Your B12 status is influenced by your diet, lifestyle and certain genetic mutations. This article discusses what those gene variants are, the different form of B12 and how it is involved in methylation.
What is MTR?
MTR stands for methionine synthase. It is a enzyme that is encoded by the MTR gene. This enzyme is involved in the methylation pathway. It uses vitamin B12 to re-methylate the amino acid called homocysteine to methionine. This is important because homocysteine needs to be kept at non-toxic levels and MTR stops the accumulation of homocysteine. A polymorphism (or mutation) affects the functionality of this enzyme and this in turn has an effect on the levels of circulating folate and homocysteine.
MTRR stands for Methionine Synthase Reductase which is essential for proper B12 recycling and methylation. It’s closely tied to MTR, and mutations in either can disrupt your methylation cycle, leading to problems with detoxification, neurotransmitter balance, energy, and mood. If MTRR is impaired, B12 is “used up” faster, and the methylation cycle stalls.
The methionine cycle is part of methylation. It involves methionine, SAMe (S-adenosylmethionine) and SAH (S-adenosylhomocysteine) and homocysteine. B12 in the form of methylcobalamin is used to regenerate methionine from homocysteine. B12 is the hero in this cycle, whereas folate (B9) is the hero in the Folate cycle which is also part of methylation. Both are essential nutrients for methylation to work smoothly. If the folate cycle is inhibited (not enough folate), then the methionine cycle is inhibited, because it needs the methyl group supplied by 5-MTHF from the folate cycle. Therefore what MTHFR mutations you have matter as does your B9 status. See my post on MTHFR and Folate.
Not everyone with these mutations in these variants needs supplementation. It will depend on the individuals diet, lifestyle, genetic mutations and specific health needs. The best way to find out if you need B12 support is through a panel of blood tests, such as homocysteine, RBC Folate, Serum folate, Serum B12 and MMA and holotranscobalamin and a Full blood count.
The Different types of B12
Cobalamin: B12 is derived from dietary sources primarily found in animal products such as beef, chicken, fish and eggs.
Cyancobalamin: This is a synthetic lab-made form B12, but it may not be ideal for people with with a poor B12 conversion capacity. (MTHFR, COMT, MTR, MTRR)
Methylcobalamin: Methylcobalamin is the active form of B12. It already has undergone methylation and therefore skips all the conversion steps. It is bio-available, meaning your body can use it immediately. It is a methyl donor.
Hydroxocobalamin:Hydroxycobalamin is the precursor form of B12. The body can convert it into active forms according to need, making it a more adaptable option. It is also highly stable and binds well in tissues, providing a steady supply of B12. It also has the unique ability to neutralize cyanide and excess nitric oxide, both of which can inhibit energy production and cause oxidative stress.
Adenesolycobalamin:Adenosylcobalamin is an active mitochondrial form of vitamin B12. It is primarily used in cellular energy production and is essential for the enzyme methylmalonyl-CoA mutase, which plays a key role in converting certain fats and proteins into energy. It directly supports mitochondrial energy production, which is especially helpful for people with fatigue or mitochondrial issues.
In discovering you need support through supplementation with B12, some of the most asked questions are:
- How much B12 should I take?
- How can I increase B12 in my diet?
- What form of B12 is best for me?
- Do I need to take B12 with folate?
- How do I know If I am deficient?
- Who should avoid cyancobalamin?
- How do B12 and B9 work together in methylation?
- How does FUT2, TCN1, TCN2, MTR, MTRR affect my B12?
These questions and answers are discussed in detail in my GENETIC WELLNESS membership. Signing up only requires a small once-off fee that gives you LIFETIME Access. This fee covers the time I take to do extensive research and present it to you in easy to understand terminology. USE Coupon code: KT464ERJ at checkout to get 20% off until 30 June 2025