71 replies to this topic

[Phoebus]

Dr. Conlon is the CEO of Nuchido, a new company that is set to launch soon. 

 

she claims NAD+ precursors long term is pointless as the body adjusts after some time and the precursors eventually have no effect. 

 

They have a cocktail called NCD201 which they claim solves this problem and continues to work to raise NAD levels long term. Results of testing will theoretically be released later this year. 

 

i know nothing about this other than whats presented here, but thought it was interesting 

 

 

https://www.leafscie...nichola-conlon/

 

However, Nuchido does not believe that NAD+ precursor supplementation alone will deliver robust long-term benefits in humans. One reason for this is because NAD+ precursors are costly when the dosage is scaled up from mouse to human body weights. Another reason is that while increasing the input to a biological system may result in increased output in the short term, it is likely to lead to a decline of efficacy in the long term as the system readjusts to the new input level.

 

To address this, the company is using systems pharmacology to design therapeutic “cocktails” that contain multiple therapies to be delivered at once. This cocktail contains NAD+ precursors along with other compounds that act on the enzymes that produce and destroy NAD+; the ultimate aim is to increase the NAD+ in the system while also increasing and maintaining the activity of the machinery that produces NAD+.

The company created its first therapeutic cocktail called NCD201, which was designed for oral consumption. Working with a university laboratory, they tested its effect on a single 57-year-old male as an initial proof of concept for the approach.

 

[Boopy!]

gotta kind of agree with her.   It's rare that the body does not adjust for almost any medicine,   bc homeostasis I think it's called?   Goldilocks effect.   Anyhow....as someone who has gotten ZERO -- that's right ZERO effects as of now from various kinds of NMN,   NR,   etc.....in various forms  (except IV)   I have to say it merely confirms what I've experienced.    Too many scientists in the past have marketed overhyped products  (antidepressants,   supplementing all kinds of vitamins,   heroin,   etc)   for me to believe they don't care about the profit.   I was only encouraged that so many intelligent people on HERE seemed willing to believe.   It's disappointing.

[stulancs]

She also says in her Undoing Aging talk that the 57 year old who the cocktail was tested on showed the NAD levels of a 19 year old after two weeks (they didn't test it for longer).

 

This is the talk (camera doesn't show the slides with the results though, unfortunately).

 

Edited by stulancs, 04 August 2018 - 08:40 PM.

[LawrenceW]

She also says in her Undoing Aging talk that the 57 year old who the cocktail was tested on showed the NAD levels of a 19 year old after two weeks (they didn't test it for longer).

 

This is the talk (camera doesn't show the slides with the results though, unfortunately).

 

 

 

Anybody can get the NAD levels of a 19 year old after 2 weeks.  The big problem is maintaining those levels at 2 months.

[zorba990]

Sounds familiar....

[XenMan]

"...it is likely to lead to a decline of efficacy in the long term as the system readjusts to the new input level."

 

This statement is contrary to animal studies for NAD+ and pretty well all pharmacological interventions.

 

[Boopy!]

what you say is strange to me because I had always believed that the reason doses are titrated UP is because the body adjusts to the minimum and so more must be given.   For example,  antidepressants are started at the minimal dosage.   The bod  gets used to that dosage,   and then they titrate UP.     For any outside intervention the body has an equal reaction,   and adjusts.   Sometimes after a few months the outside things given -- be it pharma intervention or whatever --  completely stops working or works LESS well.    Same goes for things like aspirin.   Take aspirin every day for headaches as I always had to,   and you might eventually need MORE over time and then when you don't take it,  you get the rebound headache from hell.    This is just something I came to believe in general over time (for OUTSIDE interventions but not internal changes we make on our own.)  But you are saying that for NR and some pharmacological interventions the dose doesn't need to be readjusted or that the body doesn't have different reactions?   I want to know which pharm.  interventions this is NOT true for,   because it makes a difference.

[Kevnzworld]

Her theory is just and only that..she’s developed a cocktail to address a problem that has never been demonstrated to actually exist in a published study.
Oh, and of course she’s got a product to correct said theorized problem.

[LawrenceW]

Her theory is just and only that..she’s developed a cocktail to address a problem that has never been demonstrated to actually exist in a published study.
Oh, and of course she’s got a product to correct said theorized problem.

 

 

On the contrary, the problem of homeostatic biological feedback does exist and was documented in this study:

 

https://www.nature.c...-017-0016-9.pdf

 

This study showed that 500mg per day of NR increased NAD+ by 90% at day 30 but had dropped off to about 55% by day 60.  250mg per day of NR showed an increase of what appears to be 42% at day 30 and slightly dropped to 40% by day 60. I am very curious as to whether these drops stabilized at these levels at days 90 and 120 or if the higher dose also dropped to 40%.

[John250]

On the contrary, the problem of homeostatic biological feedback does exist and was documented in this study:

https://www.nature.c...-017-0016-9.pdf

This study showed that 500mg per day of NR increased NAD+ by 90% at day 30 but had dropped off to about 55% by day 60. 250mg per day of NR showed an increase of what appears to be 42% at day 30 and slightly dropped to 40% by day 60. I am very curious as to whether these drops stabilized at these levels at days 90 and 120 or if the higher dose also dropped to 40%.

Maybe it’s best to cycle 30 days on/30 days off

[XenMan]

After the number of negs I received above I will add some comments.

 

Firstly it is good that you do not believe anyone, including me, and do your own research.

 

But I will add that it is kind of sad that many of the posters above have cherry picked partial sentences to what is in effect ‘confirmation bias’ to support an ignorant view. The area of health, and in particular life extension, is an incredibly dynamic area that unless you are objective and without bias, you will not get the best outcomes. I have changed my views and protocols over the last 30 years based on the latest research available at the time.

 

Unless you are over 50, NAD+ supplements are a waste of time. Even then, depending on your make up, results will vary. Supplements that don’t have a noticeable impact, which usually involves high doses making you feel ‘uncomfortable’ in some way, must have some serious science behind them to justify their use. NAD+ promoting supplements certainly qualify, but there is still a chance that in a few years something detrimental is discovered and we abandon them; similar to anti-oxidants which is where I started over 30 years ago.

 

Anyway, NAD+ alone is old news, as adding hydrogen sulfide is even more effective; but that is for another day...

 

References:

Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults:

 

 “Our results demonstrate that 6 weeks of NR supplementation at this dose is well-tolerated in humans and effectively increases blood cellular NAD+ concentrations”

 

Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study (link above):

 

“Our trial monitored NAD+ levels in whole blood at day 0 (baseline), day 30, and day 60. There was a robust 40% (NRPT 1X) and 90% (NRPT 2X) increase in NAD+ at day 30 over baseline, and this was fully sustained at day 60 in the NRPT 1X group and partially declined to 55% over baseline in the NRPT 2X group.”

 

“A tangible strength of this study is in the demonstration that NAD+ levels in whole blood can be significantly increased in humans in a safe and sustainable way by oral supplementation”

 

Edited by XenMan, 06 August 2018 - 08:21 AM.

[stefan_001]

@Xenman I started at age 45 and for sure it has had a very positive impact. There may be some homeostatic push back, but it seems that like with everything also that has a ceiling. I am on it 3,5 years and doing great. My litmus test is hair regrowth. Ever since i started using NR it has started to slowly claw back lost ground. As long as my hairline keeps moving down NR works - and its still moving downwards.

[Oakman]

"Dr. Conlon says long term NAD+ precursor supplementation is pointless, claims to have new cocktail that works"

 

"This cocktail contains NAD+ precursors along with other compounds that act on the enzymes that produce and destroy NAD+"

 

Sounds good, if fact, most likely many here try to take a similar cocktail approach to increasing NAD+. I certainly do. Only companies owning the patents on one molecule or another need limit their marketing and research to 'their' proprietary compound  But how does a "proof of concept" on a single "57-year-old male" for only two weeks prove anything about the long term staying power of their NAD+ cocktail they are touting? Hopefully their future testing is really long term, which unfortunately puts their results even further out. 

 

One would think if this 'cocktail' is so potent, as they explain, they would patent and sell it straight away, as it would be more potent than NR, NMN, etc., already on the market? Since they complain about the price of current NAD+ boosters, it sounds like they would sell it for less than NMN or NR to! So Win and win again for all of us!

 

That is, unless NCD201 is simply a mix of already available compounds that anyone could purchase and take/combine themselves. Their secrecy on NCD201 components leads in that direction. Still, I wish for NCD201 success. 

 

 

 

Edited by Oakman, 06 August 2018 - 09:45 PM.

[XenMan]

We will have to agree to disagree on this subject, especially on the differences of suppression, homeostasis and circulating levels of supplements.

[curious_sle]

The supplement should be out in a few months now. Will be about 55$ and 3 pills twice a day which is quite a mouth full. 

[Phoebus]

The supplement should be out in a few months now. Will be about 55$ and 3 pills twice a day which is quite a mouth full. 

 

Oh hey thanks for reminding. Supposed to launch in May. I signed up for an email alert. Should be interesting. 

 

The amount of info on their webpage is still shockingly sparse. Still no freaking clue what the heck NCD201 is or what it entails. No published research at all, google returns for NCD201 are about 3 pages. NOt really sure I want to be a guineau pig 

Edited by Phoebus, 31 March 2019 - 02:19 PM.

[bluemoon]

The supplement should be out in a few months now. Will be about 55$ and 3 pills twice a day which is quite a mouth full. 

 

Does it contain NR or NMN? 

[Phoebus]

Does it contain NR or NMN? 

 

 

No one knows. Its a complete mystery what the hell is in it. 

[male_1978]

If anyone thinks that long term NAD+ supplementation is pointless, then i would like to hear how people think about it, who have been taking it for a longer period of time.

 

My experience (after 1 year) is still positive, but maybe that wasn't long enough. 

[Rays]

Does it contain NR or NMN? 

 

"Nuchido did not use NR to achieve these results."

 

https://nuchido.com/pages/science

[Oakman]

No one knows. Its a complete mystery what the hell is in it. 

 

Until May, we could have some fun guessing what compounds it might contain. I'll start and go with:

 

1) NR and / or NMN molecules

2) some sulphur based compound(s) (e.g. allicin, NAC, taurine, etc.)

3) CD38 inhibitor(s) (e.g., quercetin, apigenin, etc.)

3) some choline enhancement compound(s)

 

I've always been in favor of an approach using the synergy of multiple compounds, so I think they are thinking along the right lines to get results.

[quizzigal]

Long term NAD precursor supplementation may or may not be pointless, but we have no evidence (yet) that long term use of this new compound does a better job.

 

I view any of these supplements as temporary measures.  With luck they'll keep me healthy enough long enough to get to the next breakthrough.

Edited by quizzigal, 01 April 2019 - 04:06 PM.

[Forever21]

If one or two or few can find such "breakthrough", why can't a large group of experts come up with a substance that can actually work? An anti-aging that can make us 20 years younger?

[curious_sle]

No precursors i.e. no NMN or NR but i think she said Nicotinamide? But still very strong sirt1 expression... Should have written it down then...

[curious_sle]

The supplement should be out in a few months now. Will be about 55$ and 3 pills twice a day which is quite a mouth full. 

 

It is a quote from the marketing guy present at undoing aging in Berlin.

Edited by curious_sle, 01 April 2019 - 08:09 PM.

[Rays]

No precursors i.e. no NMN or NR but i think she said Nicotinamide? But still very strong sirt1 expression... Should have written it down then...

 

I think in the video she said they did use a precursor in the cocktail.

[Fredrik]

Here is a poster/whitepaper on the cocktail Nuchido claims work better than NR/NMN. 

 

The presentation says it contains an inexpensive NAD-precursor in combination with molecules that inhibit NAD-catabolism, upregulates anabolism and favors "NAD salvage pathway recycling".

 

So, if it is the salvage pathway it must be nicotinamide then in combination with botanicals that is said to inhibit or express genes that regulate NAD-metabolism (conversion, breakdown, synthesis).

 

But in the interview, Nichola Conlon said: "This cocktail contains NAD+ precursors along with other compounds that act on the enzymes that produce and destroy NAD+".

 

Precursors in the plural. So niacinamide, nicotinic acid and perhaps even l-tryptophan for de novo synthesis in the liver. All inexpensive substrates and precursors for mammalian NAD-synthesis.

 

Added to that perhaps resveratrol, fisetin, EGCG, apigenin, luteolin, vitamin B6/P-5-P, a methyl donor like TMG (betaine) and taurine? Just riffing here.

 

 

 

https://cdn.shopify....orrect_size.pdf

 

https://nuchido.com/pages/our-product

 

 

 

Edited by Fredrik, 03 April 2019 - 08:20 PM.

[Phoebus]

ok, so they must have CD38 inhibitors in there then 

[tunt01]

ok, so they must have CD38 inhibitors in there then 

 

This is exactly what I thought.  My guess is that she gave this very elaborate presentation about protein networks and in reality it's just an NAD supplement with an indirect NAMPT activator (bitter melon/AMPK activation, etc.), a PARP inhibitor and a CD38 inhibitor and then woot-bang, we got higher NAD+ levels.

Edited by tunt01, 04 April 2019 - 12:29 AM.

[Fredrik]

This is exactly what I thought.  My guess is that she gave this very elaborate presentation about protein networks and in reality it's just an NAD supplement with an indirect NAMPT activator (bitter melon/AMPK activation, etc.), a PARP inhibitor and a CD38 inhibitor and then woot-bang, we got higher NAD+ levels.

 

I wonder how many of us already take unstudied (and perhaps effective?) combinations of AMPK activators and enzymatic inhibitors along the NAD-synthesis pathway.

 

I take 2x125 mg nicotinic acid, 25 mg niacinamide from a multi, 500 mg l-tryptohan and 2x750 mg of the AMPK and sirtuin 1 activator metformin daily along with drinking green tea 3-6 cups, 3 g taurine, 2x200 mg magnesium, and 500 mg TMG. I would like to take 500 mg resveratrol but the Biotivia is too expensive where I live and frankly, I am skeptic of the bioavailability of unstudied brands.

 

Edited by Fredrik, 04 April 2019 - 08:42 AM.