Is what you’re doing for MTHFR working? How would you know?

In this episode I cover the most important blood work to get to make sure what you’re doing is working. I cover the importance of homocysteine, how to interpret glycine and sarcosine levels on a plasma amino acids test, the difference between measuring serum or plasma folate and measuring red blood cell folate, and more.

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Read the Transcript

MTHFR – is what I’m doing working? That’s the topic of today’s video.

Hi. I’m Dr. Chris Masterjohn of chrismasterjohnphd.com. And you are watching Chris Masterjohn Lite where the name of the game is “Details? Shmeetails. Just tell me what works!”

And today we’re going to talk about the most important blood work to look at when you’re trying to make sure that you’re managing your nutrition for optimizing your MTHFR mutations properly.

So the first thing you want to look at is homocysteine. You want homocysteine to be between 5 and 9, probably 7 is somewhere around the sweet spot. You’re not going to get it lower than 5 and if you’re above 9 you’re getting into territory where you need to optimize it better. Now homocysteine doesn’t tell you it’s about MTHFR, it doesn’t tell you it’s about folate. In fact homocysteine could be high for reasons relating to B12 or even for reasons relating to B1, B2, B3 and B6. So, nevertheless, it’s important to look at because if what you’re doing for MTHFR really isn’t working your homocysteine is probably going to be high.

The second thing you want to look at is your blood levels of folate. One thing that’s underappreciated is that the folate outside of your cells is almost exclusively methylfolate. So if you want to estimate whether you have low levels specifically of methylfolate, which is the specific problem of MTHFR, you want to look at folate in plasma or serum and not in your red blood cells. Nevertheless I think it can be helpful to look at both because inside your red blood cells you see the totality of folate forms and if your methylfolate is low, which we’re estimating based on serum or plasma folate, and your total forms inside your red blood cells are not, then that is very suggestive that your problem is specifically related to MTHFR. Whereas if your total folate inside your red blood cells is low you probably just need to eat more folate, period.

Now if your methylfolate is low then either you need to increase your dose of methylfolate through foods or through increasing the dose of your supplement or you need to conserve it better. The way you conserve it is you get more choline, and the reason that that helps conserve it is because choline can substitute for folate, or you get more creatine, and the reason that conserves it is because it reduces your need to use it. So by increasing the alternative supply in choline and by decreasing the demand with creatine you can conserve your methylfolate better. You can’t really tell from the methylfolate level which strategy is best, maybe look at which one you seem to be placing the least emphasis on and start with that, but you’ll have to play around with it and see what normalizes your blood work best.

The third thing you want to look at is glycine. MTHFR causes you to waste glycine as methylated metabolites. This is harder to look for. Everything that we’ve talked about so far can easily be gotten through a single measure, a single purchase from any of the major laboratory providers. If you’re looking for glycine you want to look for two amino acids, glycine itself and sarcosine.

You’re going to have to order a plasma amino acid analysis for this. It’s more expensive because you’re looking at a lot of amino acids.

You also have to make sure that both glycine and sarcosine are on the list of analytes. I prefer to use Genova Ion Panel with 40 amino acids. This is a panel of both plasma amino acids and urinary organic acids. I like it because whenever I’m looking for something it’s the panel that’s most likely to have what I’m looking for. You can also use other ones from Quest, LabCorp or GreatPlains. If you use those other ones make sure that they have glycine and sarcosine in their list of analytes.

Now what you’re looking for is you want glycine to be in the middle of the range and you want sarcosine to be as low as possible. If your glycine is down drifting towards the bottom of the range or below the range or and/or your sarcosine is elevated or even high within the range then that indicates that you haven’t optimized for your MTHFR well enough yet to preserve your glycine. And that might mean that you just need to supplement with more glycine, but the reason you waste glycine is because you don’t have enough methylfolate.

So what we’ll say then is that if glycine is low and/or sarcosine is high you need to either boost your methylfolate or conserve it better in the ways we were just talking about, or you need to add glycine into the mix. And it’s probably best to attack it in a multi-faceted way so that you’re conserving your glycine as much as possible and you’re compensating for whatever you can’t conserve by adding in extra glycine.

Now those are the three most important things, but I’ll throw in a few bonuses. So if you google HDRI Methylation Panel you will find the HDRI Methylation Panel. This looks at all your intracellular folate metabolites and it can be really helpful to see if, for example, is your methylfolate low versus all your other metabolites of folate. HDRI is measuring a lot of things that no other companies measure and it’s why I like to use them, but I will offer a note of caution, which is that they’re very difficult to work with, they usually take a lot longer than they tell you they will to get your data back to you, and often they’re not responsive when you ask them questions. So I find the company frustrating to work with, but I’ll throw it in there as a bonus test.

And then another bonus test is the Quest Creatine Biosynthesis Disorders Panel. The reason I like this is because if you’re MTHFR isn’t working right you’re probably not going to synthesize enough creatine inside your body, and if that’s true what you will see is that on this panel you’ll have an increased ratio of guanidinoacetate to creatine. The problem with this test is that it’s optimized to look for severe genetic disorders in creatine synthesis and so there’s no reference range designed to tell you if you’re managing MTHFR properly. So if you’re on your own and you’re just looking at your own health I wouldn’t bother with it, but if you’re a clinician and you order lots of tests for lots of patients and clients then I think it would be good to start seeing whether you can generate enough data in your own practice with the Quest Creatine Biosynthesis Disorders Panel to see whether there’s a range where you can find that people feel better, if their symptoms are lowest or their other markers of methylation are all optimized best when that ratio is in a certain narrower range, and if that’s the case then maybe we can start making real recommendations around how to use that panel to optimize your MTHFR.

In any case remember the three most important things are Number 1: homocysteine should be in the optimal range, Number 2: plasma or serum folate should be high enough, not red blood cell necessarily, and Number 3: your glycine should be in the middle of the range, sarcosine as low as possible.

All right. I hope you found this useful.

Signing off. This is Chris Masterjohn.

You’ve been watching Chris Masterjohn Lite.

And I will see you in the next episode.