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Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesi

nad nam

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#1 Harkijn

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Posted 07 August 2018 - 02:38 PM


As you all know there have been doubts recently about the oral bioavailability of NR. This study is of interest here because the spectacular improvements compared to the control group were achieved by oral NR. 

I believe some posters still take NAM . They should read this study because once again is shown that NAM takes down SIRT1 and so counters other NADprecursors.

https://doi.org/10.1...213231718300624


Edited by Harkijn, 07 August 2018 - 02:39 PM.

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#2 able

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Posted 07 August 2018 - 05:55 PM

I could use a little help understanding what it is you see in this study.  I don’t see any spectacular results, and nothing that suggests anything new about oral bioavailabilty.

 

 

I know there is some discussion that NR is digested in the stomach, but afaik, the main concern about oral NR/NMN supplements are, very little make it out of the liver, without first conversion to NAM (According to Liu study).  

 

The research  in this thread is all about the effect on Liver only.  I don't see how that impacts the thinking on NR availability outside of the liver.  

 

I do think NR is more effective than NAM, and  point out that another study HERE implies NR reaching outside the liver and having much more benefit for heart injury than NAM.  I just am missing what is important about this particular study

 

Also I don’t see what you mean about “NAM takes down SIRT1”.  I know they repeat 

a somewhat deceptive and partially debunked claim about NAM being a Sirt1 inhibitor, but is there something in this study about NAM that I missed?

 

They also throw out a claim about NMN which I believe is quite incorrect, as well as not really relevant.  

 

 “NMN also increased NAD+ levels, which could be a useful intervention related to metabolic disorders [27], but it isn’t found in dietary constituents

 

This is clearly disputed here:

 

Finally, we found that NMN was indeed contained in some daily natural food sources (Table 1). For example, vegetables such as edamame (immature soybeans), broccoli, cucumber, and cabbage contained 0.25–1.88 mg of NMN per 100g”


Edited by able, 07 August 2018 - 06:41 PM.

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#3 stefan_001

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Posted 07 August 2018 - 08:09 PM

The link doesn't open anymore?



#4 stefan_001

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Posted 07 August 2018 - 08:20 PM

Found the study. I think it is a pretty good study, clear contrast to NAM. To me its another confirmation that NR should be taken in multiple ways. Orally to ensure liver health, sublingual to get NR to other organs, potentially through skin absorption etc.



#5 Harkijn

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Posted 08 August 2018 - 03:42 PM

@ able:

 

About NR:

Take a second look at the differences between the study group and the controls. I have seen studies that pointed to NR's positive role/roles in hepatic health of mice but these differences are considerable and they were not produced by peritoneal injection. If only small parts of oral  NR dosage makes it to the liver but still produce these results I call that encouraging.

 

About NMN:

You are right. I wondered about that too. And, yes,  why did they mention it at all? Perhaps they too have heard rumours about NR being relatively high in some beers while NMN is relatively low in say edamame. (I eat some edamame every week btw).

 

About NAM:

Afaik the researchers have not been involved in  repeating or debunking any claims. They refer to previous research and wanted to doublecheck:

 

Finally, mice were fed with ethanol diet added with 200 mg/kg NAM to serve as a SirT1 inhibitor. We found that SirT1 was significantly decreased in NAM- fed mice (Fig. S8A). NAM indeed exacerbated lipid accumulation in the hepatocytes and also exaggerated levels of serum ALT, AST, and hepatic MDA induced by ethanol.

 

@ Stefan, yes oral for liver health: but a better functioning liver has so much advantages for renal health, for regulating blood acidity levels and you name it.

 

I upload the pdf for those who want to read up on this.

 

 



#6 Boopy!

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Posted 10 August 2018 - 07:35 PM

This makes me so sad to read because my greatest hope was to improve my liver issues.   My grandmother died early from them and most likely I'm looking at the same.   My enzymes  encountered zero change each time tested (before and after NR for a few months)  and I will be going one more time to test them.   I don't drink,  eat extremely healthy,  but I USED to drink and that's probably where the damage came from -- and apparently it isn't getting better from high or low doses of NR.   I'll have to give up if the next test shows little improvement.   I don't know where to go from here,   but I'll figure something out.  


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#7 unbreakable

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Posted 03 September 2018 - 02:01 PM

@Boopy!

 

How old are you? Coul you describe your drinking habits in the past? How is your bloodwork (GOT, GPT, Gamma-GT, Bilirubin, ALP, Albumin, Platelet Count, INR or PT,,,)? Did you have ultrasound? What is the doctor's opinion (ideally that of an hepatologist, gastroenterologist)? Did your grandmother have liver cancer / cirrhosis? Has the cause been found?

 

I do believe in supplements for liver health, but obviously the underlying problem should be diagnosed and treated.

 

Supplements I'd recommend:

 

1) Essential phospholipids  / Polyenylphosphatidylcholine (EPL, PPC sold as the medication "Essentiale" in Europe or the supplement "PhosChol" in the US).

2) Silymarin or - better bioavailable - a silybin-phosphatidylcholine complex ("SiliPhos").

3) S-Adensoylmethionine

4) Betaine

5) N-Acetylcysteine

6) (R-) Alpha Lipoic Acid

 

 



#8 Boopy!

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Posted 03 September 2018 - 09:03 PM

wow --  I am at work so cannot fully respond,   but briefly:

 

I am 44 or will be in a month,   and I drank like many women -- binge drank vodka and hard liquor mostly --  between 25 and 38 or so,   but never every day.   I was actively trying to be an alcoholic,   oddly enough,   because I figured it was the only way to help extraordinarily severe depression and PTSD.   Well,  it didn't,  so I quit,  and easily.   I had no problem stopping abruptly.   I think I had a sip of red wine a month ago,   but I really don't like alcohol that much. 

 

In America doctors  assume you are fine unless you are yellow or orange and if you appear relatively healthy,  oddly enough,   they seem only worried about obesity from what I've seen.    One pressed on my liver and said it wasn't swollen yet,  so just to avoid alcohol.   So I had to beg for a liver enzyme test.   This was my third in ten  or more years,  and each time,  high enzymes.   Each time,  the doctor told me they were elevated,   not to drink (I hadn't on the last two),  and that it was not good.   But no other suggestions.   So thank you for taking FAR more time and effort to look into it a bit.   

 

My grandmother died of cirrhosis at around 70 I believe.   She drank every day,   back before they really worried about alcohol.   That is all I know -- she was severely alcoholic,   and shook if she didn't drink.   

 

They tested a few other standard things (it was a blood test for a few things I saw checked,  but I don't remember anything other than it tested a thyroid thing and it obviously tested a cholesterol thing since I was told this was "excellent"  or something like that.  Ha.  I didn't know there was anything other than okay or not okay!  I do NOT recall seeing those other things you mentioned.   

 

Again -- thank you so much for those suggestions!   I don't know if I can convince them to let me test it again until next year,   but at least I can do something in the interim.   I mean,   other than hair falling out and being tired all the time,   I am healthy enough.   But I would like to be less exhausted so I can have the energy to move across country.



#9 unbreakable

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Posted 04 September 2018 - 11:01 AM

First of all I wouldn't compare the situation of your grandmother and yours. It's quite different as you were able to stop drinking and she unluckily not. Also you describe her as a severe, physically dependent alcoholic.

 

I don't think your binge drinking years ago is the reason for your elevated liver enzymes in the present.

 

Do you take any medications? Potentially hepatotoxic supplements in high doses (e.g. https://www.livertox....gov/Niacin.htm )? Is obesity a problem (with regard to non-alcoholic fatty liver disease)?

 

An ultrasound of your abdomen would be really helpful. It's a cheap and effective way to gather Information about the liver, gallblader and to some extent the pancreas. Information that cannot be obtained with blood work.

 

Also a reasonable doctor should test for the usual suspects (e.g. hepatitis serology...) if this hasn't been done in the past.


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#10 Boopy!

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Posted 04 September 2018 - 03:02 PM

nope,   very healthy weight since I eat insanely healthy.   Asked the doc if I should try to wean off the Prozac and he said it isnt a factor.   I'm on the patch birth control.   Honestly the only thing I could figure was the drinking -- I mean I DID drink for years,  a LOT,  and have always been a thinner woman,   so maybe I just couldn't handle the excess alcohol compared to some?   I mean,   if I had more fat,   it would have cushioned the impact somewhat. 

In the meantime I am getting some more NAC  (I took it occasionally in the past),   ALA,   and PPC.    I have ALA powder but it is impossible to take that way.   I practically burned a hole in my poor tongue when I tried to use it sublingually.   It is the most acidic of all the acids I've tried.   Of course I should have known better!



#11 Phoebus

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Posted 04 September 2018 - 03:13 PM

nope,   very healthy weight since I eat insanely healthy.   Asked the doc if I should try to wean off the Prozac and he said it isnt a factor.   I'm on the patch birth control.   Honestly the only thing I could figure was the drinking -- I mean I DID drink for years,  a LOT,  and have always been a thinner woman,   so maybe I just couldn't handle the excess alcohol compared to some?   I mean,   if I had more fat,   it would have cushioned the impact somewhat. 

In the meantime I am getting some more NAC  (I took it occasionally in the past),   ALA,   and PPC.    I have ALA powder but it is impossible to take that way.   I practically burned a hole in my poor tongue when I tried to use it sublingually.   It is the most acidic of all the acids I've tried.   Of course I should have known better!

 

LEF has a fantastic liver product, its called 'European Milk Thistle with Advanced Phospholipid Delivery '

 

its milk thistle bound to phospholipids which increase its bioavailability quite a bit. I highly recommend it. 







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