Going beyond NR
A nicotinamide mononucleotide (NMN) trial
NMN is NR with an added phosphate group, and is one step closer to NAD. As oral NR and NMN appear to be broken down before absorption (at least in rats, see Ref-1 below), but are reassembled in cells, it would seem possible to increase cellular NMN production by adding a phosphate source to the N+R protocol (see Ref-2). This could be organic or inorganic. I’ve tried it separately with IP6 and disodium phosphate, which both seem to deliver more than N+R alone, in my (somewhat limited) experience.
NMN is known to raise NAD+ levels in the hippocampus (See Ref-3).
The Fission half of the protocol is thus—
N+R — 2g/5g
Rose hips (1g) — activating ampk for fission
Gypenosides (150mg) — activating ampk for fission
IP6 or inorganic phosphate (2-5g) — phosphate source to produce NMN from NR.
Gym after 1.5-2 hours.
I’m allowing more time before the gym as NMN requires another step for synthesis, and experimentally it seemed to take longer to reach its maximum, which is higher than N+R alone. Lysine and pyruvate, which I used before, are still optional. See also my comments about resveratrol at this end of this post.
Ref-1
[A study in rats] Perfused or intact intestine rapidly hydrolyzed NMN to nicotinamide riboside, which accumulated, but was not absorbed. It was slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide, which was the major if not the only labeled compound absorbed.
http://nadh.wiki/wp-...-of-the-Rat.pdf
Ref-2
Conditions Necessary for NMN Synthesis-The failure of previous workers to obtain results comparable with those reported here may be attributed to two factors. In order to obtain maximum synthesis, the cells must be washed prior to incubation and must be incubated in a medium containing inorganic phosphate in excess of that found in plasma.
http://www.jbc.org/c.../2/889.full.pdf
Ref-3
Nampt converts nicotinamide, a major precursor in mammalian NAD+ biosynthesis, and 5′-phosphoribosyl-1-pyrophosphate to nicotinamide mononucleotide (NMN), a key NAD+ intermediate. NMN is then converted to NAD+ by nicotinamide/nicotinic acid mononucleotide adenylyltransferase (Nampt). We and others have previously reported that the expression of Nampt in the brain is extremely low compared to peripheral tissues. However, Nampt has uniquely strong expression in the hippocampus. Because recent studies show that the energetic demands of stem cell proliferation and lineage specification require distinct metabolic programs, we hypothesized that [neural stem/progenitor cells] would be particularly sensitive to changes in NAD+ levels and accordingly alter their proliferation, self-renewal, and differentiation.
https://www.ncbi.nlm...les/PMC4194122/
Given the low levels of Nampt in most of the brain as reported above, a supplement to upregulate it might be useful if this protocol is to be extended to all parts of the brain. Resveratrol upregulates Nampt, and so I tried 200mg (along with 25mg DHEA to avoid joint pain) 4 hours after beginning the protocol. I got a transient sense of wellbeing from it about a half hour later, something I’d never experienced before from resveratrol. The meaning of this I don’t know, but a felling of well-being is generally a good sign. More experiments are thus in order.
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