I read through all the linked threads above including this article which was posted back in May, while the other threads go as far back as 2010. It's interesting that nothing has come of these antivirals so far as I know. They got little press and even less utilization. I'm assuming they aren't approved or that there's something that went wrong or didn't work in human trials or what happened? I know the media likes to blow things out of proportion all the time. What happens to all these amazing things that get published and then you never hear about again?
He supposedly regrew his thymus using HGH and DHEA? There was a trial for that, not sure what became of it. This was 2013. You'd think we'd have heard something by now.
EDIT: Fixed the link.
Keeping this on topic, I assume that since this is related to NAD+ still in the same way that CD38 is, but if we can boost the immune system and eradicate these otherwise suppressed infections that would be a solution to a big part of the NAD+ problem? So now we have two contributors, one possibly being an effect of the other but it appears that there may be two things affecting the rise in CD38, pathogens, and senescent cells.
Keeping this on topic, I assume that since this is related to NAD+ still in the same way that CD38 is, but if we can boost the immune system and eradicate these otherwise suppressed infections that would be a solution to a big part of the NAD+ problem? So now we have two contributors, one possibly being an effect of the other but it appears that there may be two things affecting the rise in CD38, pathogens, and senescent cells.
Two points here:
1. Optimising Immune System functioning:
I gather that to get your Vitamin D3 levels into the optimum '50' range
it's necessary to take 3000 IU per day (assuming no significant sun exposure)
Regular exercise, ample consumption of coconut oil ... oh.. and a ketogenic diet.
That should be enough to beat off the little parasitic viruses... no ?
Or at least, that would be a good basis for optimising immune system functioning.
Keeping this on topic, I assume that since this is related to NAD+ still in the same way that CD38 is, but if we can boost the immune system and eradicate these otherwise suppressed infections that would be a solution to a big part of the NAD+ problem? So now we have two contributors, one possibly being an effect of the other but it appears that there may be two things affecting the rise in CD38, pathogens, and senescent cells.
Two points here:
1. Optimising Immune System functioning:
I gather that to get your Vitamin D3 levels into the optimum '50' range
it's necessary to take 3000 IU per day (assuming no significant sun exposure)
Regular exercise, ample consumption of coconut oil ... oh.. and a ketogenic diet.
That should be enough to beat off the little parasitic viruses... no ?
Or at least, that would be a good basis for optimising immune system functioning.
We expect that CD38 inhibition will cause increases in NAD+.
Increases in NAD+ is why we're taking NR+... no ?
My question is:
Is there anyone experimenting with taking Apigenin for it's NAD+ effects ?
Specifically, is there anyone on this thread talking Apigenin for NAD boosting ?
1. I take 4000 to 6000 IU of D3 because it helps with ET to some small degree in that dosage for periods of time. I also take K as well, exercise 4x a week (varying to target HR), I currently take at least a tablespoon of coconut derived MCT oil mixed with resveratrol (which is lipid soluble) and pterostilbene. I don't know if coconut oil is the exact same as MCT, I don't think so but they are similar obviously. I don't ever plan on doing a ketogenic diet, there's no joy in that. I eat balanced, a good amount of fiber from apples, beans, rice, almonds, etc, plenty of protein and fats from salmon and fish oil separately.
2. I've been taking apigenin for a few months now. I am still uncertain of the half-life because reports are inconsistent, but it's anywhere from 12 hrs to 91 hrs. I stop for 3 days and take 50mg for 3 days at night. I don't know if that's the way to go or what. If it's 91 hrs I should be taking a week off and a week on. I wish I had a solid answer on that.
To your questions, the problem with raising NAD+ that we're talking about here is the pathogens that consume it. I don't have any idea to what degree they may be consuming the extracellular NAD+ compared to CD38 or when SIRT is activated. This is all just aging theory. I'd love to know more about regenerating the thymus but so far from what I can tell, no positive reports from research indicates they failed with HGH and DHEA.
Cycles of prolonged fasting (>3 days, mostly water only, several times a year) may not only protect against immune system damage but may also induce some immune system regeneration. Fasting -- among many other attributes -- appears to shift stem cells from dormant states to a states of self-renewal. Valter Longo's work is quite compelling.
I recall that study coming out a couple of years ago. I am pretty sure I'm the type who would literally start killing people and eating them if I tried to fast. I get incredibly moody, irritable, snappy and incapable of thinking clearly whenever I am hungry and it would greatly disrupt my sleep. I'd have to take days off work and pretty much not talk to anyone. I doubt that not eating is the answer. I would only do this if it were guaranteed 100% to regenerate the immune system in humans significantly enough to have any of the effects we want. At the end of that article it talks about additional studies to reproduce this phenomenon and also that there's some kind of rebound effect at the end which I didn't quite understand. I've seen no additional studies so the research on this is not very robust yet so far as I know. They also mention that it'd be better to synthesize the effect and eat regularly instead.
Yeah it's a bit over my head and a lot to take in. I feel like I've wasted all my time, energy and money at this point though I've read and commented on some of those threads.
If you are still hoping that NR is a simple answer to aging that enables you to ignore everything else; now is the time to turn to drink!
I don't think it is a simple one answer solution, but I didn't think it could be feeding into aging. Turn to drink?
Glad you haven't drowned your sorrows with a bottle of tequila Nate!?
It takes years of study to get your head around all this in most cases and you end up knowing how little you really know at the end of the day.
There are some exceptions to this rule. I suggest reading threads by SolarFingers and Resveratrol guy amongst others.
Also a search using the GoogleSiteSearch function in the search dropdown menu for CMV, Candida etc and lipid coated viruses will provide plenty a practical advice on keeping these in check.
The more exotic things I mentioned look like they might well be able to eradicate all these pathogens..! I will try and source them as time allows and do group buys on if successful.
Hopefully the buys will receive a warmer reception than the Dasatinib (kills senescent cells as mentioned by Steve H ) group buy.
Of Course raising NAD is a good idea. The only time depleted NAD is good is when your starving the metabolism of cancers while in chemotherapy to get that extra edge. Is there other things at work other than CD38, I believe so, and we know PARP is also another major consumer as are a number of other enzymes. What would be helpful is to show a pie chart showing the consumption of each and graphs showing their consumption over the life of an organism. So I think strategies addressing the major consumers is relevant. I think consumers like our PARP's should be favored because they save off damage from ionizing radiation and oxidative stress, while those producing , processes need remediation.
Don't ever let your NAD get depleted (or exclusively temporarily as in strenuous exercise). Raising it on a permanent basis however is something which may not always and for everybody be the right thing.
The vast impact which (for instance) CMV has on aging just might be augmented by comparatively small amounts of NR. No alarm here from me, just pointing out a possible issue of careful consideration.
This is all pretty alarming to me actually. I would definitely like to see a chart of consumption as well.
I don't know if I'm infected with CMV or not.
Nate, CMV is just one example. I posted about pathogens, because we need to take the concerns about NR tendonitis etc. very seriously and this perhaps might be a clue for those afflicted by it. I, too, would like to have more clarity about who 'eats' what.
Side note: you probably are infected with CMV. Most people are. It's been with us since the Stone Age and only gets in full attack if we are undernourished or otherwise frail. However, our immune system is having a lifelong struggle against it. Over the course of the years more and more of our killer T-cells have to specialize in fighting CMV and therefore there are less and less killer cells available for the fight against other pathogens. A medicine able to eradicate CMV would be a huge step forward towards healthspan and longevity. The Fight Aging blog has a lot of info about CMV.
Quite so!
Do note that CMV is a lipid coated virus.
This lipid coat disguises the virus as a 'nutrient' to the immune system... and the same trick allows it to dock with and infect cells.
So what would stripping away this disguise do to those nasty incurable infections that "there is no cure for"/immunisation shot for...?
See Virgin Coconut Oil/lauric acid/monolaurin and capric etc acids of similarly carbon #. (It has a similar effect on a good # of bacteria too)
Also BHT.
Rosmarinic acid is also worth a damn good look for this reason IIRC and its AGE blockin/breakin? abilities. Note that AGEs increase NF-kB/inflammation just like pathogens do...
Yeah it's a bit over my head and a lot to take in. I feel like I've wasted all my time, energy and money at this point though I've read and commented on some of those threads.
If you are still hoping that NR is a simple answer to aging that enables you to ignore everything else; now is the time to turn to drink!
I don't think it is a simple one answer solution, but I didn't think it could be feeding into aging. Turn to drink?
Glad you haven't drowned your sorrows with a bottle of tequila Nate!?
It takes years of study to get your head around all this in most cases and you end up knowing how little you really know at the end of the day.
There are some exceptions to this rule. I suggest reading threads by SolarFingers and Resveratrol guy amongst others.
Also a search using the GoogleSiteSearch function in the search dropdown menu for CMV, Candida etc and lipid coated viruses will provide plenty a practical advice on keeping these in check.
The more exotic things I mentioned look like they might well be able to eradicate all these pathogens..! I will try and source them as time allows and do group buys on if successful.
Hopefully the buys will receive a warmer reception than the Dasatinib (kills senescent cells as mentioned by Steve H ) group buy.
Then DRACO and Bavituximab should take care of the viruses.
Having taken care of the pathogens, NR an co. should be effective for everyone, but possibly no longer required..?
Thanks, I'll look for those guys in my reading. I didn't find much on managing CMV except this thread and this one on CRISPR. I don't know if I am CMV negative but will find out. I looked up DRACO and there has been no activity on that front since 2013 or 2014, on this thread or anywhere on the internet.
I read through all the linked threads above including this article which was posted back in May, while the other threads go as far back as 2010. It's interesting that nothing has come of these antivirals so far as I know. They got little press and even less utilization. I'm assuming they aren't approved or that there's something that went wrong or didn't work in human trials or what happened? I know the media likes to blow things out of proportion all the time. What happens to all these amazing things that get published and then you never hear about again?
Lets say you make a grand living selling anti dandruff shampoo to the same people, month after month and someone came along with a shampoo that cured dandruff after just one bottle and asked you to sell that instead...
This lipid coat disguises the virus as a 'nutrient' to the immune system... and the same trick allows it to dock with and infect cells.
So what would stripping away this disguise do to those nasty incurable infections that "there is no cure for"/immunisation shot for...?
See Virgin Coconut Oil/lauric acid/monolaurin and capric etc acids of similarly carbon #. (It has a similar effect on a good # of bacteria too)
Also BHT.
Rosmarinic acid is also worth a damn good look for this reason IIRC and its AGE blockin/breakin? abilities. Note that AGEs increase NF-kB/inflammation just like pathogens do...
Rosmarinic acid is something I took for about 3 months in high doses, 6%. I also applied it topically with argan oil. I don't think it really does anything as far as AGE breaking in humans, though it might work in animals, because it wasn't tested on glucosepane and the only RA research on this was in vitro.
As for coconut oil, I might have asked in another thread or earlier in this one, is coconut derived MCT oil the same thing? What is the theory regarding that?
Why BHT? Most threads on that are pretty dead for a couple years.
Lets say you make a grand living selling anti dandruff shampoo to the same people, month after month and someone came along with a shampoo that cured dandruff after just one bottle and asked you to sell that instead...
I'd sell them for considerably more money per bottle.
For every one person who profits selling treatments there is another potential competitor ready to undercut you and sell the cure, unless of course you use the government to protect you from said competition somehow, which is done all the time mostly via the patent system. There's a way to monetize everything. CRISPR kits are selling for $140 ea. Though currently we have no idea what to do with them yet as far as fixing any of this stuff. At some point we'll need a whole forum on how to's for CRISPR kits.
He supposedly regrew his thymus using HGH and DHEA? There was a trial for that, not sure what became of it. This was 2013. You'd think we'd have heard something by now.
EDIT: Fixed the link.
Keeping this on topic, I assume that since this is related to NAD+ still in the same way that CD38 is, but if we can boost the immune system and eradicate these otherwise suppressed infections that would be a solution to a big part of the NAD+ problem? So now we have two contributors, one possibly being an effect of the other but it appears that there may be two things affecting the rise in CD38, pathogens, and senescent cells.
Study to Evaluate the Effect of Nicotinamide Riboside on Immunity
The essential part of the idea I bolded above. There will be a human study on the effect of Nicotinamide Riboside on Immunity shortly. The animal studies have already suggested we should see benefits by increasing NAD. There are so many things effecting immunosuppression in humans and pathogens can and do deplete NAD but what are you going to do, starve them? The evidence favors stimulating higher NAD as apposed to depleted levels in Immunity response situations. Depletion opens the door like an invitation to do havoc. Higher T-cell response is just one aspect of many benefiting from higher NAD. While pathogens may steal some of this “available” NAD, your immune response also needs NAD to mount that response. Turn off the NAD and you might as well give up the fight. So higher NAD levels will help to fend off these freeloaders and the other stresses our environment throws our way like ionizing radiation or oxidative stress.
Thats my story and I'm sticking to it!
JMHO Bryan
Edited by Bryan_S, 04 October 2016 - 06:21 AM. link
Cycles of prolonged fasting (>3 days, mostly water only, several times a year) may not only protect against immune system damage but may also induce some immune system regeneration. Fasting -- among many other attributes -- appears to shift stem cells from dormant states to a states of self-renewal. Valter Longo's work is quite compelling.
Thanks for mentioning Valter Longo, sthira !
I wasn't aware of this study.
Very, very interesting...
The relevance of this study to NR+ is that,... we currently suspect
that NAD+ is stolen by certain varieties of pathogen. As people age
their NAD+ levels decline but also the ability of their immune system
to resist pathogenic infections also declines.
The suggestion that you can restore the functioning of your immune
system to some earlier, more efficient state, might make the critical
difference that allows us to maintain higher NAD+ levels for longer.
The Valter Longo study is consistent with the research into the effects
of a ketogenic diet. (lowering IGF-1 and insulin, promoting autophagy
and macrophagy etc)
It's looking increasingly likely that human beings are designed to survive
frequent periods of famine.... and that our biology expects famine ... and ...
schedules epigenetic cleanup and regeneration 'programmes' to run
during those periods of fasting. So that, we _need_ to fast if we are going
to optimise our health, well being and longevity.
It's interesting that most of the world's religions urge that their followers
undergo periodic fasting.
For those wishing to read the original paper on this:
Yet nothing since 2014, no replication, no variation, nothing. It would take a lot more than a single study to convince me to put myself through that for even a day.
If religions have been making people fast for millennia I think we would notice something about these people. I just don't find this at all convincing.
I agree that it's relevant to NR and NAD+ but I don't agree that it works like that, everyone is basing this off a 2014 study and I can't imagine that there haven't been other studies trying to replicate it and failing. I mean, it takes maybe a month of finding subjects, 72 hrs to complete a study like that, and maybe a week at most to figure out the results. This is the problem with not publishing negative results.
what a discussions here on NR feeding bad boys......I share Brian's view, NAD+ will enable the body to fight:
sirtuin-activating drugs inhibit the replication of diverse viruses, as we demonstrate for human cytomegalovirus, a slowly replicating DNA virus, and influenza A (H1N1) virus, an RNA virus that multiplies rapidly. Furthermore, sirtuin defense functions are evolutionarily conserved, since CobB, the sirtuin homologue inEscherichia coli, protects against bacteriophages.
what a discussions here on NR feeding bad boys......I share Brian's view, NAD+ will enable the body to fight:
sirtuin-activating drugs inhibit the replication of diverse viruses, as we demonstrate for human cytomegalovirus, a slowly replicating DNA virus, and influenza A (H1N1) virus, an RNA virus that multiplies rapidly. Furthermore, sirtuin defense functions are evolutionarily conserved, since CobB, the sirtuin homologue inEscherichia coli, protects against bacteriophages.
Thanks for this interesting link Stefan. It certainly makes clear that raising NAD+ is the way to go forward, also as an antiviral action. (The study might also be a relief for those who spend a lot of money on resveratrol btw)
However the authors reaffirm that there are viruses that seem to know how to tackle SIRTs. It is exactly these types of viruses which may be of concern for some because one way or another they will get their share of supplementary NAD+. Some additional strategies are necessary to combat such pathogens. But let's not worry overmuch: some strategies are here already( see above)
Hangout Schedule: Oct 10, 2016 - 3.30 pm EST, 2.30 pm CST, 12.30 pm PST, 1 am IST Oct 11, 2016
Research Interests
Cellular function and differentiation depend on an ability to read environmental cues and to execute a gene expression program that is appropriate to time, place and context. Nutrient availability is among the most important signals to which cells respond. Importantly, nutrients are not only transmitted from outside an organism, i.e., by feeding, but are also transmitted from cell to cell and from tissue to tissue. Metabolic control of gene expression is critical to the maintenance of cellular longevity. Dysregulation of the nutritional control of gene expression underlies a series of conditions including nondetection of satiety, which can lead to obesity and diabetes, and diseases such as cancer.
Our laboratory is engaged in several projects that dissect specific problems in the metabolic control of gene expression. In particular, we are interested in how changing environmental conditions lead to reversible transfer of two carbon, i.e. acetyl, and one carbon, i.e. methyl, groups to proteins and DNA, respectively. These processes are fundamentally important because two carbon transfers link carbohydrate and fat metabolism to nicotinamide adenine dinucleotide (NAD) biosynthesis and because one carbon transfers link the folate cycle and methionine biosynthesis to S-adenosyl methionine metabolism. Trainees in our group are engaged in interdisciplinary projects, performing protein purification, enzymology, structural biology, yeast and somatic cell genetics, genomics, and chemical biology.
For more information on current projects, see the current research page.
Recent Publications
S.A.J. Trammell, B.J.Weidemann, A.Chadda, M.S. Yorek, A. Holmes, L.J.Coppey, A. Obrosov, R.H. Kardon, M.A. Yorek & C. Brenner, “Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice,” Scientific Reports, v. 6, 26933 (2016). DOI: 10.1038/srep26933. Download pdf reprint.
S.-C. Mei & C. Brenner, "Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous," PLoS Biology, v. 13, e1002048 (2015). Download pdf reprint.
C. Brenner, “Boosting NAD to Spare Hearing,” Cell Metabolism, v. 21, pp.926-927 (2014). DOI: 10.1016/j.cmet.2014.11.015. Download pdf reprint.
B.-K. Wu & C. Brenner, "Suppression of TET1-Dependent DNA Demethylation is Essential for KRAS-Mediated Transformation," Cell Reports, v. 9, pp. 1827-1840 (2014). DOI:10.1016/j.celrep.2014.10.063. Download pdf reprint.
C. Brenner, "Metabolism: Targeting a fat-accumulation gene" Nature, v. 508, pp. 194-195 (2014). DOI: 10.1038/508194a. Download pdf reprint.
R.L. Fagan, D.E. Cryderman, L. Kopelovich, L.L. Wallrath & C. Brenner, "Laccaic Acid A is a Direct, DNA-Competitive Inhibitor of DNA Methyltransferase 1," J Biol Chem, v.288, pp. 23858-23867 (2013). DOI: 10.1074/jbc.M113.480517. Download pdf reprint.
S. Ghanta, R.E. Grossmann & C. Brenner, "Mitochondrial protein acetylation as a cell-intrinsic, evolutionary driver of fat storage: chemical and metabolic logic of acetyl-lysine modifications" Critical Rev Biochem & Mol Biol, v. 48, pp. 561-574 (2013). Download pdf reprint.
S.A.J. Trammell & C. Brenner, "Targeted, LCMC-Based Metabolomics for Quantitative Measurement of NAD+ Metabolites," Computational and Structural Biotechnology Journal, v. 4, e201301012 (2013). DOI: 10.5936/csbj.201301012. Download pdf reprint.
F. Syeda, R.L. Fagan, M. Wean, G.V. Awakumov, J.R. Walker, S. Xue, S. Dhe-Paganon, & C. Brenner, "The RFTS Domain is a DNA-competitive Inhibitor of Dnmt1", JBC, v. 286, pp. 15344-15351 (2011). Dowload pdf reprint
P. Belenky, F.G. Racette, K.L. Bogan, J.M. McClure, J.S. Smith & C. Brenner, "Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+," Cell, v. 129, pp. 473-484 (2007). Download pdf reprint
Visit Google Scholar for all of Dr. Brenner's publications.
Secondary Appointment
Internal Medicine
Affiliations
Molecular & Cellular Biology Ph.D. Program
Genetics Ph.D. Program
Holden Comprehensive Cancer Center
Center for Biocatalysis and Bioprocessing
Edited by Bryan_S, 09 October 2016 - 06:24 PM. 2nd link added
The T allele is associated with:
Patients carrying one or two T-alleles had higher levels of visfatin/NAMPT, and a greater proportion of the patients with CT or TT genotypes reported appetite loss ®.
The T or common allele was more frequent in women with preeclampsia (P<0.05) ®.
rs9770242 SNP: Me AA
The C allele is associated with
Patients carrying one or two A-alleles had higher levels of visfatin/NAMPT, and a greater proportion of the patients with AC or AA genotypes reported appetite loss ®.
Looking at some genetics aspects, the SelfHacked site mentions (bold mine):
“SelfDecode has the NAMPT gene, which controls NAD+ levels. If your genes are not producing NAMPT as well, that would suggest that you’ll have a higher need for NR. Check out your SNPs (need 23andme or other genetic service to then sign up):
RS1319501 (NAMPT)
RS9770242 (NAMPT)
NAD(+) level decrease in aged mice and humans, which is a result of lower NAMPT ®.” (1)
This study gives a more complete picture of the genetics studies:
“…The visfatin/PBEF gene consists of 11 exons and 10 introns spanning 34.7-kb and is located on chromosome 7q22.2. Few studies of polymorphic markers in the visfatin gene have been reported to date. Bottcher et al. [37] did not find any association with either T2DM, in a cohort of 503 diabetic subjects and 476 healthy controls, or with T2DM-related traits in 626 non-diabetic subjects from Germany. However, they found an association between the -948 G > T single-nucleotide polymorphism (SNP) and fasting insulin levels in non-diabetic subjects (p < 0.05). The ratio of visceral/subcutaneous visfatin mRNA expression was associated with all three genetic polymorphisms studied (rs9770242, -948G > T, rs4730153).
To investigate the role of visfatin gene variants in obesity-related phenotypes, Bailey et al. [38] genotyped a total of 13 SNPs in the promoter region of the gene in 918 participants from 208 families evaluated in the Quebec Family Study. A significant association was found between two SNPs (rs9770242and rs1319501) and fasting insulin levels (p = 0.002). These SNPs were also associated with fasting glucose (p = 0.02). Furthermore, they found that a more distal SNP (rs7789066) was significantly associated with the apolipoprotein B component of VLDL (p = 0.012).
Zhang et al. [39] studied a group of 814 white patients from the USA and a group of non-diabetic controls (n = 320). They found a significant association between -948C > A and T2DM (p = 0.021). In a non-diabetic population (n = 630), the same -948C allele that conferred increased risk of T2DM was significantly associated with higher plasma levels of fibrinogen and C-reactive protein (p = 0.0022 and 0.0038, respectively). However, no significant associations were observed with BMI, waist circumference, serum glucose levels, or fasting insulin levels. They suggested that the visfatin gene may play a role in determining T2DM susceptibility, possibly by modulating chronic, low-grade inflammatory responses.
Korner et al. [40] studied 731 schoolchildren and an independent cohort of 167 obese children from Germany. They genotyped 3 SNPs (rs9770242, -948G > T, rs4730153). The authors did not find association of any of the 3 polymorphisms or their haplotypes with BMI, waist-to-hip ratio, glucose, insulin, or lipid levels. However, the -948G variant was associated with significantly higher diastolic blood pressure in obese children (p < 0.05 after adjusting for age, sex, pubertal stage, and height).
Blakemore et al. [41] studied 1,709 severely obese subjects together with 2,367 T2DM individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818from a general population sample. This rare SNP, rs10487818, located in intron 4, was associated with protective effect against severe obesity. This is one of the first rare SNPs shown to be protective against a common polygenic disease like obesity and provides further evidence that rare alleles of strong effect can contribute to this kind of complex diseases.
More recently, Yan et al. [42] suggested that Visfatin -1535C > T polymorphism might be associated with reduced risk of CAD in a Chinese population. There was a significant association between Visfatin -1535C > T polymorphism and triglyceride levels in both CAD patients and controls (p = 0.003). In non diabetic Japanese subjects, Tokunaga et al. [43] found that the -1535T/T genotype modulates lipid levels promoting lower serum triglyceride levels and higher HDL-cholesterol levels. In this investigation, reporter gene assay of 3T3-L1 adipocytes revealed that the promoter activity of -1535T and -1535C was similar, suggesting that the observed association may reflect linkage disequilibrium between -1535T > C and other causative variations of the visfatin gene.
Taken together, these studies suggest that genetic variants in the Visfatin gene can be associated with some phenotypes related to glucose, lipids, and other metabolic and vascular traits. Further studies in other populations must be carried out to better clarify these points…” (2)
NAMPT looks, as everything related to metabolism, a complex issue with up and down sides (e.g. pro-inflammatory in its extra cellular form). The Part 5 of the huge NAD blog by Jim Watson tries to tackle this:
“…But then, a dark side of all of this begin to emerge as it was realized that NAMPT has long been known to be a traveler using various aliases, especially outside of cells where it did shocking things. NAMPT was often behaving inappropriately for its princely role when it is outside our cells. Not to be trusted, extra-cellular NAMPT (eNAMPT) can be caught creating horrible inflammation and is closely associated with highly disreputable diseases. Oozing out of fat cells and helping create colorectal cancer is not politically correct for a supposedly good guy. The same is true for destroying cartilage in both osteo and rheumatoid arthritis. We have written before about the good side of NAMPT when it is in cells. This present blog entry is an expose of the bad inflammation-generating side of eNAMPT. And, it turns out that eNAMPT is not completely bad, after all.” (3)
(1) Top 9 Health Benefits of Nicotinamide Riboside
Samuel A. J. Trammell, Mark S. Schmidt, Benjamin J. Weidemann, Philip Redpath, Frank Jaksch, Ryan W. Dellinger, Zhonggang Li, E. Dale Abel, Marie E. Migaud & Charles Brenner
Nicotinamide riboside (NR) is in wide use as an NAD+ precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD+ metabolism in humans. We report that human blood NAD+ can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD+ with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD+ metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD+, is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD+ repletion.
OK guys here is the long awaited full Brenner study release.
Samuel A. J. Trammell, Mark S. Schmidt, Benjamin J. Weidemann, Philip Redpath, Frank Jaksch, Ryan W. Dellinger, Zhonggang Li, E. Dale Abel, Marie E. Migaud & Charles Brenner
Nicotinamide riboside (NR) is in wide use as an NAD+ precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD+ metabolism in humans. We report that human blood NAD+ can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD+ with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD+ metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD+, is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD+ repletion.
OK guys here is the long awaited full Brenner study release.
I am again impressed by the fact that these findings occur after single doses!
Somewhere the authors suggest that 400mg would be an ok dose for humans.
It is a pity that no further specifics are given about how participants in the clinical trial took the NR. We are just told: after overnight fasting. But not: with breakfast or well before it....
I thought there had already been dozens of human clinical trials at this point. How is this the first?
You read the study we posted by Samuel Trammell correct? That was Samuel Trammell's Postdoc PhD thesis.Download thesis. This new one was the full study release from the University of Iowa under Charles Brenner just published in the prestigious Publication Nature. So it represents the conclusions of the entire team. It included the pre-trial of a 52-year old man (Charles Brenner was the subject) and the first Clinical trial of 12 healthy men and women under the 100, 300 and 1,000 mg dosages. Here is the raw study data so you can confirm this for yourself https://www.ebi.ac.u...lights/MTBLS368
Edited by Bryan_S, 10 October 2016 - 07:09 PM. misspelling
You read the study we posted by Samuel Trammell correct? That was Samuel Trammell's Postdoc PhD thesis.Download thesis. This new one was the full study release from the University of Iowa under Charles Brenner just published in the prestigious Publication Nature. So it represents the conclusions of the entire team. It included the pre-trial of a 52-year old man (Charles Brenner was the subject) and the first Clinical trial of 12 healthy men and women under the 100, 300 and 1,000 mg dosages. Here is the raw study data so you can confirm this for yourself https://www.ebi.ac.u...lights/MTBLS368
You read the study we posted by Samuel Trammell correct? That was Samuel Trammell's Postdoc PhD thesis.Download thesis. This new one was the full study release from the University of Iowa under Charles Brenner just published in the prestigious Publication Nature. So it represents the conclusions of the entire team. It included the pre-trial of a 52-year old man (Charles Brenner was the subject) and the first Clinical trial of 12 healthy men and women under the 100, 300 and 1,000 mg dosages. Here is the raw study data so you can confirm this for yourself https://www.ebi.ac.u...lights/MTBLS368
So does this give us anything new on half-life?
I didn't see anything specific to half-life. Watching Brenner live now. Watch Lots of great insight!!!!!!
Edit:
Brenner is asked about the half-life of NR at the end and replies with a discussion on peak NAD levels. So not a direct answer about our blood plasma levels or how long it takes for NR to fall off after an oral dose id taken.
Edited by Bryan_S, 11 October 2016 - 12:58 AM. answered question after reviewing full video
Also tagged with one or more of these keywords: nicotinamide riboside, nicotinamide, nad boosting, charles brenner, david sinclair, leonard guarente, niagen, niacinamide, nicotinamide mononucleotide
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