When supplementing with oral nutrients there are 3 unspoken rules that are key to any successful administration.

1. You want what you are taking to be the actual supplement that is labeled on the bottle. Working with reputable companies with integrity is essential to ensure you are getting what you are taking.
2. You want what you are taking to be properly digested and assimilated by the body.
3. You want what you are taking to have the positive effect on the body or body systems that the manufacturers are claiming.

Bioavailability is the study of point number 2, how a supplement is digested in the GI tract and then absorbed and assimilated by the body. For the majority of nutrients, this process involves digestion and absorption through the small intestine.

Historical Research on NAD+ and NAD+ Precursors

In the world of oral NAD+ supplementation, the market is currently dominated by companies selling 4 forms of NAD+: 1-Nicotinamide (Nam), 2-Nicotinamide riboside (NR), 3-Nicotinamide mononucleotide (NMN) and 4-Nicotinamide adenine dinucleotide (NAD+). NAD+ is the key end goal molecule that produces the beneficial biological effects desired in the body. All 4 molecules are related as they represent larger and larger building blocks of the ultimate NAD+ molecule. Nam being the smallest building block, is converted into NMN by the critical enzyme NAMPT (Nicotinamide Phosphoribosyltransferase) with the addition of a phosphate group. NMN is then converted into NAD+ by the enzyme NMNAT (Nicotinamide mononucleotide adenylyltransferase) with the addition of another phosphate group, an additional ribose group and an adenosine group. Intracellular NR can feed into NMN production but taken as an oral supplement still needs to be broken down into Nam.

All the major digestion and absorption studies done on these molecules have to date been done on rat intestines. The major study published in the Journal of Nutrition in 1982 entitled, “Digestion and absorption of NAD+ by the small intestine of the rat.” by Gross and Henderson, showed that NAD+ taken orally is rapidly hydrolyzed into NMN, then into NR and then ultimately absorbed by the small intestine as Nam and its other constituent parts (ribose groups, phosphate groups, and adenine). The enzymes responsible for this would be the protease enzymes in charge of cleaving peptide and nitrogen bonds. Similar studies on oral NMN and NR showed that they needed to be hydrolyzed into Nam as well before being absorbed by the small intestine. It would seem that Nam acts as the smallest building block to NAD+ which can absorbed by the small intestine mucosal brush border cells.

The benefit of taking an oral NAD+ over Nam, NR or NMN is that in addition to the hydrolysis of Nam, oral NAD+ provides 2 phosphate groups, 2 ribose groups and 1 adenosine group. Digestive enzymes in the stomach and small intestine cleave the NAD+ molecule at certain key points in its structure. Each cut leaves a piece of the puzzle available for reassembly later once it has been absorbed by the body. We know from those initial rat studies done in the 80s that the ribose, phosphate and adenosine groups are also preserved and make it across the small intestine enterocyte cells [5]. These additional elements are key building blocks that are needed for reconstituting the final NAD+ molecule once inside the cells of the body.