How do your genes influence your vitamin B12 levels?

Vitamin B12 is essential for your health! It is a cofactor for biological reactions such as creating the myelin sheath in nerve cells and the synthesis of DNA (rather important!). A lack of vitamin B12 (also known as cobalamin) can create a cascade of effects. [ref]

There are several genes that can influence your absorption, transport, and need for vitamin B12.  Some people need higher amounts of B12, and some people thrive on different forms of B12. Looking at your genetic data may help you figure out what is going on in your body.

Background Info on Vitamin B12

Vitamin B12 as a supplement can be found in four different forms: cyanocobalamin, methylcobalamin, adenosylcobalamin, and hydroxocobalamin.  The cyanocobalamin form is often found in cheaper vitamins and added to processed foods. It must be converted by the body before use.  The methylcobalamin and adenosylcobalamin are active forms used by the body.

Vitamin B12 deficiency or insufficiency has been shown to cause:[ref]

  • mental confusion
  • tingling and numbness in the feet and hands
  • memory loss
  • disorientation
  • megaloblastic anemia
  • gastrointestinal symptoms

To be able to absorb B12 from foods, you need to have adequate intrinsic factor produced in the stomach. This is something that is often depleted in the elderly, leading to B12 deficiency.


Genetic variants that influence vitamin B12:

These genetic variants don’t usually cause frank vitamin B12 deficiency on their own. Instead, they decrease or alter the use and availability of it in the body. So these variants are more about optimizing B12 status rather than overcoming a disease state.

MTRR gene:

This gene codes for methyltransferase reductase, an enzyme that is involved in using methylcobalamin (methyl B12) in the methylation cycle. Without sufficient B12, homocysteine levels can increase.

Check your genetic data for rs1801394 A66G (23andMe v4, v5; AncestryDNA):

  • AA: normal
  • AG: decreased enzyme activity, increased homocysteine levels
  • GG: decreased enzyme activity, increased homocysteine levels[ref]

MTHFR gene:

The MTHFR gene codes for an enzyme that converts folate into the active form, methyl folate, that the body uses. This methylation pathway is also dependent on B12.

Check your genetic data for rs1801133 C677T (23andMe v4, v5; AncestryDNA):

  • G/G: normal (wildtype)
  • A/G: one copy of C677T allele (heterozygous), MTHFR efficiency reduced by 40%, associated with increased homocysteine and lower B12 levels
  • A/A: two copies of C677T (homozygous), MTHFR efficiency reduced by 70 – 80%, associated with increased homocysteine and lower B12 levels[ref][ref]

TCN1 gene:

This gene codes for a transporter for vitamin B12.

Check your genetic data for rs526934 (23andMe v4,v5; AncestryDNA):

  • AA: normal
  • AG: lower circulating vitamin B12 levels
  • GG: lower circulating vitamin B12 levels [ref][ref]

TCN2 gene:

The TCN2 gene codes for a B12 binding protein.

Check your genetic data for rs9606756 (23andMe v4, v5):

  • AA: normal
  • AG: possibly reduced B12
  • GG: reduced B12 levels [ref][ref]

FUT2 gene:

This gene codes for an enzyme that affects glycoproteins on the cell membranes. Carriers of the AA genotype (below) do not secrete their blood type in their mucus, saliva, or semen. This changes the gut microbiome (due to intestinal mucosa changes) and also alters B12 levels. Initial studies just associated the genotype with higher B12 levels.  More recent studies point to the idea that carriers of the AA genotype may show higher B12 on a serum test, but that probably does not reflect the active B12 in the body.[ref]

In other words, non-secretors should not rely on a serum B12 test. Testing methylmalonic acid would give a better reflection of B12 status.

Check your genetic data for rs601338 (23andMe v4, v5)

  • GG: normal
  • AG: normal or slightly elevated serum B12
  • AA: can show elevated serum B12,[ref] but may not reflect true B12 status[ref]

Lifehacks:

Vegan and Vegetarian diets:
Vitamin B12 is only found in animal-based foods, so vegans and vegetarians are often deficient or marginal in their B12 status.[ref]  B12 is often added to breakfast cereals and other refined products, so eating a vegetarian diet that includes packaged and refined foods may actually result in higher B12 levels (although probably not in better health…).

It takes several years to completely deplete your liver’s store of B12, so people who have recently started a vegan or vegetarian diet may still have moderate vitamin B12 levels.[ref]

Dietary sources:
Foods that are highest in B12 include: [ref]

  • beef liver
  • mussels
  • lamb
  • caviar
  • chicken livers

High Homocysteine:
If your homocysteine levels are high and you carry the MTHFR or MTRR variants above, supplementing with vitamin B12, methylfolate, riboflavin, and B6 may help to lower your levels. [ref][ref][ref]

Supplemental B12:
Clinicians often caution people who carry the COMT rs4680 A/A genotype (lower COMT levels) to avoid methylcobalamin and stick to adenosylcobalamin or hydroxocobalamin instead. This avoids an influx of too many methyl donors for those with lower COMT enzyme levels. (Read more about COMT)

Toxicity:
Vitamin B12 is a water-soluble vitamin with little risk of toxicity or overdose. There is no upper limit of dosage set by the US Food and Nutrition Board.

If you are older or have problems with intestinal absorption, sublingual B12 lozenges are available. Or if you are low in B12, your doctor can prescribe B12 as an injection.

Testing:
In most US states, you can order your own blood tests online if you don’t want to go through your doctor and insurance. I’ve set up a way that users can access inexpensive lab tests through Ulta Lab Tests.  They are usually the cheapest option but do check around since all of these online lab companies run sales all the time.

More to read:

How Well Do You Convert Beta-Carotene to Vitamin A?

Should you take folic acid?

 



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2 Comments on “How do your genes influence your vitamin B12 levels?

  1. I thought perniscious anemia which is caused by a deficiency of B-12 due to insufficient amounts being absorbed by a lack of intrinsic factor in the stomach was a hereditary condition, but this article doesnt mention anything about it or what genetic variant it is.

    • Hi Brik –
      There is a hereditary form of pernicious anemia due to rare mutations in the GIF gene (not well covered by 23andme). This is a congenital form that affects people from infancy.
      For the vast majority of people with people pernicious anemia, it is an autoimmune disorder. There are probably genetic variants that alter your risk for the autoimmune condition, but I don’t have any information on those.
      Debbie

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