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MDMA lowers serotonin
Not before it overloads the brain with serotonin, down-regulating receptors... duh?
This is raypeatforum. Have you read any of Ray Peat's articles? I suggest you read this one:That's actually quite a... out of the box view. I never heard of anything like that. And I researched MDMA extensively. According to this theory, what would produce the euphoria and pleasurable effects, if not the massive amount of Serotonin in the brain?
woot!I heard from RP interview with Josh Rubin ( at 94 minutes http://www.blogtalkradio.com/eastwesthe ... -endoto) that nicotinic acid and Inositol hexanicotinate increases Serotonine but not niacinamide. I was confused for a while. Then i read the article you cited by Prousky, ND, that is a report on niacinamide improving anxiety in his patients. He did not measure their serotonin or anything. He guessed that niacinamide might have increased serotonin since his patients were feeling better. He made that assumption based on a rat study that used niacin in nicotinic acid form. He did not mention that in his report.
Tryptophan metabolism in various nutritive conditions. - PubMed - NCBI
These ND people are flooding the net with these kind of scholarly research. If someone does not have an advance degree in science they should not be writing scientific reports.
"master metabolic murderers"I will digress a little before I answer the question. Hopefully my digression will help answer future questions about RP recommendations. Just to keep you interested in my rant I will say this - niacinamide actually lowers serotonin, or at least acts an antagonist to it. More on that towards the end of my rant:)
I have read all of Peat's books and articles, and I regularly scour PubMed and all sorts of medical news sources. After doing that for several years a clear trend began to emerge. Most of the supplements/vitamins RP recommends have multiple modes of action, all consistent with Ray's ideas. This is opposed to pharma drugs, wich typically have a very specific (preferably one) mode of action and end up destroying the balance in the body.
For instance Vitamin E is a direct estrogen receptor antagonist, and directly lowers levels of estrogen in the body. I know Ray does not believe in the receptor theories and he talks mostly about how vitamin E acts in ways approximately opposite to estrogen. Be that as it may Vitamin E seems to not just negate the effects of estrogen but also directly lowers it:
Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen receptor-positive, but not HER-2 breast cancer. - PubMed - NCBI
Dietary tocopherols inhibit cell proliferation, regulate expression of ERα, PPARγ, and Nrf2, and decrease serum inflammatory markers during the dev... - PubMed - NCBI
Mixed tocopherols prevent mammary tumorigenesis by inhibiting estrogen action and activating PPAR-γ
Novel interactions of vitamin E and estrogen in breast cancer. - PubMed - NCBI
From one of the studies above:
"...Serum E2 levels were significantly reduced by the treatment with 0.5% γ-TmT."
Btw, the estrogen reduction mention above was about 65% compared to controls.
In addition, Vitamin E and zinc also lower prolactin:
Effect of vitamin E therapy on sexual functions of uremic patients in hemodialysis. - PubMed - NCBI
Zinc: an inhibitor of prolactin (PRL) secretion in humans. - PubMed - NCBI
This would explain the raging libido boost I get from taking some zinc, tocopherol, and vitamin B6. It truly makes you feel like you are back in high school:)
Same with magnesium, sodium, aspirin, etc. - i.e. they all have similar effects via multiple pathways and they all have studies about them that they all lower simultaneously estrogen, prolactin, serotonin, PTH, TSH, etc. In other words, it seems that every supplements Ray talks about has studies about it showing it reduces multiple "bad" metabolic markers that according to Peat need to be minimized/reduced somehow.
As far as I am concerned, this is a major evidence in favor of Peat's ideas. When a substance acts consistently via multiple pathways, many of which have confirmed beneficial effects, chances are the theory behind it is correct.
So, rule of thumb for future questions related to supplements suggested by RP. If you read somewhere about supplement X reducing something bad (say prolactin) go on Pubmed and do a search of that substance and all other "bad" things that RP warns about. You will see that in the majority of cases there will be studies about that substance X reducing other bad metabolic markers such as estrogen, serotonin, interleukins, NO, CO, etc.
For example, search Pubmed for "aspirin prolactin", "aspirin estrogen", "aspirin serotonin" and you will see what results you get.
Case in point. I stumbled on this gem while doing the exact same thing. I was interested in how niacinamide helps with inflammatory conditions such as rheumatoid arthritis and psoriasis, and protects against radiation damage and immunosuppression. After doing some reading on Pubmed, I found this old article:
Tranquilizing and antiserotonin activity of nicotinamide. - PubMed - NCBI
I emailed it to RP and he liked it a low, and he updated his website to include it as a reference to one of his older articles posted there. For those of you who don't have access to the full study - the doses used in the study were pretty high.The study was done with mice and the dosage was as follows:
To completely antagonize high serotonin - 1300mg/kg in mice, HED 93mg/kg.
To completely antagonize moderate serotonin - 800mg/kg in mice, HED 57mg/kg.
So, as you can see to antagonize serotonin completely you'd need a dose of about 100mg/kg for a human. That's in the range 7g-9g a day, and is close to the doses used by Hoffer et al. to treat mental disorders and cancer.
NOTE: This is applicable for niacinamide/nicotinamide only. As you all know, plain niacin and other varieties such as inositol hexanicotinate actually increases serotonin and histamine.
Finally, another rule of thumb (mine): If you interested in whether a specific supplement you've heard about it is good or bad and RP's website and interviews have no information about it - do a quick search on Pubmed for the supplement and the keywords "estrogen" or "serotonin". So if the supplement you are interested in is "supervitamin" then to a search for "supervitamin estrogen" or "supervitamin serotonin". It seems that estrogen and serotonin are such broadly acting substances that almost anything you introduce into your body (food or supplements) will tilt the scale for these two in one direction (high: pro-stress) or the other (low: anti-stress). Based on the results you'll know what the answer is. Anything that increases one or both of these two master metabolic murderers is not worth ingesting.
Well, hopefully my rant answers the direct question, and gives direction on future questions.
Pardon my verbosity, but I get really excited when I feel like I am starting to get the big picture of RP's ideas and how every supplement he mentions fits in there.
@Burguul, this thread is about whether niacinamide can serotonin.
Here is a thread about MDMA: How Does MDMA Make One High Through Serotonin?
Abram Hoffer took himself 1g niacin three times a day, and lived to 92 in perfect health.
()
He explained in his books that NIACINAMIDE DOESN'T regularize blood lipids as do Niacin and Inositol hexaniacinate.
This is an important factor in those with high triglycerides and diabetics; Ray explained high triglycerides can impair normal production of energy.
I don't know where this situation leaves serotonin production, but it certainly didn't seem to do harm to Hoffer's health.
And of course, the migraines triggered by niacin are caused by it's flush, vasodilatation effect, not by the fillers in the vitamin.
As i take myself 3 g/day, i experienced them too in the very beginning. The more regularly i take niacin, the less flush and the less migraines i get. And it's absolutely true, you do feel like you were back in highschool.
Yes, I take a lot of B3 (niacinamide only, no niacin) and it helps tremendously with brain function, anxiety, energy levels, etc. My dosage is 1500mg twice a way - morning and evening, for a total of 3000mg. Why this exact dosage?
Many reasons, but it seems to be within the effective range for reducing serotonin and is used in a human trial for treating Alzheimer's Disease (AD), which as we all know manifests mainly as a memory disorder. Here is the clinical trial that also mentions the dosage I am taking:
Safety Study of Nicotinamide to Treat Alzheimer's Disease - Full Text View - ClinicalTrials.gov
I am still in my 30s, so hopefully I don't have AD but aside from that fact, that dosage for me represents good balance between results and side effects. The study I mentioned on niacinamide and serotonin said that in high doses niacinamide causes "profound sedation", which is obviously something you don't want during the day
Some other notes. A person I know took 3000mg a day of niacinamide for 2 months and it put their autoimmune condition in such state of remission that the doctor treating the person thought there was some fraud or mistake going on. I mean, within 2 months the tests went from progressing disease to virtually no disease markers at all, so the doctor thought that either the original diagnosis was wrong or the second set of results was from a different person. As RP said - when modern medicine is faced with something they cannot explain they will say either original diagnosis was wrong or new results are wrong
Final note, my recommendation if you decide to go with 3000mg niacinamide is to only take it until your pulse/temperature/test results show progress and then go back to maybe 500mg morning and evening for a total of 1000mg. That dosage seems to be sufficient to protect from the bad effects of sunlight (UVB) as well, so it should give you many more reasons to spend more time in sun.
I hope that helps, but if you have specific questions about a condition or dosage for it just send me a PM.
P.S. I almost forgot - if you get a headache with niacinamide - it's either from some toxic fillers in the pills (even if they are not listed on the label) or hypoglycemia. If it's the latter, try taking with a glass of orange juice and this should fix it. If it doesn't then it;s most likely the fillers. It took me trying at least 6 different brands of niacinamide pills before I could find one that does not disturb my stomach. So, try to get powder if you can or keep trying different pill brands until you find one that does not give you headaches.
How to mitigate the low fat woe but require approx 30gms of fat in order for vitamin k2 to be absorbed. As currently I have 2 litres of Fat Free a2 milk, besides 75gms of whey protein concentrate. And hv been using 2 drops of "kuinone" transdermally, plus 2 drops Kuinone with evo oil orally. Pls help.Many things could be causing this, but let's start with the ones I know have happened in the past. Vitamin E lowers prolactin. I posted a study about that on another thread in this forum so if you search around you will find it. Lower prolactin means higher dopamine, higher testosterone, and lower serotonin. Now, some of that testosterone may aromatize to estrogen if you are under stress but this is where again Vitamin E and vitamin K come into play. Vitamin K (only menatetrenone a.k.a. MK-4 has been shown to do this) is a true aromatase inhibitor. Here are some studies:
Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells - PubMed
A calcium-deficient diet caused decreased bone mineral density and secondary elevation of estrogen in aged male rats-effect of menatetrenone and elcatonin - PubMed
Finally, even if any testosterone does aromatize then vitamin E acts like an estrogen "receptor" antagonist and in doses of 2,500mg lowered estrogen levels by 65%. Since you are taking more than that, you should be getting even lower estrogen. If you add vitamin A and vitamin D to this duo you have what I like to call "Tetra Titans". Retinol, D3 are also aromatase inhibitors so should help with estrogen even more.
I personally, take the Tetra Titans like this (all orally): 75,000 IU vitamin A (retinol), 45mg menatetrenone (MK-4), 5,000 IU D3, 2,500mg mixed tocopherols (70% gamma).
Just make sure that you eat enough fat when you take those vitamins. They are all fat-soluble but there was a study I saw recently that unless your meal has at least 27g of saturated fat in it, vitamin K would not get properly absorbed and gets excreted in fecal matter, which would be a waste (pun intended).
Finally, a good test for estrogen would be to get a device that measures water saturation in tissues. A good way you approximate this is to get one of those scales that measure body fat percentage. Well, in reality they measure body water percentage and use that to approximate body fat. When estrogen is low, as Ray peat said, you should NOT be retaining any excess water. Cells take up water under the influence of estrogen and for them it is a signal to divide. So, no estrogen excess means no water uptake excess. Use one of those fat measuring scales to periodically measure your weight and your body fat percentage. If your estrogen drops, your body will drop the excess water and you will see a dramatic "drop" in reported body fat but a much smaller drop in weight. The drop in body fat is the excess water you dumped. With low estrogen you will start losing body fat too but that will take more time, definitely not overnight like the scale would have you believe
Haidut can you speak on how Naicinamide affects one hydration? Because I can't get past one 500mg pill of niacinamide. It starts to dry out my tongue and mouth. Then my sense of taste goes away and no matter how much water I drink my mouth is still dry.I will digress a little before I answer the question. Hopefully my digression will help answer future questions about RP recommendations. Just to keep you interested in my rant I will say this - niacinamide acts an antagonist to serotonin. More on that towards the end of my rant
I have read all of Peat's books and articles, and I regularly scour PubMed and all sorts of medical news sources. After doing that for several years a clear trend began to emerge. Most of the supplements/vitamins RP recommends have multiple modes of action, all consistent with Ray's ideas. This is opposed to pharma drugs, wich typically have a very specific (preferably one) mode of action and end up destroying the balance in the body.
For instance Vitamin E is a direct estrogen receptor antagonist, and directly lowers levels of estrogen in the body. I know Ray does not believe in the receptor theories and he talks mostly about how vitamin E acts in ways approximately opposite to estrogen. Be that as it may Vitamin E seems to not just negate the effects of estrogen but also directly lowers it:
Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen receptor-positive, but not HER-2 breast cancer. - PubMed - NCBI
Dietary tocopherols inhibit cell proliferation, regulate expression of ERα, PPARγ, and Nrf2, and decrease serum inflammatory markers during the dev... - PubMed - NCBI
Mixed tocopherols prevent mammary tumorigenesis by inhibiting estrogen action and activating PPAR-γ
Novel interactions of vitamin E and estrogen in breast cancer. - PubMed - NCBI
From one of the studies above:
"...Serum E2 levels were significantly reduced by the treatment with 0.5% γ-TmT."
Btw, the estrogen reduction mention above was about 65% compared to controls.
In addition, Vitamin E and zinc also lower prolactin:
Effect of vitamin E therapy on sexual functions of uremic patients in hemodialysis. - PubMed - NCBI
Zinc: an inhibitor of prolactin (PRL) secretion in humans. - PubMed - NCBI
This would explain the raging libido boost I get from taking some zinc, tocopherol, and vitamin B6. It truly makes you feel like you are back in high school
Same with magnesium, sodium, aspirin, etc. - i.e. they all have similar effects via multiple pathways and they all have studies about them that they all lower simultaneously estrogen, prolactin, serotonin, PTH, TSH, etc. In other words, it seems that every supplements Ray talks about has studies about it showing it reduces multiple "bad" metabolic markers that according to Peat need to be minimized/reduced somehow.
As far as I am concerned, this is a major evidence in favor of Peat's ideas. When a substance acts consistently via multiple pathways, many of which have confirmed beneficial effects, chances are the theory behind it is correct.
So, rule of thumb for future questions related to supplements suggested by RP. If you read somewhere about supplement X reducing something bad (say prolactin) go on Pubmed and do a search of that substance and all other "bad" things that RP warns about. You will see that in the majority of cases there will be studies about that substance X reducing other bad metabolic markers such as estrogen, serotonin, interleukins, NO, CO, etc.
For example, search Pubmed for "aspirin prolactin", "aspirin estrogen", "aspirin serotonin" and you will see what results you get.
Case in point. I stumbled on this gem while doing the exact same thing. I was interested in how niacinamide helps with inflammatory conditions such as rheumatoid arthritis and psoriasis, and protects against radiation damage and immunosuppression. After doing some reading on Pubmed, I found this old article:
Tranquilizing and antiserotonin activity of nicotinamide. - PubMed - NCBI
I emailed it to RP and he said he thinks the results are legit, so he updated his website to include it as a reference to one of his older articles posted there. For those of you who don't have access to the full study - the doses used in the study were pretty high.The study was done with mice and the dosage was as follows:
To completely antagonize high serotonin - 1300mg/kg in mice, HED 93mg/kg.
To completely antagonize moderate serotonin - 800mg/kg in mice, HED 57mg/kg.
So, as you can see to antagonize serotonin completely you'd need a dose of about 100mg/kg for a human. That's in the range 7g-9g a day, and is close to the doses used by Hoffer et al. to treat mental disorders and cancer.
NOTE: This is applicable for niacinamide/nicotinamide only. As you all know, plain niacin and other varieties such as inositol hexanicotinate actually increases serotonin and histamine.
Finally, another rule of thumb (mine): If you interested in whether a specific supplement you've heard about it is good or bad and RP's website and interviews have no information about it - do a quick search on Pubmed for the supplement and the keywords "estrogen" or "serotonin". So if the supplement you are interested in is "supervitamin" then to a search for "supervitamin estrogen" or "supervitamin serotonin". It seems that estrogen and serotonin are such broadly acting substances that almost anything you introduce into your body (food or supplements) will tilt the scale for these two in one direction (high: pro-stress) or the other (low: anti-stress). Based on the results you'll know what the answer is. Anything that increases one or both of these two master metabolic murderers is not worth ingesting.
Well, hopefully my rant answers the direct question, and gives direction on future questions.
Pardon my verbosity, but I get really excited when I feel like I am starting to get the big picture of RP's ideas and how every supplement he mentions fits in there.