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Peter Attia MD#46–Chris Masterjohn, Ph.D.: Pathways to health and disease (NAD, sirtuins, methylation, choline...
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At a glance
WHAT IT’S REALLY ABOUT
Masterjohn and Attia Explore Choline, Methylation, MTHFR, COMT, and NAD Precursors
- Masterjohn argues choline is essential for exporting triglycerides from the liver via VLDL, so deficiency causes fatty liver in humans on parenteral nutrition and in animals regardless of whether sugar, alcohol or fat is the cause.
- He discusses the TMAO scare, putting his belief in the story that eggs and meat harm the heart via TMAO near zero, noting fish carry far more TMAO, and he prefers phosphatidylcholine from food over choline bitartrate.
- On methylation, both speakers describe MTHFR and COMT variants as continuous spectrums rather than binary mutations, and Masterjohn explains how low MTHFR activity raises choline needs and how riboflavin, B6 and TMG fit in.
- On NAD precursors, Masterjohn explains the liver converts oral NR to circulating nicotinamide, doubts NMN and IV NAD make physiological sense, and warns that high-dose NR may drain methyl groups, while noting human trials so far show no benefit.
- The two also discuss how to weigh evidence versus personal risk tolerance, the pitfalls of judging supplements by feel or placebo, and the importance of understanding flux rather than static blood snapshots.
IDEAS WORTH REMEMBERING
5 ideasCholine deficiency alone can produce fatty liver
Because phosphatidylcholine is needed to build VLDL particles, low choline traps triglycerides in the liver; Masterjohn notes nine of ten people on a choline-free diet developed fatty liver in controlled studies.
Diet changes bundle many variables
Masterjohn points out that cutting fructose also changes protein, choline and micronutrients, so human results like the fructose-reduction study are hard to attribute to one factor, and animal data help make sense of them.
MTHFR and COMT variants lie on a spectrum
Masterjohn says there is no true wild type; activity is spread fairly evenly across the population, and the effect of the genotype depends on nutrient supply such as riboflavin and methyl donors.
Homocysteine response depends on which step is the problem
Masterjohn explains that B6 helps break down homocysteine in the fed state, while recycling in the fasted state relies on folate or choline-derived TMG, which may explain why Attia's patient responded only to TMG.
Oral NR acts mainly through liver-made nicotinamide
Based on the Rabinowitz tracer studies, Masterjohn says tissues outside the liver get NAD from circulating nicotinamide, and NR likely works better than plain nicotinamide because it avoids immediate detoxification in the liver.
WORDS WORTH SAVING
5 quotesI think that the idea that mistaking a concentration for flux is one of the overwhelming interpretive problems in science and in popular science. In both.
— Chris Masterjohn
We all have MTHFR.
— Chris Masterjohn
if you're gonna tinker, you're gonna tinker a lot more successfully if you have a working model of what's going on than if you don't.
— Chris Masterjohn
You can't understand flux with a snapshot. You have to have the goddamn video, right?
— Peter Attia
I really think we really throw the baby out with the bathwater if we don't look at what's been done by the people who are hardcore conventionals.
— Chris Masterjohn
High quality AI-generated summary created from speaker-labeled transcript.
