Methylene Blue (MB) Lowers Prolactin By Opposing Estrogen

haidut · May 15, 2015

It looks like methylene blue may have a few tricks up its sleeve in addition to the well-known effects on mitochondria. The studies below show that MB was able to antagonize the effect of estrogen on prolactin, pituitary size, and dopamine levels.

http://www.ncbi.nlm.nih.gov/pubmed/11343835
"...Methylene blue decreased anterior pituitary prolactin levels and inhibited increases in anterior pituitary prolactin after estradiol benzoate administration. The present results suggest that anterior pituitary DA may play an important role in estrogen-induced anterior pituitary hyperplasia and tumor formation and that antioxidant drugs such as methylene blue may attenuate estrogen-induced pituitary growth. This may occur via increases in anterior pituitary DA levels associated with down-regulation of anterior pituitary D-2 receptors."

http://www.ncbi.nlm.nih.gov/pubmed/10984069
"...We found that the treatment with T3 or MB prevented both estrogen-induced catecholaminergic inhibition and dopamine DA-2 receptor increment in the anterior pituitary. In contrast to T3, MB given alone also slightly decreased the anterior pituitary weight. Serum levels and anterior pituitary content of prolactin were increased after treatment with estradiol benzoate (EB), whereas T3 or MB partially attenuated prolactin hypersecretion after estrogen administration. This is in accord with the attenuation of EB-induced inhibition of dopaminergic system by T3 and MB. MB given in combination with EB also partially attenuated EB-promoted rise of adenohypohyseal NO synthase activity which plays an important role in the regulation of prolactin secretion. Further studies on central catecholaminergic systems, pituitary receptors, the nitrergic system and mechanisms of intracellular signal transduction are necessary for better understanding of pituitary tumor transformation and possibly for the discovery of new approaches towards treating patients with these diseases."

http://www.ncbi.nlm.nih.gov/pubmed/8218149
"...Male rats received estradiol benzoate in a long acting microcrystalline suspension (1 mg/rat i.m., twice a week), methylene blue (MB) 0.5% in the food and the combination of estradiol and MB. After three weeks, MB partially inhibited the growth response of the anterior pituitary to estradiol and it partially inhibited the increase of cAMP content in anterior pituitary. The increase of anterior pituitary cGMP content was not modified by MB, neither the ratio cAMP/cGMP in the anterior pituitary which, however, decreased after estradiol. This decrease was not modified by MB. On the other hand, the prolactin (PRL) increase in the blood after estradiol was inhibited by MB, although the prolactin content in the anterior pituitary was not."

narouz · May 15, 2015

Very interesting, haidut.
Thanks!

In your study of MB,
what have you come across in terms of side effects...?

charlie · Aug 26, 2015

narouz said:
Methylene Blue (MB) Lowers Prolactin By Opposing Estrogen Very interesting, haidut.
Thanks!

In your study of MB,
what have you come across in terms of side effects...?

haidut · Aug 27, 2015

Charlie said:
https://raypeatforum.com/forums/posts/97031/

narouz said:

https://raypeatforum.com/forums/posts/80962/ Very interesting, haidut.
Thanks!

In your study of MB,
what have you come across in terms of side effects...?

Click to expand...

:1

It can give me headaches in dosed of 5mg+ which I think is a sign that it is increasing serotonin. Also, when taken before bed it knocks me out for 8-9 hours and then I am really sleepy until early afternoon the next day. Other than that I think it can replace antibiotics for all but the most serious infections. Same thing for viral issues - a few drops of MB stop the "flu" in its tracks. The latter is not surprising given Ray's view that the flu symptoms are caused by endotoxin and NO, and MB inhibits the release of both of these.

schultz · Aug 27, 2015

haidut said:
Other than that I think it can replace antibiotics for all but the most serious infections. Same thing for viral issues - a few drops of MB stop the "flu" in its tracks. The latter is not surprising given Ray's view that the flu symptoms are caused by endotoxin and NO, and MB inhibits the release of both of these.

Ray think flu symptoms are caused by endotoxin and NO? I am very intrigued by this! Do you happen to know where he has discussed this?

haidut · Aug 27, 2015

schultz said:
https://raypeatforum.com/forums/posts/97131/

haidut said:

Other than that I think it can replace antibiotics for all but the most serious infections. Same thing for viral issues - a few drops of MB stop the "flu" in its tracks. The latter is not surprising given Ray's view that the flu symptoms are caused by endotoxin and NO, and MB inhibits the release of both of these.

Click to expand...

Ray think flu symptoms are caused by endotoxin and NO? I am very intrigued by this! Do you happen to know where he has discussed this?

Oh yeah, he has mentioned it many times in articles and interviews. I don't think he completely excludes the possibility for a virus to cause the same symptoms, but I think he considers endotoxin a much more plausible explanation of the symptoms of the "flu". Here are some links:
viewtopic.php?t=3881
http://raypeat.com/articles/nutrition/carrageenan.shtml
"... Since the bowel becomes inflamed in influenze, it is reasonable to think that some of the symptoms of "the flu" are produced by absorbed bowel toxins. The variations in the post-influenza syndromes are very likely influenced by the nature of the bacteria or foods which are present, chronically or at the time of an uncompensated stress or inflammatory disease. K.M. Stevens has argued that while rheumatic fever and glomerulonephritis are caused by the antigens of streptococci, systemic lupus erythematosis (SLE) is probably caused by the antigens of gram-positive lactobacilli found in the normal flora."
http://www.toxinless.com/ray-peat-the-bean-syndrome.pdf
"...Injury to the bowel causes "flu-like" symptoms. There have been reports that the viruses of "respiratory diseases" appear in the intestine before they appear in the respiratory tract. Alvarez found that "when a dog gets distemper the gradient of latent period down its small bowel is reversed," and he suggests that in a cold "a systolic, non-progressive type of contraction appears." He says codeine is the best medicine to block a cold. (I have argued that it is vitamin C's laxative action which can interrupt cold symptoms.) Recent research shows that naloxone, the morphine antagonist, can restore normal responses to the stressed bowel. Alvarez was interested in chronic fatigue and "painful fatigue," and remarked that occasionally "a fatigue state will follow a bout with some infection such as influenza."

schultz · Aug 27, 2015

haidut said:
schultz said:

https://raypeatforum.com/forums/posts/97131/

haidut said:

Other than that I think it can replace antibiotics for all but the most serious infections. Same thing for viral issues - a few drops of MB stop the "flu" in its tracks. The latter is not surprising given Ray's view that the flu symptoms are caused by endotoxin and NO, and MB inhibits the release of both of these.

Click to expand...

Ray think flu symptoms are caused by endotoxin and NO? I am very intrigued by this! Do you happen to know where he has discussed this?

Click to expand...

Oh yeah, he has mentioned it many times in articles and interviews. I don't think he completely excludes the possibility for a virus to cause the same symptoms, but I think he considers endotoxin a much more plausible explanation of the symptoms of the "flu". Here are some links:
viewtopic.php?t=3881
http://raypeat.com/articles/nutrition/carrageenan.shtml
"... Since the bowel becomes inflamed in influenze, it is reasonable to think that some of the symptoms of "the flu" are produced by absorbed bowel toxins. The variations in the post-influenza syndromes are very likely influenced by the nature of the bacteria or foods which are present, chronically or at the time of an uncompensated stress or inflammatory disease. K.M. Stevens has argued that while rheumatic fever and glomerulonephritis are caused by the antigens of streptococci, systemic lupus erythematosis (SLE) is probably caused by the antigens of gram-positive lactobacilli found in the normal flora."
http://www.toxinless.com/ray-peat-the-bean-syndrome.pdf
"...Injury to the bowel causes "flu-like" symptoms. There have been reports that the viruses of "respiratory diseases" appear in the intestine before they appear in the respiratory tract. Alvarez found that "when a dog gets distemper the gradient of latent period down its small bowel is reversed," and he suggests that in a cold "a systolic, non-progressive type of contraction appears." He says codeine is the best medicine to block a cold. (I have argued that it is vitamin C's laxative action which can interrupt cold symptoms.) Recent research shows that naloxone, the morphine antagonist, can restore normal responses to the stressed bowel. Alvarez was interested in chronic fatigue and "painful fatigue," and remarked that occasionally "a fatigue state will follow a bout with some infection such as influenza."

Thank you for sharing this with me!

I find this incredibly interesting. I need to research this more. I'm kind of hoping I get a cold or the flu soon so I can experiment.... :lol:

Brian · Sep 18, 2015

haidut said:
It can give me headaches in dosed of 5mg+ which I think is a sign that it is increasing serotonin. Also, when taken before bed it knocks me out for 8-9 hours and then I am really sleepy until early afternoon the next day. Other than that I think it can replace antibiotics for all but the most serious infections. Same thing for viral issues - a few drops of MB stop the "flu" in its tracks. The latter is not surprising given Ray's view that the flu symptoms are caused by endotoxin and NO, and MB inhibits the release of both of these.

Do you think Methylene Blue can be as affective as antibiotics such as minocycline for general improvement of intestinal health? What doses do you think would be necessary?

I know somebody who recently was prescribed clindamycin for an oral infection and ended up with an intestinal infection of some kind. I'm trying to research if something like methylene blue would have been effective for their oral infection and might be effective now at getting rid of their intestinal infection. I haven't found much yet to suggest that it would be.

haidut · Sep 18, 2015

Brian said:
post 100327

haidut said:

It can give me headaches in dosed of 5mg+ which I think is a sign that it is increasing serotonin. Also, when taken before bed it knocks me out for 8-9 hours and then I am really sleepy until early afternoon the next day. Other than that I think it can replace antibiotics for all but the most serious infections. Same thing for viral issues - a few drops of MB stop the "flu" in its tracks. The latter is not surprising given Ray's view that the flu symptoms are caused by endotoxin and NO, and MB inhibits the release of both of these.

Click to expand...

Do you think Methylene Blue can be as affective as antibiotics such as minocycline for general improvement of intestinal health? What doses do you think would be necessary?

I know somebody who recently was prescribed clindamycin for an oral infection and ended up with an intestinal infection of some kind. I'm trying to research if something like methylene blue would have been effective for their oral infection and might be effective now at getting rid of their intestinal infection. I haven't found much yet to suggest that it would be.

Search the forum, this has been discussed many times. If you google for methylene blue and antibacterial activity you will also find a lot. MB is likely to be effective but oral doses likely to be effective are in the range 30mg+, which in some people can trigger serotonin symptoms.

Parsifal · Dec 6, 2015

haidut said:
He says codeine is the best medicine to block a cold. (I have argued that it is vitamin C's laxative action which can interrupt cold symptoms.) Recent research shows that naloxone, the morphine antagonist, can restore normal responses to the stressed bowel. Alvarez was interested in chronic fatigue and "painful fatigue," and remarked that occasionally "a fatigue state will follow a bout with some infection such as influenza."

Hmmm that's interesting. I think there might be a link between endomorphine problems and my chronic constipation and anhedonia/orgasm anhedonia and why marijuana/chocolate was the only thing that I tried that worked for the anhedonia problem I have since puberty. Would you have some infos on the endorphin/cannabinoid system regarding bioenergetic/Peat's paradigm please haidut?

haidut · Dec 7, 2015

Parsifal said:
post 112952 codein

I don't view endorphins positively and I think neither does Peat. They are usually released to mitigate the effect and pain of some stressful event. Hypoglycemia, running, surgery, etc all raise endorphins. The anti-endorphin drug naltrexone is actually used for bowel problems like IBS. You can search the forum for more info.

Parsifal · Dec 7, 2015

haidut said:
post 113059I don't view endorphins positively and I think neither does Peat. They are usually released to mitigate the effect and pain of some stressful event. Hypoglycemia, running, surgery, etc all raise endorphins. The anti-endorphin drug naltrexone is actually used for bowel problems like IBS. You can search the forum for more info.

Thank you very much haidut for taking the time to reply, I have read what you advise about Naltrexone and it seems that it helps the immune system (how?) for people with auto-immune disease and lowers histamines (so endorphins raise histamines?). Ray never really talked a lot about it but it seems important.

I asked you that question because endorphins are what causes (at least according to mainstream "science") pleasure (at least when it is release in the nucleus accubens) and as you know by now (sorry to ask you a lot of questions like that), I am plagued with very disturbing anhedonia and particularly ejaculation anhedonia and I'm trying to find the cause and a remedy for it. I wonder if that is because I may have too much endorphins or endorphins resistance (don't know why), but my endorphin system must have a problem (maybe a damage/shrinking in the nucleus accubens and/or slow metabolism/inflammation there) and as you know only dopaminergic products like Cannabis and dark chocolate seem to help (coffee or theanine no) but they are not an option as they have a lot of downsides.
I have no pain nor stress that could explain this problem (i think that apathy/aboulia and ADD is somewhat related).

Like you said running and pain seem to raise it as well as masturbation, sex and psychological pleasure or pleasure response to a stimulus. I've also read that people under stress can have a spontaneous orgasm (so maybe cortisol increases it).
All kinds of drugs that lead to "addiction" (I know that you don't believe in this phenomenon but I guess a lot of addicts would be revolted by your position) seem to raise endorphins (wether those that raise dopamine, acetylcholine or serotonin) so maybe because anything that excites cells will cause endorphins to rise? And this is the mechanism with which addiction or tolerance to drugs is explained (the more you stimulate this pathway the more tolerance you will build to the effects and the more drug you will need to feel the effects and if you stop the drug cold turkey you will have very hard withdrawal especially for heroin) but seems that you don't believe in it as well?
Also, the view in mainstream medicine is that pleasure is antistress (laughing, sex even LSD which seems counterintuitive as serotonin seems to raise endorphins as well and stimulate the pleasure response, drugs, etc) which seems to go against the view that endorphins are hormones of stress that are bad?

I wanted to know what is the relation of endorphins/anandamine (the bliss neurotransmitter according to Peat) to the stress system (histamines, cortisol, estrogen, prolactin, serotonin, NO) as Peat never really talked about endorphins (just a bit about naltrexone but not in a satisfying well) and I feel oncerned about it.

Also, in france it's almost impossible to get prescriptions drugs other than antibiotics if you have not been diagnosed with a special condition (doctors will not prescribe it to you and be very angry at you if you ask them to prescribre you something, I've experienced it many times and now lost the ability to cope with this kind of stress and don't want to see them again, the system is way more restrictive thanks to the "sécurité sociale", in the States you seem to be more free to ask your doctors things) so I wondered if there were a way to lower the endorphins naturally or try alternatives without needing drugs.
I have to say that I've been Peating very seriously since 4 month and tried a lot of supplements (no drugs) to lower inflammation, estrogens, serotonin, etc, it helped me for other symptoms but doesn't work for anhedonia. I've also tried no fap for a very long time (more than 1 year) as well but the orgasms become really non-existent the more abstinence there is...
Isn't casein an opioid that could be bad in this regard?

haidut · Dec 7, 2015

Parsifal said:
post 113069

haidut said:

post 113059I don't view endorphins positively and I think neither does Peat. They are usually released to mitigate the effect and pain of some stressful event. Hypoglycemia, running, surgery, etc all raise endorphins. The anti-endorphin drug naltrexone is actually used for bowel problems like IBS. You can search the forum for more info.

Click to expand...

Thank you very much haidut for taking the time to reply, I have read what you advise about Naltrexone and it seems that it helps the immune system (how?) for people with auto-immune disease and lowers histamines (so endorphins raise histamines?). Ray never really talked a lot about it but it seems important.

I asked you that question because endorphins are what causes (at least according to mainstream "science") pleasure (at least when it is release in the nucleus accubens) and as you know by now (sorry to ask you a lot of questions like that), I am plagued with very disturbing anhedonia and particularly ejaculation anhedonia and I'm trying to find the cause and a remedy for it. I wonder if that is because I may have too much endorphins or endorphins resistance (don't know why), but my endorphin system must have a problem (maybe a damage/shrinking in the nucleus accubens and/or slow metabolism/inflammation there) and as you know only dopaminergic products like Cannabis and dark chocolate seem to help (coffee or theanine no) but they are not an option as they have a lot of downsides.
I have no pain nor stress that could explain this problem (i think that apathy/aboulia and ADD is somewhat related).

Like you said running and pain seem to raise it as well as masturbation, sex and psychological pleasure or pleasure response to a stimulus. I've also read that people under stress can have a spontaneous orgasm (so maybe cortisol increases it).
All kinds of drugs that lead to "addiction" (I know that you don't believe in this phenomenon but I guess a lot of addicts would be revolted by your position) seem to raise endorphins (wether those that raise dopamine, acetylcholine or serotonin) so maybe because anything that excites cells will cause endorphins to rise? And this is the mechanism with which addiction or tolerance to drugs is explained (the more you stimulate this pathway the more tolerance you will build to the effects and the more drug you will need to feel the effects and if you stop the drug cold turkey you will have very hard withdrawal especially for heroin) but seems that you don't believe in it as well?
Also, the view in mainstream medicine is that pleasure is antistress (laughing, sex even LSD which seems counterintuitive as serotonin seems to raise endorphins as well and stimulate the pleasure response, drugs, etc) which seems to go against the view that endorphins are hormones of stress that are bad?

I wanted to know what is the relation of endorphins/anandamine (the bliss neurotransmitter according to Peat) to the stress system (histamines, cortisol, estrogen, prolactin, serotonin, NO) as Peat never really talked about endorphins (just a bit about naltrexone but not in a satisfying well) and I feel oncerned about it.

Also, in france it's almost impossible to get prescriptions drugs other than antibiotics if you have not been diagnosed with a special condition (doctors will not prescribe it to you and be very angry at you if you ask them to prescribre you something, I've experienced it many times and now lost the ability to cope with this kind of stress and don't want to see them again, the system is way more restrictive thanks to the "sécurité sociale", in the States you seem to be more free to ask your doctors things) so I wondered if there were a way to lower the endorphins naturally or try alternatives without needing drugs.
I have to say that I've been Peating very seriously since 4 month and tried a lot of supplements (no drugs) to lower inflammation, estrogens, serotonin, etc, it helped me for other symptoms but doesn't work for anhedonia. I've also tried no fap for a very long time (more than 1 year) as well but the orgasms become really non-existent the more abstinence there is...
Isn't casein an opioid that could be bad in this regard?

Don't know much about anhedonia reversal but many people with depression seem to have it. Some people have had success reversing it with tianeptine. Google around and you will find more info.

mayweatherking · Dec 16, 2015

This is good it has a positive effect against prolactin with increased estrogen. But haidut, what about the increased estrogen that is all ready in the body? How does that play a part?

haidut · Dec 17, 2015

mayweatherking said:
post 114917 This is good it has a positive effect against prolactin with increased estrogen. But haidut, what about the increased estrogen that is all ready in the body? How does that play a part?

I posted another study showing MB is also estrogen "receptor" antagonist and aromatase inhibitor. So, it should be able to help with existing and new estrogen as well. Finally, since Mb also helps liver function it should improve estrogen glucuronidation and excretion too.

mayweatherking · Dec 17, 2015

haidut said:
post 115124

mayweatherking said:

post 114917 This is good it has a positive effect against prolactin with increased estrogen. But haidut, what about the increased estrogen that is all ready in the body? How does that play a part?

Click to expand...

I posted another study showing MB is also estrogen "receptor" antagonist and aromatase inhibitor. So, it should be able to help with existing and new estrogen as well. Finally, since Mb also helps liver function it should improve estrogen glucuronidation and excretion too.

Very cool. I'm surprised you didn't mention it on bioenergetic view on hair loss that was just posted on danny roddy. i figured it would be a staple for it. but i just started taking it and i have to say it is helping me for sure.

do you think we should take a break from taking it or just stick with 10-15 drops a day? (diluted from 1 drop in a vial)

messtafarian · Dec 18, 2015

haidut, I so appreciate your research and the hard work you do to service this community and the pursuit of health in general.

However sometimes I wish you would also forward a disclaimer or some sort of context when you are presenting this information. Methylene Blue has certain properties but ALL refined substances have their darker side -- for example MB can induce high blood pressure and has a strong effect on brain chemistry. As great as it can be I suppose, most people with chronic or complex illnesses don't have infinite room to experiment on themselves.

MB has STRONG effects and also contraindications -- for example you have to be really careful with this substance's synergy with other drugs. Even the basic checkpoints for contraindications with conditions and drugs have not been researched, because most of the RP substances have been abandoned for fancier pharma.

I'm a fan, but please realize sometimes adding some context might be needed.

mayweatherking · Dec 18, 2015

messtafarian said:
post 115188 haidut, I so appreciate your research and the hard work you do to service this community and the pursuit of health in general.

However sometimes I wish you would also forward a disclaimer or some sort of context when you are presenting this information. Methylene Blue has certain properties but ALL refined substances have their darker side -- for example MB can induce high blood pressure and has a strong effect on brain chemistry. As great as it can be I suppose, most people with chronic or complex illnesses don't have infinite room to experiment on themselves.

MB has STRONG effects and also contraindications -- for example you have to be really careful with this substance's synergy with other drugs. Even the basic checkpoints for contraindications with conditions and drugs have not been researched, because most of the RP substances have been abandoned for fancier pharma.

I'm a fan, but please realize sometimes adding some context might be needed.

can you elaborate a little on this?

haidut · Dec 18, 2015

mayweatherking said:
post 115173

haidut said:

post 115124

mayweatherking said:

post 114917 This is good it has a positive effect against prolactin with increased estrogen. But haidut, what about the increased estrogen that is all ready in the body? How does that play a part?

Click to expand...

I posted another study showing MB is also estrogen "receptor" antagonist and aromatase inhibitor. So, it should be able to help with existing and new estrogen as well. Finally, since Mb also helps liver function it should improve estrogen glucuronidation and excretion too.

Click to expand...

Very cool. I'm surprised you didn't mention it on bioenergetic view on hair loss that was just posted on danny roddy. i figured it would be a staple for it. but i just started taking it and i have to say it is helping me for sure.

do you think we should take a break from taking it or just stick with 10-15 drops a day? (diluted from 1 drop in a vial)

Ray thinks that 1-2 drops (~1mg) is optimal for long term usage and that seems to work for me. The higher doses were used to treat specific conditions such as depression or Alzheimers, which most people do not have. Also, the MAO-A inhibition becomes really pronounced in the higher doses so that's another reason to not overdo it. The lifespan extension studies found that only the lower doses around 1mg daily increased lifespan so that's another point to not overdo it.

haidut · Dec 18, 2015

messtafarian said:
post 115188 haidut, I so appreciate your research and the hard work you do to service this community and the pursuit of health in general.

However sometimes I wish you would also forward a disclaimer or some sort of context when you are presenting this information. Methylene Blue has certain properties but ALL refined substances have their darker side -- for example MB can induce high blood pressure and has a strong effect on brain chemistry. As great as it can be I suppose, most people with chronic or complex illnesses don't have infinite room to experiment on themselves.

MB has STRONG effects and also contraindications -- for example you have to be really careful with this substance's synergy with other drugs. Even the basic checkpoints for contraindications with conditions and drugs have not been researched, because most of the RP substances have been abandoned for fancier pharma.

I'm a fan, but please realize sometimes adding some context might be needed.

I agree with you, but not sure how I can address every person's specific context. The issues you mentioned are more of a side effects thing and every substance has side effects, and many of them are still unknown. For instance, should I be pointing out that vitamin B1 is not advisable for people who already have high CO2? Or that women with PCOS should not be taking DHEA?
My point is just that - many if not all substances we consume have side effects and the point is to find what dose works for every specific person. In the specific case of methylene blue, it is one of the safest substances around and AFAIK nobody has died form it in the last 150 years of its use as a drug. In lower doses (<5mg) it should not be increasing blood pressure and if it does then it is probably a good thing as a result of opposing NO. Increasing blood pressure is not always a bad thing. Your "normal" blood pressure may be 120/80 but if you are hypothyroid then the "optimal" blood pressure may be 130/90 to avoid hypoxia. People with serious chronic disease often have low blood pressure.
Bottom line is, if methylene blue increases blood pressure in low doses then it is probably a "positive" side effect. And if it was inhibiting MAO-A that much then it would not have been found helpful for depression and bipolar in doses of just 15mg daily. The side effects of MB are hard to classify as good or bad without knowing the health status and context of the person, but most of the stuff Peat writes about and I post on is pretty safe.
Anyways, point taken but I think you see my point as well - I can't warn every possible person about every possible side effect of every substance, which btw have typically been in use for decades or centuries and are much safer than what people ingest daily in their food from the local deli.

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