NRNew research finds large dosage of NR may be harmful for heart function in mice

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jocko6889
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New research finds large dosage of NR may be harmful for heart function in mice

Post by jocko6889 » Wed Aug 04, 2021 11:08 pm

Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication
This study examined the effect on NAD+ levels from DNA damage leading to heart failure in mice, and the efficacy of Nicotinamide Riboside (NR) supplementation to restore NAD+

They found the increased activity of PARP enzymes required to repair the DNA damage resulted in diminished NAD+ levels.

However, NR supplementation of 400 mg/kg a day did not increase NAD+ levels in the heart, or improve heart function. This is roughly equivalent to 2,000 mg a day for a 70 kg human.

In addition, they found that treatment with a high dose of NR may have negative effect on heart function.

DNA damage lowers NAD+ levels

As expected, they found the increased activity of PARP enzymes required to repair the DNA damage resulted in diminished NAD+ levels. According to the authors,

“depletion of the NAD+ pool would cause cellular harm due to loss of sirtuin activity and a dysregulation of a number of protective pathways”.
NR supplementation improved NAD+ levels in the liver

Supplementation with 400 mg/kg a day of NR did improve NAD+ levels in the liver.

“We did detect an increase in NAD+ levels in the livers of mutUNG1-expressing mice”

Supplementation did not improve NAD+ levels in the heart of control mice (Wt), or the experimental mice with DNA damage (mU1)

“We did not see any increase in cardiac NAD+ levels with NR supplementation”

NR supplementation did not restore heart function

NR supplementation did not improve NAD+ levels in the heart

The researchers wanted to find if a higher dosage of NR might be more effective, so increased the dosage from 400 mg/kg to 1000 mg/kg a day.

They were surprised to find the higher dosage was detrimental to heart health, possibly due to excessive buildup of Nicotinamide (NAM) which inhibits Sirtuins.

Protein acetylation was increased (bad) in mice with DNA damage in heart tissue (mU1). Acetylation was greatly increased with 1,000 mg/kg of NR.
“To our surprise, a high dose of NR caused an even higher overall mitochondrial protein acetylation than the lower dose”

“Treatment with a high dose of NR as a tool to increase NAD+ levels may inhibit rather than increase sirtuin activity due to accumulation of nicotinamide (NAM). Our findings suggest that NR might have disadvantageous effects on cardiomyocyte mitochondria, at least in high dosages.”
“NR supplementation did not lead to any significant changes in the cardiac phenotype”

Higher dosage of NR had a negative effect on heart function

For more, click the link below:
https://alivebyscience.com/new-research ... e-in-mice/


smokinjoe
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Re: New research finds large dosage of NR may be harmful for heart function in mice

Post by smokinjoe » Fri Aug 06, 2021 12:24 pm

Hi Jocko
Am I correct in recalling that large doses of NMN in mice did not have this effect at all?
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jocko6889
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Re: New research finds large dosage of NR may be harmful for heart function in mice

Post by jocko6889 » Sat Aug 07, 2021 2:22 pm

smokinjoe wrote:
Fri Aug 06, 2021 12:24 pm
Hi Jocko
Am I correct in recalling that large doses of NMN in mice did not have this effect at all?

 
That's correct.  NMN is more stable in the bloodstream than NR, which is a smaller molecule and breaks down very quickly into NAM.  We already knew that but this study points out the very bad side effects from too much NAM in the system.  They used doses that are considered normal by most people, which makes it even more scary.

Having said that, it is still wise to take NMN sublingually, unless you're using a liposomal version which can be swallowed.   There will be far less NMN broken down.
 
TedB
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Joined: Wed May 19, 2021 1:55 pm

Re: New research finds large dosage of NR may be harmful for heart function in mice

Post by TedB » Mon Aug 09, 2021 7:05 pm

Not a concern for me, i am NMN episcopalian.
ChrisBON
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Joined: Mon Sep 16, 2019 6:09 pm

Re: New research finds large dosage of NR may be harmful for heart function in mice

Post by ChrisBON » Wed Aug 11, 2021 4:38 am

Ok, so if you are taking NR and it is processed in the stomach... then it could be detrimental.

But either way... taking SL or even better LSG Capsule NMN will get you the right stuff in the right way.

 
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