What is the Best Form of B12 for You?
Which B12 form is best for you (based on your genetics)?
One of the most common nutrients to consider when supplementing the methylation cycle is the proper form of B12. There are 3 different types of B12 that are considered extremely beneficial to the body (hydroxocobalamin, methylcobalamin & adenosylcobalamin). Many automatically think that if you have an MTHFR defect, then you need the form of B12 called methylcobalamin, but that is simply NOT true. It is important to realize that the MTHFR status does not necessarily determine the type of B12 that’s best for you, instead it’s the status of genes like COMT, MTR, MTRR as well as VDR Taq. It is true that methylfolate and methylcobalamin work together synergistically along the methylation cycle pathway, but that doesn’t necessarily mean that if you tolerate methylfolate well you’ll also need, want or tolerate methylcobalamin well (even if that’s what most doctors, nutritionists, etc. are currently saying right now).
It seems there may be a general lack of education available to most doctors about the different forms of B12 and what those forms are as well as how they get converted within the body and what each is most beneficial for (not to mention which set of genes or genetic mutations could benefit most from which B12 type). So do your homework when it comes to B12 to see which you may tolerate the best.
The most common form of B12 that you’ll find everywhere is cyanocobalamin and it is not very active or beneficial to the body because the absorption rate is fairly low and it has some cyanide content. It is cheap and it's usually what's found in vitamins as well as fortified foods. Cyanocobalamin does not absorb well because the body has to convert it a few times before it becomes bioidentical and available for use. Cyanocobalamin must first get converted into hydroxocobalamin before the body can actually use the B12, and from there the hydroxocobalamin then gets converted into both adenosylcobalamin and methylcobalamin which have further downstream effects. If the body has genetic mutations then any of these conversions may not happen well and the effect is that the cells cannot absorb or use the nutrient properly.
What is Hydroxocobalamin good for?
Hydroxocobalamin is a lesser-used bioactive form of B12 that is tolerated by many and understood to help the body promote neurotransmitters (for healthy brain function), protect against anemia (sometimes used for pernicious anemia), detoxify, manufacture myelin sheath, and much more. Hydroxocobalamin can also act as a scavenger of peroxynitrites that may build up in the body (particularly for those who may have COMT & other such mutations), converting the reactive oxidant back into methionine. This kind of "mopping up" activity can be beneficial for those dealing with headaches and/or migraines, inflammation, cold hands and feet, sore muscles and joints, fatigue, lack of motivation, memory challenges, feeling lightheaded when standing, brain fog, as well as symptoms of Chronic Fatigue and/or Fibromyalgia. Hydroxocobalamin also gets converted into methylcobalamin as well as adenosylcobalamin (or cobamamide) in the body - both are also bioidentical forms of B12 that can increase B12 sufficiency.
What is Methylcobalamin good for?
Methylcobalamin is probably the most well-known bioidentical form of B12 that is becoming much more available in vitamins and supplements. Methylcobalamin is known to promote methylation, reduce homocysteine, support brain & nerve health, and positively affect anemia as well as the circulatory & immune systems. While all forms of B12 are well-tolerated by many, Methylcobalamin is the form of B12 that is most known for causing some mild side effects related to methylation. For some it can cause the heart to race or the body to become overstimulated, agitated or even anxious in some cases. Some may have trouble sleeping if they take it too late in the day, as it can overexcite the body via the methylation pathway.
What is Adenosylcobalamin (or Cobamamide) good for?
Adenosylcobalamin (also sometimes labeled as Cobamamide) is probably the most expensive and least-known bioidentical form of B12 to consumers. And while all forms of B12 are generally well-tolerated, clinically, doctors may find cobamamide to be the most well-tolerated of the three bioactive forms. Adenosylcobalamin helps in muscle recovery, myelin sheath repair, supporting mitochondria, and similarly to the other active forms, it also helps with anemia. According to research and clinical studies, B12 has a connection to Parkinson's and the adenosylcobalamin form particularly may be thought of as a valuable aid due to its action upon the muscles.
What is the best way to take B12 – pill, shot, sublingual?
It’s a well-known fact that B12 does not absorb well via the gut (only approximately 1-4% gets absorbed through the gut), so taking B12 via sublingual or under the tongue is the best absorption avenue (holding it under the tongue or between the gums and cheek is most common). Consider some form of liquid or tablet/lozenge that can be sucked on or dissolved in the mouth. Holding the B12 in your mouth for as long as possible is best for maximizing absorption through the sublingual route.
And believe it or not, recent research shows that taking B12 in a sublingual oral form is more effective for treating B12 deficiencies than actually getting B12 intramuscular shots (and it's usually much more convenient and affordable as well) - https://pubmed.ncbi.nlm.nih.gov/30632091
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. However, it doesn’t really matter what term you use (chewable tablet, lozenge, sublingual tablet, liquid, etc.) for maximum absorption the main idea is to hold it in your mouth for as long as you can. Another way to absorb B12 is intramuscularly through shots, however, as noted above, the research tells us that sublingual (or mouth) absorption is even more effective than absorption via the muscles … and shots may cost significantly more money. Also, be aware with shots (many doctors still give cyanocobalamin shots) that though you may need higher doses of active B12(s) (like myself), you may not do well when given higher doses of cyanocobalamin in a shot because your body may not be able to do the conversions and you could have negative side effects.
What is the best test to determine if you are B12 deficient and need B12 supplementation?
Unfortunately most medical professionals test for B12 sufficiency using a blood serum test. However a blood serum test merely indicates how much B12 is swimming around in the bloodstream, NOT what is actually getting into the cells where it's needed for use by the body. B12 must be transported and absorbed intracellularly - only there does it benefit health and kick off important other downstream processes. So understanding what's in the bloodstream is only showing how much B12 you have that's not been absorbed or used yet by the body (it assumes that if it's in the blood, your body can absorb it, but that's just not the case with a lot of folks regarding B12).
B12 is much more complicated, it requires transportation as well as multiple conversions and many people have mutations or conditions which don't perform these biopathway tasks in the body that are needed to make B12 useful to health. So if you want to understand a more accurate picture of your B12 status (whether or not you are getting B12 to the places it's needed and you have a sufficient amount of B12), you either have to do a test for B12 amounts in the spinal fluid (I don't know of any doctors who are doing this kind of test for that), OR you could get levels tested for both MMA (methylmalonic acid) & homocysteine via blood tests. This is actually better for determining a true B12 deficiency - if both test levels come back as high, then it's very likely that you are B12 deficient. If you are low in B12, consider one or all of the 3 active forms of B12 to make more of the bioidentical B12 forms available to your cells (hydroxocobalamin, adenosylcobalamin, methylcobalamin). DO NOT TAKE CYANOCOBALAMIN!!
What does it mean if your B12 blood serum level comes back high?
The most important thing to realize is that 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 also show virtually no B12 in the spinal fluid, meaning the B12 is not being transported from the blood stream into the cells where it should be absorbed and used. So high B12 blood serum tests typically mean you are not converting, transporting or absorbing B12 properly.
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).
Since I personally have a number of mutations in all of the B12 absorption genes (COMT, MTR, MTRR, VDR Taq), I actually need all 3 types of B12, but not everyone does. If you have your genetic test results, you can use those to help guide you as you try the specific B12 forms to see how they do for you. You’ll notice below that, 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 below should be able to tolerate B12 in the form of hydroxocobalamin (and this is why our methylation protocol suggests hydroxocobalamin as the B12 form to begin with):
- 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
- And Dr. Amy Yasko (https://dramyyasko.com - who developed the table below) talks about folks with a particular mutation status combination for COMT & VDR Taq as best needing the below forms of B12:
| 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 |