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Chris Masterjohn, Ph.D.: Podcast on NAD and sirtuins, methylation, MTHFR and COMT, choline deficiency and NAFLD & more

nad sirtuins chris masterjohn methylation mthfr comt choline deficiency nafld tmao creatinine

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#1 Engadin

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Posted 25 March 2019 - 01:19 PM


Dr. Peter Attia podcast:

 

Chris Masterjohn, Ph.D.: Navigating the many pathways to health and disease – NAD and sirtuins, methylation, MTHFR and COMT, choline deficiency and NAFLD, TMAO, creatine and more

 

“People are gonna make a decision to. . . either wait 10 or 20 years until we know something better, or you take the position that you're going to tinker. And if you're going to tinker, you're a lot more successful if you have a working model of what's going on than if you don't.” —Chris Masterjohn

 

 

Part of the content:

 

  • Choline: what it is, why it is important, and how a deficiency can cause non-alcoholic fatty liver disease [11:45];
  • NAFLD: increasing prevalence and potential causes [25:00];
  • TMAO: Should we be worried about the TMAO content in choline and our foods? [39:15];
  • Types of fatty acids: How they may predispose us to different types of illnesses [53:30];
  • Why don’t we see low VLDL in patients with NAFLD? [59:45];
  • Understanding flux, and how machine learning may affect medicine in the near future [1:03:15];
  • NAD: How it works, supplements, sirtuins, and the central role of the liver [1:09:30];
  • Intravenous NAD [1:33:00];
  • Oral NR: Is it the optimal way to get more NAD? [1:38:30];
  • What is the possible harm of taking an NAD precursor? [1:47:15];
  • The MTHFR gene [1:49:45];
  • The methylation pathway [1:58:15];
  • The COMT gene [2:04:30];
  • Creatine: The uses and benefits and it’s important role in methylation [2:10:15];
  • Dietary strategies for MTHFR: choline, creatine, folate and glycine [2:16:45];
  • How to mitigate the negative effects of NAD supplements [2:23:45];
  • A case study of a person with high homocysteine [2:28:00];
  • What is the level of evidence that you need to take an action? [2:32:15];
  • Does Chris supplement with NAD precursors? And can it improve symptoms of rosacea? [2:35:45]; ...

 

 

Source: https://peterattiamd...hrismasterjohn/


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#2 Engadin

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Posted 26 March 2019 - 06:48 PM

ABN notes on this podcast: https://alivebynatur...tuins-and-more/

 

" For some reason, he thinks NMN is hydrolyzed in the gut more than NR, which doesn’t   match the     research.  It is not questioned that   NR much less stable than NMN and is hydrolyzed more easily, which is why NMN is  found in bloodstream, but NR is not –  even after large dosages.

 

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 NR might be better, as he believes (wrongly imo) that NR survives digestion better than NMN.

 

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.   Doesn’t acknowledge that NMN shows even more access and effect on muscle than NR.  

 

Chris also 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, it seems that like nearly all doctors, he is skeptical of things not mainstream.     He says he is   not as adventurous as Dr Attia, and seems prejudiced against anything that “bio-hackers” do.   Unless it has clinical evidence, which is likely why he favors NR over NMN.

 

 

 

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 causes it to be hydrolyzed and doesn’t make it past small intestine.   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 B12.

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). "

 

And more ...

 

 


Edited by Engadin, 26 March 2019 - 07:12 PM.


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