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