#46-Chris Masterjohn, Ph.D.: Pathways to health and disease (NAD, sirtuins, methylation, choline...
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- เผยแพร่เมื่อ 6 ม.ค. 2020
- Full title: #46 - 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
Original release date: 3/25/19
In this episode, Chris Masterjohn, entrepreneur, independent researcher and doctorate in nutrition, elucidates the latest research on the risk and benefits of NAD supplements, and shares his personal intuition on the topic. We also dive deep into choline deficiency and its role in the rising prevalence of nonalcoholic fatty liver disease. From there, Chris enlightens us on the importance of methylation, a simple yet profoundly important biochemical process affecting our physical and mental health. He also describes the variations of the genes MTHFR and COMT, enzymes which play important roles in methylation and which have profound impacts on our well-being.
We discuss:
-Chris’s background, falling in love with biochemistry, and decision to pursue research over medicine [7:45];
-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];
-Decision making in the face of inconclusive data, and trying to disentangle the placebo effect [2:39:00];
-What does Chris believe to be true that very few people would agree with him about? [2:43:15];
-How to follow Chris’s work [2:48:45]; and
-More.
Show notes page: peterattiamd.com/chrismasterj...
About:
The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 10 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.
Peter is the founder of Attia Medical, PC, a medical practice with offices in San Diego and New York City, focusing on the applied science of longevity. The practice applies nutritional biochemistry, exercise physiology, sleep physiology, techniques to increase distress tolerance, lipidology, pharmacology, and four-system endocrinology to increase lifespan (delaying the onset of chronic disease), while simultaneously improving healthspan (quality of life).
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Masterjohn is fantastic. He solved my allergy problems with his histamine bucket talk. My allergist was surprised when I told him, he had never heard of this before.
How, You had a consultation with him?
Chris's insights about methylation are next level brilliance: the folic acid cycle stops in the protein fed state because there is already plenty of methionine, so no need to recycle homocysteine. MTHFR status is a spectrum and 90% of us don't have "perfect" MTHFR genes. But getting enough B2 will overcome MTHFR issues (because they are caused by riboflavin having less affinity caused by genetic variants), and without enough B2, we'll just switch over to methyl groups getting supplied by choline, in which case it helps to increase choline consumption even up to double. How creatine levels can be a better indication of methylation status than homocysteine. I love too how Chris keeps in mind the nutrients needed to break down and excrete supplements and medicines: methyl groups for B3 (so excess consumption drains our vital methyl groups) and glycine for aspirin (different podcast).
Peter adds a lot of depth and provides for further insights with his hypothesis that MTHFR SNPs may have a higher risk of fatty liver due to choline used in greater amounts for SAM/methylation and less for fatty acid export, and also how clinically B6 is effective in his practice in reducing homocysteine. Thanks for a phenomenal interview!
I just love how hands-on Peter is with his questions.
And I thought I was smart by passing the real estate exam…
Love listening to the truly smart people. May God bless them❤️
I am slowly loosing my wife to these podcasts, but it's worth it
That's funny.
I am also lost in these podcasts and my partner is unable to get how much I get from the info
Please do a round 2! Great content!
Dr. Attia's material and ability to transmit scientific information is absolutely amazing. He is a standout physician and teacher. I am definitely going to be a member because I want to support his work.
Best discussion about NAD, Nicotinomide, Nicotinamide Riboside, TMAO, NAFLD ... on earth, as of today.👍
Best health science podcast on TH-cam. Wow
Great to see all the Attia content uploaded onto TH-cam and with the fantastic breakdown of content by time line. Thanks Peter, please persist with the channel and it will take off as big as the podcast!
Such a wonderful episode! Got so much clarity on my MTFHR gene variant. Thank you Peter and Chris!
So what have you changed . ?
I fall asleep and wake up to this. How did I get here?
My hypothesis on elevated numbers of fatty liver, heart disease, anxiety, even obesity itself is that we started injecting our food with lab junk enrichments and high fructose corn syrup in 1992…We have become grossly over fed and have caused polymorphic/mutation driven depletion in half the population.
Such a brilliant podcast. I have Ehler Danlos syndrome which is associated with choline deficiency. This connects so many dots.
They just connected MTHFR to us.... look up Tulane April 2023 study Folate Dependent Hypermobiltiy Syndrome. I had blood work done and bingo! Going to see a functional edicine doc! This is what led me to this video!
awesome
We’re a wonderfully made machine
Great stuff. I like the short CV discussion. A guy's career history is usually not useful information, interesting enough, but doesn't need to be half a podcast.
For collagen plz reference Dr. Keith Baar. Solid!
32min in the only person I've listened to note the problem with every diet study ever. Via negativa.
This is wild
I tried taking NMN with TMG and major brain fog. By itself NMN is awesome but i do need to eat meat that day and rather early when i take it
Is there a reason people always consider niconamide, but never nicotinic acid (with carboxyl functionality) form of vitamin B3 when considering NAD boosters? Because when I take nicotinic acid, I can literally feel the flush in my peripheral vasculature, proving the nicotinic acid is bypassing the hepatic portal 1st pass metabolism because I can literally feel the flush (due to nicotinic acid) throughout my body?
Is there something I’m missing or something I’m overlooking? I realize when nicotinic acid enters the cell, there are several enzymes needed to turn this nicotinic acid into NAD? Perhaps the regulation or kinetics of the enzymes involved in nicotinic acid -> NAD have negligibly small rate constants or have regulation that minimizes the flux of this pathway? I doubt the PRPP or ATP cofactors would be rate limiting assuming we’re in the fed state with glucose and insulin (and therefore PPP activation and sufficient ATP levels).
Afaik nicotinic acid is preferable. I believe taking nicotinamide is heavily promoted as a "must have" for reasons of misunderstanding and profit without outlining the downsides compared with niacin or nmn
Because supplements are mostly a scam and they want to sell you tons of expensive garbage. I'm sure it has some use but it's probably not going to be as good as simply fasting one day a month, and that's free.
@Richard Breeze my understanding is that ingested NAD boosters enter the portal system where the liver converts them into niacinamide which apparently leads to a net result of decreased NAD activity through what resembles a negative feedback loop... nicotinic acid bypasses this however nicotinic acid still needs other functionalities (which can come from tryptophan) but this process still has rate limiting bottle necks that are difficult to overcome.. theoretically compounds that effect CD38 which would attenuate NAD Degredation seems like it would make sense? Honestly I’m confused I feel like there is something I’m missing idk what is wrong with this model and perhaps I have a misunderstanding of NMN and NR metabolism because I never hear about this and I genuinely don’t think it’s just some conspiracy? And there do seem to be some studies showing specifically NMN and NR benefits so idk and NMN and NR theoretically do not need the other functionalities needed to produce NAD so idk maybe there is utility for them idk the older I get the more I realize idk anything everything there is a paper showing me I’m 100% backwards in my thinking
@Richard Breeze sorry I haven’t thought about this topic for a while so I had to look it up but yeah when sirtuins do their chemical modifications, they produce niacinamide as a byproduct which then induces a negative feedback effect on sirtuins? So if nad boosters are converted into niacinamide, wouldn’t that inhibit sirtuins activity? Does nicotinic acid get converted into niacinamide in the liver(or microbiome) maybe partially its a simply chemical modification and I’ve seen some data but definitely a large portion of nicotinic acid gets to periphery because I can literally feel it. To be honest I’m so over basic sciences and trying to use first principles in medicine and using theories like nad boosters boosting sirtuins activity like if anyone can show me human data that proves this fine but then does it prove it actually at the end of the day leads to net positive? Ugh I’ve become so disenchanted with medicine it’s so frustrating and impossible to have any confidence in anything whatsoever sometimes it feels like even the best and brightest Ivy League experts are just really guessing especially when it comes to something like aging where it takes decades to connect cause and effect it feels hopeless
@Richard Breeze there does seem to be evidence that NMN supplementation has real benefits in mouse models but I’ve had difficulty wrapping my head around the biochemistry and implications on humans.
I still remember Kahn going off about TMAO right after his line about "not scooping cigarette smoke from arteries".
Around 1:01:00 the interrupting each other got really annoying. I was already expecting this escalation, since Doc Attia does this very much from the beginning - asking long winded questions talking much, then interrupting Chris shortly in his response, only to then talk himself again.
Sorry, this way you suffocate your interview partner and don't get Chris' insight delivered to your audience well. It appears that your prime motive was to show off to Chris what you already knew about his topics.
I see this type of comment on this channel often, and while I will AGREE with you, I think in many instances we need to remember that Peter is usually on the level of the folks on his show, so these podcasts tend to be more of a discussion rather than an interview or lecture. There is going to be reciprocation and interruptions as they feed off of each others genuine interest and knowledge.
Just imagine yourself a fly on the wall at a restaurant where these two have met for lunch. It’s not a classroom lecture with moderated questions.
I like some back and forth
Attia’s clipping off of Master john’s informative explanations deprive me of knowledge, perhaps including results contrary to Attia’s conclusions.
Please Dr Attia, kindly, DO NOT INTERRUPT.
Rushing to beat others to ‘the answer’ is childish, to put it kindly.
@@eugeniebreida1583 honestly, I'd say he's made tremendous progress since this interview. His most recent conversations are just amazingly detailed, respectful and patient.
Hep vaccine and enviro insults are the unspokenelephants in the roomas usual.