MTHFR: What is the Best Form of B12? – Methyl-Life Supplements

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MTHFR: What is the Best Form of B12?

MTHFR: What is the Best Form of B12?

When supplementing the methylation cycle, it is important to consider which form of B12 is right for you.

Sounds easy, right?
Unfortunately, we’ve found that doctors do not necessarily have all the information about what the different forms of B12 are, which genes and genetic mutations benefit most from which forms, and how B12 gets converted within the body.

As part of our commitment to bringing you up-to-date information regarding MTHFR, we’re here to help you understand which form of B12 you may tolerate best.

The Different Types of B12: Methylocalamin, Hydroxocobalamin, Adenosylcobalamin, and Cyanocobalamin

There are 3 types of B12 that are considered extremely beneficial to the body: methylcobalamin, hydroxocobalamin, and adenosylcobalamin.

Yet, the most common form of B12 is actually a form called cyanocobalamin, which it is not very active or beneficial to the body because of its cyanide content and low absorption rate. The reason it doesn’t absorb well is that the body first has to convert it into hydroxocobalamin, which itself has to then be converted into both adenosylcobalamin and methylcobalamin. Especially if the body has genetic mutations, these conversions don’t happen well. As a result, the body cannot absorb or use the nutrient as effectively.

MTHFR: Choosing the best form of B12 based on your genetics

Because of their difficulty converting cyanocobalamin all the way through this process, it is often assumed that people with an MTHFR deficiency require supplementation of the methylcobalamin type of B12. But it’s actually a bit more complicated.

Your MTHFR status does not determine the type of B12 that’s best for you.

Here’s a well-known fact: methylfolate and methylcobalamin work together synergistically along the methylation cycle pathway. So, most doctors and nutritionists are currently saying that a methylcobalamin supplement would be beneficial for individuals with MTHFR deficiency. However, it doesn’t necessarily follow that if you tolerate methylfolate well you’ll tolerate methylcobalamin well.

What does determine the best type of B12 for your body is the status of genes like COMT, MTR, MTRR, VDR Taq.

So, what does this mean for you?

If you have your 23andme genetic test results, you can use those to guide you as you try the different B12 forms and see how well they do for you. For example, since our founder, Jamie, has a number of mutations in all of the B12 absorption genes (COMT, MTR, MTRR, VDR Taq), she actually need all 3 types of B12.

The table below, developed by Dr. Amy Yasko, helps folks determine their potential B12 needs based on their particular mutation status for COMT & VDR Taq:

COMT V158M VDR Taq B12 Types That Should Be Tolerated
– – + + (TT) All 3 types of B12
– – + – (Tt) All 3 types of B12 with less Methylcobalamin
– – – – (tt) Hydroxocobalamin and Adenosylcobalamin
+ – + + All 3 types of B12 with less Methylcobalamin
+ – + – Hydroxocobalamin and Adenosylcobalamin
+ – – – Hydroxocobalamin and Adenosylcobalamin
+ + + + Hydroxocobalamin and Adenosylcobalamin
+ + + – Hydroxocobalamin and Adenosylcobalamin
+ + – – Mostly Hydroxocobalamin


According to Dr. Amy Yasko, the most well-tolerated active form of B12 for folks seems to be hydroxocobalamin. Every single one of the genetic combinations she lists should be able to tolerate B12 in the form of hydroxocobalamin. This is why our methylation protocol suggests hydroxocobalamin as the B12 form to begin with.

Here are a few more handy conclusions:

  • Folks with multiple COMT mutations tend to do very well with hydroxocobalamin (it helps mop up excess peroxynitrites, which can cause problems)
  • Folks with MTR & MTRR mutations may do well with methylcobalamin & adenosylcobalamin supplementation

 Methylation Protocol

Methylfolate: What’s the Right Dosage for me?

Sublingual, Mouth Absorption, or Shots? Taking Your Vitamin B12

Vitamin B12 does not absorb well through the gut, so it’s best to take it under the tongue (sublingual) or through mouth absorption (holding it between the gums and cheek). Consider taking it in some form of liquid or tablet/lozenge that can be sucked on or dissolved in the mouth. Holding the B12 in your mouth for at least 90 seconds is good, and the longer the better.

Note: Different manufacturers use different terms for tablets that are meant to dissolve sublingually in the mouth. But “sublingual” is considered a pharmaceutical term by the FDA, so dietary supplements are moving away from using that term. That said, it doesn’t really matter what term or form you use (chewable tablet, lozenge, sublingual tablet, liquid, etc). For maximum absorption, the main idea is to hold it in your mouth for 90 seconds or more, if you can.

Another way to absorb B12 is through shots to your muscle. However, the research tells us that sublingual (or mouth) absorption is equally as effective as muscular absorption, and shots may cost significantly more money! You should also be aware that many doctors still give cyanocobalamin shots. While you may need higher doses of active B12(s) (like Jamie does), you may not do well when given the higher doses of cyanocobalamin that comes in a shot. Your body may not be able to do the conversions and you could have negative side effects.

How to interpret your B12 blood tests

When determining what form of B12 is best to help mitigate your MTHFR symptoms, it’s important to test your B12 blood serum levels. But it’s important to know what to make of the results.

What does it mean if your B12 blood serum level comes back high?

Don’t panic! Blood tests for B12 are highly inaccurate at detecting actual cellular levels of B12 (meaning the B12 that’s available for the cells to use). Studies have shown that people can have high or normal B12 levels in the blood and actually show virtually no B12 in the spinal fluid, meaning the B12 is not being transported from the bloodstream into the cells where it should be absorbed and used.

What can you do if you have high B12 blood test results?

Dr. Amy Yasko and Nutritionist Cynthia Smith, both suggests you can consider taking low dose lithium orotate (Cynthia Smith suggests approximately 4.6 mg pulsed a couple times a week before adding the B12 form in that’s most likely best for you).

Vitamin B12 at Methyl-Life

At Methyl-Life, we currently sell B12 as

Hydroxocobalamin in a 2.5 mg lozenge (chewable tablet)
All 3 active B12 forms in one 5 mg lozenge/chewable tablet dose as B12 Complete
Methylcobalamin (together along with methylfolate) as our B-Methylated II lozenges/chewable tablets

Want to learn about how Vitamin B12 benefits your brain and cognitive function!

    Written By,
    - Jamie Hope



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