Summary
Dr. Joel Miller and Dr. Tim Augustiniak continue their methylation deep-dive by walking through key genetic markers (MTHFR, MTR, MTRR, COMT, AHCY, and PEMT) and explaining what each enzyme does in the methylation cycle. They emphasize that having a genetic SNP does not destine anyone for a life of health issues -- what matters more is addressing the underlying oxidative stressors that drain methylation capacity. The practical second half covers what runs down methylation (caffeine, heavy metals, histamine, excess hormones, and cortisol) and specific strategies to reduce that burden. They recommend supporting liver detox pathways with NAC, liposomal glutathione, and artichoke extract, and outline a targeted supplement stack for methylation support: activated B9 (5-MTHF), P5P (activated B6), zinc, magnesium (citrate or glycinate), and TMG (trimethylglycine from beets). They stress the importance of a foundation-first approach and warn listeners to stop supplementing if symptoms worsen.
Key Points
- MTHFR, MTR, MTRR, COMT, AHCY, and PEMT are the core genetic markers related to methylation
- Having genetic SNPs does not destine you for health issues -- epigenetics and environment matter more
- Over 75% of methylation goes toward creatine production
- Oxidative stressors that drain methylation include caffeine, heavy metals, histamine, hormones, and cortisol
- Boosting immune tolerance and balancing TH1/TH2 immune response improves methylation independently of genetics
- Key methylation-support supplements: 5-MTHF (activated B9), P5P (activated B6), zinc, magnesium, and TMG
- NAC, liposomal glutathione, and artichoke extract support liver hormone detox pathways and free up methylation capacity
- Folic acid (synthetic B9) drains vitamin B3 to convert, so use activated forms instead
Key Moments
Creatine production consumes over 75% of methylation
Over 75% of the body's methylation capacity goes toward producing creatine, making it one of the most important downstream products of the methylation cycle and a key reason to support methylation status.
"And then the biggest component, over 75% of methylation goes towards increasing creatine. And that's a key topic or a key point that we're going to kind of continue on today as to strategies to boost methylation, boost how you feel. Creatine is an important piece of that."
What drains methylation -- oxidative stressors
The main oxidative stressors that drain methylation are caffeine, heavy metals, histamine, hormones, and stress hormones. Reducing these burdens improves methylation independent of any genetic mutations.
"So on that list, we already talked about this last week, what is caffeine, metals, hormones, histamine, and stress, stress hormones. And so with this, the overarching theme is something that we talked about before, and it is boosting immune tolerance."
NAC, glutathione, and artichoke for liver detox pathways
Supporting the three liver hormone detox pathways -- glucuronidation, sulfation, and glutathione conjugation -- with NAC, liposomal glutathione, and artichoke extract takes a huge load off methylation so it can do other jobs like producing creatine and neurotransmitters.
"If you really want to nail down all three of those pathways, you can take NAC, liposomal glutathione, and then artichoke extract."
Targeted supplement stack for methylation support
Dr. Miller outlines a practical methylation support stack: activated B9 (5-MTHF, 1mg from Thorne), P5P (activated B6), zinc chelate, magnesium (citrate or glycinate), and TMG (trimethylglycine from beets via Standard Process Beta Food).
"I would say the first and foremost when we talk about methylation is going to be using an active form of B9. So that's not just folate, but it's going to be 5-MTHF."
Warning signs when starting methylation supplements
Dr. Augustiniak warns that starting methylation supplements like 5-MTHF or P5P can occasionally cause hyperactivity, headaches, or brain fog. If symptoms worsen, stop immediately -- things can get jammed up in the glutathione synthesis pathway.
"One thing that I really want everybody at home listening to keep an eye on is it may feel almost hyperactive or give you headaches, brain fog, anything like that. It doesn't happen much. Bad symptoms. If you notice that you start taking those and for some reason things feel worse, stop."
