Niacinamide Or Just Plain Niacin?

[Terma]

A dNA search engine confirms RORα response element within niacin N-methyltransferase gene, yet it also has domains many more transcription factors. I had restricted the search to transcription factors that I knew something about, and what I'd excluded are: c-rel, HIF-1, STAT3, Sp1, ERα, etc. Included in the gene sequence are: YY1, RORα, PPARγ, RARα, AP-1, AhR, and the glucocorticoid receptor (GR). [Link 'saved for 7 days.']

Interesting it's responsive to RAR (since RA also affects methylation cycle metabolites through GNMT).

Given your link (7 days = perfect) I assume you meant PPARalpha, which is also interesting since it's related to the starvation response in liver.

No way I'll connect this today, but more clues.

Perhaps the methylation has more to do with solubility than anything? The N-methyl group of niacin could increase its penetrance into nervous tissue, and could potentially effect transmembrane flux. Yet, if this were the intention a person could rightly assume that O-methylation would be more effective as this would neutralize niacin's negative charge. However: since niacinamide is already neutral and the amide nitrogen makes O-methylation impossible, the N¹-methylation might appear an intuitive contrivance to increase niacinamide lipid-solubility. Would this N¹-methyl group enhance brain uptake? while transporting one methyl group per niacinamide to the brain for increased cholinergic activity & myelination? However: the fact that niacin has actually been shown to increase cerebrospinal fluid homocysteine concentrations—albeit at massive doses—might imply that N-methylniacinamide does not effectively contribute to cerebral methionine formation. Nonetheless; this enzyme had evolved under natural niacin concentrations, those log orders below those used by: '80s cardiologists, Humphry Osmond, @Amazoniac, and Abram Hoffer. Thus, it may still seem appropriate to imagine niacin N-methylation as a pharmacokinetic ploy that'd evolved with the intent of shifting the body niacin pool towards the muscle, brain, and peripheral nervous tissue. This idea also suggests increased adipocyte compartmentalization as well, which can perhaps be seen either as an intentional way of increasing oxidative metabolism there or merely as an incidental consequence of the more important and intentional CNS uptake.

Interesting idea. The only issue I have with that is that according to Nicotinamide: A double edged sword - ScienceDirect , methylation of nicotinamide prevents it from leaving the brain (thought to contribute to Parkinson's):

Once charged with the N-methyl group, no toxin can cross the blood/brain barrier, so the toxication step has to take place in the brain. The enzyme NNMT has recently been shown to be present in the brain of humans [26] and rats [27]. The enzyme’s activity, protein and RNA levels are increased in the brain of patients with PD [26,28].

I assumed he was focused on toxins exiting the brain (rather than entering). Do you think it behaves completely differently for NMA going from body->brain? Fraid I haven't studied this much.

 

[Travis]

Interesting idea. The only issue I have with that is that according to Nicotinamide: A double edged sword - ScienceDirect , methylation of nicotinamide prevents it from leaving the brain (thought to contribute to Parkinson's):

I think this supports the idea because the brain is very lipophilic. The brain has a propensity to assimilate lipophilic species, especially aromatic ones, meaning that you might expect N¹-methylniacinamide to have higher a CNS/plasma distribution ratio. On account of its N-methyl group, I would bet my bottom dollar that N¹-methylniacinamide has a greater octanol∶water partition coefficient than niacinamide.

 

[Curiousman]

"Essentially it works so that nicotinamide is the salvageable breakdown product that can be recycled back to NAD+. But that pathway gets saturated really easily. Excess nicotinamide floating around will be sensed by the body as there being too much NAD+ around. Which is not at all the case, if you just artificially boosted its breakdown product nicotinamide. This puts the brakes on NAD+ synthesis and all goes down the hill. This is also why nicotinamide is really really toxic to the liver, which is particularly dependent on NAD+. And similarly this is exactly why nicotinamide puts the brakes on SIRT1 expression, which depends on NAD+. So, if you want to mess up your metabolism, increase your risk for diabetes2/syndrome X and age FASTER..then by all means whine about niacin rash and opt for nicotinamide instead"

David Sinclair strikes again - Page 10 - Supplements - LONGECITY - Page 10

 

[Hans]

About B3 and NAD, years ago I saved the following quote from a longecity user:



It is really that way? I mean too much Nicotinamide really causes putting brakes on NAD+ synthesis? I read here and there about NAD and SIRT1 regulation when supplementing with Nicotinamide but I never saw any study depicting it so dramatically as above. Any help welcome.

No, niacinamide actually increases NAMPT and inhibits Sirt1, thus boosting NAD+ levels. Naicinamide boosts NAD to a greater extent than nicotinic acid.

 

[RayPeatFan777]

If you look on reviews for Niacin and Niacinamide on Amazon, Iherb etc..

You will notice some people say Niacin worked for their mental health when Niacinamide didnt, I wonder why this is?

 

[ddjd]

Niacin liberates PUFA in your blood.

But if you want to lose weight you're going to have to liberate that pufa at some point. Is that correct?

 

[ddjd]

Nicotinic acid also seems to decrease cholesterol in high doses, which is probably bad, as it could indicate some liver damage

How does that indicate liver damage?

 

[Curiousman]

No, niacinamide actually increases NAMPT and inhibits Sirt1, thus boosting NAD+ levels. Naicinamide boosts NAD to a greater extent than nicotinic acid.

Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells

 

[bdawg]

No, niacinamide actually increases NAMPT and inhibits Sirt1, thus boosting NAD+ levels. Naicinamide boosts NAD to a greater extent than nicotinic acid.

yo I read your writeup on naturalsupremacy, what do you say to studies like this?

Moreover, cumulative exposure to N1-methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/NADH ratio, and increased plasma H2O2 levels. Decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to N1-methylnicotinamide in vitro.

These findings suggest that nicotinamide overload, which induced an increase in plasma N1-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

Nicotinamide has been demonstrated to induce insulin resistance due to excess reactive oxygen species and methyl depletion

 

[Hans]

I think if someone has upregulated NNMT due to other factors such as inflammation, excessive niacinamide could pose a problem. But MNAM inhibits NNMT in a negative feedback loop.
I don't think it's necessary to take large amounts of niacinamide if you're not trying to treat a specific condition such as arthritis. Meat are rich in vit B3, so if you are eating a good diet with sufficient protein there is no need for for B3 supplementation.
There is a study in there where niacinamide does not cause insulin resistance in humans, but niacin does.
Haidut has also put up a few studies showing the same.
There is also a rat study that shows that niacinamide inhibits SIRT1.

 

[Amazoniac]

- Effects of Salts of Nicotinic Acid on Serum Cholesterol

Summary:

"It seems well established that nicotinic acid in relatively high doses decreases serum cholesterol in healthy and sick human beings. The toxicity of the substance is discussed, and it is pointed out that the high acidity rather than a specific action may be responsible for the occasional disturbances, such as gastro-intestinal reactions.
Tests on 12 healthy young individuals showed that a buffered solution of nicotinic acid is as efficacious in decreasing serum cholesterol as is the pure nicotinic acid.
In cases of poor tolerance of nicotinic acid a solution of nicotinic acid buffered with NaHCO3 (or NaHCO5 and KHCO3) deserves to be tried."


"In 1939 Unna pointed out that the toxicity of nicotinic acid, as reported by Elvehjem et al. (1938) for one single dog, was likely due to the high acidity of nicotinic acid rather than to a specific action. This was borne out by the innocuity of sodium nicotinate used by Ackermann (1912), whose experiment had been repeated by Elvehjem et al., but substituting nicotinic acid for the sodium salt. Unna showed that the acid has a pH of 3.3, whereas a solution of sodium nicotinate, corresponding to 10% of the acid, has a pH of 7-7.1. Unna stated further: "Sodium nicotinate is completely dissociated in solution, and thus no difference in the action of this compound from that of the acid itself is to be expected."

Even after Unna had explained the toxic action of very large doses of nicotinic acid by its high acidity and suggested the use of its sodium salt in animal experiments, a number of authors have continued to study the toxic effect of large doses of nicotinic acid and to ascribe this effect to a specific action, thus disregarding the findings of Unna."

"[..]there are human cases reported in which the treatment with large doses (3 to 6 g. daily of nicotinic acid) had to be interrupted for certain periods, or discontinued altogether, because of intervening gastro-intestinal disturbances. According to Achor et al. (1957), in a series of 45 patients the treatment had to be abandoned in three cases on account of nausea and diarrhoea. In our opinion this may be due to the high acidity-that is, to an unspecific factor rather than to a specific action of nicotinic acid. Therefore we decided to test large doses of buffered nicotinic acid in order to find out whether or not their effect on serum cholesterol is comparable to that of pure nicotinic acid. As a matter of fact, many clinicians who treat various diseases, but mainly such of the circulatory system, with small--that is, "vitamin"--doses of nicotinic acid do not use the acid proper, but either sodium or magnesium nicotinate, and that per os or by injections."

"We submitted a group of university students to a test in which they received 1 g. of buffered nicotinic acid (0.6 g. of sodium bicarbonate for each gramme of acid) three times a day for two weeks."

"[Our] observations show that the response to both nicotinic acid and nicotinic acid buffered with sodium salts is practically identical."

"Obviously, in those cases in which sodium intake should be kept low potassium bicarbonate can be substituted in any desired proportion for the sodium bicarbonate. A very practical preparation seems to be the following: to 500 ml. of distilled water containing 32 g. of sodium bicarbonate (or 16 g. of NaHCO3 and 16 g. of KHCOs) is added slowly 50 g. of pure nicotinic acid, preferably in a wide container, to avoid " overbubbling." Of this solution, 1 tablespoonful of 10 ml. will contain buffered nicotinic acid corresponding to, 1 g. of pure nicotinic acid. The best way to take this seems to be 1 tablespoonful diluted in one glass of water after lunch, 2 tablespoonfuls in one glass of water after the evening meal. In case larger doses are required, the amount is increased in proportion. Sipping of this solution over a prolonged period (approximately 60 minutes) may decrease the vascular dilatation, which is in some sensitive people an unpleasant side-effect. Since this vascular reaction usually disappears after three to seven days, the precaution of sipping the solution may then be discontinued. Of course, for practical reasons, especially in those cases where the patients do not take their meals at home, nicotinic acid, sodium (and potassium) bicarbonate, and some starch may be pressed into effervescent tablets and dissolved prior to taking the drug, possibly again after the main meals. Finally, sodium nicotinate may be prescribed in the pure form, but it seems to us that in this case an unnecessarily large amount of sodium is being given."​

- Buffered Nicotinic Acid and Serum Cholesterol


@OB-1 @Terma @yerrag

 

[yerrag]

- Effects of Salts of Nicotinic Acid on Serum Cholesterol

Summary:

"It seems well established that nicotinic acid in relatively high doses decreases serum cholesterol in healthy and sick human beings. The toxicity of the substance is discussed, and it is pointed out that the high acidity rather than a specific action may be responsible for the occasional disturbances, such as gastro-intestinal reactions.
Tests on 12 healthy young individuals showed that a buffered solution of nicotinic acid is as efficacious in decreasing serum cholesterol as is the pure nicotinic acid.
In cases of poor tolerance of nicotinic acid a solution of nicotinic acid buffered with NaHCO3 (or NaHCO5 and KHCO3) deserves to be tried."


"In 1939 Unna pointed out that the toxicity of nicotinic acid, as reported by Elvehjem et al. (1938) for one single dog, was likely due to the high acidity of nicotinic acid rather than to a specific action. This was borne out by the innocuity of sodium nicotinate used by Ackermann (1912), whose experiment had been repeated by Elvehjem et al., but substituting nicotinic acid for the sodium salt. Unna showed that the acid has a pH of 3.3, whereas a solution of sodium nicotinate, corresponding to 10% of the acid, has a pH of 7-7.1. Unna stated further: "Sodium nicotinate is completely dissociated in solution, and thus no difference in the action of this compound from that of the acid itself is to be expected."

Even after Unna had explained the toxic action of very large doses of nicotinic acid by its high acidity and suggested the use of its sodium salt in animal experiments, a number of authors have continued to study the toxic effect of large doses of nicotinic acid and to ascribe this effect to a specific action, thus disregarding the findings of Unna."

"[..]there are human cases reported in which the treatment with large doses (3 to 6 g. daily of nicotinic acid) had to be interrupted for certain periods, or discontinued altogether, because of intervening gastro-intestinal disturbances. According to Achor et al. (1957), in a series of 45 patients the treatment had to be abandoned in three cases on account of nausea and diarrhoea. In our opinion this may be due to the high acidity-that is, to an unspecific factor rather than to a specific action of nicotinic acid. Therefore we decided to test large doses of buffered nicotinic acid in order to find out whether or not their effect on serum cholesterol is comparable to that of pure nicotinic acid. As a matter of fact, many clinicians who treat various diseases, but mainly such of the circulatory system, with small--that is, "vitamin"--doses of nicotinic acid do not use the acid proper, but either sodium or magnesium nicotinate, and that per os or by injections."

"We submitted a group of university students to a test in which they received 1 g. of buffered nicotinic acid (0.6 g. of sodium bicarbonate for each gramme of acid) three times a day for two weeks."

"[Our] observations show that the response to both nicotinic acid and nicotinic acid buffered with sodium salts is practically identical."

"Obviously, in those cases in which sodium intake should be kept low potassium bicarbonate can be substituted in any desired proportion for the sodium bicarbonate. A very practical preparation seems to be the following: to 500 ml. of distilled water containing 32 g. of sodium bicarbonate (or 16 g. of NaHCO3 and 16 g. of KHCOs) is added slowly 50 g. of pure nicotinic acid, preferably in a wide container, to avoid " overbubbling." Of this solution, 1 tablespoonful of 10 ml. will contain buffered nicotinic acid corresponding to, 1 g. of pure nicotinic acid. The best way to take this seems to be 1 tablespoonful diluted in one glass of water after lunch, 2 tablespoonfuls in one glass of water after the evening meal. In case larger doses are required, the amount is increased in proportion. Sipping of this solution over a prolonged period (approximately 60 minutes) may decrease the vascular dilatation, which is in some sensitive people an unpleasant side-effect. Since this vascular reaction usually disappears after three to seven days, the precaution of sipping the solution may then be discontinued. Of course, for practical reasons, especially in those cases where the patients do not take their meals at home, nicotinic acid, sodium (and potassium) bicarbonate, and some starch may be pressed into effervescent tablets and dissolved prior to taking the drug, possibly again after the main meals. Finally, sodium nicotinate may be prescribed in the pure form, but it seems to us that in this case an unnecessarily large amount of sodium is being given."​

- Buffered Nicotinic Acid and Serum Cholesterol


@OB-1 @Terma @yerrag

How does nicotinic acid work to lower serum cholesterol? Does it stop cholesterol production the same way statins and fish oils do? Or does it help cholesterol conversion to hormones?

 

[bdawg]

I think if someone has upregulated NNMT due to other factors such as inflammation, excessive niacinamide could pose a problem. But MNAM inhibits NNMT in a negative feedback loop.
I don't think it's necessary to take large amounts of niacinamide if you're not trying to treat a specific condition such as arthritis. Meat are rich in vit B3, so if you are eating a good diet with sufficient protein there is no need for for B3 supplementation.
There is a study in there where niacinamide does not cause insulin resistance in humans, but niacin does.
Haidut has also put up a few studies showing the same.
There is also a rat study that shows that niacinamide inhibits SIRT1.

Thanks

Yes I agree with you excess Niacinamide is not needed unless treating a condition

Its not worth upregulating NMNT in your fat cells

 

[Amazoniac]

- Negative and Positive Side Effects of Vitamin B3 - Abram Hoffer

"[..]our hypothesis called for enough niacin to absorb methyl groups and thus to decrease the formation of adrenalin and therefore of adrenochrome."

"To say that something is toxic is meaningless, since theoretically everything is toxic if the dose is pushed high enough."

"One of my patients, a 16-year-old schizophrenic girl, swallowed the whole bottle of niacin pills I had given her, all at once. She took 200 tablets of the 500-milligram size because she was angry with her mother. For the next three days she complained of a stomach ache. Another patient, not mine, increased her dose until she was taking 60 grams daily. At that level her auditory hallucinations (voices) ceased. Eventually she was maintained on 3 grams. No one has ever committed suicide with vitamin B3." : idi

"Toxicity or negative side effects can never be considered in the absence of the therapeutic value of the substances. If there is no therapeutic value it will never be used, whether it is toxic or not. If the therapeutic value is great, as for example in the use of insulin for treating diabetes mellitus, even toxic compounds will be used. Doctors are taught how to deal with toxic substances and only they are permitted to prescribe these to their patients. If doctors think a substance has no therapeutic value they will argue that even the remotest degree of toxicity is too much and that substance cannot be used. If they consider that it is valuable, even the greatest degree of toxicity will be tolerated. Thus, the consensus among the psychiatric profession is that vitamins are of no value in the treatment of schizophrenia, therefore they search assiduously for evidence of toxicity and often, when they cannot find any evidence, it is hypothesized or grossly exaggerated. If they consider a drug very valuable, its toxicity is minimized."

Factors in the Flush Intensity:

"(1) The amount of niacin taken in one dose. There will be very little flush with 50 mg or less, while most patients will flush with 100 mg or more. The relationship is not linear. There is a threshold effect and the flush does not appear until that threshold is reached. This can be used to introduce niacin gradually. I also use it to decrease the reactivity of patients with severe allergies. I start with 25 mg after each meal, at the same time giving 1 g of vitamin C." "The niacin releases histamine, which is partially responsible for the flush, and the ascorbic acid destroys the histamine dumped into the blood. In this way it is possible to increase the dose to its full therapeutic value."

"(2) The amount of food in one’s stomach and whether taken with a hot drink or cold drink. The rate of absorption is important and heat accelerates this. Taken right after a meal the flush is minimal; taken on an empty stomach it is maximal. The greatest flush is experienced when it is injected intravenously. I suspect that dissolved in hot tea and swallowed immediately on empty stomach niacin would produce the kind of flush seen after IV administration."

"(3) Time elapsed between dosages. Most patients tend to flush more in the morning after their first daily dose because they have gone all night without taking any. This can often be remedied by taking the last dose just before bed."

"(4) Aspirin. An aspirin tablet taken once a day, beginning two days before starting on niacin, can minimize the flush. Once the first flush has occurred, aspirin is no longer needed, as niacin itself is the best anti-flush preparation if it is taken regularly. Some anti-histamines can also minimize the flush and the early tranquilizers such as chlorpromazine were very effective in preventing excessive flushing. Schizophrenic patients flush much less than do patients who are not schizophrenic or have other diseases. David Horrobin21 developed this into a diagnostic test. It is based upon the observations I reported in 1962 that schizophrenic patients are usually less disturbed by the flush. A patch with four pockets each containing different amounts of methyl nicotinate is applied to the forearm, left on for five minutes and then stripped off. In most schizophrenic patients the areas in contact with the nicotinate do not turn red. There is very little overlap.22 Many schizophrenic patients do not flush after starting to take 3 grams of niacin daily. This inability to flush may well be related to their disease, as an appreciable number of schizophrenic patients begin to flush after several years of medication. This is a good prognostic sign and usually coincides with complete recovery.23"

"(5) Age. Usually patients over age 50 flush less than young people do."

"(6) Skin color. Dark skinned people will flush less but the reaction may be just as uncomfortable. Patients who tan very poorly may have more severe reactions."

"(7) Patients’ need for the vitamin. I have observed that patients who need it the most, such as patients with high blood cholesterol levels, or patients with arthritis or schizophrenia, flush much less than other patients."

"(8) Motivation. Patients motivated by the disease that they have and the explanation given to them by their doctors find the flush much more tolerable."

"(9) Physicians’ comfort with niacin. [?] Parsons24 in his excellent book makes the point that physicians must know niacin before they work with it. For many patients, the flushing form is much better than the non-flush or slow release preparations, particularly patients with the chronic diseases such as chronic fatigue syndrome and multiple sclerosis, as mentioned earlier, and many patients do like the flush."​

"In 1962, I reported that occasionally niacin caused nausea and vomiting. This reaction is dose related. Everyone will react if the dose taken is high enough and this level varies from 3 to up to 30 grams daily. I use this nauseant dose as an indicator of how much is needed. Patients who respond best include schizophrenic patients, patients with elevated cholesterol levels and arthritics. Elderly patients and these patients can usually tolerate much more than younger patients. Niacinamide also has a narrower threshold level than niacin."

"Niacinamide can also cause nausea and vomiting and it is apt to be present at lower doses than is the case with niacin."

"In 1950, the disease of that year was that produced by methyl deficiency. This caused fatty livers in animals. Niacin and niacinamide combine with methyl groups and are two of the few methyl acceptors. Thus it made sense to think that a large dose of this vitamin would cause a methyl deficiency. Another methyl acceptor is noradrenalin; methylation of noradrenalin produces adrenalin. We hoped to decrease the production of adrenochrome by inhibiting the product of adrenalin from noradrenalin. This was one of many factors that pointed in the direction of this vitamin in the treatment of schizophrenia. But we were concerned about the possible danger of producing fatty livers. In 1942, a study on animals suggested that niacin did injure the liver. Altschul repeated this animal study and, on the contrary, found no evidence of any liver toxicity; their livers were normal when examined histologically and chemically. We tested a small series of patients being treated with niacin and again found no evidence of liver damage. Rarely a patient would develop an obstructive jaundice. I would routinely stop the niacin until the jaundice cleared because of the possibility of a reaction. One of my patients became very psychotic again and I resumed the niacin but his jaundice did not recur. The incidence of jaundice was very rare and I have seen no cases in the past 20 years."

"However, when the modern liver function tests came into use some of the patients on niacin and niacinamide showed elevated liver function tests."

"I do not give this vitamin in large doses to anyone with hepatitis, not because I think it will be harmful but because I know the niacin will be blamed even if it is not responsible if something does happen."

"Capuzzi25 has been studying niacin for several decades. He found that giving patients lecithin, 1.2 grams twice daily, prevents any elevations of liver function tests. McCarty26 suggested that high demand for methyl groups created by niacin could reduce levels of S-adenosylmethionine, which could lead to an increase in production of homocysteine. This, he suggested, could be avoided by using betaine supplements with the niacin. But lecithin is much cheaper and more readily available. Both lecithin and betaine are methyl donors."
@haidut @Terma

"Parsons found that niacin increased blood uric acid levels slightly but concluded that this should not interfere with niacin therapy. In the Coronary Drug Project the average blood uric acid levels before entering the project was 6.75 and after five years on niacin 6.80. Men on niacin had uric acid levels above 8.0. However, this was insignificant because there was no increase in any of the symptoms of gout including increase in uric acid stones or acute gouty arthritis. This has been my conclusion as well. I do not consider niacin as a risk factor for gout." "The slight increase in blood uric acid levels may be a positive side effect."

"Garg et al31 found that niacin increased homocysteine levels about 55% in a series of 52 patients given 3 grams of niacin daily. These two sets of findings have suggested that niacin might also increase this risk. However I cannot take this very seriously since the Coronary Drug Project showed that niacin decreased mortality 11% and increased longevity nearly two years in a large group of men already having suffered one stroke."

"About 40% of cancer patients are deficient in niacin."​

- Rosacea, inflammation, and aging: The inefficiency of stress

"The "orthomolecular" ideas of Hoffer and Linus Pauling were developed in a context of biochemistry governed by genetics, molecular biology, in which the goal was to provide a chemical that was lacking because of a genetic defect in metabolism. Their idea of using nutrients as drugs has led to many unphysiological practices, in which an isolated nutrient is supposed to have a drug-like action, and if in isolation it doesn't act like a drug, then it should be used only according to the normal genetically determined nutritional requirement."​

- Niacin - Wikipedia

"niacin was derived from nicotinic acid + vitamin"​

 

[chrismturner89]

A lot of these posts are really putting me off niacinamide. I take a low dosage two to three times daily. It has worked absolute wonders for my anxiety and mental health. I become easy going, playful and extremely social when taking it. I think it works for me by reducing/using up methyl groups. I have a mutations on the COMT genes meaning I don't breakdown neurotransmiters as fast as I should leading to some negative mental symptoms such as irritation, anxiety and ocd. Betaine, methyl b12 and folate provide me with great energy but bring these mental symptoms straight back.

Anyone know of something else that uses/reduces methyl groups that doesn't have such risks as niacinamide?

 

[Amazoniac]

A lot of these posts are really putting me off niacinamide. I take a low dosage two to three times daily. It has worked absolute wonders for my anxiety and mental health. I become easy going, playful and extremely social when taking it. I think it works for me by reducing/using up methyl groups. I have a mutations on the COMT genes meaning I don't breakdown neurotransmiters as fast as I should leading to some negative mental symptoms such as irritation, anxiety and ocd. Betaine, methyl b12 and folate provide me with great energy but bring these mental symptoms straight back.

Anyone know of something else that uses/reduces methyl groups that doesn't have such risks as niacinamide?

It is quite safe, especially in low doses. It's just that if the person is already deficient (functionally or not) in methyl groups, it can make it worse. Addressing both in this case is advisable.

Spoiler: Textbook of Biochemistry - O.P. Agrawal

(ESPNs: 8185842655, 9788185842653)
Seems to be an excellent book.

@Travi

 

[Pulstar]

Without going into science too much, my overall impression was that Abram Hoffer was using both niacin and niacinamide for his patients. Andrew Saul was doing the same. At glance, it may look like both forms of B3 are almost the same or interchangeable. However, after reading their articles, it really feels like that for difficult cases of depression, autism and schizophrenia the preferred supplement was niacin. At least, I think niacin was mentioned more often than niacinamide. But I still don't know for sure. They've never said to avoid one form and take another. From the other hand, Ray Peat clearly prefers niacinamide.

It was already mentioned in this thread, that there are lots of positive feedback on niacin's impact on mental condition. Some folks went as far as saying than niacin literally saved their lives. The question is, what other tools they've tried? Perhaps anti serotonin and pro allopregnanolone approach combined with anything that boosts metabolism / ATP is more effective.

My personal observation is that niacin can have quite rapid anti anxiety and anti depression effect at relatively small doses 100-200 mg. Most people will flush even with 100 mg.

Just my 2c.

 

[Terma]

I'm going to try to use Niacinamide in a solution (with the usual NaCl and NaHCO3) for nasal irrigation. Not for BBB penetration or anything, purely irrigation.

If I don't report back within 3-4 weeks it's either because these proxies finally got banned or something went terribly wrong. Well that's redundant.

There doesn't seem to be any info on using it this way. If you know of any... Maybe it burns terribly. Does burn my face a bit.

(^ I think aspirin did increase my niacin flush threshold)

 

[Curiousman]

Nicotinic Acid-Mediated Activation of Both Membrane and Nuclear Receptors towards Therapeutic Glucocorticoid Mimetics for Treating Multiple Sclerosis

 

[Pulstar]

Just FYI.
Here's very brief video where Dr. Hoffer says that for schizophrenia, both niacin and niacinamide have the same effect. I have seen that in few schizophrenia cases described here, he used niacinamide:
"...I started her on niacinamide 1 gram after each meal, the same amount of vitamin C, pyridoxine 250 mg each day and zinc gluconate 50 mg each day.
And here's the video.