Please consider supporting my work by making a purchase using these links at one of my affiliates: https://chrismasterjohnphd.com/foursigmatic, https://chrismasterjohnphd.com/paleovalley, https://chrismasterjohnphd.com/seekinghealth, https://chrismasterjohnphd.com/ancestralsupplements, https://chrismasterjohnphd.com/magicspoon, https://chrismasterjohnphd.com/lmnt  Plenty more at https://chrismasterjohnphd.com/support! Question: Why is methylfolate the off-switch for the glycine buffer system? The reason is that generally in the fed state, you have lots of incoming methionine. And so you have an excess of SAMe in the fed state. In the fasting state, you have no incoming methyl groups from diet, and therefore the fasted state is the low-methylation state. So fed state, high methylation state, fasted state, low methylation state. You basically shut off MTHFR in the fed state, because in the fed state, which is a high methylation state, the incoming methionine makes you not need any MTHFR activity. If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a DISCLAIMER: I have a PhD in Nutritional Sciences and my expertise is in performing and evaluating nutritional research. I am not a medical doctor and nothing herein is medical advice.