I've been listening to a PhD named Dimitry Katz who has been studying nicotinic acid and NAD+ production and potentiation for a few years now. He's a strange dude, but he's also quite brilliant. He is using nicotinic acid and L-glutamine in a ratio of 1:1.2 respectively to treat any/all forms of mitochondrial dysfunction and dysglycemia. One of the main reasons it works is because of NAD+.
Going to see if I can explain it in a way that makes sense. If I make a mistake or have something wrong, by all means please chime in. I just want to learn and no ego involved.
"Glutamine is required for the conversion of nicotinic acid adenine dinucleotide to NAD+ catalyzed by NAD+ synthetase (Figure 2). Thus, inherited glutamine synthetase deficiency specifically affects the synthesis of NAD+ from the NAD+ precursors, tryptophan and nicotinic acid."
https://lpi.oregonstate.edu/mic/vitamin ... eference78
Now to get a little more specific, there are 3 main pathways for the synthesis of NAD+ in mammalian cells are the Preiss-Handler pathway, de novo biosynthesis pathway, and NAD+ salvage pathway. The salvage pathway is the main source of NAD+ generated in mammalian cells due to its high production efficiency, and less than 1% NAD+ is lost daily due to efficient recycling. This might explain why cells are
completely dependent on this pathway.
https://www.mdpi.com/2073-4409/11/17/2627
OK, so we use the salvage pathway the most. The first step is the rate-limiting reaction of the pathway catalysed by NAMPT, transforming
NAM to nicotinamide mononucleotide (NMN) in the presence of magnesium (Mg2+) and phosphoribosyl pyrophosphate (PRPP). In other words, NAMPT limits the amount of NAD+ that's produced this way.
This is where glutamine comes into play. It potentiates NAMPT, which we just read is a limiting part in the most used/efficient way we create NAD+.
"Glutamine appears to be crucial to the effectiveness of NAMPT activity in regulating the TCA cycle as glutamine can compensate for a reduced carbon flow from glycolysis to the TCA cycle resulting from NAMPT inhibition."
Pharmacological Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT), an Enzyme Essential for NAD+ Biosynthesis, in Human Cancer Cells
And in this paper, they demonstrated that glutamine increased the effectiveness of NAD and NADH, making them more effective in creating ATP.
"Our data show that oral L-glutamine can significantly increase the NAD redox potential and NADH level in sickle RBC. These changes may decrease oxidative susceptibility of sickle RBC and result in clinical benefit."
Oral L-glutamine therapy for sickle cell anemia: I. Subjective clinical improvement and favorable change in red cell NAD redox potential
So far I've worked my way up to 5g nicotinic acid (work up slowly...the flush isn't super fun when you first start) and 6g glutamine, following his 1:1.2 ratio. It's in that ratio because of the difference in molecular weight between the two. I put it in cold water (warm water will denature glutamine) - the nicotinic acid dissolves quickly, the glutamine does not.
Have incredible energy, do not get sore after workouts, dopamine levels have increased (not bored like usual), and sleep has gotten a lot better. Wife is experiencing the same with the added benefits of it stopping her menopausal hot flashes. Seems this stabilizes mast cells, too.
Hopefully this info helps!
