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It's a good time to review what is NAD, what is a coenzyme, what is a vitamin, what do we get in food, and why might NR have benefits for ppl. /1
NAD refers to 4 molecules (technically: coenzymes) inside all cells that are the central catalysts of metabolism. NAD is equally essential for your brain function as it is for beef liver, broccoli florets and brewer's yeast. It's also in all whole foods as the 4 coenzymes. /2
Levels of NAD+ and NADPH, in particular, are under attack in conditions of metabolic stress including DNA damage, overfeeding, alcohol use, loud noise, time zone disruption, free radical damage, postpartum, infection/inflammation, heart failure & neurodegeneration. /3
There is additional evidence that NAD is under decline some tissues as a function of aging. When we eat any whole food, we are getting all the macronutrients & the micronutrients in that food. Proteins are digested into amino acids & are regenerated into cellular proteins. /4
In digestion, NADP+ & NADPH lose an adenosine plus 3 phosphates while NAD+ & NADH lose adenosine plus 2 phosphates to form NR, which is the largest piece of NAD that can be taken up by cells. Further digestion of NR yields nicotinamide (NAM). NAM can be degraded to niacin (NA)./5
NR, NAM and NA are the NAD precursor vitamins. They are also known as 3 forms of vitamin B3. /6
Some cells can make NAD from the amino acid tryptophan in an energetically expensive process that depends on 8 genes not all cells express. Also, not all cells can make NAD from NA, again because not all cells express the key gene that converts NA into a larger piece of NAD. /7
But know this: some of your cells do convert NA to NAD and this proves that there is ENDOGENOUS NIACIN metabolism even for those of us who never supplement with niacin (sorry for shouting 
). /8
). /8
The gene for NA utilization was present in the earliest animals half a billion years ago. Why? Because our bodies (including our microbiomes) break NAD down into NA and many of our cells use NA to regenerate the NAD. /9
Nutrition books say that particular foods are a "good source of niacin" but what this really means is that the food has a lot of NAD & NAD breakdown products in it. We aren't niacin deficient unless we are below 15 mg of "niacin equivalent" per day. /10
Our research (for example https://doi.org/10.1016/j.celrep.2019.01.007) shows that many conditions of metabolic stress make tissues LOW IN NAD & that rodents (& in this case, their offspring) are much healthier when given NR supplements in addition to a diet that already has NAD in it. /11
Our research shows that supplementation can prevent diseases & conditions & optimize health. It raises 2 additional questions. Does the supplement have to be NR or could it be another NAD precursor? Is NR being generated endogenously to maintain health? /12
In the failing heart, NAM can't substitute https://doi.org/10.1161/CIRCULATIONAHA.116.026099 because the NAM use gene is going down while one of the NR use genes is spiking up. We reasoned that the NMRK2 gene is spiking up because failing hearts are trying to grab all the NR available. /13
Of course this means that NR must be circulating and there ought to be consequences for a mouse if you take the NR pathway away for a mouse NOT TAKING NR supplements. And this is true as well ( https://www.nature.com/articles/s41467-019-12262-x). Once again, NAM can't substitute for NR. /14
I'm sure we also get NR in our diet when food is digested into NAD precursors. But the body of research is indicating that NR has greater health promoting activities than other NAD precursors, largely because when NAD is under attack, the NR utilization genes get turned up./end
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