18 replies to this topic

[resveratrol]

The answer is probably somewhere in the forums, but I hope you'll forgive me for saying I've been digging for an hour and unable to find a satisfactory answer. Now that I'm getting an MBA I no longer have as much time to keep up to date with the latest research.

I'm reading a lot in the forums about the importance of optimizing one's NAD+/NADH ratio and getting worried about my niacinamide intake.

Could I kindly ask that you help out a layman and fill me in as to

* Why this is important
* What supplements I should take to compensate if my diet already includes a relatively large intake of niacin (almost inevitably in the form of niacinamide) thanks to multivitamins and 1 or 2 energy drinks per day

[resveratrol]

Anyone ...?

[medicineman]

caloric restriction or a ketogenic diet would (i think)

why this is important is because basic cell cycles such as glycolysis and krebs cycle are dependent on an optimum nad/nadh ratio.

i tried to explain it, and believe me when i say i typed a million times an explanation, but i am really sleepy and tired, or maybe im just not sure.... i know that cr and kd definitely to improve the ratio since that is one of their benefits..... but how, is a bit complex, and requires delving deep into biochemistry, which my brain at its current state is unable to handle. i apologise, and i will look this up asap tomorrow...

Edited by medicineman, 25 January 2010 - 01:46 AM.

[kitinje]

The answer is probably somewhere in the forums, but I hope you'll forgive me for saying I've been digging for an hour and unable to find a satisfactory answer. Now that I'm getting an MBA I no longer have as much time to keep up to date with the latest research.

I'm reading a lot in the forums about the importance of optimizing one's NAD+/NADH ratio and getting worried about my niacinamide intake.

What about oxaloacetic acid supplementation to improve NAD+/NADH ?

[hamishm00]

It seems to be your best bet at the moment.

There were some theories floating around that Malic acid (because it converts to oxaloacetic acid in vivo) could be useful in this regard. However, this argument seems to be flawed as Malate converstion to Ocaloacetate will decrease NAD+ and increase NADH (Oxaloacetate + NADH = Malate + NAD+ (equation favourable to the right))

Discussed further here:

http://www.imminst.o...p?s=&...3&st=0

Edited by hamishm00, 25 January 2010 - 10:56 AM.

[maxwatt]

It seems to be your best bet at the moment.

There were some theories floating around that Malic acid (because it converts to oxaloacetic acid in vivo) could be useful in this regard. However, this argument seems to be flawed as Malate converstion to Ocaloacetate will decrease NAD+ and increase NADH (Oxaloacetate + NADH = Malate + NAD+ (equation favourable to the right))

Discussed further here:

http://www.imminst.o...p?s=&...3&st=0

There is also the possibility that aspartic acid will increase the NAD/NADH ratio: trans-aminization will convert aspartic acid to oxolacetic acid, and it is more stable than the later. This has not been tested in vivo, but some Krebs Cycle charts do show the two as acting at the same point in the cycle.

Another amino acid that has been found to increase the NAD ratio is l-serine. I found this claim in a patent search, where the effect was claimed to be found only when l-serine was combine with caffeine. If it does indeed inrease the NAD/NADH ratio, it acts at a different point in the KREBS cycle involving alcohol-dehydrogense. The patent was for a method to speed the metabolization of alcohol and prevent ill effects from alcohol by speeding its metabolization.. The suggested dose was 2 grams of l-serine with 200 mg of caffeine. It was claimed to prevent "Asian Flush" and I believe is intended to be marketed to Japanese men so they can drink more.

Methylene blue oxidizes NADH into NAD*, and increases the NAD/NADH ratio.** However , the effect on longevity was seen at very low concentrations, and the human dose that have been suggested range from 60 mcg (micro-grams) to one drop of a 2% solution. There is a thread on this http://www.imminst.o...=methylene blue .

So far, in Spindler's longevity test on mice, he mentioned in a talk that he is seeing good results from oxolacetic acid.

*Appl Environ Microbiol. 1985 December; 50(6): 1368-1374
Effect of reducing-equivalent disposal and NADH/NAD on deamination of amino acids by intact rumen microorganisms and their cell extracts.
T Hino and J B Russell

**FASEB J. 2008 Mar;22(3):703-12. Epub 2007 Oct 10.
Methylene blue delays cellular senescence and enhances key
mitochondrial biochemical pathways.
Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN.

Edited by maxwatt, 25 January 2010 - 05:02 PM.
spellng

[hamishm00]

Very interesting and well referenced post, thanks Max!

[resveratrol]

Thanks, everybody! This is very helpful.

[stephen_b]

Another amino acid that has been found to increase the NAD ratio is l-serine.

I've started taking l-serine because (esp. with glycine) it reduces methionine. Methionine restriction "is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in [dietary restriction]" (PMID 20041736).

Perhaps methionine depletion is the key to serine's increasing the NAD ratio.

[tunt01]

Another amino acid that has been found to increase the NAD ratio is l-serine.

I've started taking l-serine because (esp. with glycine) it reduces methionine. Methionine restriction "is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in [dietary restriction]" (PMID 20041736).

Perhaps methionine depletion is the key to serine's increasing the NAD ratio.

this is an extremely good idea.

[maxwatt]

Another amino acid that has been found to increase the NAD ratio is l-serine.

I've started taking l-serine because (esp. with glycine) it reduces methionine. Methionine restriction "is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in [dietary restriction]" (PMID 20041736).

Perhaps methionine depletion is the key to serine's increasing the NAD ratio.

this is an extremely good idea.

Another factor: NAD activates Sirt1, and this is increased by a conformational change promoted by resveratrol*; NAD further acts on NAMPT and the circadian clock genes. All very interesting pieces of a puzzle that may not have a neat solution.

*THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 280, No. 17, Issue of April 29, pp. 17187–17195, 2005
Mechanism of Human SIRT1 Activation by Resveratrol
Margie T. Borra‡, Brian C. Smith§, and John M. Denu‡¶
From the Departments of ‡Biomolecular Chemistry and §Chemistry, University of Wisconsin-Madison,
Madison, Wisconsin 53706

[neogenic]

I know this has been discussed before, but thoughts on oral/sublingual NAD+ tabs by NOW (25mg.). I take two of those things and I get a potent nootropic effect. I love them. That and the Brain B-12 (methylcobalamin) - 5000mcg tabs and I don't need a bit of coffee or anything else in the morning.

[Sillewater]

Another amino acid that has been found to increase the NAD ratio is l-serine.

I've started taking l-serine because (esp. with glycine) it reduces methionine. Methionine restriction "is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in [dietary restriction]" (PMID 20041736).

Perhaps methionine depletion is the key to serine's increasing the NAD ratio.

Where do you buy your serine?

[stephen_b]

Where do you buy your serine?

At iHerb.

[Sillewater]

Where do you buy your serine?

At iHerb.

Thanks, I missed that.

[health_nutty]

Alcohol makes the ratio worse:

http://findarticles...._n6357649/pg_7/

[david ellis]

Where do you buy your serine?

Here is another source.

[seldomawake]

Another amino acid that has been found to increase the NAD ratio is l-serine.

I've started taking l-serine because (esp. with glycine) it reduces methionine. Methionine restriction "is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in [dietary restriction]" (PMID 20041736).

Perhaps methionine depletion is the key to serine's increasing the NAD ratio.

Any thought as to what dosage you've found helpful? Thanks!

[tommix]

Methylene Blue

No significant change of NADH, NAD+ and ATP could be observed

Methylene Blue (0.5), 1.0, 2.0 or 5.0 micrograms/ml) significantly decreased the concentration of NADPH, increased that of NADP+ and decreased the NADPH/NADP+ ratio in a dose-dependent manner

http://www.ncbi.nlm....ov/pubmed/38164

Edited by tommix, 19 March 2014 - 08:12 AM.