This is a Great podcast. I like the way Chris explains things – much more understandable than most PHD’s. It helped me understand better about methylation, where clearly he is an expert and he believes is a potential roadblock to getting the most from a NAD+ booster.
Fortunately, people a lot smarter than me designed our new NAD+ Energizer product that has Taurine, NAC, Allicin, Astaxanthin, and a little methyl folate – all of which are shown to help prevent or deal with repercussions of methylation problems.
Chris believes the phosphate in NMN means it doesn’t get past cell membrane (1:41) , but is likely cleaved to NR, implying it should work the same as NR.
Peter says he thinks sublingual NMN is likely most effective. Chris doesn’t disagree, but says “if you didn’t have that choice “(sublingual or IV) then ….
Chris believes Rabinowitz research is correct and that NR and NMN do not escape liver, only NAM is excreted. But he says that some NR does make it to muscle, which is why it is more effective than NAM. I’m not sure how he squares that up with his belief that NO NR or NMN escape the liver.
Chris doesn’t seem aware of the research on slc12a8 transporter- maybe this was recorded months ago?
Chris says that NAD+ definitely does get into some cell types (1:18 and 1:35) , and that NAD+ is normally found in bloodstream. But says we don’t know how it gets to bloodstream and theorizes it is mostly due to autophagy or dead cells releasing their NAD+. This doesn’t make sense at all, since NAD+ levels in the blood are high in youth, and drop in aging or sick. Why is NAD+ so low in aged animals?
He says he thinks people feel bad when getting NAD+ IV because it is a signal that lots of cells are dying and releasing NAD+. Then he (and Peter), say to ignore the fact that people feel wonderful after a NAD IV. They are saying, the bad feeling means something. But ignore the good feelings. Not consistent.
The high dosage used in clinics is the reason for ill feeling. It is ultra expensive and inconvenient to hook someone up to an IV for 8 hours. So they must force as much NAD+ in as quickly as possible. Clinics that start with a lower dose find it doesn’t cause tightness in chest and ill feeling. Sublingual NAD+ is slower and we have never had a single complaint about feeling bad from it.
He believes NAD+ is a signaling molecule, and it could make good things happen (1:38), but doesn’t know or acknowledge NAD+ passes the Blood Brain barrier and is taken up directly by hypothalamus – which is the master regulator or metabolism.
He believes that feeding NR to the liver provides a source for NAD+ that doesn’t inhibit Sirt, as NAM does, which makes sense to me. But he ignores that NAD+ in IV gets filtered by liver and doesn’t inhibit Sirt.
Overall, while clearly brilliant and great at explaining complex science, it seems he is a bit cautious and skeptical of things not mainstream. He says he is not as adventurous as Dr Attia, and is a bit prejudiced against anything that “bio-hackers” do, unless it has clinical evidence.
He does say he is taking 75 mg of NR twice a day, just playing around, and may step it up.
Some notes I took are below – excluding the sections that are not NAD+ related.
1:12:30. – he thinks NAD/NADH ratio problem is due to overfeeding
1:14. We definitely do not absorb NAD intact thru intestines.
Nothing but NAM makes it past liver… there is some NAD and NADH in blood, but not a lot
If you take NR, trace amounts get to blood and into other cells.
Overwhelmingly, is just NAM that tissues use to create NAD
1:17. – virtually all NAD+ in body is from NAM in liver
1:18 – NAD DOES enter cells, if you are injecting it.
1:20. – NR is a form of pressure relief/storage for NAM before conversion to NMN and NAD
1:22. – Very little NR in blood from 1 gram. None goes to brain. Fairly decent at crossing into muscle
1:23. – tiny trace makes it thru. Had to blow up the graph to show it – basically meaningless
1:25. – Peter believes sublingual NMN is best
1:27 – 2016 Rabinowitz showed NR raised NAD in muscle more than NAM
1:29. – NAM in the liver is a liability for sirts, that requires resources to upgrade it to NMN
1:35 – there are a variety of cell types that have ability to take NAD into cells
1:36. How does NAD get into blood normally? Theorizes it is from dead or stressed cells, secreting it as a signal
1:37 There is a whole class of enzymes that consume extracellular NAD – it is clearly a signaling molecule
1:38 Maybe the signal has good consequences – we don’t know
1:41 – Chris believes the phosphate in NMN means it doesn’t get past cell membrane, but is likely cleaved to NR. Doesn’t seem at all aware of Slc12a8 – when was this recorded?
1:47 potential risk – sapping methyl group supply. Studies show huge increase in urine and blood of methylated metabolites
1:50. – folate B9, can methylate homosyteine back to b-12. Cholate does the same. About 50-50
1:52 – we all have mthfr. If you have more mthfr, you simply use more cholate to methylate homosystein back to b-12
2:04 – take phosphate choline, not choline salt
2:10. 1,000 mg of choline a day – preferable from food
2:20. – low methyl folate causes excretion of glycine and requires more glycine. 3-5 grams of glycine a day = better sleep. 3-6 grams with a meal = better blood glucose levels – gelatin or 1-2 cup bone broth
2:23. How to mitigate negative effects of NAD supplements
2:25 – methylating a lot of NAM can decrease creatine levels – take 5 grams of creatine a day.
2:27 – anecdotes of NR leading to seesaw depression could be methyl problems. He recommends methyl folate and equal amount of TMG (TMG further downstream of choline)
If you’re taking a NAD+ booster, whether NR, NMN or NAD+, you probably do want to take something to prevent methylation issues that Dr Masterjohn explains so well. Our new NAD+ Energizer product has Taurine, NAC, Allicin, Astaxanthin, and a little methyl folate – all of which are shown to help prevent or deal with repercussions of methylation problems.