even if I did, they are just a couple individuals saying one thing when a mountain of research and medical professionals are saying something else. So I'm going to be skeptical of what they're saying, and they need to be, and should be, aware that people will in general be skeptical, and so they should make the extra effort to overcome that. And if they don't realize that or can't or won't do that, then that's just hurting their cause. I'm here trying to learn, and I like to try to keep an open, yet skeptical, mind, and some of the ideas are interesting and merit further investigation, but there's also a lot that just doesn't add up, and what seems like a lot of false assumptions and correlations and interpretations being made.

    Thanks. Good and interesting read, but as I stated in the last paragraph in my reply to tankasnowgod, there do seem to be some errors in logic in there, some of which I've mentioned in the above response. Furthermore, as I stated above, I am already a bit skeptical of published research articles due to possible errors, bias, and the effect of researchers' interests. So I'm definitely skeptical of something that somebody I don't know wrote up as essentially a blog post emulating a research article which, as far as I can tell, is not peer-reviewed or published and is one person's interpretation of possibly cherry-picked sources, the most recent of which is 19 years old, along with, I'm sure, his own "knowledge." I quote knowledge because, just like the medical profession doesn't know everything, and much of what they "know" very well be prove at some point in the future to be incorrect, the same applies to what Ray "knows." So I'm not saying it in a derogatory manner, just being fair by equating both sides. I'm also not saying he cherry-picked the sources to meet his own agenda, but rather that I don't know if he did or not, just like I don't know with any given published journal article if they did or not. My point is that one should always be skeptical, and in my opinion more so of somebody posting stuff on the internet that goes against common medical "knowledge." And frankly, I would expect him to anticipate and welcome skepticism, since he is encouraging it (of currently held medical beliefs) in his readers. And the same goes for haidut.

    Pretty sure I already did. Estrogen is a treatment for prostate cancer. If giving something treats something else, taking it away typically would have the opposite effect of treatment. But here's a couple links grabbed off a quick search:

    Hormone Therapy for Prostate Cancer
    The Role of Estrogens in Prostate Carcinogenesis: A Rationale for Chemoprevention

    Now, the second link actually goes into the possible involvement of estrogen in prostate carcinogenesis. But the bottom line is it's an established fact that estrogen is a treatment for prostate cancer (and therefore it can be extrapolated that estrogen suppression would likely be harmful) whereas it is a /potential/ causative agent. And again, I'm not saying it's wrong, or that it shouldn't be presented to people to make them ask questions, but I feel more caution should be used in telling people they should suppress something that is /known/ to treat a condition when it /might/ also contribute to the condition.

    I haven't read through your whole post yet, though I will (I wanted to put out a reply to everyone, yourself included). But this part of it, which was also in the link posted earlier by HDD, I did want to respond to now. To me, this only highlights the complexity of anatomy and physiology and, specifically, the endocrine system and the interaction of the various hormones. The fact is, we know so little about all of this. It's chaos theory applied to biology. You can try changing one thing to evaluate the results, but there will always be other factors at play and other variables changing as a result, muddying the waters. We know testosterone is a major player, and we know reducing it significantly is a viable, though short-lived, treatment. We also know that increasing estrogen is a treatment option, though not a very good one. This would seem to indicate that it takes two to tango, so to speak, and therefore perhaps an alternating significant reduction in one and then the other would be a useful strategy (though I can only imagine the havoc it would wreak on the body). It also doesn't make a lot of sense that testosterone alone wouldn't have the effect since some of that should be converting to estrogen, meaning it's not just testosterone.


    I've said it a couple times already, but I'll say it again. My issue isn't with the contradictory thoughts. Independent thought, critical thinking, and skepticism are important. My problem was with how the information was presented. Despite my skepticism, I do try and keep an open mind, and I ended up here because I'm trying to learn more about prostate cancer and possible treatments, so while I'm not going to accept what I read here without some doubt, it does give me some other angles from which to approach this and some things to consider. In fact, for a while I've wondered about a possible link between decline of sexual activity and increased prevalence of prostate cancer.
     
  14. sladerunner69

    sladerunner69 Member

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    What is proper niacinimide dosage for estrogen blocking?
     
  15. meatbag

    meatbag Member

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    Second Paragraph of Haidut's post holds the answer you seek :happy:
     
  16. OP
    haidut

    haidut Member

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    I will just post a few high-level pointers before we go in a heated debate, which I suspect we will.

    1. Prolactin has a very well-known and widely acknowledged role in prostate cancer initiation AND development.
    Prolactin regulation of the prostate gland: a female player in a male game. - PubMed - NCBI
    Prolactin and cancer: Has the orphan finally found a home?
    Prolactin in Breast and Prostate Cancer: Molecular and Genetic Perspectives - Eric M Jacobson - Discovery Medicine

    If you accept the role of prolactin in prostate cancer you cannot seriously advocate estrogen as treatment. Both hormones are like mirror images of each other, each one depending on the other for manifesting its effects and each one dependent on the other for its synthesis. For the same reason, advocating estrogen treatment for osteoporosis cannot be taken seriously either - i.e. estrogen stimulates prolactin secretion like no other hormones and prolactin melts bone like sun does ice.

    2. Estrone (and especially estrone sulfate) is a known carcinogen, for any cancer, not just prostate or breast. It also happens to be the most reliable prognostic factor for prostate cancer development and progression.
    Estrone - Wikipedia, the free encyclopedia
    "...Estrone is known to be a carcinogen for human females as well as a cause of breast tenderness or pain, nausea, headache, hypertension, and leg cramps in the context of non-endogenous exposure.[1][4] In men, estrone has been known to cause anorexia, nausea, vomiting, and erectile dysfunction.[2] Estrone is relevant to health and disease states because of its conversion to estrone sulfate, a long-lived derivative. Estrone sulfate acts as a reservoir that can be converted as needed to the more active estradiol. It is the predominant estrogen in postmenopausal women.

    Test For Estrogenic Activity And Prostate Cancer
    Estrone sulfate (E1S), a prognosis marker for tumor aggressiveness in prostate cancer (PCa)

    3. Testosterone can stop even metastatic, terminal, prostate cancer.
    Cancer "paradox": Testosterone Inhibits Prostate Cancer

    4. Estrogen (estrone, estradiol and estriol) are officially known carcinogens, while no such labelling exists for T or DHT.
    Known and Probable Human Carcinogens
    "...Even if a substance or exposure is known or suspected to cause cancer, this does not necessarily mean that it can or should be avoided at all costs. For example, estrogen is a known carcinogen that occurs naturally in the body."

    Note that I tried to use "official" sources as much as possible. By official, I mean sources like Wikipedia and government sites that describe what the mainstream medical consensus is. So, according to the mainstream consensus, which apparently nobody cares to read about, we know the following:
    Estrogen is a known carcinogen, and publicly listed as such on pretty much any official list you care to look at. Estrone (E1) and and its long-lived derivative estrone sulfate (E1S), are estrogens and serve as estrogenic reservoirs. They both cause and promote prostate cancer and serve as biomarkers of how likely the prostate cancer is to kill the person. Prolactin, which is stimulated by all estrogens, and is a biomarker and stimulator of estrogenic activity - is causally implicated in prostate cancer. Testosterone, a non-carcinogen, and an androgen stops even terminal prostate cancer in humans. Testosterone is a functional antagonist to both estrogen and prolactin, so its therapeutic effects in prostate cancer are not surprising.

    Now, something like DHT would probably be much more effective at treating prostate cancer but I think even with testosterone the point is clear. Actually, it is not my point but the official position to which you also claim to adhere.
    Do you want to go into the details of how estrogens cause cancer (including prostate) or do you think this is enough info to make you reconsider or at least research more?

    Finally, estrogen has NO role in ANY cancer treatment. None. The only reason it is being used clinically is to mask the cancer deaths and assign them to other cause. When somebody with prostate or breast cancer gets estrogen treatments they are guaranteed to die from a vascular event (stroke or heart attack) or even secondary cancer. So, in a very sick way estrogen can be used to officially claim effectiveness against cancer - i.e. by guaranteeing that people will die from something else before the cancer kills them. Is that the kind of treatment you advocate by saying estrogen is a possible treatment but with "side effects"?!? Can you come up with even one condition that has shown benefit from estrogen treatment?
     
  17. Drareg

    Drareg Member

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    Your final paragraph is alarming,do they really do this? Do they knowingly do this or is it just thought and they accept it?

    I have suspected for a while now they are doing similar to alzheimer patients.
     
  18. OP
    haidut

    haidut Member

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    The doctors on the front line are probably just following official guidelines and not doing it on purpose. But the people creating the public policy know very well what's going on and push it on purpose, mostly for profit, but like the effects of being able to lower death stats while making a few bucks. Just like Peat said, cancer is now the leading cause of death and given the abysmal failure of the "War on cancer" anything will be done to push the stats down, even through fraud.
    No. 1 cause of death: Cancer is catching up to heart disease - CNN.com

    The cholinergic drugs for AD do the same, as you noted. Estrogen manifests much of its ill-effects through the cholinergic system, so cholinergic drugs make people die from some estrogenic condition other than AD (stroke, heart attack, etc) and thus skew stats in favor of Big Pharma.
     
  19. PakPik

    PakPik Member

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    Even with something as "simple" as the harm caused by corticosteroids (I think they can be useful if used only a short period of time when a situation would really call for them, but unfortunately this is not how they are used in most cases) I see much reason in what haidut says about the pharma and medical industry. I feel compelled to mention this since I saw an elder relative of mine today who has been afflicted by the condition called "topical steroid withdrawal" or "red skin syndrome", where chronic use of corticosteroids on the skin destroys it and destroys the quality of life of the person from all the secondary symptoms it generates, even in some cases patients have commited suicide (you can search images in google and see how horrible it is). Sad thing is Dr. Marvin Rapaport, one of the pioneer doctors noticing this "phenomenon" as early as the 70s, has had his research and wake-up calls thoroughly ignored by the dermatological associations. So even something as "simple" as the problems with topical corticosteroids as they have been used by the medical industry just falls on deaf ears at best, or more likely, has fallen on the ears and hands of corrupt people on positions of authority and power and big money leading these dermatological and medical associations. Shame, shame on these medical/"science" figures who become who make "a few bucks" or maintain their power through the suffering of millions.

    Dr. Marvin Rapaport, MD
    White Paper on Steroid Addiction

    "In 1978 I initiated and set up the contact and photo dermatitis clinic at UCLA. There was a need to evaluate a large group of patients who exhibited severe eczematoid rashes, especially on the face. ... It became increasingly clear that the physician’s therapy, the corticosteroids, was invariably causing the problem. I wrote 7 scientific articles that were published in the most august peer-reviewed dermatologic journals and I gave many lectures at various dermatology meetings. To this day an unfortunate reluctance exists on the part of most physicians to accept this simple concept."

    "3200 cured patients demonstrate that there is no “bad” eczema warranting newer and potentially more dangerous interventions. Instead, the worsening conditions of patients’ eczema are due to the prolonged usage of corticosteroids – the misguided dermatological standard for five decades. All 3200 of my patients were treated with only one changed variable – the cessation of all corticosteroids – and they were all cured."

    "Red Skin Syndrome (RSS) – Topical Steroid Addiction – A Conspiracy of Silence
    ...
    1. IT APPEARS THE NEA TASK FORCE IS DISINGENUOUS IN THEIR COMMITMENT TO PUBLIC HEALTH: The National Eczema Association (NEA) created a task force that sponsored and funded a physician review to ascertain if topical steroid addiction actually exists, to define steroid addiction, to explore the clinical findings, and to determine how common addiction is. Their narrow review of the literature examined only 34 articles that they fully admit are limited by low quality evidence, variability in the extent of data, and the lack of studies with rigorous steroid addiction methodology. Their review conspicuously failed to include my own comprehensive paper analyzing 1500 patients. All of the items the task force was charged to find answers for had already been answered and documented in my detailed paper directly contradicting the NEA who refused to identify topical steroid addiction leading to RSS as the dominant problem of all eczema patients. Instead, they concluded that topical steroid withdrawal is “likely” due to misuse of steroids but is a rare and minor problem only seen on the face and in the groin. Theirs is a grievously wrong conclusion that ignores the 10,000 patients suffering with RSS today. Truthful findings would have eliminated the need for the existence of the NEA. Shame on the NEA and the authors of their disingenuous review.
    2....
    3. IT APPEARS THE DRUG COMPANIES VALUE PROFIT ABOVE PUBLIC HEALTH: Instead of finding cures for diseases the drug companies are attempting to find new diseases for their new drugs including biologicals, monoclonal antibodies, and anti-mitotic. Pure science requires the atopic RSS patients cease the use of steroids when they enter into research projects. Pharmaceutical companies have RSS patients continue their use of steroids during the study and that completely skews the results. This poor scientific methodology is a conflict of interest and makes pharmaceutical studies on RSS useless. Further, since they have not looked at the literature about RSS nor recognized its existence they insist that they are studying and treating “bad eczema” patients.

    4. IT APPEARS THE ACADEMY OF DERMATOLOGY SACRIFICES PUBLIC HEALTH BY VALUING DRUG COMPANY RESEARCH ABOVE INDEPENDENT FINDINGS: The Academy of Dermatology disseminates pharmaceutical company sponsored research, papers and lectures at the meetings of the Academy and in their journals instead of independent research. Why are there no oversight and questioning of methodology or conflicts of interest? If the peer reviewed journals that I am discussing did not find my papers’ findings appropriate and above reproach then let them either retract the results of my work or concur with my findings using the editorial mode and stop this charade.

    5. IT APPEARS THAT DERMATOLOGISTS HAVE GOTTEN LAZY AT THE EXPENSE OF PUBLIC HEALTH: My fellow dermatologists continue to write prescriptions for the corticosteroids that continue to endanger RSS patients. Why have they also continued to write prescriptions for the “new” side- effect ridden drugs that I mentioned above and needlessly expose the patients? In a recent Academy of Dermatology Journal article looking again at a new drug intervention, the drugs cited as being used previously by these RSS patients included systemic corticosteroids, cyclosporin, mycophenolic acid, azathioprine, phototherapy, methotrexate, interferon gamma, omalizumab, and calcineuin inhibitors and this was only in six patients. My evaluation of the patients’ histories was that they were all steroid addicted."
     
  20. cats

    cats Member

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    I noticed an odd passage in one of the webpages linked in the first post, stating that increased NAD+ from niacinamide increased SIRT activity:

    "SIRT1 deacetylase activity is dependent upon NAD+, and NAD+ depletion during
    excitotoxic and ischemic conditions would therefore be expected to decrease SIRT1 activity
    (Yang and Sauve 2006), although SIRT1 activity may not be affected by NAD+ fluctuations
    within the physiological range (Anderson et al. 2003). Our findings suggest that SIRT1
    levels and activity in neurons are influenced by cellular NAD+ levels, and that nicotinamide
    treatment attenuates depletion of NAD+ and preserves SIRT1 activity in neurons under
    excitotoxic and ischemic conditions"
     
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