115 replies to this topic

[Bryan_S]

Which is why NA has been documented as an effective NAD+ precursor for ages. You must really dislike that flush? Let's keep this on topic guys!

 

 

No my wife will not take 500mg of niacin or any dosage in-between and she's not alone, I have no such aversion and back in my 20s I enjoyed the flush. Now I take a deliberate approach and use inversion as a vasotonic to reach all the tissues spaces of my body and increase Vaso-Muscular tone.

 

I've seen that paper and Dr. Charles Brenner was involved and is currently the researcher involved in the new PK study just commencing. Let me tell you guys I don't mess around and have forwarded our questions directly to the source asking for the "long" explanation. Who knows we may influence the questions in this new study. They may or may not answer us, in fact I've already received a statement that falls short of directly answering our questions but I'm told a definitive answer will be forthcoming within the next 12 months. And I know this isn't helpful for those on the fence.

 

So what can I tell you, if you ask an (NR) researcher "today" the best approach to raising NAD levels, they are going to say; "Nicotinamide Riboside!"

 

Are there alternative paths, yes. Which NAD precursor will give you the highest possible NAD levels within the cytoplasm of the cell. This is the true question. Researchers have already established NAD levels did not raise equally in all tissue samples across the different NAD precursors. So far I'm hitting a unified front indicating (NR) is the precursor of choice for all tissues.

 

Oh . . . I did get an unquotable response to the "Is (NR) broken down into nicotinamide (NAM) before it's absorbed? 

And I've been told;

"NR does not digest or metabolize into NAM"

& "NR is superior in every way."

 

So from a group of researchers who all have some skin in the game "Nicotinamide Riboside" is heralded as the NAD solution.

 

And I will quote someone when they agree to go on the record. Until then I will respect privacy until that person is willing to have their name mentioned.

[Phoenicis]

Yeah ask the NR researcher... Was that researcher being funded by a company with a financial stake in NR? No conflicts of interests to worry about? Why don't you ask the researcher what Human Nrk and Pnp do with NR. http://www.jbc.org/c...8.full.pdf html

 

Better yet have actual references ready. 

 

Most people don't doubt the viability of NR. But wasn't the pricing increased after the 2013 Aging study?  We are trying to correct what boils down to a vitamin b3 deficiency, and NR has been identified as vitamin by researchers before the hype. Didn't the company that makes NR recently purchase process patents for producing this vitamin from a university? What are the prospects for competition then?

 

Nam, the most common form of b3 stops working due to decreasing NAMPT, inhibits SIRT1 and the RDA for B vitamins may need to be updated; so we need a replacement. NR and NA can fulfil that need, but one is priced through the roof. People keep saying the price will come down, but personally I believe this will only happen when the NR producers realize that NA is competition. I will watch these studies closely to see if they are ignoring NA or are making it look bad by for example failing to distinguish between immediate release (good safety profile) and sustained release (fail).

 

I've seen people recommend doses of NR of as much as 1.5g, wouldn't that come close to $9.50/day with current pricing of NR? $3,384 / year? For Niacin the daily price (using 100 x 250mg 5$ bottle) for 1.5g would be $0.30, or $108.00 / year.

Edited by Phoenicis, 23 July 2014 - 12:43 AM.

[Kevnzworld]

Most people don't doubt the viability of NR. But wasn't the pricing increased after the 2013 Aging study? We are trying to correct what boils down to a vitamin b3 deficiency, and NR has been identified as vitamin by researchers before the hype. ...

Nam, the most common form of b3 stops working due to decreasing NAMPT, inhibits SIRT1 and the RDA may need to be updated; so we need a replacement. NR and NA can fulfil that need, but one is priced through the roof.

Both seem effective, but evidently in different physiologic areas. I for one, and I think most people would agree, find that 500-750 mg of NA intolerable.
I'm taking both, to cover the bases..but only 100 mg of NA

Edited by Michael, 14 May 2017 - 03:47 PM.
trim quotes

[Bryan_S]

Here is the latest news, the human clinical study that has just begun will be evaluating three different NR doses, at 100mg, 300mg and 1g per day.

 

ChromaDex has offered to answer our questions and would like to organize our inquiries into a FAQ for all to read. So what I'd like to do is document exactly what we want to know and have them offer answers with side bar research references? So lets kick this around and see what we come up with over the next 7 days and Ill prioritize and submit the best questions we can find.

 

Let's also keep in mind the current PK study is designed to answer many questions we currently have about dosage and we will need to wait for the completion of the study to get those answers.

[Kevnzworld]

Here is the latest news, the human clinical study that has just begun will be evaluating three different NR doses, at 100mg, 300mg and 1g per day.

ChromaDex has offered to answer our questions and would like to organize our inquiries into a FAQ for all to read. So what I'd like to do is document exactly what we want to know and have them offer answers with side bar research references? So lets kick this around and see what we come up with over the next 7 days and Ill prioritize and submit the best questions we can find.

Let's also keep in mind the current PK study is designed to answer many questions we currently have about dosage and we will need to wait for the completion of the study to get those answers.

The first would be , What is the design of the study and what metrics are they evaluating and measuring?

[Bryan_S]

 

The first would be , What is the design of the study and what metrics are they evaluating and measuring?

 

 

A Study of the Pharmacokinetics of Three Dosages of Niagen in Healthy Subjects (14NBHC)
 
That is easy I already have that information:
 
http://clinicaltrial...riboside&rank=1

 

 

Tracking Information First Received Date  ^ICMJE July 11, 2014 Last Updated Date July 15, 2014 Start Date  ^ICMJE July 2014 Estimated Primary Completion Date August 2014   (final data collection date for primary outcome measure) Current Primary Outcome Measures  ^ICMJE 
 (submitted: July 15, 2014) t1/2 (terminal half-life) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

24 hour dosing period; 3 dosing periods each separated by 7 day washout

Original Primary Outcome Measures  ^ICMJE Same as current Change History Complete list of historical versions of study NCT02191462 on ClinicalTrials.gov Archive Site Current Secondary Outcome Measures  ^ICMJE Not Provided Original Secondary Outcome Measures  ^ICMJE Not Provided Current Other Outcome Measures  ^ICMJE 
 (submitted: July 15, 2014)

• Area under the curve (AUC(0-24h) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  24 hour dosing period; 3 dosing periods each separated by 7 day washout
• AUCI (AUC to infinity) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  24 hour dosing period; 3 dosing periods each separated by 7 day washout
• AUC(0-24h)/AUCI [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  24 hour dosing period; 3 dosing periods each separated by 7 day washout
• Maximum observed concentration (Cmax) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  24 hour dosing period; 3 dosing periods each separated by 7 day washout
• Time of maximum concentration (Tmax), [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  24 hour dosing period; 3 dosing periods each separated by 7 day washout
• λ (terminal disposition rate constant) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  24 hour dosing period; 3 dosing periods each separated by 7 day washout
• AUCReftmax (Area under the curve to tmax) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  24 hour dosing period; 3 dosing periods each separated by 7 day washout
• Blood Safety parameters [ Time Frame: 24 hour dosing period; pre dose and 24 hr post dose ] [ Designated as safety issue: Yes ]
  CBC
• Blood Safety parameters [ Time Frame: 24 hour dosing period; pre dose and 24 hr post dose ] [ Designated as safety issue: Yes ]
  electrolytes
• Blood Safety parameters [ Time Frame: 24 hour dosing period; pre dose and 24 hr post dose ] [ Designated as safety issue: Yes ]
  glucose
• Blood Safety parameters [ Time Frame: 24 hour dosing period; pre dose and 24 hr post dose ] [ Designated as safety issue: Yes ]
  creatinine
• Blood Safety parameters [ Time Frame: 24 hour dosing period; pre dose and 24 hr post dose ] [ Designated as safety issue: Yes ]
  AST
• Blood Safety parameters [ Time Frame: 24 hour dosing period; pre dose and 24 hr post dose ] [ Designated as safety issue: Yes ]
  ALT
• Blood Safety parameters [ Time Frame: 24 hour dosing period; pre dose and 24 hr post dose ] [ Designated as safety issue: Yes ]
  GGT
• Blood Safety parameters [ Time Frame: 24 hour dosing period; pre dose and 24 hr post dose ] [ Designated as safety issue: Yes ]
  uric acid
• Blood Safety parameters [ Time Frame: 24 hour dosing period; pre dose and 24 hr post dose ] [ Designated as safety issue: Yes ]
  bilirubin
• Vital Signs [ Time Frame: 24 hour period: pre-dose, 1h, 4h, 6h, 12h, 24h post-dose ] [ Designated as safety issue: Yes ]
  Heart Rate
• Vital Signs [ Time Frame: 24 hour period: pre-dose, 1h, 4h, 6h, 12h, 24h post-dose ] [ Designated as safety issue: Yes ]
  Blood Pressure

Original Other Outcome Measures  ^ICMJE Same as current   Descriptive Information Brief Title  ^ICMJE A Study of the Pharmacokinetics of Three Dosages of Niagen in Healthy Subjects Official Title  ^ICMJE A Randomized, Double-blind, Cross-over Study of the Pharmacokinetics of Three Dosages of Niagen in Healthy Subjects Brief Summary

The purpose of this study in to analyse the way in which the body processes Niagen (nicotinamide riboside) in healthy people. Blood and urine samples from subjects who are given a dose of Niagen will be analyzed for metabolites over the 24 hours after taking the dose.

Detailed Description Not Provided Study Type  ^ICMJE Interventional Study Phase Phase 1 Study Design  ^ICMJE Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Condition  ^ICMJE Pharmacokinetics Intervention  ^ICMJE

• Dietary Supplement: Niagen 100mg
• Dietary Supplement: Niagen 300mg
• Dietary Supplement: Niagen 1000mg

Study Arm (s)

• Experimental: Niagen 100mg
  1 Niagen capsule (1 x 100 mg capsule) and 9 Placebo capsules
  Intervention: Dietary Supplement: Niagen 100mg
• Experimental: Niagen 300mg
  3 Niagen capsules (3 x 100mg capsule) and 7 Placebo capsules
  Intervention: Dietary Supplement: Niagen 300mg
• Experimental: 1000mg Niagen
  10 Niagen capsules (10 x 100mg capsule)
  Intervention: Dietary Supplement: Niagen 1000mg

Publications * Not Provided
*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.   Recruitment Information Recruitment Status  ^ICMJE Recruiting Estimated Enrollment ^ICMJE 12 Estimated Completion Date August 2014 Estimated Primary Completion Date August 2014   (final data collection date for primary outcome measure) Eligibility Criteria  ^ICMJE

Inclusion Criteria:

• Healthy Male or female age 30-55 years
• BMI 18.5-29.9 kg/m2
• If female, subject is not of child bearing potential, OR Females of childbearing potential must agree to use a medically approved method of birth control and have a negative urine pregnancy test result.
• Healthy as determined by laboratory results and medical history
• Agrees to maintain current level of physical activity throughout the study
• Agrees to avoid vitamins and St. John's Wort for 30 days prior to enrollment and during the study
• Agrees to avoid nutritional yeast, whey proteins, energy drinks, dairy products, grapefruit and grapefruit juice and alcohol 7 days prior to enrollment and during study
• Has given voluntary, written, informed consent to participate in the study

Exclusion Criteria:

• Women who are pregnant, breastfeeding, or planning to become pregnant during the course of the trial.
• Use of natural health products (NHPs)/dietary supplements within 7 days prior to randomization and during the course of the study.
• Use of vitamins or St. John's Wort in the last 30 days before the study enrollment,
• Use of natural health products containing Nicotinamide riboside within 7 days prior to randomization and during the course of the study
• Use of nutritional yeast, whey proteins, energy drinks, grapefruit and grapefruit juice, dairy products, alcohol for 7 days prior to the study
• Subjects who are smokers
• Subjects with blood pressure ≥140/90
• Use of blood pressure medications
• Use of cholesterol lowering medications
• Metabolic diseases or chronic diseases
• Use of acute over the counter medication within 72 hours of test product dosing
• Unstable medical conditions as determined by the Qualified Investigator
• Immunocompromised individuals such as subjects that have undergone organ transplantation or subjects diagnosed with human immunodeficiency virus (HIV)
• Clinically significant abnormal lab results at screening (e.g. AST and/or ALT > 2 x ULN, and/or bilirubin > 2 x ULN) will be assessed by the Medical Investigator
• Subjects who have planned surgery during the course of the trial
• History of or current diagnosis of any cancer (except for successfully treated basal cell carcinoma) diagnosed less than 5 years prior to screening. Subjects with cancer in full remission more than 5 years after diagnosis are acceptable
• History of blood/bleeding disorders
• Blood donation in the past 2 months
• Alcohol abuse (>2 standard alcoholic drinks per day) or drug abuse within the past 6 months
• Participation in a clinical research trial within 30 days prior to randomization
• Allergy or sensitivity to study supplement ingredients or to any food or beverage provided during the study
• Individuals who are cognitively impaired and/or who are unable to give informed consent.
• Any other condition which in the Investigator's opinion may adversely affect the subject's ability to complete the study or its measures or which may pose significant risk to the subject

Gender Both Ages 30 Years to 55 Years Accepts Healthy Volunteers Yes Contacts  ^ICMJE Contact: Mal Evans, PhD (519) 438-9374 ext 239 mevans@kgksynergize.com   Location Countries  ^ICMJE Canada   Administrative Information NCT Number  ^ICMJE NCT02191462 Other Study ID Numbers ^ICMJE 14NBHC Has Data Monitoring Committee Not Provided Responsible Party KGK Synergize Inc. Study Sponsor  ^ICMJE KGK Synergize Inc. Collaborators  ^ICMJE Chromadex Inc. Investigators  ^ICMJE Principal Investigator: Dale Wilson, MD KGK Synergize Inc.   Information Provided By KGK Synergize Inc. Verification Date July 2014
^ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

TO TOP

 

 

 

[Kevnzworld]

Good info
I don't see where they are measuring NR's actual effectiveness at raising NAD+ at these doses...
Wouldn't that be what most people that spend the $ for NR want to know?
That doesn't seem to be one of the parameters being measured. Curious why that wouldn't be measured.

[Bryan_S]

"Blood and urine samples from subjects who are given a dose of Niagen will be analyzed for metabolites over the 24 hours after taking the dose."

 

I dont know but I thought they'd take tissue biopsies to gain those results so there could be no question. Maybe there are other resulting markers to substantiate the NAD levels?

Edited by Bryan_S, 01 August 2014 - 07:45 PM.

[follies]

Has anyone measured bioavailability between sublingual and invested Niagen?

[Bryan_S]

Has anyone measured bioavailability between sublingual and invested Niagen?

 

No

 

I've specifically asked ChromaDex this question.

 

"As far as we can tell, manipulation of the bioavailability of NR, in the form of sublingual or some other suitable alternative would not be necessary.  NR is a highly water soluble compound that does not appear to have any adsorption or bioavailability issues."

 

This may well be true and I do not argue this response. I do however feel this precise question has not been explored in terms of which method provides the highest blood serum levels. (the best bang for the buck) Now this is a 2 part question and this brings us back to the question that initiated this thread, "Is nicotinamide riboside (NR) broken down into nicotinamide (NAM) before it's absorbed?"

 

ChromaDex answered:

"NAM is not a cost effective replacement for NR, far from it. All of the data we have right now clearly shows that NR does not digest or metabolize into NAM and we will soon have human clinical data to support that."

 

This answer also raises a question that was asked earlier about measuring NAD levels and how they will determine this. As far as I can tease out from the PK study they will be measuring blood serum levels. "Blood and urine samples from subjects who are given a dose of Niagen will be analyzed for metabolites over the 24 hours after taking the dose."

 

I believe the sublingual path holds promise to increasing bioavailability but no clinical data exists to support this. This PK study would have been an excellent opportunity to compare absorption from different approaches. I will acknowledge when a study is designed clear targets have to be defined and the comparison we seek would require additional funding. I will also add I don't believe it's in anyones interest to design a study to prove a sublingual approach, except maybe the consumer wanting to save money or increase the effects at lower cost.

 

Next is unscientific observation and I'll get to the sublingual approach at the end.

 

I took the recommended dose for a month in the beginning and didn't feel a perceptible difference. My wife and I discussed it and because of the price I decided it was a waste of money. So I went off Niagen for a week and discovered I didn't feel as well. The effect I hadn't noted in the previous month was a subtle gradual increase in focus. I was sleeping sounder and upon waking I was more alert and wasn't feeling my typical morning fog. (This was my old normal from years past.) It took going off Niagen to realize it had improved my general well-being and I put my second bottle on order. Then during my second bottle I started looking for methods to enhance these subtle effects and this brings us back to the sublingual approach which I'd read about here on Longecity. Now for the last 4 months this is how I've taken my Niagen. From a muscular and energy standpoint I feel I'm getting more from the Niagen I take. However only a clinical setting could definitively determine if this approach realy makes a difference.

 

It makes sense that if I don't dilute the Niagen with all the rest of my intestinal contents I should be absorbing more. Is it worth the effort? Right now only you can determine that. ChromaDex will soon complete its Pharmacokinetics study on the oral ingestion of nicotinamide riboside, so we will soon know if taking an alternate approach is worth the effort. What do I mean by that; if Niagen @ 300mg or Niagen @ 1000mg proves to be the target dose I'd say from a cost standpoint a sublingual approach may be worth the effort but if you can afford to ingest more orally this is by far the easiest method.

Edited by Bryan_S, 02 August 2014 - 03:42 PM.

[Bryan_S]

Off topic: High Performance Nutrition (HPN) sent me the specifics of this months 30% discount offering for Niagen | Nicotinamide Riboside. See URL

[Primal]

I hope they will be very careful to measure Nicotinamide Riboside, not Nicotinamide, in the blood/plasma samples to determine AUC, Tmax, Cmax, etc

Edited by Michael, 14 May 2017 - 03:49 PM.
trim quotes

[Primal]

 

The purpose of this study in to analyse the way in which the body processes Niagen (nicotinamide riboside) in healthy people. Blood and urine samples from subjects who are given a dose of Niagen will be analyzed for metabolites over the 24 hours after taking the dose.

 

 

I'm also very interested in this, especially to know if the metabolism/excretion of NR will pull methyl groups (ie be excreted as methylated compounds) similar to how nicotinamide and niacin are excreted. My guess is that NR will be cleaved to nicotinamide and riboside and then nicotinamide will be excreted as usual (putting a strain on methylation, just as niacin does).

 

 

 

Are NR and NMN methyl acceptors, like NA and NAM (1-methylnicotinamide (MNA), 1-methyl-2-pyridone-5-carboxamide (M2PY) and 1-methyl-4-pyridone-5-carboxamide (M4PY))? Ie does their metabolism and excretion use methyl groups?

 

 

[Kevnzworld]

The purpose of this study in to analyse the way in which the body processes Niagen (nicotinamide riboside) in healthy people. Blood and urine samples from subjects who are given a dose of Niagen will be analyzed for metabolites over the 24 hours after taking the dose.

I'm also very interested in this, especially to know if the metabolism/excretion of NR will pull methyl groups (ie be excreted as methylated compounds) similar to how nicotinamide and niacin are excreted. My guess is that NR will be cleaved to nicotinamide and riboside and then nicotinamide will be excreted as usual (putting a strain on methylation, just as niacin does).

Are NR and NMN methyl acceptors, like NA and NAM (1-methylnicotinamide (MNA), 1-methyl-2-pyridone-5-carboxamide (M2PY) and 1-methyl-4-pyridone-5-carboxamide (M4PY))? Ie does their metabolism and excretion use methyl groups?

As I previously posted, my homocysteine actually declined slightly after taking 750mg NR and 100mg NA daily. 7.2 to 6.4 I haven't added any additional methyl donators .
Somebody, I believe it was SmithX wondered about NR supplementation and thyroid health.
My TSH dropped from 2.4 to 1.7

[Bryan_S]

Thanks guys thats a good start, we have their ear, our community at Lonecity is the most active on this front. I'm still hoping for some more questions and with the PK study ending soon I don't want to be premature in our question submission. I expect they'll format our questions in a white paper similar to these once this years University studies have been completed.

https://chromadex.co...nts/NIAGEN.html

 

Guys if you want to look over the current studies and formulate questions based on whats about to be published here are a few of the current research projects awaiting results this year 2014:

If I've missed any current or planned NR projects please add them.

 

Wageningen University

Prof. Jaap Keijer, chair holder of the Human and Animal Physiology Group of Wageningen University, will investigate the health benefits of NR in an experimental model of metabolic disease. Together with Dr. Maria Hegeman and Dr. Dorien van Dartel, he aims to obtain detailed insight in the processes affected by NR which will help to establish optimal dietary NR concentrations to maintain or even improve metabolic health.

http://www.wageninge...ow/Mitofood.htm

http://www.wageninge...up/Research.htm

http://www.wageninge...lthy-ageing.htm

Australian Institute

Dr. David Thorburn, Mitochondrial Research group head at Murdoch Childrens Research Institute, will investigate the health benefits of NR through studies of cellular and animal models of mitochondrial respiratory chain diseases. Together with Dr. Ann Frazier and Dr. Bi-Xia Ke, and supported by a grant from the Australian Mitochondrial Disease Foundation, Dr. Thorburn will study the response to NR in mouse models with mitochondrial Complex I deficiency and in a range of human and mouse cell lines with impaired mitochondrial function.

http://www.mcri.edu....david-thorburn/

Groningen Biomolecular Sciences & Biotechnology Institute (GBB)

Dr. Michael Jaehme, a researcher at the GBB, will investigate the uptake of NR into cells and how it is converted in the biologically active nucleotides NMN and NAD+. In addition to co-crystallization experiments to study the molecular basis of NR protein interactions, he aims to determine binding constants to quantify the efficiency of cellular NR utilization. Examining these interactions at the molecular level can yield valuable insight into how NR exerts its biological effects.

http://www.rug.nl/st....jahme/projects

University of Iowa

The study will engage the laboratory of Dr. Charles Brenner, Roy J. Carver Chair of Biochemistry and Professor of Internal Medicine at University of Iowa. Brenner, is credited with discovery of NR as a vitamin in organisms from yeast to people as published in Cell in 2004.

The human clinical study is designed to determine the pharmacokinetics (PK) and bioavailability of NIAGEN™ as well as provide information about an effective NR dose range in humans. Most importantly, this study aims to confirm earlier animal studies conducted by various universities and research institutes, which showed that oral dosing of the compound results in an increased level of nicotinamide adenine dinucleotide (NAD+) and NAD+ metabolites in the body.

http://clinicaltrial...riboside&rank=1

University of Copenhagen

Dr. Jonas Thue Treebak, Assistant Professor of the Novo Nordisk Foundation Center for Basic Metabolic Research, will investigate the role of NAD+ salvage systems for maintaining mitochondrial function and insulin sensitivity. Specifically, various in vitro and in vivo experimental models with defects in these systems will be treated with NR to determine the ability of this compound to restore a healthy phenotype. This project is made possible in part by a recent prestigious grant obtained by Dr. Treebak from the Novo Nordisk Foundation.

http://metabol.ku.dk/staff_overview/Ansatte/?pure=en%2Fpersons%2Fjonas-thue-treebak(a648ef82-ccb3-4add-83c1-384e0d90952b).html

[meth_use_lah]

Nobody has (subjectively) compared resveratrol + NA/NAM to NR? I would definitely do so before I give some triple price patent jokers my money.

[Bryan_S]

Actually the Robert Kane Pappas videos touches on resveratrol, MIT's Dr Leonard Guarente comments on that. 

[trance]

 

[Logic]

I have a theory:

According to this study NR is not absorbed through the intestines, but "...slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide..."
http://www.researchg...yces_cerevisiae

So barring sublingual absorption it looks like swallowed NR is just expensive, slow release Nicotinamide that does nothing more than bypass the de novo kynurenine pathway.
But what about the slow release Ribose? I think this may be where the secret lies:

What we are interested in is not the standard NAD+ metabolic pathways, but minimising SIRT limiting Nicotinamide by maximising turning it back into NAD+ via the:
Nam salvage pathway enzyme NamPRT
and then using up in producing:
poly-ADP-ribose (PARP),
mono-ADP-ribosyl-protein (MARTs),
cyclic-ADP-ribose (cADPR),
acetyl-ADP-ribose (SIRTs)
etc.
and eventually 5-phosphribosyl-1-pyrophosphate, which is itself used up by the:
Nam salvage pathway enzyme NamPRT.
 
Note that NA is also salvaged by using up 5-phosphribosyl-1-pyrophosphate.

The other word that's everywhere is phosphate...

So possiblibly Ribose is rate limiting and supplementing with Niacin, Ribose may give similar results and that adding a Phosphate may also be benificial?



http://mmbr.asm.org/...t/70/3/789.full

[Bryan_S]

Sorry it took awhile to get back with you. Did you have another study in mind this first link was about species of yeast, nicotinamide and its lifespan extension. NR wasn't mentioned, they did however mention NR in the 2nd link and talked about the salvage pathway but not about digestive absorption. The only study I read that suggested NR was broken down in the intestine was an outdated 1983 study and it also said it might be directly absorbed without cleavage. 

 

 

[Logic]

Sorry it took awhile to get back with you. Did you have another study in mind this first link was about species of yeast, nicotinamide and its lifespan extension. NR wasn't mentioned, they did however mention NR in the 2nd link and talked about the salvage pathway but not about digestive absorption. The only study I read that suggested NR was broken down in the intestine was an outdated 1983 study and it also said it might be directly absorbed without cleavage.

Oops sorry; I have way too many tabs open at once.
here is the correct link:
http://jn.nutrition..../113/2/412.long
It is the study you mention.

My understanding of the study is that prior to the study the possibility existed that NR may be absorbed without further cleavage but that the study proved that NR was "...slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide..." and "...further evidence that cleavage to NAm occurs before absorption is the observation that NR was not found in testinal tissue or the perfusate fractions..."

The study may be old but is the most current study showing what happens to NR in the gut and I don't see any problems with the scientific method. Could you please expound on the issues you have with the study Bryan.

Here is a study "...suggesting that a limiting factor for the rate of resynthesis of ATP is the availability of ribose and thus PRPP..." wich is used up in the NanPRT salvage pathway:
http://ajpregu.physi...tent/286/1/R182

 

Its from 2004, so not quite as old as Newton's laws of gravity! 

[Logic]

PHARMACOKINETICS About 88% to 100% of an oral dose of D-ribose, up to 200 milligrams per kilogram per hour, is absorbed from the small intestine, from whence it is distributed to various tissues of the body, including cardiac muscle and skeletal muscle. Very little first-pass metabolism occurs in the liver. Following transport into cells, D-ribose is phosphorylated to D-ribose-5-phosphate.
http://www.naturalpe...Cardiac-31.html

Check out where D-ribose-5-phosphate is in the above diagram...

[Bryan_S]

 

Sorry it took awhile to get back with you. Did you have another study in mind this first link was about species of yeast, nicotinamide and its lifespan extension. NR wasn't mentioned, they did however mention NR in the 2nd link and talked about the salvage pathway but not about digestive absorption. The only study I read that suggested NR was broken down in the intestine was an outdated 1983 study and it also said it might be directly absorbed without cleavage.

Oops sorry; I have way too many tabs open at once.
here is the correct link:
http://jn.nutrition..../113/2/412.long
It is the study you mention.

My understanding of the study is that prior to the study the possibility existed that NR may be absorbed without further cleavage but that the study proved that NR was "...slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide..." and "...further evidence that cleavage to NAm occurs before absorption is the observation that NR was not found in testinal tissue or the perfusate fractions..."

The study may be old but is the most current study showing what happens to NR in the gut and I don't see any problems with the scientific method. Could you please expound on the issues you have with the study Bryan.

Here is a study "...suggesting that a limiting factor for the rate of resynthesis of ATP is the availability of ribose and thus PRPP..." wich is used up in the NanPRT salvage pathway:
http://ajpregu.physi...tent/286/1/R182

 

Its from 2004, so not quite as old as Newton's laws of gravity! 

 

GROSS AND HENDERSON were ground breakers for sure but my problem is of course the time frame and this study has never been repeated concerning NR. There have been so many other researchers down this path since them and consistently its absorbed.

 

Lets look at Gross and Henderson's process: [14C]NR was prepared by hydrolyzing [14C]NAD to [14C]NMN with intestinal contents, then incubating the [14C]NMN with

snake venom phosphatase according to the methods of Rowen and Kornberg (12). The incubation mixture was treated with two vol

designed to relate better the perfused intes tine results with those of the live animal. Rats were anesthetized with sodium pentabarbital and a midline incision was made. The intes

umes of absolute ethanol and centrifuged to Perfused live

remove protein. The supernatant was taken to dryness in vacuo and resuspended in water. By this method 89% of the radioactivity was in NR, 9% in NAm and 2% in NMN.

 

No, no, no this is 2014 Lets order radioactive nicotinamide riboside with a confirmed purity and repeat the rat experiment.

 

I mean Gross and Henderson no disrespect however in 1983 you had to chemically build a radioactive nicotinamide riboside for tracing its movement. 32-yers later we are going to challenge the results of Charles Brenner 2004 and every one who has followed him based on outdated 1983 data where they conceded; "The possibility exists that NR may be absorbed without further cleavage."

 

If their were anything to the 1983 suggestion that nicotinamide riboside was broken down and destroyed do you think we would have the money spent on the number of NR experiments pending from this list? http://www.longecity...e-2#entry680166

 

Convince the study designers we should run Niacin against all these experiments. 

 

I'm looking for cheaper methods of dosing also but you asked me; "Could you please expound on the issues you have with the study Bryan." The one answer, and I say this with all do respect, is that data is archaic by todays standards.

 

Stick around I'm not trying to change your mind or chase you away. I think we have some of the best questioning minds on this forum and we are all looking for the best science to guide our health.

[Logic]

GROSS AND HENDERSON were ground breakers for sure but my problem is of course the time frame and this study has never been repeated concerning NR. There have been so many other researchers down this path since them and consistently its absorbed....

Lets order radioactive nicotinamide riboside with a confirmed purity and repeat the rat experiment.

I mean Gross and Henderson no disrespect however in 1983 you had to chemically build a radioactive nicotinamide riboside for tracing its movement. 32-yers later we are going to challenge the results of Charles Brenner 2004 and every one who has followed him based on outdated 1983 data where they conceded; "The possibility exists that NR may be absorbed without further cleavage." ...

I'm looking for cheaper methods of dosing also but you asked me; "Could you please expound on the issues you have with the study Bryan." The one answer, and I say this with all do respect, is that data is archaic by todays standards.

My theory is that we want to salvage the SIRT limiting Nam via the NamPRT pathway and that Ribose is required to do that.
I think its possible that NR may be a good way to do this as THE ONLY study we have on what happens to NR in the gut says NR is slowly cleaved into Nam and Ribose before being absorbed into the bloodstream.
There are a number of negative reports from people who have taken large doses of D-ribose, which is why I feel that NR may be the best, but not the only, means of getting a slow, constant supply of Nam and also the Ribose required to turn it back into NAD+ before it can limit SIRT.

The reason for the large number of studies on NR is due the fact that so far it is shown to work and it is highly profitable due to patent protection.
None of these studies look at or care about what happens to NR in the gut; they look at results and what is happening in the cell as a means to explain the results.

It would be nice if someone took a fresh look at what happened to NR in the gut, but I doubt whether the money is going to so if there is a chance that doing so is going to make it clear that their patented and profitable NR producing process can be circumvented with a slow release Nam and Ribose capsule.

I think you are still miss understanding Gross and Henderson's paper:
What they are saying is that before their study it was possible that NR was "absorbed without further cleavage" but that their study proved that NR was "slowly cleaved ... to nicotinamide"

Also the ex vivo study with dead, removed stomach lining where NR was produced from NMN with snake venom phosphatase was done to confirm IN VIVO results showing that intestinal flora were not involved in the breakdown of food sourced NAD to NR and then to Nam. This process occurred in the lining itself.

At the end of the day they proved that NAD from food sources was broken down to NMN then NR then Nam by the intestinal walls before reaching the bloodstream.

A re-quote from their conclusion:
"...cleavage to NAm occurs before absorption ...NR was not found intestinal tissue or the perfusate fractions..."


The tech to prove this was available in 1983 and did so.
Similar studies to confirm this would be most welcome, but superfluous IMHO and I doubt we will see them from the NR money.

My initial reading on the benefits of Ribose supplementation seem to be very similar to those seen from NR and negative effects may be explainable as overdosing of Ribose in the absence of sufficient Nicotinamide?
I will post more on this later.

Edited by Michael, 14 May 2017 - 03:56 PM.
trim quotes

[Bryan_S]

I agree the experiment needs to be repeated. I will say however the ChromaDex influence was only recent, interest in NR was high before the patent grab on making the stuff. I take it under my tongue anyway, only to boost whats absorbed.   

[Logic]

I agree the experiment needs to be repeated. I will say however the ChromaDex influence was only recent, interest in NR was high before the patent grab on making the stuff. I take it under my tongue anyway, only to boost whats absorbed.

Do you notice any difference between sublingual and just swallowing NR?

[Logic]

Now I'm thinking that possibly slow release Ribose without or a low dose of Nicotinamide may increase SIRT potential even more?
Niacin may possibly be better than Nicotinamide?

RiboCeine looks very interesting for possibly boosting NAD+, SIRT etc. as well as Glutathion levels but is also very expensive.
GetMaxed's blog has been read by Vince Guiliano and Dr. James Watson and been declared his "...blogs regarding Redox, Glutathion, and Cysteine were fabulous and should be applauded as outstanding blog journalism..."
http://www.longecity...e-2#entry691562
That's as good as peer reviewed IMHO!

Its interesting that Resveratrol is said to be “...significantly more soluble in the ribose solution than in the other four solutions...” and is coming out as a lozenge.
http://www.longecity...-shows-promise/
Is it really or is it more effective in Ribose? 

Oxaloacetate, aka Benagene is said to increases NAD+
http://www.longecity...benagene/page-2

"...isonicotinamide (isoNAM), which competes for free NAM binding but does not react appreciably with the intermediate, increases Sir2 activity..."
http://www.ncbi.nlm....pubmed/22539348

[Bryan_S]

I dont know how subjective this is but fresh out of bed in the morning I power up the laptop put some under my tongue and open up my morning reading. I feel fully aware just minutes after dosing that way. Where as before it took my mind about a half hour or so to wake up fully, and that was with a cup of coffee and 2 capsules. I'm shooting for the most bang for the buck and cant see diluting it in my stomach contents. There have been no studies to support taking it this way but if you can achieve higher blood serum levels with NR as you can some other small molecules it could boost levels.

 

http://www.ijppsjour...Suppl2/1092.pdf

 

http://en.wikibooks....ines/Sublingual

 

ChromaDex says there is no need to ingest it this way and I don't see that it would be in their interest to find out because those of us who do take it this way are trying to save money instead of buying more product.

[krillin]

RiboCeine looks very interesting for possibly boosting NAD+, SIRT etc. as well as Glutathion levels but is also very expensive.
GetMaxed's blog has been read by Vince Guiliano and Dr. James Watson and been declared his "...blogs regarding Redox, Glutathion, and Cysteine were fabulous and should be applauded as outstanding blog journalism..."
http://www.longecity...e-2#entry691562
That's as good as peer reviewed IMHO!
 

 

Until we have evidence that says otherwise, we should assume that RiboCeine interferes with Nrf2 like NAC does. Glucosamine works via the AMPK/NAD+ pathway and its effects are abolished by NAC.

[Logic]

Whey, L-Serine, and Methylene Blue, oxaloacetic acid:
http://www.longecity...-nadnadh-ratio/
http://www.longecity...-nadnadh-ratio/