Niacinamide Or Just Plain Niacin?

Terma

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Yeah sure, I still have to get back to you another day. Only question: where did you read that dietary creatine goes straight to the liver? That doesn't seem correct since it absorbs like an amino acid and that suggestion seems like an evolutionary disadvantage. The way that makes more sense is that it has trouble crossing the BBB according to one article (I think the transporter has to be induced).
 

Amazoniac

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Yeah sure, I still have to get back to you another day. Only question: where did you read that dietary creatine goes straight to the liver? That doesn't seem correct since it absorbs like an amino acid and that suggestion seems like an evolutionary disadvantage. The way that makes more sense is that it has trouble crossing the BBB according to one article (I think the transporter has to be induced).
- The role of dietary creatine

"Some effects of creatine may be related to the route taken in the assimilation of dietary creatine, for instance the gastrointestinal tract and the liver are both exposed to dietary creatine before it is taken up by muscles and other tissues."​

It's just something that I've read a few times and seemed to make sense, never bothered to investigate in details, so it's not too reliable.
 

Terma

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I need more articles under my belt, but I don't think that's what they mean. They mean depending on the dose and saturation of absorption (e.g. higher doses) of the amino-like mechanism, it can afterward absorb through a second mechanism.
 

Amazoniac

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I need more articles under my belt, but I don't think that's what they mean. They mean depending on the dose and saturation of absorption (e.g. higher doses) of the amino-like mechanism, it can afterward absorb through a second mechanism.
I didn't interpret it like that, if you mean because of the abstract, it seemed not to be constructed as a narrative, but could've been my impression.
"[..]creatine is structurally similar to basic amino acids (e.g. arginine and lysine) and may enter the systemic circulation through the amino acid transporter or peptide transporters located in the proximal small intestine. Creatine is a hydrophilic and polar molecule containing carboxyl and guanidino functional groups possessing negative and positive charges, respectively (figure 3). The charge on these functional groups would hinder passive diffusion of creatine through membranes."

"Although creatine is not subject to first-pass metabolism, other routes are possible for decreasing systemic creatine exposure after oral administration."

"Following administration, creatine can be taken up by a variety of cells, including blood cells, the brain/nervous tissue, cardiac muscle, spermatozoa and the retina; however, the predominant absorption site is skeletal muscle.[55]"​

- Clinical Pharmacology of the Dietary Supplement Creatine Monohydrate (same authors as above)

What I find confusing is that after leaving intestinal cells, amino acids pass through the liver from portal blood, so I assumed the same happens with creatine. Why would it not? Perhaps what they mean is that there's no 'first-pass effect' or abatement in doing so.

:confused2


- Cardiac output - Wikipedia

"For a wealthy person weighing 70 kg, the cardiac output at rest averages about 5 L/min; assuming a heart rate of 70 beats/min, the stroke volume would be approximately 70 mL."​

- Regulation of hepatic blood flow: The hepatic arterial buffer response revisited

"The hepatic artery accounts for the remaining 25% with well-oxygenated blood."​

Without accounting for what passes through it indirectly, the blood flow is 1.25 L/min or 75 L/h. Bloody volume is claimed to be about 7% of body weight, or 5 L in total for a random pimp(ess).

I don't know how exactly lacking the meal stimulus affects it, but it usually takes more than 1 h to reach maximum concentration in blood, and (at least in the experiment below) it coincided with the time needed to peak in musculus. Therefore it stays elevated in circulation for hours having the chance to pass through the liver multiple times and mix with what's released from it and have the sparing effect either way.
- Single- and Multiple-Dose Pharmacokinetics of Oral Creatine
 

Terma

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Yeah they might have meant that instead, and yeah the liver just filters the blood afterward. Pharmacokinetics of the Dietary Supplement Creatine was one I skimmed through. I wouldn't have been surprised if there's a second absorption mechanism in the intestines because creatine could be a pivotal factor in human survival (one caveman next to the other). We're not top experts on this one.
 

Amazoniac

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Yeah they might have meant that instead, and yeah the liver just filters the blood afterward. Pharmacokinetics of the Dietary Supplement Creatine was one I skimmed through. I wouldn't have been surprised if there's a second absorption mechanism in the intestines because creatine could be a pivotal factor in human survival (one caveman next to the other). We're not top experts on this one.
So.. what is the truth? Yay or nay for creatine? I'm holding my breath..

upload_2019-8-16_19-49-14.png
 
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Terma

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Yaybe?

I come at this mostly from the angle that I would try to increase endogenous creatine synthesis (arginine, glycine, growth hormone, ...), because dietary might not work great for sleep modulation (factoring in the BBB), and of course as a methyl sink, though at the same time I'm getting worried that maybe I don't get enough methyl in my brain at nighttime currently, or it's flipped. Maybe it would be useful to find out what factors control the creatine transporter at the BBB (besides ammonia). Since ketones + THC (Trp uptake) I've lost some interest in B3 altogether, with the exception of its effects on liver DAG, which someone just brought up again in a thread. Depends on your ultimate goal.
 

Amazoniac

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Yaybe?

I come at this mostly from the angle that I would try to increase endogenous creatine synthesis (arginine, glycine, growth hormone, ...), because dietary might not work great for sleep modulation (factoring in the BBB), and of course as a methyl sink, though at the same time I'm getting worried that maybe I don't get enough methyl in my brain at nighttime currently, or it's flipped. Maybe it would be useful to find out what factors control the creatine transporter at the BBB (besides ammonia). Since ketones + THC (Trp uptake) I've lost some interest in B3 altogether, with the exception of its effects on liver DAG, which someone just brought up again in a thread. Depends on your ultimate goal.
From the 'Pharmacology' link above:

"Other factors that have been shown to regulate Cr synthesis include typhoid hormone, growth hormone, testosterone, ornithine, and dietary deficiencies (e.g., fasting, vitamin E) (Walker, 1979; Wyss and Kaddurah-Daouk, 2000)."​
 
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TruthSeeker

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Abram Hoffer reported in his book fixing a lifelong gums issue as a side effect from taking a high dose niacin for only 2 weeks. Any idea whether niacinamide would also do such a trick?
 

Amazoniac

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[..]the recommended daily allowance for NA is in milligrams, whereas an estimated 6 to 9 g of NAD+ are required daily to match turnover [58]. This is facilitated by the high affinity of NAMPT for Nam; thus, even small amounts of Nam are effectively converted to NMN and then NAD+ [221].
Recycling has to be very important, and the same for enzymes that are required in the process. Check this out:

- Aerobic and resistance exercise training reverses age‐dependent decline in NAD+ salvage capacity in human skeletal muscle

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"The exercise training programs consisted of 12 weeks of aerobic exercise (treadmill, stationary cycle, or elliptical trainer) or 12 weeks of resistance exercise (upper and lower body exercises). For the aerobic training, a target heart rate zone equivalent to 70–75% of VO2peak was set for a total of 180 min/week (3–4 sessions per week). For the resistance exercise training, alternating upper and lower body exercises were performed for ~45 min/session (3 sessions per week). Resistance was increased by 5% when subjects could complete 12 repetitions on two consecutive occasions."

upload_2020-3-20_9-2-9.png


"Figure 2. NAMPT protein levels in human skeletal muscle declines with increasing age and body fat. Correlation of the baseline skeletal muscle NAMPT with
  • A, age (n = 57, r2 = 0.297, P < 0.001)**;
  • B, BMI (n = 57, r2 = 0.151, P < 0.01)*;
  • C, body fat (n = 57, r2 = 0.305, P < 0.001)*;
  • D, VO2peak (n = 57, r2 = 0.403, P < 0.001)*;
  • E, lean body mass (n = 57, r2 = 0.139, P < 0.01)**;
  • F, total blood cholesterol (n = 57, r2 = 0.113, P < 0.05)*;
  • G, blood LDL cholesterol (n = 57, r2 = 0.112, P < 0.05);
  • H, M-value (n = 57, r2 = 0.172, P < 0.01)*.
*Pearson correlation coefficient, r was used. Significance of Pearson coefficient was tested using the t-distribution.
**Spearman correlation coefficient, rs was used."

upload_2020-3-20_9-2-25.png


"Figure 3. NAMPT protein levels increase with aerobic and resistance exercise training in human skeletal muscle.
  • A) Skeletal muscle NAMPT in response to aerobic exercise for 12 weeks, ** indicates main effect of training versus baseline (P < 0.01) ## indicates main effect of age versus young (P < 0.01), no interaction effect.
  • B) Skeletal muscle NAMPT after 12 weeks of resistance exercise training, ** indicates main effect of training versus baseline (P < 0.01), tendency of effect of age P = 0.077, no interaction effect.
  • C) Skeletal muscle NRK2 after aerobic exercise (n = 9).
  • D) Skeletal muscle NRK2 of resistance exercised individuals.
  • E) Skeletal muscle NMNAT1 in aerobic exercise.
  • F) Skeletal muscle NMNAT1 in resistance exercise.
  • G) NMNAT3 in aerobic exercise, # indicates main effect of age versus young (P < 0.05).
  • H) NMNAT3 protein levels in resistance exercise.
Number in bar graph indicates number of participants.
Statistical test performed: 2-way RM ANOVA with Tukey as post hoc."

I don't know how its consumption is affected but can't imagine boosting NAD+ synthesis the savage way being dangerous, therefore it shouldn't be regulated as drugs.
 
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Curiousman

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Elevation of Cellular NAD Levels by Nicotinic Acid and Involvement of Nicotinic Acid Phosphoribosyltransferase in Human Cells

NAD plays critical roles in various biological processes through the function of SIRT1. Although classical studies in mammals showed that nicotinic acid (NA) is a better precursor than nicotinamide (Nam) in elevating tissue NAD levels, molecular details of NAD synthesis from NA remain largely unknown. We here identified NA phosphoribosyltransferase (NAPRT) in humans and provided direct evidence of tight link between NAPRT and the increase in cellular NAD levels. The enzyme was abundantly expressed in the small intestine, liver, and kidney in mice and mediated [(14)C]NAD synthesis from [(14)C]NA in human cells. In cells expressing endogenous NAPRT, the addition of NA but not Nam almost doubled cellular NAD contents and decreased cytotoxicity by H(2)O(2). Both effects were reversed by knockdown of NAPRT expression. These results indicate that NAPRT is essential for NA to increase cellular NAD levels and, thus, to prevent oxidative stress of the cells. Kinetic analyses revealed that NAPRT, but not Nam phosphoribosyltransferase (NamPRT, also known as pre-B-cell colony-enhancing factor or visfatin), is insensitive to the physiological concentration of NAD. Together, we conclude that NA elevates cellular NAD levels through NAPRT function and, thus, protects the cells against stress, partly due to lack of feedback inhibition of NAPRT but not NamPRT by NAD. The ability of NA to increase cellular NAD contents may account for some of the clinically observed effects of the vitamin and further implies a novel application of the vitamin to treat diseases such as those associated with the depletion of cellular NAD pools.

Nicotinic acid seems doesn't give negative feedback on the NAD production.
 

Amazoniac

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Amazoniac

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- Determination of niacin profiles in some animal and plant based foods by high performance liquid chromatography: association with healthy nutrition

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"In plants, especially mature cereal grains like corn and wheat, niacin may be bound to sugar molecules in the form of glycosides, which significantly decrease its bioavailability [20]. During the cooking of cereals, particularly in products that are slightly alkaline by the use of baking soda, the availability of niacin increases [21]."
 

ChopSuey

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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.


I think I read somewhere that Dr. Hoffer took 3 grams of niacin/niacinamide daily (wonder which one).

One thing that impressed me is how remarkably sharp he was mentally until the end. Even in his 90s, in his last interviews he has fluid speech and recalls events on specific days from decades ago with ease.
 

Ras

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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.
Here is the post.
 

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