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MTHFR and Vitamin B12

MTHFR Mutations and Vitamin B12 Deficiencies

MTHFR and Vitamin B12

Confused about MTHFR, B12, and what a genetic mutation could mean for your health?

Around 40%+ of people around the world have some form of MTHFR genetic mutation, and yet most of them don’t know it.

MTHFR (methylenetetrahydrofolatereductase) is the enzyme produced by the MTHFR gene. It’s required for metabolizing folate and breaking down the amino acid homocysteine. Vitamin B12 also plays a major role as a cofactor in the methylation process of folate and the conversion of homocysteine to methionine.

However, mutations of the MTHFR gene can significantly affect your ability to turn vitamin B12 and folate into forms the body can utilize. This can lead to low levels of B12, which has serious consequences for your health and wellbeing.

This is what you need to know about MTHFR, B12 (vitamin B), and B12 deficiency.

What Does Vitamin B12 Do?

Vitamin B12 is involved in almost every bodily function. It helps make DNA and red blood cells, and plays a key role in the brain and nervous system. B12 is required alongside folate for healthy methylation, and the production of S-adenosylmethionine (SAMe).

B12 and folate are both required for the conversion of homocysteine to methionine. Deficiency of either nutrient may lead to increased homocysteine levels, a major risk factor in cardiovascular disease and many other chronic conditions such as diabetes.

Without B12, your body simply cannot function as it should. Because this nutrient is so intimately involved in red blood cell production and nervous system maintenance, deficiency is a major cause of fatigue, neurological disorders, anxiety, nerve pain, and depression, among others.

Overdosing on B12 is extremely unlikely because your body will only absorb as much as it needs; any excess will simply be flushed out in your urine. In fact, a dosage of 5,000 mcg or more of Vitamin B12 is often recommended for those who have a health condition that affects their B12 absorption.

What Are the Benefits of B12?

Healthy red blood cell formation for energy and alertness: Vitamin B12 works closely with vitamin B9 (also called folate) to help make red blood cells which are required for carrying oxygen to all parts of your body.

Reducing homocysteine levels in your blood: B12 works alongside folate and vitamin B6 to maintain normal concentrations of homocysteine. When taken alongside folate, B12 helps to lower homocysteine levels more significantly than taking folate alone.

Preventing and/or treating Parkinson’s Disease: Adenosylcobalamin (an active form of B12) acts as an inhibitor of the kinase activity of LRRK2 in cultured cells and brain tissue. Animal studies have shown adenosylcobalamin can significantly prevent the neurotoxicity of the Leucine-Rich Repeat Kinase 2(LRRK2) variants associated with Parkinson's disease.

Supporting mood/reducing risk of depression: Studies suggest that up to 30% of patients hospitalized for depression are deficient in B12. Sufficient vitamin B12 is required for methylation, which is necessary for the production of serotonin as well as other monoamine neurotransmitters and catecholamines.

Preventing loss of neurons: B12 is essential for the proper functioning and development of the brain and nerve cells. It helps maintain the myelin sheaths that cover and protect the nerves of the central and peripheral nervous system.

Cofactor in the synthesis of methionine: Methionine is an amino acid that donates the methyl groups required for methylation reactions to occur. Myelin and the many neurotransmitters required for neurological development, maintenance, and functions cannot be produced without methionine.

Supporting healthy sleep: B12 is involved in regulating sleep-wake cycles by helping to keep circadian rhythms in sync. Studies also show a connection between low Vitamin B12 and insomnia.

How Does An MTHFR Mutation Affect the Body's Ability to Use Vitamin B12?
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How Does An MTHFR Mutation Affect the Body's Ability to Use Vitamin B12?

A MTHFR mutation reduces the amount of active folate being produced in the body. B12 requires the active form of folate in order to be absorbed. Depending on the combination of the mutation, this can affect the body’s ability to convert B12 and folate into glutathione by around 20-70%.

MTR and MTRR variants are genetic SNPs (single nucleotide polymorphisms) that may significantly impact the conversion and absorption of B12 in the body. Numerous studies show that homozygosity for the C677T mutation (a double mutation on the 677 SNP - sometimes denoted as 677TT) is also strongly associated with B12 deficiency.

A study involving people with B12 deficiency found that the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid.

It’s worth noting that active folate ((6S)-5-methyltetrahydrofolate) is the form that bypasses MTHFR mutations, while folic acid does not.

Can MTHFR Cause a B12 Deficiency?

An MTHFR mutation doesn’t necessarily mean you will end up with a B12 deficiency. Symptoms will depend on which variant of the mutation you have, and whether both of your MTHFR genes are affected. Knowing which variant you have can help you to make healthy changes to your diet and lifestyle to optimize your methylation and reduce the risk of symptoms.

The main causes of B12 deficiency include inadequate dietary intake and malabsorption issues. However, genetic predisposition to vitamin B12 deficiency has been demonstrated in various studies. Mutations and polymorphisms in gastric intrinsic factor GIF and metabolic enzymes such as methylenetetrahydrofolate reductase MTHFR are also linked.

Conversion of Vitamin B12 to the active form, methylcobalamin, takes place through the MTRR enzyme. Up to 30% of the population has a down-regulated MTRR SNP (single-nucleotide polymorphism) potentially impairing this vital process.

On the MTHFR gene, two variants of mutations can occur:

  • C677T. It’s estimated that 30-40% of the American population may have a mutation at gene position C677T. Those who are homozygous for this variant (meaning they have a double mutation) include about 25% who are of Hispanic descent and 10-15% who are of Caucasian descent.

  • A1298C. Less is known about this variation, but a 2004 study involving 120 blood donors of Irish heritage found that 46.7%, were heterozygous for this variant, and 14.2%, were homozygous.

A 2006 study found that 59% of women with a history of recurrent miscarriages had multiple homozygous gene mutations, including MTHFR, compared to only 10%of women with no mutation.

An MTHFR polymorphism can slow enzymatic reactions down by 40-70%. This leads to elevated homocysteine levels which reduce the body’s ability to eliminate toxins. Vitamin B-12 status was also found to be lower in patients who had C677T and/or A1298C polymorphisms and high levels of plasma homocysteine.

A 2013 study found that hyperhomocysteinemia and vitamin B12 deficiency were found to be significant risk factors for recurrent pregnancy loss. Folate deficiency was more common in controls (63.47%) as compared to the case group(2.56%).

Is Folate Deficiency the Same as B12 Deficiency?

No. In folate deficiency, homocysteine levels are elevated and methylmalonic acid levels are normal. In vitamin B12 deficiency, both homocysteine levels and MMA levels are elevated. (The body makes large amounts of MMA when vitamin B-12 levels drop).

Other Causes of B12 Deficiency

Vitamin B12 deficiency can also be caused by:

Malabsorption: Because intrinsic factor is produced by the parietal cells in the stomach, any damage to the terminal ileum (caused by inflammatory bowel disease, Celiac disease or infection) can impair the absorption of B12 and lead to a deficiency.

Dietary Insufficiency: Excess vitamin B12 is stored in the liver. However, people who eat a strict vegan diet for approximately three years may develop a B12 deficiency due to a lack of dietary intake.

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Identifying a B12 Deficiency

Identifying a B12 Deficiency

Low B12 is associated with poor memory performance, memory loss, disorientation, and dementia with or without mood changes. Other signs include:

● Extreme and/or ongoing fatigue

● Lack of energy

● Poor appetite

● Feeling dizzy or faint

● Headaches

● Numbness or tingling in the limbs

● Dermatitis

● Ringing in the ears

● Feeling out of breath

● Confusion or brain fog

● Anxiety and/or paranoia

● Pale or yellowed skin

How Can You Treat a B12 Deficiency?

If your diet is not providing adequate B12 or your body is unable to absorb it properly, it’s vital that you take a quality ‘active’ B12 supplement to support your body’s needs.

In a study involving people with C677Tgenotypes, researchers found that TThomozygotes responded better with both folate and B levels above the median.

Unfortunately, many commercial supplements contain forms of B12 that the body cannot use effectively (cyanocobalamin), especially in the case of MTHFR gene defects or enzyme deficiencies. The synthetic form, cyanocobalamin (most often used in vitamins and fortified foods), occurs only in trace amounts in human tissues and is not absorbed well by the body.

The three active forms of Vitamin B12 include Hydroxocobalamin, Adenosylcobalamin, and Methylcobalamin. These forms are bioidentical to those naturally occurring in your body and in the foods we eat. Complex conversions are not required: your body can use and benefit from these forms immediately.

Two ways that you can get more B12 into your body include:

  1. Eating foods that are high in B12 and
  2. Through supplementation

Food Sources with B12

Unlike the other B vitamins, B12 is almost exclusively available in animal products because it is synthesized by bacteria in a process that takes place in the gut of ruminant animals. This is one of the reasons that vegans and vegetarians are often deficient in B12. However, plenty of people who eat animal products are also lacking in this vital nutrient.

Foods that contain vitamin B12

● Lean meats: red meat, poultry, fish

● Eggs

● Shellfish: clams, oysters, mussels

● Organ meats: liver

● Fish: trout, salmon, canned tuna

● Dairy products: yogurt, cheese, milk


In the case of digestive malfunction or MTHFR mutation(s), supplementing B12 may be more efficient than obtaining it through food. If your gut is lacking in intrinsic factors, your uptake of vitamin B12 will be impaired. This can result in a B12 deficiency.


The absorption, assimilation and methylation of B12 is a very complex process, which leaves many opportunities for error. For this reason, those with an MTHFR mutation may end up with a B12 deficiency even if they consume sufficient amounts of vitamin B12 in their diets.

Methyl-Life’s® B12 Complete is a proprietary formula that contains all three active forms of B12. It’s suitable for vegans, vegetarians, as well as those who have B12 deficiencies, Parkinson’s, Crohn’s, mental health issues, or people with MTR, MTRR, COMT or other gene defects affecting B12 metabolism.


An MTHFR genetic mutation should be taken seriously. By impairing your body’s ability to create methylfolate, this mutation has a domino effect on many other nutrient levels, especially vitamin B12.

Because symptoms can vary depending on the type of mutation you have and whether the variations affect one or many of your MTHFR genes, it is imperative to understand the risks associated with your particular genotype. This can be identified through an MTHFR test.

A B12 deficiency can affect every aspect of daily function: mood, homocysteine metabolism, energy levels, DNA replication, neurological function, and more. But making changes to your diet and lifestyle — and supplementing with a quality B12 formula — can help you optimize your body’s methylation processes and reduce the risk of symptoms.

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    Written By,
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