529 replies to this topic

[APBT]

I will publish an excerpt from my video taped interview (conducted on January 22, 2014) with Dr. Leonard Guarente
at MIT. In it, he explains that both NMN and NR raise NAD levels, either of these will do the job; they don't have
to be taken together. The effect of taking them with resveratrol is greater than additive, rather, it is multiplied. This
is new research and certain things are still being worked out this year. Could negative information come out?
Possibly, but it's looking good.

Thank you for posting your video interview. You may or may not be able to shed any light on these questions.

As several bright contributors have alluded to, plain ole nicotinic acid (niacin) may achieve NAD+ boosting, thoughts? Dosage?

Do you have an idea what the human dose of NR would be? Post #124 (page 5) by smithx hypothesized 2500mg. Post #125 by niner thought the conversion may be 2333mg; both assuming 70kg body weight. Nyles7 in post #143 thought a lower dosage would work. And in post #239, the link I posted, it mentions 3500mg.

The most readily available source of NR (Niagen), recommends 250mg daily on an empty stomach first thing in the AM.

Thoughts on sublingual verses oral consumption?

Edited by APBT, 17 March 2014 - 10:40 PM.

[APBT]

My Medline intuition has been near,perfect lately . All intuited things backed by old science. Must be the higher NAD+ levels http://www.jbc.org/c.../33395.full.pdf

Ukko, thanks for all of your contributions to this topic. Would you mind posting your current approach for increasing NAD+ and blocking CD38?

NAD+:
What supplements do you take?
What quantities of each?
Timing (i.e. time of day)?
With or without food?
How taken (oral ingestion or sublingual)?
Any foods you specifically include or exclude to increase NAD+?

CD38 inhibition:
What supplements do you take?
What quantities of each?
Timing (i.e. time of day)?
With or without food?
How taken (oral ingestion or sublingual)?
Any foods you specifically include or exclude to inhibit CD38?

[APBT]

Slightly off topic and can be moved if there is enough interest, but does anyone have an opinion on how Niagen might affect a 17 year old dog and what the dosage might be for a body weight of 16 lbs?

Her deterioration is becoming more rapid and due to her advanced age I'm looking for a slightly more aggressive approach than my own dose of 250mg every morning. She's also currently on C60 so it's something to take into account.

Thanks in advance!

This may help: http://en.wikipedia.org/wiki/Allometry

[Kevnzworld]

I take Niagen, 375 mg per day, that being said.....
Some of this reminds me of a debate on longecity a few years back regarding supplements that either shortened ,promoted or supported telomere length. There are various data and studies that show various and often conflicting results.
I take Metformin and aspirin, both inhibit NAD. I take many supplements,hormones etc that enhance NAD levels.
I agree that there is compelling evidence that higher NAD levels are associated with a healthier lifespan, though not necessarily a longer one. There is evidence that some things that support a healthier and possibly longer lifespan also happen to inhibit NAD.
My takeaway is moderation. I think we can over think this. I now believe that it's especially important that people who take things like Metformin or aspirin also take some form of niacin.

[Ukko]

My Medline intuition has been near,perfect lately . All intuited things backed by old science. Must be the higher NAD+ levels http://www.jbc.org/c.../33395.full.pdf

Ukko, thanks for all of your contributions to this topic. Would you mind posting your current approach for increasing NAD+ and blocking CD38?

NAD+:
What supplements do you take?
What quantities of each?
Timing (i.e. time of day)?
With or without food?
How taken (oral ingestion or sublingual)?
Any foods you specifically include or exclude to increase NAD+?

CD38 inhibition:
What supplements do you take?
What quantities of each?
Timing (i.e. time of day)?
With or without food?
How taken (oral ingestion or sublingual)?
Any foods you specifically include or exclude to inhibit CD38?

NAD+ precursors. There are four paths essentially. The de novo synthesis from tryptophan, which I do not supplement for given that the main intermediary in this path is the notorious neurotoxin quinolinic acid and that this path is very inefficient. The other path is recycling from nicotinamide. That gets saturated easily, any multivitamin will do. Then there's the synthesis from niacin, which needs glutamine to function. And then there's the recently found path from nicotinamide riboside. What I take is like 1000-2000mg of niacin around noon. The Niagen recommended dose of Niagen upon waking up, though I suspect that this time is not optimal. The only one I take sublingually is this one. No tryptophan. And then I just re-added like 20g of glutamine upon waking up to prepare my body for the supplemental niacin around noon.

As to CD38 blockers...well I take the Swanson C3G pills and Swanson Apigen pills as well as a Now Foods quercetin pill around noon.

And then I do take AMPK induces, which also boost NAD+. Such as resveratrol, alpha lipoic acid, acetyl-l-carnitine....

Once my regime gets more locked down, I will revert with more details and experiences. Just started a couple of months back.

[Marty D]

As to CD38 blockers...well I take the Swanson C3G pills and Swanson Apigen pills as well as a Now Foods quercetin pill around noon

This is vague.

While I do agree it'd be easy to over think the process, well, at a pedestrian level, I absolutely agree with the idea of acting in concert with our circadian rythym. I have trouble however with the assumption that everyone rises and sleeps at the same time of day. When you say noon is that plus 6 hours or is it plus 4 hours after waking up or what exactly is your schedule. Just for future reference and thanks for your input.

[APBT]

Slightly off topic and can be moved if there is enough interest, but does anyone have an opinion on how Niagen might affect a 17 year old dog and what the dosage might be for a body weight of 16 lbs?

Her deterioration is becoming more rapid and due to her advanced age I'm looking for a slightly more aggressive approach than my own dose of 250mg every morning. She's also currently on C60 so it's something to take into account.

Thanks in advance!

This may help: http://en.wikipedia.org/wiki/Allometry

You may find these sources more useful:
https://ncifrederick...ents/ACUC42.pdf
http://ora.georgetow...cConversion.htm
See page 4 of this document: http://www.atsdr.cdc...Methodology.pdf

Edited by APBT, 18 March 2014 - 09:27 PM.

[APBT]

Does anyone know, or have a theory as to how the 250 mg dose and early AM timing, of Niagen (NR) was arrived at?

[Ukko]

Does anyone know, or have a theory as to how the 250 mg dose and early AM timing, of Niagen (NR) was arrived at?

This is just a hunch, but I would expect it to be based on guaranteeing that it is taken before and separately from any meals. I tend to eat my first meal far later, like around noon, which is why I probably could and should postpone Niagen as well. Just a hunch though. Never seen any science actually supporting early morning timing for NAD+ precursors.

[APBT]

Does anyone know, or have a theory as to how the 250 mg dose and early AM timing, of Niagen (NR) was arrived at?

This is just a hunch, but I would expect it to be based on guaranteeing that it is taken before and separately from any meals. I tend to eat my first meal far later, like around noon, which is why I probably could and should postpone Niagen as well. Just a hunch though. Never seen any science actually supporting early morning timing for NAD+ precursors.

Any idea on how the 250 mg dose was arrived at?

[Ukko]

Does anyone know, or have a theory as to how the 250 mg dose and early AM timing, of Niagen (NR) was arrived at?

This is just a hunch, but I would expect it to be based on guaranteeing that it is taken before and separately from any meals. I tend to eat my first meal far later, like around noon, which is why I probably could and should postpone Niagen as well. Just a hunch though. Never seen any science actually supporting early morning timing for NAD+ precursors.

Any idea on how the 250 mg dose was arrived at?

Seems entirely random. On the Niagen bottle, they heavily emphasize the protection against sports related head trauma. Which leads me to believe that it is likely a patent issue. Remember that NR is present in for example milk and whey. Naturally occuring compound. There likely is some artificially limited sports related "method for using NR" patent that they are sticking to in terms of marketing, labeling and pushing the product. I suppose any monkey could push NR as a naturally occuring compoung without any use indication. The 250mg dose seems purely random to me, unless it features in some sport related publication or patent. Did not find that exact dose, but did find this patent, which suggests to me that the idiots patented the compound only and specifically for treating "axonopathy" and are likely in trouble for pushing into other uses under the earliest patents at least:

"A method of treating an axonopathy in a mammal in need thereof, the method comprising administering to the mammal an agent that acts by increasing sirtuin activity in diseased and/or injured neurons and supporting cells in an amount effective to decrease axonal degeneration...The specific dose can be calculated according to the approximate body weight or body surface area of the patient or the volume of body space to be occupied. The dose will also depend upon the particular route of administration selected. Further refinement of the calculations necessary to determine the appropriate dosage for treatment is routinely made by those of ordinary skill in the art. Such calculations can be made without undue experimentation by one skilled in the art in light of the activity in assay preparations such as has been described elsewhere for certain compounds (see for example, Howitz et al., Nature 425:191-196, 2003 and supplementary information that accompanies the paper). Exact dosages can be determined in conjunction with standard dose-response studies. It will be understood that the amount of the composition actually administered will be determined by a practitioner, in the light of the relevant circumstances including the condition or conditions to be treated, the choice of composition to be administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the chosen route of administration."

https://www.google.c...ved=0CDUQ6AEwAA

Edited by Ukko, 20 March 2014 - 04:15 AM.

[Breestyle]

APBT,

Thanks for your responses and message (and research). I have still not given Niagen to my dog, not because I can't convert the dose, but just want to guard against any possible toxicity before adding this substance to her regimen. I did come across this article however that specifically mentions dogs:
http://www.sciencedi...092867404004167

She is doing quite well for her age (now heading towards 18). The question I put forth is... would (any of) you personally give it to your senior dog to try to improve quality of life and/or mitigate some of the damage?

[Ukko]

As to CD38 blockers...well I take the Swanson C3G pills and Swanson Apigen pills as well as a Now Foods quercetin pill around noon

This is vague.

While I do agree it'd be easy to over think the process, well, at a pedestrian level, I absolutely agree with the idea of acting in concert with our circadian rythym. I have trouble however with the assumption that everyone rises and sleeps at the same time of day. When you say noon is that plus 6 hours or is it plus 4 hours after waking up or what exactly is your schedule. Just for future reference and thanks for your input.

Agreed. But check the Niagen bottle. Just how vague is that and the accompanying literature

Edited by Ukko, 20 March 2014 - 04:20 AM.

[midas]

Seems entirely random. On the Niagen bottle, they heavily emphasize the protection against sports related head trauma. Which leads me to believe that it is likely a patent issue. Remember that NR is present in for example milk and whey. Naturally occuring compound. There likely is some artificially limited sports related "method for using NR" patent that they are sticking to in terms of marketing, labeling and pushing the product. I suppose any monkey could push NR as a naturally occuring compoung without any use indication.

I think you are only seeing one side of the Niagen thing there.

They are using the neuroprotective thing as a target market to sell Niagen to sports people as it is a large market.

It is also advertised as

• Naturally helps those suffering from anxiety, ADD, ADHD, fatigue, depression.
• Increases energy in brain cells
• Aids in neuroprotection
• Aids in metabolism support and muscular endurance

The company that manufactures it has struck a few big deals in recent weeks to sell Niagen for both other retail markets and research..

http://newhope360.co...niagen-research

http://www.marketwir...apo-1889803.htm


http://online.wsj.co...106-904099.html

I think in the next couple of years we are going to see Niagen used in all sorts of things.

Chromadex's stock price has rocketed over the last 12 months..$0.50 to $2.07 and that is all about Niagen, its going to be a big thing......Its headed for the NASDAQ

http://uk.finance.ya...l=CDXC;range=2y

[to age or not to age]

from my interviews midas, you have hit the nail on the head

[APBT]

APBT,

Thanks for your responses and message (and research). I have still not given Niagen to my dog, not because I can't convert the dose, but just want to guard against any possible toxicity before adding this substance to her regimen. I did come across this article however that specifically mentions dogs:
http://www.sciencedi...092867404004167

She is doing quite well for her age (now heading towards 18). The question I put forth is... would (any of) you personally give it to your senior dog to try to improve quality of life and/or mitigate some of the damage?

I’ll preface my comments by saying I am not a veterinarian, nor do I play one on TV. Furthermore, I am not encouraging you to follow my lead, merely offering my thoughts. Consider me just another bozo on the bus.

As Mocha’s advocate – clearly you’re doing an exemplary job - I believe you have to prioritize the quality of life the treatment may render as numero uno; exclusive of any increase in lifespan. Dogs are quite adept at lettin’ ya know when enough is enough.

I’m not clear if Mocha is just an oldster with the accompanying ailments, or if she has some other medical conditions. I don’t believe the mice in the “Cell” study were sick, so that’s another confounding factor. But, the results were impressive and quick. So, I’d think if Mocha weren’t in too much of a weakened state and the treatment was effective, you’d see results soon. This is truly uncharted water you’re navigating.

Weighing the pros and cons, and taking the decision very seriously, personally, I’d try the Niagen treatment with the following considerations:

Prior, I would get a comprehensive blood panel done to make sure there were no issues, specifically with the liver or kidneys.

I would start with a very conservative (appropriately converted) dose, monitor her response and slowly titrate up until I reached what seemed to be the sweet spot.

I would keep my expectations realistic and cease treatment immediately if her condition worsened.

Have you considered discussing this with your vet?
Another option is contacting a veterinary medical teaching hospital, they’re often very cutting edge and interested in novel treatments.

Here are a few results using the search term “niacin toxicity in dogs”
http://multimedia.fo.../evm_niacin.pdf
http://jn.nutrition..../4/623.full.pdf
http://www.provet.co...ases/niacin.htm
http://www.justanswe...-25-lb-dog.html

Results from Google Scholar using the same search term.
http://scholar.googl...dt=1,24&as_sdtp=

Edited by APBT, 21 March 2014 - 01:43 AM.

[APBT]

The Mitochondrial Theory of Aging - David Sinclair
Around 9:45 in, he discusses the "Cell" study.

[url="http://www.youtube.com/watch?v=v3ncUYKme4k"][media]http://www.youtube.com/watch?v=v3ncUYKme4k[/url[/media]

Edited by APBT, 24 March 2014 - 07:57 PM.

[APBT]

http://www.marketwir...apo-1889803.htm

The company in the link - Vaporin - is a distributor and marketer of e-cigarettes. Seems like an odd partnership.

[midas]

http://www.marketwir...apo-1889803.htm

The company in the link - Vaporin - is a distributor and marketer of e-cigarettes. Seems like an odd partnership.

Not as odd as you may think.....the respiratory tract is a pretty efficient way of getting things into the blood stream and is thought to be the future in drug delivery by some. Vapour form E-Cigarettes would be an ideal way of doing just that.

Makes perfect sense to me, as I use an E-Cigarette.

http://waleedtaha.tripod.com/rdds/

^{"The respiratory tract provides an efficient way for the delivery of drugs. Advantages of this type of drug delivery are they act quickly, the dosage is minimized, the drugs are non-invasive, side effects are least likely to occur, and the drugs are systematically absorbed. The lungs have a large surface area, 140 meters squared, which makes it perfect for inhalation drugs to be absorbed through the lungs, especially because they possess a good blood supply separated by a thin membrane from the alveoli. The only drawback from respiratory drugs is that they must be small enough and aerodynamic enough to enter the alveoli and diffuse through the membranes before absorption takes place. Respiratory drugs can include powders or sprays."}

Edited by midas, 24 March 2014 - 11:57 PM.

[midas]

Not as odd as you may think.....the respiratory tract is a pretty efficient way of getting things into the blood stream and is thought to be the future in drug delivery by some. Vapour form E-Cigarettes would be an ideal way of doing just that.

Makes perfect sense to me, as I use an E-Cigarette.

http://waleedtaha.tripod.com/rdds/

^{"The respiratory tract provides an efficient way for the delivery of drugs. Advantages of this type of drug delivery are they act quickly, the dosage is minimized, the drugs are non-invasive, side effects are least likely to occur, and the drugs are systematically absorbed. The lungs have a large surface area, 140 meters squared, which makes it perfect for inhalation drugs to be absorbed through the lungs, especially because they possess a good blood supply separated by a thin membrane from the alveoli. The only drawback from respiratory drugs is that they must be small enough and aerodynamic enough to enter the alveoli and diffuse through the membranes before absorption takes place. Respiratory drugs can include powders or sprays."}

The way I see it is, if Sinclair is right about regenerating muscles then as the lungs are more or less just that. Vaporin will be looking at getting there before anyone else with the Niagen (Nicotinamide Riboside) thing.
I had thought about this a couple of months ago due to the fact that I smoke an E-Cig. I have already tried it with Ubiquinol Q10 in the E-Cig
And that is one of the first things I am going to try if we can get this Nicotinamide Riboside group by off the ground on the other thread on here.

Can you imagine the amount of business that Vaporin will do if this stuff works out to be as interesting as it looks like it might be. If they make a product that works, includes Niagen (Nicotinamide Riboside) and trade mark it.......

Well, lets put it this way, if I was over there in the USA and I had some money to invest in stocks, I would be throwing it at ChromaDex and Vaporin......

[to age or not to age]

Midas - this is quite intriguing. At David's lab and Lenny Guarente's lab at MIT, it's all full steam ahead.
There are a few things I can't say right now. But believe me, Chromadex is going to have competition.
I am editing a recent interview with Guarente that bears on the NAD discussion. I will post an excerpt here
within a week.

[APBT]

Midas - this is quite intriguing. At David's lab and Lenny Guarente's lab at MIT, it's all full steam ahead.
There are a few things I can't say right now. But believe me, Chromadex is going to have competition.
I am editing a recent interview with Guarente that bears on the NAD discussion. I will post an excerpt here
within a week.

Not to stray OT too much. Its been a couple of years since I watched "To Age or Not to Age," but didn't you interview Lenny Guarente in that? As well as Vince Giuliano and Anthony Loera of RevGenetics?

Edited by APBT, 25 March 2014 - 11:25 PM.

[midas]

Midas - this is quite intriguing. At David's lab and Lenny Guarente's lab at MIT, it's all full steam ahead.
There are a few things I can't say right now. But believe me, Chromadex is going to have competition.
I am editing a recent interview with Guarente that bears on the NAD discussion. I will post an excerpt here
within a week.

The more competition ChromaDex gets the better I say.

I have just spent a couple of hours looking into Lenny Guarente, interesting guy, I look forward to seeing/reading your interview with him..

I also found a couple of things on NR that I haven't read before with reference to Dr. Johan Auwerx and Dr Anthony Sauve....back in 2012

"Nevertheless, the effects of NR on metabolism "are nothing short of astonishing."

"Our published scientific work has verified that NR is perhaps the most potent NAD enhancing agent ever identified,"

http://weill.cornell...h-benefits.html

[PWAIN]

I am trying to organise a group buy of Niagen at a 30% discount ($33.60) per bottle.

I have created a new thread in the Supplements section

The link is here:

http://www.longecity...side-group-buy/

If anyone is interested, please go to that link and let me know.

Edited by PWAIN, 26 March 2014 - 12:37 AM.

[to age or not to age]

APBT, Let me respond directly. Yes, I continue to interview researchers, and began doing so 7 years ago.
I interviewed Lenny Guarente in late 2006, and through him, have had access to his many ex post docs, from SInclair
to Kennedy. A most generous person, Lenny continues to initiate my access to research that is ongoing. In "To Age or Not To Age" I interviewed Vince Guiliano, 84 years old, trained in physics, a brilliant fellow, who showed up
at Symphony Space in New York at a screening of that film in 2010, and began to question Lenny, Aubrey and the late Dr. Robert Butler in a Q&A after the film. I will at some point, post excerpts from that event. Trained as a film director, I had never done a picture on this subject. What I have learned is that the science is a moving target, multi-factorial in nature
and implication. My interest has not flagged and I am creating an ongoing series.

[to age or not to age]

Midas - Guarente goes into NAD at length and I will post excerpts. He trained David at MIT in the nineties.
David organized a major event honoring Lenny at MIT in August 2012, along with Harvard's Marsha Haigis. 75
of his ex post docs showed up. They roasted him. I filmed it.

[midas]

Midas - Guarente goes into NAD at length and I will post excerpts. He trained David at MIT in the nineties.
David organized a major event honoring Lenny at MIT in August 2012, along with Harvard's Marsha Haigis. 75
of his ex post docs showed up. They roasted him. I filmed it.

to age or not to age, thanks for all this info...
I have only recently over the last year or two gotten interested in this subject, mainly to help battle a medical condition I have, and I am loving every minute of it....I have become very disillusioned with doctors, they are so closed minded about this sort of thing and it takes them years to get anywhere with this sort of stuff...I decided to educate myself and make well thought out decisions about how I am going to fight this..And have made more progress on my own than I did with them over the past few years...I dont want to live for ever but I sure aint ready to go just yet!

I so wish I had found an interest in all this years ago..

I'll be looking forward to anything you can post/share on this subject..Thanks again.

PS, when you say "They roasted him." do you mean David Sinclair and if so how did it turn out??

Edited by midas, 26 March 2014 - 02:44 AM.

[hav]

Just got a chance to hunt down the actual Sinclair paper to check out the dosage and administration they used. Here it is:

Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging.

Wild-type C57BL/6J mice were from the National Institutes of Aging, NIH. EglN1 KO, SIRT1-iKO, and SIRT1-Tg mice were described previously (Minamishima et al., 2008; Price et al., 2012). For NMN experiments, mice were given IP injections of 500 mg NMN/kg body weight per day or the equivalent volume of PBS for 7 consecutive days at 6 PM and 8 AM on day 8 and were sacrificed 4 hr after last injection.

NMN being Nicotinamide Mononucleotide.

Howard

[tunt01]

Is anyone certain that NR is inhibiting mTOR? That is, if we are upregulating SIRT1 via NAD+/NADH are we then certainly inhibiting mTOR?

Thx.

[APBT]

Is anyone certain that NR is inhibiting mTOR? That is, if we are upregulating SIRT1 via NAD+/NADH are we then certainly inhibiting mTOR?

Thx.

Does this help? The following studies seem to indicate, that, yes, NR increases SIRT1 (study 1) and SIRT1 negatively regulates mTOR (study 2).

STUDY 1 FULL TEXT: http://download.cell...termediate=true
The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity

• NR efficiently increases NAD⁺ levels in mammalian cells and tissues
• NR supplementation increases SIRT1 and SIRT3 activities
• NR largely prevents the detrimental metabolic effects of high-fat feeding
• NR enhances mitochondrial function and endurance performance

Summary
As NAD⁺ is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38�both NAD⁺ consumers�increases NAD⁺ bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD⁺ precursor with the ability to increase NAD⁺ levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD⁺ levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.


STUDY 2 FULL TEXT: http://www.plosone.o...al.pone.0009199
SIRT1 Negatively Regulates the Mammalian Target of Rapamycin
Abstract
The IGF/mTOR pathway, which is modulated by nutrients, growth factors, energy status and cellular stress regulates aging in various organisms. SIRT1 is a NAD+ dependent deacetylase that is known to regulate caloric restriction mediated longevity in model organisms, and has also been linked to the insulin/IGF signaling pathway. Here we investigated the potential regulation of mTOR signaling by SIRT1 in response to nutrients and cellular stress. We demonstrate that SIRT1 deficiency results in elevated mTOR signaling, which is not abolished by stress conditions. The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner. Furthermore, we demonstrate that SIRT1 interacts with TSC2, a component of the mTOR inhibitory-complex upstream to mTORC1, and regulates mTOR signaling in a TSC2 dependent manner. These results demonstrate that SIRT1 negatively regulates mTOR signaling potentially through the TSC1/2 complex.