MTHFR is an enzyme that allows folate (vitamin B9) to support the cellular process of methylation, which is important for the synthesis of creatine and phosphatidylcholine, the regulation of gene expression, neurotransmitter metabolism, and dozens of other processes. There are two common polymorphisms that decrease its activity, A1298C and C677T, with C677T having the stronger effect. Genetic decreases in MTHFR activity are associated with cardiovascular disease, neurologic and psychiatric disorders, pregnancy complications and birth defects, and cancer.
While discussions of these polymorphism tend to focus on supplementing with methyl-folate, this should only be a small piece of the puzzle, and may be unnecessary in the context of a diet rich in natural food folate. The bigger pieces of the puzzle are restoring choline, creatine, and glycine.
In this episode, I describe how the methylation system works, how it's regulated, and how it's altered with MTHFR variations. I then use this to develop a detailed dietary strategy and an evaluative strategy to make sure the dietary strategy is working.
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00:35 Cliff Notes
12:15 Introduction of Living with MTHFR
13:05 Bird's eye view of methylation & MTHFR
14:25 How to know if you have MTHFR
17:00 Prevalence (these are really common)
20:30 This is not a genetic disease: this is a variation in metabolism
21:10 Health Associations
23:00 Mechanisms of what MTHFR does
31:35 Methylation system as a whole (methyltransferases)
36:50 How the system is regulated
56:05 Two Addenda: COMT and Agouti Mouse Study
01:00:10 Mechanistic impact of polymorphisms (% down in enzyme activity)
01:04:45 It's not all about 5-methyl folate
01:05:35 You can restore normal flux
01:08:45 Compensate with choline
01:13:26 Creatine
01:15:30 Glycine Buffer
01:16:42 Why upping Methionine and SAMe is bad idea
01:19:00 Dietary Strategy – Basic Objectives
01:22:15 Folate
01:26:35 Protein
01:27:50 Creatine
01:33:05 Glycine
01:35:45 Reiterate problem with methionine/and SAMe in context of meat for creatine 900-1200 mg choline
01:41:40 The evaluative strategy
01:42:00 StrateGene Report
01:43:55 Homocysteine, methionine and glycine
01:46:36 HDRI methylation panel
01:47:35 Folate in plasma and FIGLU
01:49:40 Other tests of interest
Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.
