Are Vitamin B12 Injections Safe with MTHFR?

Vitamin B12 is a crucial cofactor in DNA synthesis, cellular energy production, and myelin synthesis. It plays a key role in the brain and nervous system and functions alongside folate for healthy methylation and the production of S-adenosylmethionine (SAMe).

Vitamin B12 deficiency is common and often due to a lack of dietary sources, malabsorption, and/or genetic mutations that affect uptake. 

When detected, a B12 deficiency is usually treated with vitamin B12 injections. 

This review will outline the use and efficacy of B12 injections and how they are administered. We will explain why someone would need a B12 injection and whether injections are safe for those with MTHFR, and the possible alternatives.

Vitamin B12 injections are primarily used to treat pernicious anemia and vitamin B12 deficiency. Injections may be given to people who have malabsorption issues due to disorders such as Crohn's disease, atrophic gastritis, chronic pancreatitis, and intestinal bacterial overgrowth. Vegans and vegetarians may also require B12 treatment, especially vegan women who are pregnant or breastfeeding. 

Injections may be given every month until B12 levels have returned to normal. When starting treatment, injections may be given weekly for 4-8 weeks. Once the deficiency is corrected, treatment is often switched to oral (tablet) therapy.

Vitamin B12 shots are available as a synthetic version of vitamin B12 (cyanocobalamin) in the US. In the UK, injections are usually given as hydroxocobalamin or cyanocobalamin. It is typically an intramuscular injection in the arm administered by a nurse or a doctor.

B12 is stored in the liver for long periods; those who have adequate B12 levels should not receive B12 injections. 

Vitamin B12 shots are only available by prescription following a clinical diagnosis of low levels. 

Patients should inform their doctor if they have had Leber's disease or other forms of optic nerve damage, an iron or folic acid deficiency, or low potassium.

Women who are pregnant or breastfeeding should also advise their doctor before receiving B12 injections. B12 injections are not suitable for children or for those who are allergic to cyanocobalamin or cobalt. 

The MTHFR genetic mutation has a negative effect on B12 absorption, with studies showing an increased prevalence of low blood levels of vitamin B12 in those with the mutation. The C677T polymorphism is significantly associated with a decrease in intestinal absorption of vitamin B12.

Folate (vitamin B9) deficiency is also common in those with MTHFR. However, supplementing solely with folic acid/folate can mask an underlying B12 deficiency. This is because the folate supplementation may improve symptoms to the point that the B12 deficiency is not seen and therefore not treated. 

B12 plays an important role in the recycling of N5-methyl THF (the storage form of folate) to THF, the form of folate that serves as a coenzyme for numerous metabolic reactions involving amino acids and nucleic acids. B12 deficiency can impair this process and prevent the use of storage form of folate when needed, resulting in functional folate deficiency. This can have significantly detrimental effects on the nervous system, cell division, and other methylation processes.

Deficiency of folate with or without vitamin B12 deficiency impairs DNA synthesis, leading to cell death, ineffective red blood cell production, and anemia. Hemolytic anemia may be more prevalent in patients with both MTHFR and B12 deficiency.

Reduced levels of B12 and folate compromise the body’s ability to convert homocysteine to methionine, leading to elevated homocysteine. This, in turn, can increase the risk of blood clots and cardiovascular issues. 

Reduced methionine affects the production of SAMe, the major methyl donor for the central nervous system and essential for the production of neurotransmitters. This can lead to cognitive impairment and mental illness. 

For those with a B12 deficiency and an MTHFR mutation, one major advantage of B12 injections is that they are readily absorbed in the body and do not have to be taken as often as oral tablets. However, the bioavailability of the B12 injection depends on the form used. Synthetic B12 (cyanocobalamin) is less bioavailable by comparison and requires a three-step process to be converted to usable B12 in the body. 

One study showed that high daily doses (1000-2000 mcg) of oral (sublingual) vitamin B12 daily, weekly, and then monthly might be as effective as intramuscular administration in achieving hematological and neurological responses in vitamin B12 deficient patients.

Research published in Integrative Medicine: a Clinician’s Journal suggests that those with genetic mutations affecting B12 assimilation may improve their B12 status efficiently by using one or more natural forms of vitamin B12. 

Taking B12 in combination with vitamin B6 and folate (rather than alone) is shown to be most effective for regulating homocysteine levels for some patients and preventing the combined risk of stroke, myocardial infarction, and vascular death.

Supplementing with folate, vitamins B6 and B12 is also shown to help lower homocysteine concentrations in patients with recurrent pregnancy loss and MTHFR mutations.

The right form of these nutrients is crucial, which is why many MTHFR patients are directed to the Methyl-Life® product range. 

Methyl-Life’s® Methylated Multivitamins contain both  L-Methylfolate and active B12. Each Multivitamin is made with internationally-patented Magnafolate® PRO, which is clinically recognized as the purest methylfolate available and able to bypass the MTHFR mutation. The active B12 is provided by Hydroxocobalamin, which is readily absorbed and utilized in the body.