241 replies to this topic

[Kevnzworld]

I have some concerns over safety of LT use of this product. If anyone can answer these questions, I would be appreciative:

1. Half life of NR. How long does this stay in the system? I think it's best used in pulsatile fashion.
2. Downregulation of P53. If the NAD+/NADH ratio is adjusted substantially, SIRT1 upregulated, then P53 becomes downregulated. How do we mitigate the cancer risks associated with this outcome of opposing P53? EOD usage? Alternative solutions to upregulating P53? The dosage scheme that this company has come up with does not seem to be rooted in any scientific thought (at least for LT use).

The product is amazing, but maybe too good for a reason.

Standard nicotinamide is eliminated in .6 of an hour at 2.5 mg/ kg, longer as the dose increases. One side effect of high doses of nicotinamide is methyl group depletion.
http://diabetes.diab.../2/152.full.pdf
What the company didn't say about their in house testers,, was how effective the low 250 mg dose was at raising NAD vs 500 mg. it will be interesting to see if they publish the " ongoing clinical study ".
I believe that Metformin up regulates P53 as it's anti cancer MOA . Unfortunately it also suppresses NAD somewhat, as do NSAIDs like aspirin if I remember correctly.

[tunt01]

I believe that Metformin up regulates P53 as it's anti cancer MOA . Unfortunately it also suppresses NAD somewhat, as do NSAIDs like aspirin if I remember correctly.

Thanks for the feedback.

My concern is that there is a circadian rhythm component to upregulate SIRT1/down regulate P53 and vice versa. One would probably want to mimic this natural behavior as closely as possible, even if it is exaggerated in the NAD+/NADH portion of the cycle via NR. I think one would want P53 to periodically clear pre-cancerous cells.

[joeyo]

Edit : Never mind, 6 bottles is too much for me since Dutch customs will let me pay a lot of money for importing it (above 150$). If somebody want to share a batch i'm in though....

Still up for this? Three bottles would be ideal for myself, if you wanna split fifty-fifty.

Regardless, I'm committed up to one batch of six bottles; Thanks!

Edited by joeyo, 27 March 2014 - 09:22 PM.

[abcmanomandriepunt1]

Yes i'm still up for it! So one batch for me and joeyo, we'll pm about the transaction and stuff alright?

[APBT]

I have some concerns over safety of LT use of this product. If anyone can answer these questions, I would be appreciative:

1. Half life of NR. How long does this stay in the system? I think it's best used in pulsatile fashion.
2. Downregulation of P53. If the NAD+/NADH ratio is adjusted substantially, SIRT1 upregulated, then P53 becomes downregulated. How do we mitigate the cancer risks associated with this outcome of opposing P53? EOD usage? Alternative solutions to upregulating P53? The dosage scheme that this company has come up with does not seem to be rooted in any scientific thought (at least for LT use).

The product is amazing, but maybe too good for a reason.

This is a reply I received from the manufacturer of NR, ChromaDex www.chromadex.com

Thank you for your email. The half-life of Nicotinamide Riboside Chloride is 4 hours.
Kind regards,
Collene Villalobos
Sales Manager - Ingredients

http://pubchem.ncbi....ary.cgi?cid=936
In human volunteers (n=6) given a single dose of nicotinamide (3-9 g) as a tablet or in a liquid form plasma peak concentration (Cmax) was between 0.3 and 1.7 umol/mL and was reached after 0.5-3.0 hours (Tmax). Similar values were found in patients who received 80mg/kg bw nicotinamide during radiotherapy for 12 consecutive days (Tmax = 0.8-4 hr; Cmax = 0.5-1.4 umol/mL; T1/2 = 7.1 hr). In patients, that received nicotinamide daily (oral administration of 80 mg/kg bw/day during 5-7 weeks) a Cmax of > 0.7 umol/mL was found. Maximum plasma concentrations were reached within 0.25-3 hours after administration

The consensus of the role of sirtuins seems to be in flux:

The Dual Role of Sirtuins in Cancer
http://gan.sagepub.c...nt/2/6/648.full
SIRT1, Is It a Tumor Promoter or Tumor Suppressor?
http://www.ijbs.com/v05p0147.htm
The ups and downs of SIRT1
http://chmwww.rutger...~kyc/pdf/12.pdf

Possible P53 upregulators:
Vitamin D Analogues Increase p53, p21, and Apoptosis in a Xenograft Model of Human Retinoblastoma
http://www.iovs.org/...44/10/4192.full
Expression of the p53 Tumor Suppressor Gene Is Up-Regulated by Depletion of Intracellular Zinc in HepG2 Cells
http://jn.nutrition....130/7/1688.long

Edited by APBT, 27 March 2014 - 11:29 PM.

[PWAIN]

So far we have:

PWAIN x 2 batches
nbourbaki x 2 batches
BobSeitz
Kevnzworld x 2 batches
tintinet
prophets
APBT
Hebbeh x 2 batches
Iporuru
Adaptogen
stephen_b
zen
Ehvam
(split) tylerdurden/Joeyo
aarfai

[tunt01]

This is a reply I received from the manufacturer of NR, ChromaDex www.chromadex.com

Thank you for your email. The half-life of Nicotinamide Riboside Chloride is 4 hours.
Kind regards,
Collene Villalobos

Thx for getting this datapoint. I had previously skimmed some of the papers you mentioned about SIRT1. With such a short half-life, maybe its less risky. Without mice/rat longevity studies and a better understanding of the implications for p53/SIRT1 (something I need to spend time on), I'm still somewhat concerned.

Edited by prophets, 28 March 2014 - 12:51 AM.

[Kevnzworld]

This is a reply I received from the manufacturer of NR, ChromaDex www.chromadex.com

Thank you for your email. The half-life of Nicotinamide Riboside Chloride is 4 hours.
Kind regards,
Collene Villalobos

Thx for getting this datapoint. I had previously skimmed some of the papers you mentioned about SIRT1. With such a short half-life, maybe its less risky. Without mice/rat longevity studies and a better understanding of the implications for p53/SIRT1 (something I need to spend time on), I'm still somewhat concerned.

I would like to see the documentation of that. You would need a dose north of 1500 mg to achieve a 4 hour half life with regular nicotinamide.

[niner]

I would like to see the documentation of that. You would need a dose north of 1500 mg to achieve a 4 hour half life with regular nicotinamide.

Documentation (is it published?) would be good, but they are pretty different molecules- certainly different enough to have significantly different pharmacokinetics.

[mpe]

I'll have 2 batches

Thanks
Mike

[PWAIN]

So far we have:

PWAIN x 2 batches
nbourbaki x 2 batches
BobSeitz
Kevnzworld x 2 batches
tintinet
prophets
APBT
Hebbeh x 2 batches
Iporuru
Adaptogen
stephen_b
zen
Ehvam
(split) tylerdurden/Joeyo
aarfai
mpe x 2 batches

(I'm so frickin lazy, I copied and pasted your name lol)

[APBT]

PWAIN
Is HPN allotting a specific number of bottles of NR based on the commitments in this thread? Or, could one purchase more bottles? That is, I'm committed to six bottles but, if I decide at the time of purchase to buy 12 or 18 bottles can I do that?

[kenj]

I'm interesting in one batch, too. (I'll probably have to pay mad customs duty/tax for importing, but it seems to be a good deal with the only other option in europe being the super-smart shop at ~$81 per bottle)
Thanks PWAIN.

[Gerald W. Gaston]

I'm in for 6 bottles. Was hoping one of our resident suppliers or the big group buy would happen but doesn't look like either will before I run out of Niagen.

[aribadabar]

I am in for 6 bottles as well.

Thanks for arranging this group deal, PWAIN!

[tunt01]

I'm going to hold off participating in the group buy until I have a better understanding of some aspects of NMR. The methylation issues, circadian rhythm aspect, and other parts leave me wanting to understand more. Please remove my name. Thanks.

[koala_muncher]

I'm in for 6 bottles, kind thanks for organising this, SImon

[MarcD]

I'm in for 6 bottles...
shipping to Switzerland

[PWAIN]

So far we have:

PWAIN x 2 batches
nbourbaki x 2 batches
BobSeitz
Kevnzworld x 2 batches
tintinet
APBT
Hebbeh x 2 batches
Iporuru
Adaptogen
stephen_b
zen
Ehvam
(split) tylerdurden/Joeyo
aarfai
mpe x 2 batches
kenj
gwgaston
aribadabar
koala_muncher
MarcD

So that is 25 batches. APBT, I think you should be able to order 12 or 18 etc, I don't believe he will be limiting the amount that can be purchased.
I will be sending out a pm to everyone listed this Wednesday (Australia time) with the code to be used. I understand that it will only become active on the Friday US time but I want to make sure that everyone has received it in plenty of time.

[mikey]

So far we have:

PWAIN x 2 batches
nbourbaki x 2 batches
BobSeitz
Kevnzworld x 2 batches
tintinet
APBT
Hebbeh x 2 batches
Iporuru
Adaptogen
stephen_b
zen
Ehvam
(split) tylerdurden/Joeyo
aarfai
mpe x 2 batches
kenj
gwgaston
aribadabar
koala_muncher
MarcD

So that is 25 batches. APBT, I think you should be able to order 12 or 18 etc, I don't believe he will be limiting the amount that can be purchased.
I will be sending out a pm to everyone listed this Wednesday (Australia time) with the code to be used. I understand that it will only become active on the Friday US time but I want to make sure that everyone has received it in plenty of time.

I'll take 12 bottles, thank you!

Edited by mikey, 30 March 2014 - 11:06 PM.

[PWAIN]

So far we have:

PWAIN x 2 batches
nbourbaki x 2 batches
BobSeitz
Kevnzworld x 2 batches
tintinet
APBT
Hebbeh x 2 batches
Iporuru
Adaptogen
stephen_b
zen
Ehvam
(split) tylerdurden/Joeyo
aarfai
mpe x 2 batches
kenj
gwgaston
aribadabar
koala_muncher
MarcD
mikey x 2 batches

[mikey]

When is the group buy going to happen? I ordered a bottle from Swanson to try, which should be here in a couple days.

If it does nothing for me I wouldn't want to buy more. I'm expecting it to do something and that's what I would want a year's supply.

Sorry to be wishy-washy.

[aribadabar]

I ordered a bottle from Swanson to try, which should be here in a couple days.

If it does nothing for me I wouldn't want to buy more. I'm expecting it to do something and that's what I would want a year's supply.

Sorry to be wishy-washy.

I am in the exact same situation as mikey. I really hope it will work for me.

Would it be possible to push the purchasing window to next week so we can test it out with our Swanson order?

[abcmanomandriepunt1]

I'm calling my part of the split batch off, joeyo you're ok to take one whole batch? Sorry if i caused some inconvenience.

[BobSeitz]

Mikey and Aribadabar, if the benefits of MNM took a week to appear in mice at the full dose they were given, wouldn't it take at least three months for equivalent effects to show up in humans at a human-equivalent dose of 3-4 grams a day?

I've been taking 250 mg.(2 capsules) of Niagen twice a day for about six weeks now. With each dose, I take 200 mg. of SAMe, 250 mg. of TMG (trimethylglycine) (for methylation), and an LEF Asian Energy Boost (333 mg. of Cordyceps mushroom extract and 55 mg. of fermented Asian ginseng extract) along with one Longevinex resveratrol capsule in the morning and one LEF Calorie Restriction Mimetic capsule in the afternoon. In the morning, I add a 200 mg. capsule of S-Acetyl Glutathione, a 40 mg. MitoQ capsule, and a "Homocysteine Resist" capsule to the list. This morning, I visited our "Wellness Center" gym and began testing my physical limitations. (At 85-in-July, I'd be expected to have a few.) To my amazement, I was able to hoist my own weight with my biceps. I didn't actually chin myself... I'll try that tomorrow... but I was able to lift my own weight in the same way. Given that "Both aerobic power and muscle strength decline by as much as 10% for every decade of adult life, but a progressive exercise prescription can enhance function by 10% to 20%; thus, in terms of functional capacity, conditioning can reduce biological age.", it doesn't sound as though I'm supposed to be able to do that at my age. Do you think that the Niagen I'm taking might be affecting my presumed sarcopenia? (I have to confess that I don't feel any lighter on my feet than I did two months ago.)

[PWAIN]

I have had a private message from someone who is taking 4 grams a day and has had incredible results. They don't want to come forward at this time but I think that this stuff certainly looks like it works exceptionally well at high dose but we won't know individually until we have trialed it (maybe at a higher dose for some of us) for a few weeks at least.

I'm not sure if we will be able to organise something like this again so it will be about waiting for the bulk powder group buy after that. I am kinda wary about pushing too hard (I am not making any money out of this btw just in case anyone is wondering) esp since we already have enough participants but it would be a shame to miss out.

As for safety, I have private correspondance indicating that 12mg per 8oz glass of milk is correct so many people will have consumed quite a bit in the past.

Anyway mikey and aribadabar please confirm either here or privately that you wish to be taken off the list and I will update it.

[APBT]

I have had a private message from someone who is taking 4 grams a day and has had incredible results. They don't want to come forward at this time but I think that this stuff certainly looks like it works exceptionally well at high dose but we won't know individually until we have trialed it (maybe at a higher dose for some of us) for a few weeks at least.

I'm not sure if we will be able to organise something like this again so it will be about waiting for the bulk powder group buy after that. I am kinda wary about pushing too hard (I am not making any money out of this btw just in case anyone is wondering) esp since we already have enough participants but it would be a shame to miss out.

PWAIN
I respect the privacy of the individual using 4 grams daily. If possible, could you inquire as to:
Are they using the Niagen product?
How long have they been using NR?
Did they make any other changes to their supplement regimen or diet at the time of NR commencement?
How are they dosing? Once or multiple times daily? With or with out food? Sublingual?
What is their body weight?
What is their exercise history? Experienced athlete with years of training? Neophyte?
Any specifics on their, "incredible results?"

Regarding a future group Niagen buy, I'd think, if all goes well, HPN would be elated to unload 100+ bottles at a time - even at a 30% discount. They do offer team discounts, which I'd guess are similar to our group pricing.

[PWAIN]

They have indicated that they may write up something over the weekend so hopefully some of your questions may get answered.

I can say that they have been using Niagen, for 4 weeks at >2 grams for 2 weeks and at 4 grams for 2 weeks.

[mikey]

I have had a private message from someone who is taking 4 grams a day and has had incredible results. They don't want to come forward at this time but I think that this stuff certainly looks like it works exceptionally well at high dose but we won't know individually until we have trialed it (maybe at a higher dose for some of us) for a few weeks at least.

I'm not sure if we will be able to organise something like this again so it will be about waiting for the bulk powder group buy after that. I am kinda wary about pushing too hard (I am not making any money out of this btw just in case anyone is wondering) esp since we already have enough participants but it would be a shame to miss out.

As for safety, I have private correspondance indicating that 12mg per 8oz glass of milk is correct so many people will have consumed quite a bit in the past.

Anyway mikey and aribadabar please confirm either here or privately that you wish to be taken off the list and I will update it.

I am definitely interested in experimenting with it at 250 mg/day or higher doses, so I do want to be included.
The question for me is whether there will be another group buy within six months, as I would buy six bottles knowing that another group buy within six months would allow me to buy another six bottles or bulk material if it works optimally for me as it has for some. The idea of buying 12 bottles is founded on an assumption that it will work for me and that I will want to have plenty to last long.

So, since we are on the fine line of having to order now, where I can't be certain of how it will work, but the order I placed for a single bottle with Swanson will arrive probably on Wednesday, please include me for 6 bottles, rather than 12.
This is probably the most prudent course.
I commit to buying 6 bottles, no matter what.
Thank you for the work you do.

[Cabbage]

I'd like to be in for 6 as well, please.