Niacinamide Or Just Plain Niacin?

[bluewren]

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.

Thanks, @BrightStar

 

[Amazoniac]

After getting notified about Chris' recent discussion on niacin, it reminded me to calculate how much inosine you need to pair with nicotinamide to mimic the proportions of nicotinamide riboside (Dinkov, 2017).

Inosine by weight is almost half a ribose molecule and half hypoxanthine.
As a coincidence, nicotinamide riboside is also nearly half nicotinamide and half the ribose molecule.

Therefore when taking plain nicotinamide, it's just a matter of taking twice as much inosine.

 

[Amazoniac]

- The Vitamins: Fundamental Aspects in Nutrition and Health (978-0-12-802965-7) - Gerald F. Combs and James P. McClung

"Nicotinic acid (NA) and NAm are colorless and crystalline. Each is insoluble or only sparingly soluble in organic solvents. NA is slightly soluble in water and ethanol; NAm is very soluble in water and moderately soluble in ethanol. The two compounds have similar absorption spectra in water, with an absorption maximum at <262 nm. NA is amphoteric and forms salts with acids as well as bases. Its carboxyl group can form esters and anhydrides, and can be reduced. Both NA and NAm are very stable in dry form, but in solution NAm is hydrolyzed by acids and bases to yield NA."

"Niacin occurs predominantly in bound forms, e.g., in plants mostly as protein-bound NA and in animal tissues mostly as NAm in nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). In cow’s milk, ∼40% of the vitamin is the NAD precursor, nicotinamide riboside (NR)."

"The predominant forms of niacin in most animal-derived foods are the coenzymes NAD(H) and NADP(H). These are digested to release NAm, in which form the vitamin is absorbed (Fig. 13.1). Both coenzyme forms can be degraded by the intestinal mucosal enzyme NAD(P)+ glycohydrolase, which cleaves the pyridine nucleotides into NAm and ADP-ribose. NAm can also be cleaved at the pyrophosphate bond to yield nicotinamide mononucleotide (NMN) and 5′-AMP, or by a phosphodiesterase to yield NR and ADP. The dephosphorylation of NMN also yields NR, which can be converted to NAm either by hydrolysis (yielding ribose) or phosphorylation (yielding ribose 1-phosphate)."

"The presence or absence of food in the gut appears to have no effect on niacin absorption. Because NR is not found in plasma, it appears not to be absorbed per se, but first converted to NAm."

"Niacin is retained in the liver and other tissues, which take it up as NA and/or NAm and convert it to the pyridine nucleotides NAD(H) and NADP(H) (Table 13.3). By far the greater amount is found as NAD(H), most of which, in contrast to NADP(H), is found in the oxidized form (NAD+)."

"The conversion of tryptophan to NAD is an inefficient process. Balance studies in humans demonstrated that this conversion varies among individuals in the range of 34–86 mg tryptophan per niacin equivalent,[16] on which basis Horwitt recommended the use of a 60:1 ratio for practical purposes.[17] Henceforth, it is normally taken that humans normally require ∼60 mg of tryptophan to produce 1 mg of niacin metabolically.[18] This ratio is similarly wide for the chick (45:1) and the rat (50:1), and extremely wide for the duck (175:1). Conversion is reduced under conditions of nutritional iron deficiency and enhanced by niacin deprivation. Niacin-deficient humans are estimated to use nearly 3% [(× 3/100) → (÷ 100/3) → (33:1)] of dietary tryptophan for niacin biosynthesis and, thus, are able to satisfy two-thirds of their requirement for the vitamin from the metabolism of this indispensable amino acid."

"It would appear that protein turnover may preempt niacin synthesis under conditions of limiting tryptophan. In such circumstances the amount of tryptophan available for niacin synthesis would be expected to be low, rendering the calculation of niacin equivalents inaccurate."

"The conversion of tryptophan to niacin is also reduced by high-fat diets or diets containing excess leucine.[21] These effects appear to be due to ketosis, which has been noted as a common feature of diets of individuals with pellagra. NAD synthesis is increased by such factors as caloric restriction and hypoxia and in response to increased sirtuin[22] signaling, suggesting that NAD+ levels may serve as indicators of physiological stress."

"It has also been suggested that the deficiency of zinc, an essential cofactor of pyridoxal kinase [], may also impair tryptophan–niacin conversion by reducing the production of pyridoxal phosphate."​

 

[Amazoniac]

flushing niacin increases histamine and nitric oxide etc...

Histamine and serotonin applies to both:
- Niacinamide Or Just Plain Niacin?

Regarding nitric oxide, I could only find indirect effects but only when doses were high enough to affect cholesterol metabolism.
- Suppression of Bleomycin-Induced Nitric Oxide Production in Mice by Taurine and Niacin
By the way, why do you post that everything increases nitric oxide?

The main concern appears to be the prostaglandins, but I don't think this is an issue if the person takes physiological doses and consumes it with meals (to slow down the delivery). In one of the classic publications, some pimps found that only 1 in every 20 people experienced flushing from 50 mg; whereas if the dose wased increased to 100 mg, 10 in 20 experienced it. In another one, it took 200 mg of ingested nicotinic acid to get a consistent flushing effect and only 10 mg if inject'd.

There's also the adaptation aspect, and such effects should be greatly minimized even when the person insists on taking supraphysiological doses as tolerance is develop'd.
- Tolerance to nicotinic acid flushing

So when you combine reasonable dosing, ingestion with meals, and the adaptation, problems seem remote. Yet, if something is off, it won't go unnoticed, the person should feel the discomfort and can adjust to the ideal amount.

In this context, I couldn't find anything against it so far, which makes me suspect that you're all actually getting paid to repeat that.

 

[ddjd]

Histamine and serotonin applies to both:
- Niacinamide Or Just Plain Niacin?

Regarding nitric oxide, I could only find indirect effects but only when doses were high enough to affect cholesterol metabolism.
- Suppression of Bleomycin-Induced Nitric Oxide Production in Mice by Taurine and Niacin
By the way, why do you post that everything increases nitric oxide?

The main concern appears to be the prostaglandins, but I don't think this is an issue if the person takes physiological doses and consumes it with meals (to slow down the delivery). In one of the classic publications, some pimps found that only 1 in every 20 people experienced flushing from 50 mg; whereas if the dose wased increased to 100 mg, 10 in 20 experienced it. In another one, it took 200 mg of ingested nicotinic acid to get a consistent flushing effect and only 10 mg if inject'd.

There's also the adaptation aspect, and such effects should be greatly minimized even when the person insists on taking supraphysiological doses as tolerance is develop'd.
- Tolerance to nicotinic acid flushing

So when you combine reasonable dosing, ingestion with meals, and the adaptation, problems seem remote. Yet, if something is off, it won't go unnoticed, the person should feel the discomfort and can adjust to the ideal amount.

In this context, I couldn't find anything against it so far, which makes me suspect that you're all actually getting paid to repeat that.

are you insane. why would I post in a forum with barely any traction if I wanted to make money.
literally just search ' ray peat' and regular niacin.
and please by all means start taking regular niacin and see how it affects your
hairline in comparison to niacinamide. as ray always repeats, "the true method of knowledge is experiment"

on the topic of nitric oxide, there's a huge amount of information (also on the forum if you searched) regarding the aging and destructive effects of high nitric oxide.



The Nitric Oxide (NO) Theory Of Aging

@Amazoniac if you still can't find any information on why niacinamide is preferable to niacin I will help you find the relevant posts, but I'm sure you don't need to be spoonfed

 

[Amazoniac]

are you insane. why would I post in a forum with barely any traction if I wanted to make money.
literally just search ' ray peat' and regular niacin.
and please by all means start taking regular niacin and see how it affects your
hairline in comparison to niacinamide. as ray always repeats, "the true method of knowledge is experiment"

on the topic of nitric oxide, there's a huge amount of information (also on the forum if you searched) regarding the aging and destructive effects of high nitric oxide.



The Nitric Oxide (NO) Theory Of Aging

@Amazoniac if you still can't find any information on why niacinamide is preferable to niacin I will help you find the relevant posts, but I'm sure you don't need to be spoonfed

Joey, I don't know what tractors have to do with this, but you must have skipped most of the post for the key terms.
Why do you sound just like Hugh Johnson when he was 'exposed' some time ago? Are you him? I wonder if you're now working for the amide industry.

Can't tell, but in case you're a rat or a marine cell, these might also interest you:
- Effects of niacin on nitric oxide synthase expression in rat lungs exposed to silica
- Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by resveratrol, a potent proteasome inhibitor

From what I understood, you had a negative experience with it and attributed to nitric oxide for having experienced a similar effect with other substances that are supposed to increase it, correct?

 

[ddjd]

Joey, I don't know what tractors have to do with this, but you must have skipped most of the post for the key terms.
Why do you sound just like Hugh Johnson when he was 'exposed' some time ago? Are you him? I wonder if you're now working for the amide industry.

Can't tell, but in case you're a rat or a marine cell, these might also interest you:
- Effects of niacin on nitric oxide synthase expression in rat lungs exposed to silica
- Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by resveratrol, a potent proteasome inhibitor

From what I understood, you had a negative experience with it and attributed to nitric oxide for having experienced a similar effect with other substances that are supposed to increase it, correct?

now it's quite obvious you're just trying to wind me up. im going to block you

 

[Amazoniac]

now it's quite obvious you're just trying to wind me up. im going to block you

I'm not trying to do that. It's difficult for me to think that such absurd parts are going to be taken seriously by anyone.

But I have been trying to find reasons not to take nicotinic acid for quite a while without success, yet since then reading the same repeated loose warnings.

 

[Amazoniac]

Depending on conditions, you might be even getting some nicotinic acid from it without realizing..

- The Vitamins: Fundamental Aspects in Nutrition and Health (978-0-12-802965-7)

"The cleavage of NAm to free NA appears to be accomplished by intestinal microorganisms and is believed to be of quantitative importance in niacin absorption."​

 

[Amazoniac]

It just occurred to me that there were people reporting flushing from nicotinamide in an experiment posted a few pages ago. Researchers responsibilized the cerebra for the effect, but perhaps it wasn't mere imagination.

There's also the related thread below by @methylenewhite:
- Flush From Niacinamide?

It can be due to histamine as well, which nicotinamide can increase.

 

[Amazoniac]

I don't think regular niacin is safe for long term use, especially in doses at which it causes flushing. And the human studies with CKD used niacinamide, not niacin.

Guru, check out the previous messages here. It should be safe in lower doses at a time.

There are people who drink a lot of coffee at once or in a day.
Their nicotinic acid intake can be surprisingly high.

- Coffee Constituents

Spoiler

 

[haidut]

Guru, check out the previous messages here.

It should be safe in lower doses at a time.

There are people who drink a lot of it at once or in a day.
Their nicotinic acid intake can be surprisingly high.

- Coffee Constituents

Spoiler

View attachment 13677

Agreed, that's why I said "in doses that cause flushing", which is usually above 100mg per pop for most people. In doses <50mg it quickly converts into niacinamide and does not seem to cause issues, but I would still choose NAM over NA if I had a choice.

 

[Amazoniac]

Agreed, that's why I said "in doses that cause flushing", which is usually above 100mg per pop for most people. In doses <50mg it quickly converts into niacinamide and does not seem to cause issues, but I would still choose NAM over NA if I had a choice.

On a recent podcast, Mito and his friend (Alex Leaf) discuss'd something related to this (expand options * * * > transcription > '40 m').

- Understanding niacin formulations

"Niacin undergoes extensive, saturable, first-pass metabolism in the liver, where it is metabolized by 2 hepatic pathways (Figure 1)."

Spoiler

"In one pathway, niacin is conjugated with glycine to form nicotinuric acid. This conjugative pathway is a low-affinity, high-capacity pathway that generates metabolites that are associated with flushing. The second pathway involves several general oxidation-reduction metabolic reactions that produce nicotinamide and a series of related products, such as nicotinamide adenine dinucleotide, and ultimately several pyrimidine metabolites. This amidation, or nonconjugative, pathway is a high-affinity, low-capacity pathway with metabolites that are associated with hepatotoxicity.[9] Thus, the absorption rates of the different formulations dictate the extent of metabolism by each pathway, the type of metabolites generated, and the side effect profile. Niacin IR is usually completely absorbed within 1 to 2 hours; niacin SR absorption rates vary from product to product and even batch to batch, but generally exceed 12 hours.[9] Niacin ER has an absorption rate of 8 to 12 hours.[6] Niacin IR quickly saturates the amidation pathway, resulting in most of the drug being metabolized by the conjugative pathway and thereby causing a high incidence of flushing. Conversely, niacin SR is metabolized to a greater extent by the amidation pathway, saturating it more slowly. As a result, niacin SR has a lower incidence of flushing, but a higher incidence of hepatotoxicity.[9] Niacin ER, with its intermediate dissolution rate, better balances metabolism along the 2 pathways, resulting in a lower rate of flushing and hepatic effects compared with niacin IR and niacin SR, respectively."

"The differences in metabolism and related side effects can be most clearly understood in a simulation model of drug metabolism after administration of either niacin IR or niacin SR. Niacin IR is absorbed at a rate of approximately 500 mg/hour, and, therefore, a 1-g dose of niacin IR would be completely absorbed and metabolized within 2 hours. In contrast, niacin SR is released at an approximate rate of 50 mg/hour. Therefore, absorption of a 1-g dose of niacin SR would take >20 hours. The rate of metabolism of the amidation pathway (low capacity, high affinity) is fixed at approximately 40 mg/hour, and once this pathway is saturated, the remaining niacin must be metabolized by the higher-capacity, lower-affinity conjugative pathway. For example, at 2 hours, niacin IR will generate approximately 80 mg of amidation metabolites and 920 mg of nicotinuric acid, the glycine conjugate of niacin. In contrast, niacin SR in the same time would form approximately 80 mg of amidation metabolites and 20 mg of the glycine conjugate."

"This simulation indicates that with the use of niacin IR, large amounts of nicotinuric acid (920 mg) are produced and excreted in the urine, and, as such, niacin IR is likely to produce flushing. However, 12 hours after niacin SR administration, approximately 480 mg of amidation metabolites, but only 120 mg of nicotinuric acid, are generated. Following the simulation to 24 hours, approximately 800 mg of amidation metabolites are generated with niacin SR, along with approximately 200 mg of nicotinuric acid. These amounts are in stark contrast to the 80 mg of amidation metabolites and 920 mg of nicotinuric acid, (~92% of the original niacin dose) generated with niacin IR over the same time period. Thus, approximately 10 times more amidation metabolites are excreted when niacin SR is administered, while 4.6 times more nicotinuric acid is excreted with niacin IR versus SR administration. Therefore, the side effects observed with niacin are determined by the absorption rate of niacin from different formulations: flushing with niacin IR and hepatotoxicity with niacin SR."​

So the average rate of absorption is 500 mg/h and metabolism through the amidation pathway is 40 mg/h. I don't know about immediate capacity to metabolize it, but it seems indeed challenging to overwhelm this with foods rich in nicotinic acid. But if it's isolated, it won't require digestion of other elements to release it and the dispersion from the meal isn't enough for a marked interference.

One of the reasons for the safety of niacin is that it's readily and completely absorbed in moderate doses, with all parts of the digestive system being capable of absorbing some. There will be absorption from the stomach and even the mouth on contact.
- Niacinamide Or Just Plain Niacin?

Complete absorption might be after an hour or more but the peak is earlier, this complicates interpretation on limits. It's logical for a meal to hinder the efficiency of digestion but only by a bit considering the points above, making the person not tolerate much more than those 40 mg without adaptation, and safe intakes at a time should be close to the value that thou and Gerson suggested. This is reinforced by the usual doses that cause initial flushing. How did you arrive on such figure? Humanoid intuition?

By the way, Raj has commented about the importance of having magnesium along with supplemental typhoid hormones, and me wonders why there isn't the same emphasis when it comes to niacin.

 

[Amazoniac]

- How to Take Niacin Without Getting Diabetes | Mito Lite #140

@Mito, why not simply renew the dose if needed for a next meal?

This is another aspect that Gerson got right: 6 doses of 50 mg throughout the day for steady suppression.

 

[Amazoniac]

- The Vitamins: Fundamental Aspects in Nutrition and Health (978-0-12-802965-7)

 

[Spondive]

Niacin for NAFLD

New Indication for Use of Niacin (Nicotinic Acid) for Treatment, Prevention and Reversal of Fatty Liver Disease - Available technology for licensing from the University of California, Irvine

 

[Amazoniac]

@Terma, since you're around, what's your experience with creatine?

Proponents of betaine supplementation along with niacin can be overlooking that once a methyl group is transfered from betaine to a niacin metabolite, methylated glycine still has the potential to donate two more, so if the others are recovered somewhere along the way before excretion, it won't be a neutralizing act. Especially because it's uncertain how well you can metabolize them all. It's more assured through creatine and its sparing effect.

What is the truth?

 

[Terma]

I've used creatine (micronized) with no problems but I never made massive gains or whatnot. I've always liked the idea of restricting methyl groups but supplementing the end-products of methylation instead, though like you say there's a sparing effect especially with major products like creatine. Organ differences probably matter in the overall effect since TMG mostly is methylated by the liver (and kidneys? I always forget that one) and BHMT seems to get induced by stressors. It would be a good topic for a study because it's all about quantifying and the organs most affected. I'll have to think about it more another day, I was gonna get back to creatine eventually. I thought about trying to use it in some dosage relating to sleep: Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats. - PubMed - NCBI

 

[Terma]

Briefly this is what I meant, as in GAMT is not liver-specific although highest there: Expression and function of AGAT, GAMT and CT1 in the mammalian brain. - PubMed - NCBI
Overall GAMT is more widespread.

It's gonna be species-specific, just recently read that some animals even have BHMT in the brain, though didn't see indication this applies to humans:
Homocysteine Homeostasis and Betaine-Homocysteine S-Methyltransferase Expression in the Brain of Hibernating Bats

 

[Amazoniac]

Briefly this is what I meant, as in GAMT is not liver-specific although highest there: Expression and function of AGAT, GAMT and CT1 in the mammalian brain. - PubMed - NCBI
Overall GAMT is more widespread.

It's gonna be species-specific, just recently read that some animals even have BHMT in the brain, though didn't see indication this applies to humans:
Homocysteine Homeostasis and Betaine-Homocysteine S-Methyltransferase Expression in the Brain of Hibernating Bats

Guru, the amounts required seem to be fairly low for the sole purpose of negating the depleting effect on methyl groups. Going by those previous calculations (which might be already overestimating needs -- assuming there were no errors in their method -- given that basal loss wasn't discount'd), it's something like 85 mg of creatid for every 50 mg of niacin. But this is for niacin in physiological doses; if you go pharma, you'll start to need them in disproportionate quantities.

Since ingested creatine must first pass (tut) through the liver before being distributed, it doesn't have much chance to be used prior to this, so it's as if it was being synthesized there and being released into circulation: it should have the sparing effect regardless of where it ends up. But even if it's used before the hand, such effect is still valid because the liver is a major synthesizer.

The value is so low that it becomes suspicious. However, it has to be straight-forward, at least more so than with betaine (that has a lot of confounders, making predictions challenging).

- Creatine and the Liver: Metabolism and Possible Interactions ("permeable")
- Pharmacokinetics of the Dietary Supplement Creatine
- Distribution of creatine, guanidinoacetate and the enzymes for their biosynthesis in the animal kingdom. Implications for phylogeny

And the classic:
- The metabolic burden of creatine synthesis