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

Foods that are high in vitamin B12 include meat, fish, eggs, and dairy. Vegetarian and vegan diets are lacking in vitamin B12, and supplementation is usually recommended.

Vitamin B12 as a supplement can be found in four different forms:

  • cyanocobalamin
  • methylcobalamin
  • adenosylcobalamin
  • 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.

Deficiency in B12:

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:

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The following 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):

  • A/A: typical
  • A/G: decreased enzyme activity, increased homocysteine levels
  • G/G: decreased enzyme activity, increased homocysteine levels[ref]

Members: Your genotype for rs1801394 is .

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: typical
  • 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]

Members: Your genotype for rs1801133 is .

TCN1 gene:

This gene codes for a transporter for vitamin B12.

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

  • A/A: typical
  • A/G: lower circulating vitamin B12 levels
  • G/G: lower circulating vitamin B12 levels[ref][ref]

Members: Your genotype for rs526934 is .

TCN2 gene:

The TCN2 gene codes for a B12-binding protein.

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

  • A/A: typical
  • A/G: possibly reduced B12
  • G/G: reduced B12 levels[ref][ref]

Members: Your genotype for rs9606756 is .

FUT2 gene:

This gene codes for an enzyme that affects glycoproteins on the cell membranes. Carriers of the A/A 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 A/A 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 for methylmalonic acid would give a better reflection of B12 status.

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

  • G/G: typical
  • A/G: typical or slightly elevated serum B12
  • A/A: can show elevated serum B12,[ref] but may not reflect true B12 status[ref]

Members: Your genotype for rs601338 is .


Lifehacks:

Dietary considerations:

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 and B12:

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.