2255 replies to this topic

[Hebbeh]

This is what I have been using since Darryl's December 2013 post  ....  http://www.swansonvi...n-50-mg-90-caps

 

I also have been eating a very generous helping (~2 cups) of blueberries for breakfast every day for at least the past 10 years and I have also been using quercetin at least that long.  I have also added black rice since Darryl's post.  And I've always used plenty of oregano in cooking... even at the table.  I also have been using alpha lipoic acid (racemic) for years.  I also maintain a vigorous exercise regimen.  I was doing all these things before starting NR in April 2014.  Perhaps that is why I never really noticed any apparent effect with NR even at a gram per day in spite of being 59 (although my health is excellent for my age) .... but I've continued with the NR on blind faith in the science.

 

BTW what ever happened to Darryl?  We seemed to have lost some of the best contributors over the past couple years

Edited by Hebbeh, 15 June 2016 - 03:18 AM.

[Bryan_S]

Oh by the way the LongeCity NR group buy starts tonight. There are 3 categories 3, 6 and 12 bottle orders. The 3 bottle orders are continuous, meaning you can use that code anytime. The 6-12 orders are on a 60-day cycle and the Code lasts a just week and they offer the deepest discount.

http://www.longecity...e-8#entry778516

Edited by Bryan_S, 15 June 2016 - 03:22 AM.

[Nate-2004]

I did some Googling and found a few interesting links regarding apigenin. 

 

This one talks about its inhibition of CD38. 

 

Chamomile Tea has lots of apigenin in it but who's to say what 1.2% ends up being? Herbal extracts from chamomile say 1.2% but others say 98%. Swanson has it and supposedly the dosage is anywhere from 20 to 120mg. I just ordered some because the details regarding aromatase inhibition were enough to make me want to try it.

 

Hebbeh I just noticed your post, you beat me to it haha. How much do you take per day? Apigenin can make you sleepy so I hear because it acts on benzo receptors. I also saw a reference in Wikipedia that claims it is an NMDA receptor antagonist which I thought would not be good for memory, however when searching apigenin and memory I got the opposite results.

 

Could apigenin or the like be a low cost replacement for NR?

Edited by Nate-2004, 15 June 2016 - 04:38 AM.

[normalizing]

hebbeh what is excellent health for 59 year old you would say anyway? my grandfathers were living in extreme poverty never ate blueberries or take NR and lived to 90. i dont get this statement sorry

 

low bioavailbility of lots of common flavonoids, anthocyanins is widely available and im surprised people havent read about it. there is not a single thing in blueberries thats bioactive to such extent to actually cure or prevent any disease and people stating such should be jailed and FDA should interfere in this regard. this is absolutely ridiculous we live in 21st century, as far as i know most of you are from 1st world countries, and to believe crap like blueberries cure alzheimer, you gotta be out of your minds. my personal experience is this, i used to eat up to 300 grams of blueberries daily for a week and i actually gained weight, i did not feel a single benefit whatsoever. but because its just one person dubious report, take it with grain of salt but i just about had it with those advertisings of crappy sugary fruits curing diseases, sorry!

[normalizing]

I did some Googling and found a few interesting links regarding apigenin. 

 

This one talks about its inhibition of CD38. 

 

Chamomile Tea has lots of apigenin in it but who's to say what 1.2% ends up being? Herbal extracts from chamomile say 1.2% but others say 98%. Swanson has it and supposedly the dosage is anywhere from 20 to 120mg. I just ordered some because the details regarding aromatase inhibition were enough to make me want to try it.

 

Hebbeh I just noticed your post, you beat me to it haha. How much do you take per day? Apigenin can make you sleepy so I hear because it acts on benzo receptors.

 

Could apigenin or the like be a low cost replacement for NR?

 

according to https://labdoor.com/ and few other labs testing supplements, swanson is of super poor quality. anyway, ive tried apigenin and luteolin (the vital ones mentioned on here for various benefits) and they didnt do anything. i tried high purity powders too, im skeptical some poorer quality like swanson will deliver

[Hebbeh]

hebbeh what is excellent health for 59 year old you would say anyway? my grandfathers were living in extreme poverty never ate blueberries or take NR and lived to 90. i dont get this statement sorry

 

low bioavailbility of lots of common flavonoids, anthocyanins is widely available and im surprised people havent read about it. there is not a single thing in blueberries thats bioactive to such extent to actually cure or prevent any disease and people stating such should be jailed and FDA should interfere in this regard. this is absolutely ridiculous we live in 21st century, as far as i know most of you are from 1st world countries, and to believe crap like blueberries cure alzheimer, you gotta be out of your minds. my personal experience is this, i used to eat up to 300 grams of blueberries daily for a week and i actually gained weight, i did not feel a single benefit whatsoever. but because its just one person dubious report, take it with grain of salt but i just about had it with those advertisings of crappy sugary fruits curing diseases, sorry!

 

Well what I can say is that I'm currently engaged to a 34 year old beautiful and fit woman with a July wedding date.  When introduced to her family, nobody would believe I was (58 at the time) and believed I looked and acted no older than 45.  Of course when I was 45, everybody thought I was 35.  I'm in better physical condition than most of the guys I know 20 years younger and everybody I know comments on this.  We are planning on children and I am personally looking forward to raising a second family... how many can honestly claim that?  I'm not making this stuff up.  I may be blessed with good genetics but the point of my story is lifestyle can go a long way...and that is what sets me apart from the average Joe.  Diet and exercise.... smart supplementation is the icing on the cake.  I have no medical conditions what so ever... the same blood markers from 30 years ago.  I could go on but I hope I've answered your question as to what I consider excellent health for 59 (or 39 for that matter).

 

And in respect to the blueberries, I don't believe there are any studies indicating benefit from a week of eating berries... it's a small part of a life long lifestyle that contributes incrementally over a long lifetime... and I'm sorry to hear that it sounds like it may be too little too late for you normalizing.  I can say I've been dedicated and worked very hard over the past 30 years to get where I am and I feel like I have a long way to go.  But it is not any single magic bullet ... but rather the whole is the sum of the parts.

[mrkosh1]

Hebbeh,

 

Since you have been taking all those supplements, do you feel that you have aged any in the last ten years?

 

Do you look any older?

[normalizing]

its interesting how people will take his word for it without any problem. i met dozen of people in their 50s claiming they look or feel younger because few friends commented on it and they go for it because its what drives them and makes them feel good. he is not a special case at all. and what does "and I'm sorry to hear that it sounds like it may be too little too late for you normalizing" even mean?

[Hebbeh]

Certainly I've aged.  Each additional year seems to require a little more effort to maintain physical conditioning.  Even though it appears I'm in better condition than many younger than me, I still realize I'm not as strong and fit as I was 10 years ago.  Life span is a lofty goal but my real goal is health span.  To age more slowly and gracefully.  To enjoy an active and healthy retirement (raising my second batch of kids ... which should actually contribute to my health and longevity in many ways including quality of life).  And I believe that a side effect of health span will be some increased life span.  I am probably blessed with good genetics as I have no medical concerns and most of my ancestors on both sides of my family tree are either still living in relatively good health or lived well into their 90's without living a particularly healthy lifestyle (in my opinion) however they did work hard all their lives.  I believe I can capitalize on those genetics through disciplined lifestyle and push the family tree to 100 perhaps. But we never know what tomorrow will bring... we can only live life the best for today.  But beyond genetics, I believe disciplined diet, exercise, and quality of lifestyle is 95% of the battle... supplements are just for the extra "edge" and to tweak what you have to work with.  Perhaps supplements give a bigger boost and help some manage specific genetic issues.

 

Now we have strayed off topic far enough and need to discuss CD38 further... which I feel has great potential.

 

 

Hebbeh,

 

Since you have been taking all those supplements, do you feel that you have aged any in the last ten years?

 

Do you look any older?

 

[Harkijn]

To give credit where credit is due: some years ago Vince Giuliano and Jim Watson in their huge NAD world blog already mentioned CD38 as an NADguzzler and apigenin as a possible  'remedy' for this. (Since that time I have been taking an apigenin supplement, but irregularly because it was/is not clear to me to  what extend you can tone down CD38 without causing damage)

[Black Fox]

To give credit where credit is due: some years ago Vince Giuliano and Jim Watson in their huge NAD world blog already mentioned CD38 as an NADguzzler and apigenin as a possible 'remedy' for this. (Since that time I have been taking an apigenin supplement, but irregularly because it was/is not clear to me to what extend you can tone down CD38 without causing damage)

I got the same concerned! down-regulating PARP would raise our NAD levels cause PARP is a main NAD consumer but we wouldn't want knock out our PARP , would we? As main genetic stabilator I want my PARP up and running , I'll worry about feeding it ...

What's CD38 main purpose ? How long could we inhibit it for with no side effects?

Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome.

http://www.ncbi.nlm....pubmed/23172919

Edited by Black Fox, 15 June 2016 - 07:28 AM.

[Harkijn]

Black Fox: Yes CD38 seems to have many functions, some of them still unknown. But also : this somewhat older study

http://www.ncbi.nlm....les/PMC2883294/

 

warns that some CD38 inhibitors might also inhibit SIRT1, a 'potential unwanted side effect' :-). So though we have something very important here, I'll just go on eating capers, oregano and lots of herbs and spices and wait with regular supplementation until some experts weigh in.

[Ethic]

I thought CD38 (and PARP) depleting NAD storages is old cake

[midas]

http://www.ncbi.nlm....pubmed/27193174

 

2016 May 18.

 

Abstract

Infective endocarditis is caused by Streptococcus sanguinis present in dental plaque, which can induce inflammatory responses in the endocardium. The present study depicts research on the properties of apigenin in embryonic mouse heart cells (H9c2) treated with lipoteichoic acid (LTA) obtained from S. sanguinis. Interleukin-1β and cyclooxygenase (COX)-2 expression were detected by reverse transcriptase polymerase chain reaction. In addition, western blot assays and immuno-fluorescence staining were used to assess translocation of nuclear factor kappa beta (NF-κB), degradation of IκB, as well as activity of the mitogen activated protein kinases: extracellular signal-regulated kinase (ERK)1/2, p38, and c-Jun N-terminal kinase (JNK). Effect of apigenin on cell viability was equally assessed in other experimental series. Our results showed that apigenin blocked activation of ERK, JNK, and p38 in cardiomyocytes treated with LTA in a dose-dependent fashion. Moreover, apigenin showed no cytotoxic effects; it blocked NF-κB translocation and IκB degradation. Our findings suggested that apigenin possessed potential value in the treatment of infectious endocarditis.

 

 

More here........

 

 

http://www.ncbi.nlm....pubmed/23172919

 

Edited by midas, 15 June 2016 - 01:39 PM.

[normalizing]

discussion of cd38 is off topic in here, please follow it elsewhere

[midas]

its interesting how people will take his word for it without any problem.

 

What's more interesting is that you seem to feel that you trolling this thread is going to make a difference to anyone that is genuinely interested in it.........You are nothing more than an annoying little fly buzzing around in a large room, you will get tired eventually or a moderator will deal with you....You remind me of my neighbours five year old, but in fairness to her she's young enough not to know any better.

[Bryan_S]

If anyone isn't sure whats on topic or not see the initial post on this thread. CD38 is part and parcel of what we are discussing here. The term "NAD replacement" is synonymous with "NAD boosting" and it was prevalent throughout the article I posted and Nicotinamide Riboside was also identified within the article. So the article was about 2 topics we hold dear and CD38 appears to be an antagonist to our goals of raising NAD+ levels. "We further identified that CD38 is the main enzyme metabolizing the NAD precursor NMN in vivo" Since (NR) is converted to NMN before it becomes NAD+ this should be raising some eyebrows.

 

So does CD38 do anything useful before consuming our NMN?

 

What tissues produce CD38 and why?

 

Can we block CD38 from being produced (epigenetically at the source) in the first place, or can we take a CD38 inhibitor?

 

I think those are the questions upon us and as long as the board stays within the charter posted at the beginning of the thread I'm OK with that. So any disruptive elements to that, please move that conversation elsewhere or I will remove you from the conversation. I expect everyone to be respectful of one another, we have an enlightened academic audience and this behavior shames us all, so lets take this down a notch.

Edited by Bryan_S, 15 June 2016 - 07:13 PM.

[Logic]

...CD38 regulates several important immunological processes, such as DC and neutrophil trafficking in response to inflammatory challenges (19, 20),B cell activation (21) and Ig isotype switching (22), as well as NK and  T  cell  activation  (23–25).  Thus,  most  defects  attributed  to CD38 deficiency have heretofore been associated with attenuated immune  responses  rather  than  impaired  tolerance  induction...

http://www.jimmunol....5/2939.full.pdf

 

...To quote Jim Watson, “The most important three things about aging are inflammation, inflammation, and inflammation...

http://www.anti-agin...n-inflammation/

 

I have posted and posted about  the major causes of inflammation.  I also believe in survival of the fittest (mentally) so I wont bore everyone with the details yet again.

 

 

Anti-Aging Firewalls' NAD+ blog posts:

 

NAD+ an emerging framework for health and life extension — Part 1: The NAD World

http://www.anti-agin...he-nad-world-2/

 

NAD+ an emerging framework for life health and life extension — Part 2: Deeper into the NAD World, hopeful interventions

http://www.anti-agin...-interventions/

 

30 Major Factors that Control SIRT1 Expression, SIRT1 Activity, and SIRT1-mediated Aging. Part 3 of the series NAD+ an emerging framework for health and life extension

http://www.anti-agin...life-extension/

 

Part 4 of the NAD world: the NQ01 gene, the Warburg effect, SIRT 1 and inflammation, and possible interventions

http://www.anti-agin...-interventions/

 

Part 5 of the NAD world: the conflicting roles of NAMPT – inflammation or rescue? Also Part 1 on a new series on inflammation

http://www.anti-agin...n-inflammation/

[Bryan_S]

So anything we can do to blunt inflammation helps mediate CD38, thanks Logic.

[Tom Andre F. (ex shinobi)]

Thanks logic. Is there another reason to use willow bark / aspirin along NR ?

 

Links between TNFa and CD38 (since I believe TNFa is the root of the inflammatory process)

 

TNF-alpha induced CD38 expression in human airway smooth muscle cells: role of MAP kinases and transcription factors NF-kappaB and AP-1. http://www.ncbi.nlm....pubmed/17322278

 

Transcriptional regulation of CD38 expression by tumor necrosis factor-alpha in human airway smooth muscle cells: role of NF-kappaB and sensitivity to glucocorticoids. http://www.ncbi.nlm....pubmed/16571778

 

miR-140-3p regulation of TNF-α-induced CD38 expression in human airway smooth muscle cells (In human ASM (HASM) cells, TNF-α induces CD38 expression through activation of MAPKs, NF-κB, and AP-1) http://www.ncbi.nlm....pubmed/22773691

 

Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-alpha and dexamethasone. CD38 is expressed in human airway smooth muscle (HASM) cells, regulates intracellular calcium, and its expression is augmented by tumor necrosis factor alpha (TNF-alpha) http://www.ncbi.nlm....pubmed/18341691

 

So again.. CD38 as tgfb, as nfkb etc is mediated via TNFa. and important TNFa inhibitor are willow bark / aspirin and honokiol :

 

willow bark water extract STW 33-1 and of its water-soluble fraction by inhibiting pro-inflammatory cytokines (TNFα), COX-2 and nuclear translocation of the transcription factor NF-κB in pro-inflammatorily activated monocytes http://www.ncbi.nlm....pubmed/20570123

 

the anti-inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor-α and nuclear factor-kappa B http://www.ncbi.nlm....pubmed/25997859

 

Honokiol: an effective inhibitor of tumor necrosis factor-α-induced up-regulation of inflammatory cytokine and chemokine production in human synovial fibroblasts. http://www.ncbi.nlm....pubmed/21511722

 

 

 

 

Edited by Tom Andre F. (ex shinobi), 15 June 2016 - 08:05 PM.

[stefan_001]

Removed

Edited by stefan_001, 15 June 2016 - 08:30 PM.

[Nate-2004]

Our results showed that apigenin blocked activation of ERK, JNK, and p38 in cardiomyocytes treated with LTA in a dose-dependent fashion.

 

 

What does this mean exactly?

 

Thanks for the links Logic, lots -o- reading to do.

 

@Tom honokiol inhibits CD38?

[Tom Andre F. (ex shinobi)]

What we want is not to decrease CD38 or PARPs directly but via safer way: using anti inflammatory pathway and targeting TNFa like seems to also does the apigenin for instance. It also block p53 means will also increase PGC1a..  The indirect pathway is the solution. The question is then not if it inhibits CD38, but more how strong it will calm dalm the root of the inflammatory pathway.

 

@hebbeh, thank you also for the research. However I would like we look deeper into it since for instance quercetin was shown to decrease SIRT1 activity unlike pterostilnene or resveratrol : http://www.pterostil...irt1-activator/

[normalizing]

 

its interesting how people will take his word for it without any problem.

 

What's more interesting is that you seem to feel that you trolling this thread is going to make a difference to anyone that is genuinely interested in it.........You are nothing more than an annoying little fly buzzing around in a large room, you will get tired eventually or a moderator will deal with you....You remind me of my neighbours five year old, but in fairness to her she's young enough not to know any better.

 

 

 

yeh thats actually a compliment that i act so young lately. maybe nicotinamide riboside does work for me, since i have been told few other times in other forums i act like a child (lately) havent had that problem in the past actually. in fact i was a bit too serious... interesting finding something i havent thought of at all, but now i did check some of my recent posts and some of my posts last year, there is a difference :s
 

Edited by normalizing, 16 June 2016 - 12:29 AM.

[midas]

 

 

its interesting how people will take his word for it without any problem.

 

What's more interesting is that you seem to feel that you trolling this thread is going to make a difference to anyone that is genuinely interested in it.........You are nothing more than an annoying little fly buzzing around in a large room, you will get tired eventually or a moderator will deal with you....You remind me of my neighbours five year old, but in fairness to her she's young enough not to know any better.

 

 

 

yeh thats actually a compliment that i act so young lately. maybe nicotinamide riboside does work for me, since i have been told few other times in other forums i act like a child (lately) havent had that problem in the past actually. in fact i was a bit too serious... interesting finding something i havent thought of at all, but now i did check some of my recent posts and some of my posts last year, there is a difference :s
 

 

 

Dementia?, Alzheimer's?.......... or maybe just stupid?.......who knows........ I know which one my money's on!
 

Edited by midas, 16 June 2016 - 02:21 AM.

[normalizing]

 

 

 

its interesting how people will take his word for it without any problem.

 

What's more interesting is that you seem to feel that you trolling this thread is going to make a difference to anyone that is genuinely interested in it.........You are nothing more than an annoying little fly buzzing around in a large room, you will get tired eventually or a moderator will deal with you....You remind me of my neighbours five year old, but in fairness to her she's young enough not to know any better.

 

 

 

yeh thats actually a compliment that i act so young lately. maybe nicotinamide riboside does work for me, since i have been told few other times in other forums i act like a child (lately) havent had that problem in the past actually. in fact i was a bit too serious... interesting finding something i havent thought of at all, but now i did check some of my recent posts and some of my posts last year, there is a difference :s
 

 

 

Dementia?, Alzheimer's?.......... or maybe just stupid?.......who knows........ I know which one my money's on!
 

 

 

is it on the fact i been taking lots of shit including nicotinamide riboside and i act like a childish thug? then you win!

lately, i feel like a child and act like it too, it feels liberating to say the least!  wow its profound and strange for me to find out this through some brit hooligan's arrogant crap on a forum....

 

Edited by normalizing, 16 June 2016 - 03:23 AM.

[stefan_001]

What we want is not to decrease CD38 or PARPs directly but via safer way: using anti inflammatory pathway and targeting TNFa like seems to also does the apigenin for instance. It also block p53 means will also increase PGC1a..  The indirect pathway is the solution. The question is then not if it inhibits CD38, but more how strong it will calm dalm the root of the inflammatory pathway.

 

@hebbeh, thank you also for the research. However I would like we look deeper into it since for instance quercetin was shown to decrease SIRT1 activity unlike pterostilnene or resveratrol : http://www.pterostil...irt1-activator/

 

I agree to this view, tamping down inflamation seems a smart thing to do. Personally I would not risk directly inhibiting CD38. A polyphenol cocktail may make sense.

[Yajerman]

 

What we want is not to decrease CD38 or PARPs directly but via safer way: using anti inflammatory pathway and targeting TNFa like seems to also does the apigenin for instance. It also block p53 means will also increase PGC1a..  The indirect pathway is the solution. The question is then not if it inhibits CD38, but more how strong it will calm dalm the root of the inflammatory pathway.

 

@hebbeh, thank you also for the research. However I would like we look deeper into it since for instance quercetin was shown to decrease SIRT1 activity unlike pterostilnene or resveratrol : http://www.pterostil...irt1-activator/

 

I agree to this view, tamping down inflamation seems a smart thing to do. Personally I would not risk directly inhibiting CD38. A polyphenol cocktail may make sense.

 

I can honestly say I get lost in translation about a lot of what you, Bryan and Tom talk about at times; which is to say I am only understanding the peripheral at best. That being said though, what would (in your mind) be a good polyphenol cocktail. I am taking Basis at the moment and I started to take the r-lipoic acid but not fully understanding everything (even after my own research) and because of partial negative remarks herein I opted not to take it anymore, so what would also mix with Basis? Honokiol? (we that be part of your polyphenol coctail?)

 

Excuse my ignorance as I am slowly trying to understand all this.

 

Thank you.

[Logic]

So anything we can do to blunt inflammation helps mediate CD38, thanks Logic.

 

Blunt it!?  To hell with that!  Go after the root causes and kill it completely!

 

Causes:

 

Gut turnover is 5 days.

ie: The barrier between the rest of you and instant death by septicemia ages faster than the rest of you.

The gut becomes ever more leaky with age, so the body has to try to compensate for the increased toxic (LPS etc) and pathogenic load... = increased inflammation... IMHO

 

Gut turnover is 5 days.  

So Telomere length is an issue...

The stem and progenitor cells that replace the gut have 'direct access' to oral telomerase activators...

Inflammation blocks telomerase. 

So do telomerase activators work systemically, or is most of their work done in the gut; lowering inflammation, and thus felt systemically..?

 

Dysbiosis (the increase in bad bacteria and their toxic 'shit') increases with age exacerbating the above.

 

AGEs increase inflammation!!!

Metals and heavy metals (in all food and supps) catalyse (vastly speed up)  AGE formation, so they accumulate faster than they can be eliminated...

All? AGE blockers/breakers are chelators..!

(AGEs etc block the signalling that tells stem cells to become/replace whatever cells are reqd...)

They get in through...?  So a chelator in supps and with meals would...?

(FYI the mitochondrial chelator Tiron provides 100% protection against UV damage to skin)

 

Chronic, low level infections.  Like CMV, HSV etc. which are Lipid coated virii...

 

All the info an ameliorating, eliminating and even reversing the above is on this forum.

I'm just glad  the big picture is slowly dawning on some?

[Hebbeh]

https://www.scienced...60614155722.htm

"The future of our research will be to develop compounds that can inhibit the function of CD38 to increase NAD levels during aging," says Dr. Chini. "We are also investigating the mechanisms that lead to the increase in CD38 during the aging process."