9 replies to this topic

[Phoebus]

Full study here 

 

https://elifescience...eoYE6g4=.RmdNXZ

 

ABS write up on it 

 

 

NR supplementation did not increase NAD+ levels in the heart, or improve heart function.

In addition, they found that treatment with larger dosages of NR seemed to have an increasingly negative effect on heart function due to excess NAM buildup.

A dosage of 1,000 Mg per Kg of NR in the chow significantly depressed PARPs from repairing DNA damage.

This dosage is roughly equivalent to 569 mg a day for a 70 kg human.

 

NR supplementation improved NAD+ levels in the liver

 

NR supplementation did not improve NAD+ levels in the heart

 

NR supplementation did not restore  heart function

 

Increasing doses of NR progressively inhibit deacetylation and PARP cleavage

 

Conclusion: Large dosages of oral NR may have negative consequences

 

[LawrenceW]

I took 1,000 mg per day of Niagen NR for 3 months back in 2017.  At the end of the 3 months there were no changes in my blood biomarkers and I felt like crap on top of it.

 

Now I know why!

[male_1978]

So what would be your conclusion for us from this study? The effect is probably similar with NMN, or no?

How can NAM be removed from the body?

[stephen_b]

Nicotinamide (NAM) when coupled with taurine in some animal models protects against fibrosis (PMID 7520944). I couldn't find any direct support for this, but I wonder if taking taurine with the niacin source might help in this situation too.

[able]

Studies with NR show  a 40x increase in NAM, soon methylated to MeNAM for excretion.  Taking 1,000 mg or more make it even worse.

 

It seems obvious the body doesn't need or want that much NAM.

 

I've long noticed that many people here like lawrence and others have experimented with larger dosages but can't recall a single one that felt they noticed any benefit and all dropped back down below  1 gram.

 

It sounds like in this case, it is not only diminishing returns, but actually bad for us.

 

Maybe TMG is a good idea to protect against methylation issues.  

 

But would methyl donors actually help us clear out excess NAM and avoid issues like it this study?  Or do they just ensure methyl is available for other important processes?

 

 

[MikeDC]

Full study here

https://elifescience...eoYE6g4=.RmdNXZ

ABS write up on it

Bad math. It is more like 5.6g for a 70kg human.

[Oakman]

This sounds perhaps troubling for those taking NR, however results & conclusions remain unclear, at least to (me) a lay person trying to understand the study.

 

1. Dose - is MikeDC's understanding correct? And if so, they used nothing close to what we take as humans adjusted for weight. Does dose make the "poison", or not in this study?

2. Transgenic mice - we aren't transgenic humans, so is using them and their inferences to humans simply exacerbating an induced pathology to produce unfavorable results by overdosing them?

3. Might this study be more indicative of how to (possibly) treat humans already afflicted with similar metabolic failures? And not normal, healthy humans?

 

To wit: "The present study has some limitations. Not all findings were statistically significant, and these data must be interpreted with caution. Association does not necessarily mean any causal relationship and additional experimental studies are needed to fully support our conclusion. Moreover, the relevance of these studies to human pathology is still uncertain."

[stephen_b]

From the study:

NR (Niagen from Chromadex) was added to the diet, either as 400 mg/kg chow (medium dose) or 1000 mg/kg chow (high dose), after 6 weeks of mutUNG1 induction (with a total of 2 weeks of NR treatment). These numbers were chosen based on the parameters that a mouse in average weighs 30 g, and eat 3 g chow per day, and published experiments performed by other groups (Gariani et al., 2016; Zhang et al., 2016).

 

 

 

 

So 400mg NR / 1kg chow * 3e-3 kg chow/day = 1.2 mg NR/day. 

 

Then 1.2 mg NR / 30e-3 kg mouse weight  = 40 mg NR /kg mouse.

 

Divide by 12.3 for the the human equivalent dose (HED) of 3.25 mg/kg. For a 70 kg person, that comes out to 227 mg of NR.

 

Did I get that right?

 

Edited by stephen_b, 12 September 2021 - 10:31 PM.

[able]

I think you're right Stephen_b.

 

It gets confusing converting the dosage of NR in chow to how much the mouse consumes.

 

Alivebyscience lays it out step by step and has a chart at the bottom of this page that shows the middle dose had mice consuming the equivalent of 569 mg per day for 70 kg human.

 

If that was incorrect, you can be sure ChromaDex would have responded to let us know.  Crickets.

 

Edited by able, 13 September 2021 - 01:27 AM.

[stephen_b]

Thanks for checking that. 228 mg is not that high a dose.

 

I'm taking taurine and beta-alanine (ref) and betaine (ref, ref) when I take the niacinamide + ribose as part ofTurnbuckle's mitochondria and stem cell protocols. The middle reference proposes taking equimolar dosages of betaine with niacin (in the context of preventing liver damage).

 

I see Thorne is promoting taking of methyl donors with NR, calling betaine "one of the most important" of the methyl donors:

 

As NAD+ does its work, it is broken down to nicotinamide (also known as niacinamide), which is mostly converted to methylnicotinamide (MeNAM). So, the more NAD+ there is, the more MeNAM there is. The methyl group for this bioconversion must come from a methyl donor, but if the methyl group comes from the methyl pool in your body, then it puts stress on that pool.