Question: Nutritional recommendations for MTR and MTRR polymorphisms. In the methylation cycle, I've talked a lot about MTHFR, which helps finalize the methyl group of methyfolate. But then folate has to donate that methyl group to vitamin B12 in order for vitamin B12 to donate it to homocysteine. In that process, that's how you clear homocysteine primarily in the fasting state rather than the fed state. It's also how you recycle homocysteine to methionine to use for methylation, again, primarily in the fasting state rather than the fed state. If your MTHFR is working fine, then the creatine is much less relevant, and the glycine really isn't that relevant. Glycine is still important for everyone, but it's not specifically relevant because of the genetic variations. With that said, I do think that because some tissues rely more on folate and B12 than they do on choline that there might be some tissues that would benefit from supplementing creatine, so you could play around with it. I supplement creatine, and I don't have any problems. I mean, there's no harm in trying out the creatine. In my view, there's no blanket recommendation for someone with MTRR polymorphisms. What I say is because in theory you will be bad at repairing B12 when your B12 gets very damaged, you should thoroughly look at your B12 status at least once. Then every time you enter a new health era, you should monitor your B12 status again. What I mean by health era is your health changes or your developmental stage changes in a way that could impact your health. So, change in health eras, and I'm making this term up, this is not a medical term, but the change in health eras means you get sick with a sickness you never had before. That's a change in your health era. Or you go through puberty. That's a change in your health era. You go through menopause. That's a change in your health era. Or you go on birth control. That's a change in your health era. Look, my MTRR, as I said before, looks terrible on paper. I measured everything I could think of about my B12 status, and everything looked fine. I'm not talking about just serum B12. I'm talking about all the functional markers too. They looked just fine. That just reinforced my belief and the observational data that these things are so common. If these things dramatically impacted your B12 status in a very negative way most of the time, not many people would have the polymorphisms. And yet, they're very common. Those are huge reductions in activity. They're very, very common. So, I think it's ridiculous to make a generalized nutritional protocol around either of those. MTR, it gives you a couple ideas you can experiment with. MTRR, be proactive about monitoring your B12 status. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 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