ChromaDex Corp. (CDXC)

[KMBJN]

Thanks, Karin, for the prompt for me to do some long overdue homework!

It looks like the NR patent-holder's (Charles Brenner) student's (Samuel Trammell) U of Iowa PhD thesis sheds some light on the issue in mouse livers in Chapter 5, recently published in Nature Communications here:

http://www.nature.com/articles/ncomms12948

185 mg/kg NR was given to mice orally (7 doses over 12 hours), along with equimolar doses of NA and NAM. Figure 5b shows that NR increased mouse liver NAD+ levels with an AUC of ~16,000, significantly more than NA (AUC ~8,000) and slightly more (not significantly so) as NAM (AUC ~14,000).

One could perhaps conclude that in mice, NR is 2x as effective at increasing liver NAD+ vs NA, and ~15% more effective than NAM. In general, mice started with around ~1 mM NAD+. This increased to ~2 mM NAD+ with NA, a peak of ~3 mM NAD+ with NAM, and to >4 mM NAD+ peak with NR.

It's interesting that NR did not increase NAD+ levels significantly in the mouse heart (but it did increase NMN and NAM in heart).

They used a mouse dose of 185 mg/kg to match approximately the human dose given - 1000 mg (to a 66.5 kg, 52 yo male - Dr. Brenner? born in 1961), using mouse to human conversion factor of 12.3 based on BSA.

Apparently recommended daily dose of Vitamin B3 as NA or NAM is 15 mg /day to prevent pellagra. They say the equivalent dose of NR would be 35.7 mg (not sure on that conversion). The study tested humans with 100, 300, or 1000 mg doses of NR, and measured NAD+ increases in human blood cells (N=12). Figure 8b shows that NR increased concentrations from ~12 uM to slightly above that, say ~16 uM at 100 mg, and to ~18 uM at 300 or 1000 mg. Quantitatively, the NAD+ increase was dose dependent, with huge amount of variability between subjects.

I believe the larger Elysium study (N=120, 10x larger) showed that 250 mg/day supplementation in 60-80 year olds increased blood NAD+ levels 40% and 500 mg/day 80% over 4-8 weeks. Look forward to seeing the details published.

Would love to see the comparison of NA, NAM, and NR in humans in terms of increase in NAD+ in blood and perhaps muscle biopsy (with effects on mitochondrial number). I would be really interested to know what are the NAD+ levels in brain, heart, muscle, blood, and CSF.

One thing to keep in mind is that if NA is 10 times cheaper for equivalent dose of NR, does it really matter if NA is only 1/2 as potent? It would still be 5x better value for increase in NAD+.

There are benefits to avoiding the flushing, for sure. Perhaps the flushing will not allow people to increase their NAD+ levels high enough.

Normal human ageing shows decline in skin tissue NAD+ levels from ~4 mM at age 20, to ~3 at 40, ~2 at 60, and ~1 at 80 years in women, and perhaps worse (lower levels) in men.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042357

Figure 4.


Another important consideration the SA author brings up besides the 3 vitamins/supplements' effects on NAD+ levels is the NR markup. I recall CDXC charging $1,000/kg or $1/g of NR to Elysium. Other companies then sell say 125 mg x60 pills = 7.5 g for $40, a ~5x markup! Maybe CDXC could sell direct to consumer to cut out the middle man?



I remain long CDXC. I think this is another overreaction, and that NR will show to be an important neuroprotectant and anti-aging supplement/medicine.