Are Vitamin B12 Injections Safe with MTHFR?

Are Vitamin B12 Injections Safe with MTHFR?

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Conor Sheehy - PharmD, BCPS

Medical Reviewer:

Dr. Conor Sheehy - PharmD, BCPS
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

January 30, 2025

Table of Contents

    What are Vitamin B12 Injections for?

    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. 3 Vegans and vegetarians may also require B12 treatment, especially vegan women who are pregnant or breastfeeding.


    B12 shots are not given to help with weight loss, and they are unlikely to cause you to lose weight. 


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

    Some naturopathic practitioners in the US may also offer methylcobalamin injections or IVs. Be sure to check which form of B12 is used in the injection.

    Who Should Take B12 Injections?

    B12 shots are recommended for people who are deficient in B12. If you have been diagnosed with low B12, your doctor may prescribe Vitamin B12 shots. 


    However, some people may not be suitable for B12 injections. This includes children or those who are allergic to cyanocobalamin or cobalt. If you have had Leber's disease (or other forms of optic nerve damage), an iron or folic acid deficiency, or low potassium, your doctor may not recommend it.


    Women who are pregnant or breastfeeding should also get advice from their doctor before receiving B12 injections.

    Benefits of B12 injections

    B12 injections are a relatively quick and efficient way to restore healthy B12 levels, especially in people who have very low B12 or are unable to absorb it from food.


    Vitamin B12 shots may help reduce the risk of serious conditions such as heart disease and stroke as well as cognitive issues, infertility, and neural tube defects (when mothers have B12 deficiency).

    Side effects of B12 injections

    Some people may experience side effects following injections with the cyanocobalamin form of B12, such as nausea, headaches, vomiting, itching, and dizziness. 

    Side effects are not common with methylcobalamin injections, but it’s possible to have some pain and redness in the injection area. Injections are usually given in the upper arm, the bottom, or in the upper thigh. Some people may also experience adverse effects like mild diarrhea, itching, or a swelling sensation in the body. 


    In rare cases, intramuscular B12 may cause a drop in potassium. If you experience muscle cramps, weakness, or an irregular heartbeat, consult your healthcare professional.

    Dosage of B12 injections

    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 B12 levels improve and you are no longer deficient, your treatment may be switched to supplements.

    MTHFR and Vitamin B12 Absorption

    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 variant is significantly associated with a decrease in intestinal absorption of vitamin B12. 4

    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 folate supplementation may improve symptoms to the point that the B12 deficiency is not detected in tests, and therefore is 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. 5 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. 6

    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. 

    Low methionine levels can affect the production of A-adenosylmethionine (SAMe), a major methyl donor for the central nervous system and an essential nutrient required for the production of neurotransmitters. This can lead to cognitive impairment and mental illness. 7 

    Are there Alternatives for People With MTHFR?

    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. 8

    One study compared the effectiveness of sublingual B12 with B12 injections for raising levels in patients with vitamin B12 deficiency. The results showed that while both methods are effective, sublingual vitamin B12 is actually more efficient in raising b12 levels than injections, especially in patients with very low levels.9 The researchers also noted that sublingual B12 has many practical advantages over injections, which are painful, costly, and require repeated clinic visits. Additionally, sublingual B12 bypasses intestinal absorption issues, and is a more accessible treatment option for vitamin B12 deficiency. 10


    Research also suggests that those who have genetic mutations may boost their B12 levels more effectively by taking natural forms of B12. 11 It’s also important to note that 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 (heart attack), and damage to heart cells. 12

    Supplementing with folate, vitamins B6 and B12 is also shown to help lower homocysteine concentrations in patients affected by recurrent pregnancy loss (such as miscarriages) as well as MTHFR mutations. 13


    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 one of the purest methylfolates available and able to bypass the MTHFR mutation. The active B12 is provided by Hydroxocobalamin, which is readily absorbed and utilized in the body. 14


    While B12 injections do work, sublingual vitamin B12 is proven to be more efficient in boosting B12 levels, especially in patients with very low levels. 15 Sublingual B12 is also much more affordable than injections, and avoids the pain and cost of repeated clinic visits. Sublingual B12 bypasses intestinal absorption issues and potential barriers caused by genetic variants, which makes it a more accessible treatment option for vitamin B12 deficiency.

    Sublingual B12 Supplementation: Pros and Cons

    Pros


    • Easily absorbed: Sublingual B12 tablets are absorbed into the bloodstream through the mucous membranes when placed under the tongue. This means they bypass the digestive system and any malabsorption issues. The most bioavailable forms of B12 are methylcobalamin, hydroxocobalamin, and adenosylcobalamin. These are readily absorbed and utilized by the body. These forms can be taken in tablet form.

    • Convenient: Sublingual B12 can be purchased OTC and taken at home, without a prescription.

    • Painless: Tablets are non-invasive: no needles involved.

    • Cost-effective: Sublingual B12 can be easily purchased online or in stores, and it is generally more affordable than prescription injections.


    Cons


    • Variation in quality There are hundreds of B12 supplements available now, and it can be difficult to know which works, or which is best for you. Quality can vary significantly between different brands, depending on the form and the manufacturing process.


    • Taste: Many sublingual B12 supplements are flavored to improve the taste. It’s worth noting that cheaper supplements may contain artificial additives or sweeteners. 


    • The absorption rate varies, but improvements in symptoms can often be observed within a week or two of starting supplementation.

    B12 Injections: Pros and Cons

    Pros

    • Injections deliver B12 directly into the muscle, where it is absorbed rapidly into the bloodstream. This method bypasses the digestive system that can compromise absorption. It also helps to correct severe deficiencies very quickly (if the deficiency is not based on genetic abnormalities which may require a specific form(s) of B12).

    Cons


    • Painful: B12 shots can be painful for some people, and very unpleasant for those who are afraid of needles.

    • Clinic visit: B12 injections can only be given by a doctor or nurse, which requires a clinic visit. This can be time consuming and costly. Initial treatments may require several injections per week, followed by maintenance doses every month.

    • Form of B12: Many clinics use cyanocobalamin (a synthetic form of B12 which requires a number of conversions) for their B12 shots.

    Are Vitamin B12 Injections Safe with MTHFR?

    Key Takeaways

    Vitamin B12 is a crucial cofactor in DNA synthesis, 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).


    B12 deficiency is quite common in both the US and UK, affecting around 6% of people aged under 60, and nearly 20% of those 60 and over. 1 Deficiency is often due to a lack of B12 foods in the diet, absorption issues, and/or genetic mutations that affect uptake.
     

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

    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.

    • Icon Vitamin B12 injections are often recommended by healthcare professionals in the case of severe B12 deficiency
    • Icon Sublingual B12 tablets are shown to be as effective as B12 shots, but are available OTC and are completely non-invasive.2
    • Icon Sublingual B12 is an excellent option for those with B12 deficiency or other issues with B12 absorption.

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    Frequently Asked Questions about B12 Injections

    What does a B12 injection do to you?

    A B12 injection can increase your B12 levels if you have a deficiency. B12 is essential for healthy blood cell production, energy levels, neurotransmitter production, and many other bodily processes.

    How long does B12 injection shot last?

    How long a B12 shot lasts depends on the form of B12 used in the injection, how severe your deficiency is, and how well your body absorbs the form that’s being injected. One study found that after injecting high doses of vitamin B12 (specifically cyanocobalamin) into rodents, the B12 stayed in the bloodstream for a relatively short period, with a half-life ranging from 20 to 50 minutes. This means that the concentration of B12 dropped by half within that time. 16
    B12 has a half-life of approximately six days in the blood, which usually means that it takes around six days before half of the injected amount is eliminated from the body.
    Typically, intramuscular injections might be given daily during the first week, followed by weekly shots for one month, and then every month or two months for life.

    Is sublingual B12 as effective as injection?

    While B12 injections do work, sublingual vitamin B12 has been shown to be more efficient in boosting B12 levels, especially in patients with deficiency. 17 Sublingual B12 bypasses intestinal absorption issues, which makes it a more accessible treatment option for vitamin B12 deficiency. It also avoids the pain and cost of repeated clinic visits.

    Is sublingual B12 better absorbed?

    Sublingual B12 tablets are held in the mouth under the tongue, and are absorbed into the bloodstream through the mucous membranes. This allows the B12 to bypass the digestive system and any malabsorption issues. According to research, sublingual B12 is better absorbed than B12 shots. 18
    The most bioavailable forms of B12 are methylcobalamin, hydroxocobalamin, and adenosylcobalamin. These are readily absorbed and utilized by the body. These forms can be taken in tablet form and bypass potential barriers caused by genetic variants.

    References

    1. Johan F B Arendt, Ebba Nexo; "Unexpected high plasma cobalamin: proposal for a diagnostic strategy"; Clinical Chemistry And Laboratory Medicine; 2013 Mar

      https://pubmed.ncbi.nlm.nih.gov/23241600/

    2. Merav Jacobson Bensky, Irit Ayalon-Dangur, Roi Ayalon-Dangur, Eviatar Naamany, Anat Gafter-Gvili, Gideon Koren, Shachaf Shiber; "Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency", Drug Delivery And Translational Research; 2019 Jun

      https://pubmed.ncbi.nlm.nih.gov/30632091

    3. Advait Vasavada, Preeti Patel, Devang K. Sanghavi; "Cyanocobalamin"; StatPearls [Internet], 2024 Jan

      https://www.ncbi.nlm.nih.gov/books/NBK555964/

    4. Avinoam Shiran, Eric Remer, Ihab Asmer, Basheer Karkabi, Eran Zittan, Aliza Cassel, Mira Barak, Orit Rozenberg, Khaled Karkabi, Moshe Y Flugelman; "Association of Vitamin B12 Deficiency with Homozygosity of the TT MTHFR C677T Genotype, Hyperhomocysteinemia, and Endothelial Cell Dysfunction"; The Israel Medical Association Journal; 2015 May

      https://pubmed.ncbi.nlm.nih.gov/26137654/

    5. Elysia Tjong, Manjari Dimri, Shamim S. Mohiuddin; "Biochemistry, Tetrahydrofolate"; StatPearls [Internet], 2023 June

      https://www.ncbi.nlm.nih.gov/books/NBK539712/

    6. Takaaki Sugihara, Masahiko Koda, Toshiaki Okamoto, Kenichi Miyoshi, Tomomitsu Matono, Kenji Oyama, Keiko Hosho, Jun-ichi Okano, Hajime Isomoto, Yoshikazu Murawaki; "Falsely Elevated Serum Vitamin B12 Levels Were Associated with the Severity and Prognosis of Chronic Viral Liver Disease"; Yonago Acta Medical Journal Of Medical Sciences; 2017 Mar

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355842/

    7. B R Hutto; "Folate and cobalamin in psychiatric illness"; Comprehensive Psychiatry; 1997 Nov-Dec

      https://pubmed.ncbi.nlm.nih.gov/9406735/

    8. Cristiana Paul, David M Brady; "Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms", Integrative Medicine: A Clinician's Journal (Encinitas); 2017 Feb

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312744/

    9. Merav Jacobson Bensky, Irit Ayalon-Dangur, Roi Ayalon-Dangur, Eviatar Naamany, Anat Gafter-Gvili, Gideon Koren, Shachaf Shiber; "Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency"; Drug Delivery And Translational Research; 2019 Jun

      https://pubmed.ncbi.nlm.nih.gov/30632091/

    10. Merav Jacobson Bensky, Irit Ayalon-Dangur, Roi Ayalon-Dangur, Eviatar Naamany, Anat Gafter-Gvili, Gideon Koren, Shachaf Shiber; "Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency"; Drug Delivery And Translational Research; 2019 Jun

      https://pubmed.ncbi.nlm.nih.gov/30632091/

    11. Cristiana Paul, David M Brady; "Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms", Integrative Medicine: A Clinician's Journal (Encinitas); 2017 Feb

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312744/

    12. Neetu Kataria, Poonam Yadav, Rajesh Kumar, Niraj Kumar, Mritunjai Singh, Ravi Kant, Vasantha Kalyani; "Effect of Vitamin B6, B9, and B12 Supplementation on Homocysteine Level and Cardiovascular Outcomes in Stroke Patients: A Meta-Analysis of Randomized Controlled Trials"; Cureus, 2021 May

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191525/

    13. Danielius Serapinas, Evelina Boreikaite, Agne Bartkeviciute, Rita Bandzeviciene, Mindaugas Silkunas, Daiva Bartkeviciene; "The importance of folate, vitamins B6 and B12 for the lowering of homocysteine concentrations for patients with recurrent pregnancy loss and MTHFR mutations"; Reproductive Toxicology; 2017 Sep

      https://pubmed.ncbi.nlm.nih.gov/28689805/

    14. Cristiana Paul, David M Brady; "Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms", Integrative Medicine: A Clinician's Journal (Encinitas); 2017 Feb

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312744/

    15. Merav Jacobson Bensky, Irit Ayalon-Dangur, Roi Ayalon-Dangur, Eviatar Naamany, Anat Gafter-Gvili, Gideon Koren, Shachaf Shiber; "Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency"; Drug Delivery And Translational Research; 2019 Jun

      https://pubmed.ncbi.nlm.nih.gov/30632091

    16. Alejandro A Nava-Ocampo, Aleksandra Pastrak, Tony Cruz, Gideon Koren; "Pharmacokinetics of high doses of cyanocobalamin administered by intravenous injection for 26 weeks in rats"; Clinical And Experimental Pharmacology & Physiology; 2005 Jan-Feb

      https://pubmed.ncbi.nlm.nih.gov/15730428/

    17. Merav Jacobson Bensky, Irit Ayalon-Dangur, Roi Ayalon-Dangur, Eviatar Naamany, Anat Gafter-Gvili, Gideon Koren, Shachaf Shiber; "Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency"; Drug Delivery And Translational Research; 2019 Jun

      https://pubmed.ncbi.nlm.nih.gov/30632091

    18. Merav Jacobson Bensky, Irit Ayalon-Dangur, Roi Ayalon-Dangur, Eviatar Naamany, Anat Gafter-Gvili, Gideon Koren, Shachaf Shiber; "Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency"; Drug Delivery And Translational Research; 2019 Jun

      https://pubmed.ncbi.nlm.nih.gov/30632091

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      https://www.freepik.com/

    Katie Stone - Naturopath

    About the Author

    Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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