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Supplementing NAD directly to influence NAD+/NADH ratio


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#1 FunkOdyssey

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Posted 17 June 2008 - 04:19 PM


Here's the product I'm looking at:

Now Foods NAD, 25mg lozenges

Is there some reason this would be less effective than, for example, nicotinamide riboside at elevating cellular NAD+ levels? Is it like glutathione in that it is not well absorbed or utilized directly, hence the precursor approach? If not, why have I never heard of anyone using NAD? I just read a paper advocating the consumption of multi-gram quantities of nicotinic acid in order to raise NAD+ enough to activate SIRT1... so why wouldn't NAD itself be more efficient?

Edited by FunkOdyssey, 17 June 2008 - 04:21 PM.


#2 krillin

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Posted 17 June 2008 - 09:33 PM

Aubrey said that NAD+ would be reduced to NADH in the bloodstream pretty quickly, but I have found several papers that measured blood NAD+ and Inawe found this paper before he went insane. It looks like we've found a big blank spot in our supplementation knowledge.

Front Biosci. 2007 Jan 1;12:2728-34.
Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia.
Ying W, Wei G, Wang D, Wang Q, Tang X, Shi J, Zhang P, Lu H.
Department of Neurology, University of California at San Francisco and San Francisco Veterans Affairs Medical Center; 4150 Clement Street, San Francisco, CA 94121, USA. shine863@gmail.com

Excessive poly(ADP-ribose) polymerase-1 (PARP-1) activation plays a significant role in ischemic brain damage. Increasing evidence has supported the hypothesis that PARP-1 induces cell death by depleting intracellular NAD+. Based on our in vitro finding that NAD+ treatment can abolish PARP-1-mediated cell death, we hypothesized that NAD+ administration may decrease ischemic brain injury. In this study, we used a rat model of transient focal ischemia to test this hypothesis. We observed that intranasal NAD+ delivery significantly increased NAD+ contents in the brains. Intranasal delivery with 10 mg/kg NAD+ at 2 hours after ischemic onset profoundly decreased infarct formation when assessed either at 24 or 72 hours after ischemia. The NAD+ administration also significantly attenuated ischemia-induced neurological deficits. In contrast, intranasal administration with 10 mg/kg nicotinamide did not decrease ischemic brain damage. These results provide the first in vivo evidence that NAD+ metabolism is a new target for treating brain ischemia, and that NAD+ administration may be a novel strategy for decreasing brain damage in cerebral ischemia and possibly other PARP-1-associated neurological diseases.

PMID: 17127275

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#3 inawe

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Posted 17 June 2008 - 09:40 PM

Here's the product I'm looking at:

Now Foods NAD, 25mg lozenges

Is there some reason this would be less effective than, for example, nicotinamide riboside at elevating cellular NAD+ levels? Is it like glutathione in that it is not well absorbed or utilized directly, hence the precursor approach? If not, why have I never heard of anyone using NAD? I just read a paper advocating the consumption of multi-gram quantities of nicotinic acid in order to raise NAD+ enough to activate SIRT1... so why wouldn't NAD itself be more efficient?

There are several papers by the Brenner group where they propose supplementation with Nicotinamide Riboside (NR). I have been looking but couldn't find a good source of NR. Do you know where to get NR?
In PMID: 18429699 one can read: "current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation".
As for the NAD from NOW they state: "unlike NADH, NAD is not altered by the acids present in the stomach". But acording to Wikipedia: "Solutions of NAD+ are colorless and stable for about a week at 4 degrees C and neutral pH, but decompose rapidly in acid or alkalis".
If I have to, I'll bet NAD doesn't make it through the acid.

#4 krillin

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Posted 17 June 2008 - 09:46 PM

If I have to, I'll bet NAD doesn't make it through the acid.

It made it through in this study, but it's just a black box as to what it does to the NAD+/NADH ratio.

J Nutr Sci Vitaminol (Tokyo). 2006 Apr;52(2):142-8.
Comparison of metabolic fates of nicotinamide, NAD+ and NADH administered orally and intraperitoneally; characterization of oral NADH.
Kimura N, Fukuwatari T, Sasaki R, Shibata K.
Laboratories of Food Science and Nutrition, Department of Life Style Studies, School of Human Cultures, The University of Shiga Prefecture, Japan.

Since NADH has been implicated in medication for some symptoms and as a possible supplement for health, we characterized the metabolic fate of NADH orally given to mice by comparing with those of nicotinamide (Nam), NAD+ and NADH intraperitoneally or orally administered. Mice were individually housed in metabolic cages, and divided into two sets of four groups. Within each set, one group was intraperitoneally or orally administered saline and the other three groups received intraperitoneal or oral administration of a pharmacological dose of Nam, NAD+ or NADH (5 micromol/mouse). Twenty-four hour urine samples for the day before and days 1 to 4 after administration were collected and analyzed for Nam and its metabolites. When mice were administered saline alone, urinary excretion of Nam and its metabolites, such as nicotinamide N-oxide (Nam N-oxide), N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py), and N1-methyl-4-pyridone-3-carboxamide (4-Py), was unchanged from day 0 to day 4. Intraperitoneal injection of Nam, NAD+ and NADH produced significant increases in urinary excretion of Nam and its metabolites. Similar results were obtained when Nam and NAD+ were given orally. On the other hand, oral administration of NADH did not bring about an increase in urinary excretion of Nam and its metabolites, suggesting that NADH in digestive organs has been decomposed to a compound(s) that cannot yield Nam. In fact, incubation of NADH at acidic pH to mimic the stomach resulted in rapid conversion of NADH to an unknown compound. Better understanding of the fate of oral NADH is needed for its therapeutic and supplemental use.

PMID: 16802695

#5 FunkOdyssey

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Posted 17 June 2008 - 09:53 PM

If I have to, I'll bet NAD doesn't make it through the acid.


The study krillin posted above seems to indicate that, unlike NADH, it does make it through the stomach acid. Also considering that its a lozenge, you may be able to absorb some of it sublingually. And in the first study from krillin, "We observed that intranasal NAD+ delivery significantly increased NAD+ contents in the brains." So far, so good.

In PMID: 18429699 one can read: "current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation".


I did read that in the abstract. What do they know that we don't? Why can't we skip the encourage-neurons-to-synthesize-NAD+-with-precursors strategy and just give them NAD+?

Edited by FunkOdyssey, 17 June 2008 - 09:59 PM.


#6 inawe

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Posted 18 June 2008 - 12:14 AM

Seems NAD is easily ionized to NAD+. In an acidic environment there are plenty of H+. So the probability is high that it'll be reduced: (NAD+)+(H+)+2e -> NADH.

#7 edward

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Posted 18 June 2008 - 01:07 AM

I believe influencing this ratio is what benagene is trying to do. http://www.imminst.o...amp;hl=benagene

#8 inawe

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Posted 18 June 2008 - 01:42 AM

I believe influencing this ratio is what benagene is trying to do. http://www.imminst.o...amp;hl=benagene

Precisely. If increasing NAD+/NADH ratio were as easy as to swallow NAD+, then Benagene wouldn't have any reason to exists.

#9 nicklesprout

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Posted 23 January 2017 - 05:55 PM

anybody know where to get IV or intranasal form of NAD? iv treatment at facilities is just too expensive these days...sheesh...



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#10 Journey2016

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Posted 25 January 2017 - 11:10 PM

anybody know where to get IV or intranasal form of NAD? iv treatment at facilities is just too expensive these days...sheesh...


Im also interested in the "nasal" NAD spray possibly rg3




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