Can Niacinamide Increase Serotonin?

bradley

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Meant to paste this which is what sparked the question

Journal of Orthomolecular Medicine Vol. 20, No. 3, 2005

Serotonin Synthesis

Another biochemical reason for niacinamide’s anxiolytic effects might have to do with the vital role that it has upon the synthesis of serotonin.

For example, in a patient with anorexia nervosa an insufficient supply of vitamin B3 or protein resulted in reduced urinary levels of the serotonin breakdown product, 5-hydroxy-indolacetic acid (5-HIAA).32 The authors of this report postulated that a deficiency of vitamin B3 reduced the feedback inhibition upon the kynurenine pathway, resulting in more tryptophan being diverted to the kynurenine pathway, making less substrate available for the synthesis of serotonin.

By contrast, the use of pharmacological doses of vitamin B3 can increase the production of serotonin.33 In a rat study, the administration of 20 mg of niacin resulted in increased levels of 5-HIAA and decreased levels of xanthurenic acid via the kynurenine pathway.34 Taking pharmacological doses of niacinamide (or any other form of vitamin B3) would increase the production of serotonin, by diverting more tryptophan to become substrate for serotonin synthesis. Niacinamide’s therapeutic ability to increase serotonin production might explain why it was successful in reducing the anxiety symptoms of the three patients
 

fabiomln

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I think yes.
I tried high levels of b3 and I had the same effects as when I take to much melatonin.
Serotonin is a precursor of melatonin.

I woke up in the morning with neck pains and sometimes with headache.
 

Mittir

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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.
http://www.ncbi.nlm.nih.gov/pubmed/1244091
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.
 

haidut

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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.
 
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honeybee

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Thats some really interesting reserach. Are you taking any b3? if so, how much and have you experinced any side effects? I take 250 mg at bedtime and I believe it helps me sleep. I have tried 500 mg at one time, and i got a headache.
 

haidut

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honeybee said:
Thats some really interesting reserach. Are you taking any b3? if so, how much and have you experinced any side effects? I take 250 mg at bedtime and I believe it helps me sleep. I have tried 500 mg at one time, and i got a headache.

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:
http://clinicaltrials.gov/show/NCT00580931

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.
 

jyb

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I had also wondered whether the sedative effects of high doses could be due to being converted to tryptophan.

In one of his newer articles, RP talks more about it. It doesn't seem like the sedation would be a serotonin increase issue.

http://raypeat.com/articles/articles/rosacea-inflammation-aging.shtml

Niacinamide, one of the B vitamins, provides energy to this mitochondrial system. Under stress and strong excitation, cells waste niacinamide-NADH, but niacinamide itself has a sedative antiexcitatory effect, and some of its actions resemble a hormone. Estrogen tends to interfere with the formation of niacin from tryptophan. Tryptophan, rather than forming the sedative niacin (pyridine carboxylic acid), can be directed toward formation of the excitatory quinolinic acid (pyridine dicarboxylic acid) by polyunsaturated fatty acids. Excitation must be in balance with a cell's energetic resources, and niacinamide can play multiple protective roles, decreasing excitation, increasing energy production, and stabilizing repair systems. The state of excitation and type of energy metabolism are crucial factors in governing cell functions and survival.
 

haidut

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Jenn said:
I take 500 mg at a time, 4-6 times per day. Multiple smaller doses is better than 1 large dose. I had to ramp up slowly due to intestinal issues.


Depends on what you mean by better. The so called Area Under the Curve (AUC) is much higher with bolus doses of niacinamide. So, taking two doses of 1500mg each would have higher AUC that 6 doses of 500mg each. Also, the suppression of fatty acid release/oxidation requires about 200mg/kg doses in rats, which translates to about 2000mg-2500mg doses in human. But I agree that everybody is unique. If that works for you then you do what works.
 

jyb

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Following comments from Jenn, haidut and the recent RP article on rosacea, I've been keen to experiment with high doses of niacinamide. My skin is not always healthy looking and I have lightly but constantly inflamed cheeks, so I thought that if niacinamide did improve my metabolism, then it should be easy to see on my skin.

After less than two weeks of 1,5g niacinamide twice daily, I notice a slight change in texture and colouration in my skin. It's a bit more uniform and some veins on the arms and hands are less salient at times, or when salient have less of a blue colour.
 

Bluebell

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Haidut (or anyone else!),

I'm interested in taking the higher doses of niacinamide, but was wondering:

What do you think about the idea that you should not take one B vitamin in isolation, and that you should also take a B complex to cover yourself if you are taking extra of one B vitamin. This idea is all around the internet, but I have no idea how true it this. They say that if you only take one separate B vitamin, it could end up depleting some of the other B vitamins.
 
J

j.

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Bluebell said:
What do you think about the idea that you should not take one B vitamin in isolation, and that you should also take a B complex to cover yourself if you are taking extra of one B vitamin. This idea is all around the internet, but I have no idea how true it this. They say that if you only take one separate B vitamin, it could end up depleting some of the other B vitamins.

I've been thinking of asking the same thing for a while. It seems like a good thing to ask Peat. Maybe that's true for most B vitamins, but there are exceptions, and maybe niacinamide is one?
 

Bluebell

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Jenn said:
b vitamins are water soluble, so excess washes away. I don't think you have to take others for niacinimide to be beneficial.

I think the idea is that the actual process of excreting the excess of one B vitamin can cause depletion of the other B vitamins. No idea how true it is.
 

Bluebell

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j. said:
Bluebell said:
What do you think about the idea that you should not take one B vitamin in isolation, and that you should also take a B complex to cover yourself if you are taking extra of one B vitamin. This idea is all around the internet, but I have no idea how true it this. They say that if you only take one separate B vitamin, it could end up depleting some of the other B vitamins.

I've been thinking of asking the same thing for a while. It seems like a good thing to ask Peat. Maybe that's true for most B vitamins, but there are exceptions, and maybe niacinamide is one?

Maybe I will ask him. We are talking very large doses of niacinamide, with no other B vitamins taken.

I think Peat recommends only 200-300mg of niacinamide a day, so maybe it's less of a concern at lower levels. Or not a concern at all.

I think I heard 200-300mg on the forums though, not a direct Peat quote.
 

Gabriel

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I think that is an excellent question.

Vitamin B1, B2 and B3 are all involved in energy production from Glucose. From that logic, a good metabolism not only requires B3 but also B2 and B1.

Vitamin B6 is required for protein metabolism. A higher protein intake would also require more vitamin B6 to metabolize it appropriately.

For the fat soluble vitamins (A,D,E,K) there already is some evidence that they antagonize each other. I.e. Vitamin A toxicity is ameliorated by Vitamin D. Vitamin D toxicity is ameliorated by Vitamin K. High dose Vitamin E depletes Vitamin K.

Would be interesting to know whether there are similar effects for the water solubles.
 

burtlancast

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Abram Hoffer took himself 1g niacin three times a day, and lived to 92 in perfect health.
(http://www.youtube.com/watch?v=naweamfmhUI)

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. :D
 
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