Tag Archives: methylation

What is the Best B12 for MTHFR Mutants?

The best B12 for MTHFR mutants is… not easy. Just like everything else about being an MTHFR mutant – but the good news is that there is a logical process of discovery that you can go through to find the best B12 for your own brand of mutant-hood.  Also, if you’re a little fuzzy on the MTHFR particulars this is a great place to start for the basics and this article will help you figure out if you’re an MTHFR mutant.

Obviously the Best B12 for MTHFR Mutations is Methyl-B12 (methylcobalamin) Right?

Nope. At least not for everyone.  It makes sense on the surface that if you can’t methylate well then you probably don’t methylate B12 any better than you methylate folate. The problem is that nothing about methylation issues is “on the surface.” Let’s look at a diagram from Dr. Amy Yasko’s awesome website, which focuses on MTHFR mutations and autism,  to help to understand this further:

Awesome (and kind of intense) view of that methylation cycle that helps to show the best B12 for MTHFR mutants from Dramyyasko.com

Awesome (and kind of intense) view of that methylation cycle that helps to show what B12 is best for MTHFR mutants from Dramyyasko.com

Just to clarify, what you’re looking at is a huge, complex, multi-step chemical reaction. Each of the green arrows signifies a vitamin or co-factor that is important for that step of the reaction.  The boxes are particular genes that also influence that step of the reaction. You’ll notice the MTHFR gene that we all know and love at the bottom left of the diagram. You’ll also probably notice that the whole picture is so much bigger than just those two genes (eek!).




The big green arrow for B12 comes straight down between the two big wheels of the methylation cycle.  There are two genes that can change that step of the process, which are called MTR and MTRR. Both MTR and MTRR genes code for enzymes that convert homocysteine to methionine. Both of these enzymes need methyl-B12 to work and your body especially needs B12 support if you have the MTR or MTRR mutations. So, in theory, the best B12 for MTHFR mutants should be methyl, and this is a great place to start but sometimes clinically this doesn’t pan out. Often clinically hydroxycobalamin, which is a slower-release, longer-acting form does much better.

Methylcobalamin, or methyl-B12, is still the best first choice. It makes the most logical sense, it’s the most rapidly active form and it’s already methylated so your body doesn’t have to convert it to anything for it to work.  It’s also the most rapidly acting (and therefore rapidly broken down form) and because of this some people with MTHFR mutations have problems with it. Especially the MTHFR mutants who have severe side-effects from taking 5-MTHF. If you’re not sure if that’s you then read more here.

Signs Hydroxycobalamin (hydroxy-B12) Could Be Better For You:

  • You take methyl-B12 and don’t notice any difference in energy level, mood or really anything else.
  • You have the MTR or MTRR mutations but don’t respond to methyl B12.
  • You have started slowly taking methylfolate but quickly started having side effects.
  • Your blood levels of B12 show up too high, but you still have symptoms of B12 deficiency.
  • Even taking a good dose of methylfolate and methylcobalamin your homocysteine levels don’t come down.
  • You take methyl-B12 and kind of start to freak out.
  • You’re taking good methyl-folate, other good B-vitamin support, and you don’t feel better at all, or feel worse.
  • You take methyl-B12 and on blood tests you still show up B12 deficient.
  • You also have the COMT or MAO mutations,  that change the way some of your neurotransmitters are broken down.

The bottom line is that if you start a good protocol with methylfolate and methyl B12 and don’t feel any better, or feel worse then either you started with too high a dose, or hydroxycobalamin (hydroxy B12) would be a better choice than methyl B12.

The Benefits of Hydroxycobalamin or Hydroxy B12

  • Hydroxycobalamin is used more slowly by your body and so can help to maintain steadier levels of B12
  • It helps prevent methylfolate from forming too much nitric oxide in your body, which helps to reduce side effects of 5-MTHF.
  • It easily converts to methyl B12
  • It helps reduce cyanide in the body (totally unrelated, but it’s a bonus!)

So does this mean hydroxycobalamin is the best B12 for MTHFR mutants? Well – no. The best B12 for MTHFR mutants is always unique to that particular person. It means that your total picture determines what’s best for you.  The logical place to start is with a methyl B12, but if that isn’t giving you the results you want or if you’re having a lot of side effects from the mthylfolate you’re taking then try switching to a hydroxycobalamin form. For many of you it will help to get you feeling energetic and happy and all the things we should feel every day.



All possible variations of MTHFR gene combinations.

Understanding the MTHFR Mutation Basics

I’m amazed at how many people are coming into my office with MTHFR mutations, and also at how difficult it can be to actually understand the MTHFR mutation basics. So let’s start from the beginning and go from there.

What is MTHFR? Why Do I Keep Hearing About It?

MTHFR, just to be confusing, is the name of both a gene and the enzyme which that gene helps your body to make. We call it MTHFR because the actual name, methylenetetrahydrofolate reductase, is just ridiculously long and cumbersome. This enzyme helps your body to methylate. If your genes have a mutation it means that the enzyme they’re supposed to make turns out just a little bit wrong.  You still make the enzyme it just isn’t exactly the right shape and so it works differently from normal. It’s become kind of a buzzword these days simply because we’re discovering that it is more common than we thought and if you happen to be a mutant (like I am) then you may be at greater risk for a number of health problems. We’ll get to those in a second.




What Does the MTHFR Enzyme Do?

The short answer is that this enzyme methylates. Since the short answer sounds like something nobody cares about, let’s also talk about a long answer.  Methylation means that you add a “methyl group” which is essentially a carbon bonded to three hydrogen that looks, appropriately, like mutant mickey mouse ears. This sounds highly anticlimactic, but actually helps your body to do almost everything, like replicating and using your DNA, activating your B vitamins, detoxifying toxic substances and a whole host of other things.

What Are The Possible MTHFR Mutations?

There are TWO MTHFR genes, the MTHFR-C gene and the MTHFR-A gene and you have two copies of each of these (one from your mother and one from your father). This means there is a whole variety of ways that things could go wrong… Let’s look at those here:

ossible good and bad copies of the MTHFR gene

Possible good and bad copies of the MTHFR gene

This means that there are two genes, each with two copies and you could have good or bad copies of one or both… So:

All possible variations of MTHFR gene combinations.

All possible variations of MTHFR gene combinations.

The basic rule is that the more bad copies of the gene you have, the more likely you are to have negative health effects from those genes. The good news is the more bad copies of the gene you have, the more benefit you can get out of working to improve your body’s methylation ability.




Can I Fix a MTHFR Gene Mutation?

Yes and no. You are born with a set of genes and you’ll die with the same set – nothing can change your genes.  That sounds like bad news, but the good news is that we can get around a slow enzyme pathway – usually by supplementing the methylated form of B vitamins (so that it doesn’t matter if your genes can’t convert them) and also methyl donors. MTHFR mutation can make your life miserable, but if you learn to deal with it correctly it can also be overcome.

Poor methylation is becoming a common topic in medicine simply because we’re realizing how common these mutations really are and how great an impact on health they have.  Learn more about some of the conditions caused by this mutation here, and about some of the problems you can run into taking methylated B vitamins here.  There is so much more to this story, but at least we’ve covered the MTHFR mutation basics here. If you suspect a problem, get tested and talk with a doctor who knows about it because that will be the quickest path forward.