For individuals with MTHFR gene mutations, the choice between methylcobalamin and cyanocobalamin as a vitamin B12 supplement can be confusing. The MTHFR gene mutation affects the enzyme responsible for converting folate into its active form, which in turn impacts the body's ability to utilize vitamin B12 effectively. This process is crucial for the proper functioning of the methylation cycle, which is involved in numerous biochemical reactions, including the regulation of homocysteine levels.

What is the prevalence of the gene?

MTHFR C677T Polymorphism:

  • Approximately 10-20% of the global population carries the homozygous TT genotype
  • In the heterozygous form (CT), about 30-40% of the population is affected.
  • For example, in Chinese populations, the prevalence of the C677T polymorphism can be as high as 20-25% for the TT genotype​ (SpringerLink)​​ (PLOS)​.

MTHFR A1298C Polymorphism:

  • The A1298C polymorphism is less well studied compared to C677T, but it also has a notable prevalence. Around 7-12% of the population may carry the homozygous CC genotype.
  • In some populations, such as those in China, around 10% may have the CC genotype, with a higher percentage being heterozygous (AC)​ (PLOS)​​ (SpringerLink)​.

Methylcobalamin vs. Cyanocobalamin

Methylcobalamin is often recommended for those with MTHFR mutations because it is a bioactive form of B12 that doesn't require conversion by the body, making it more readily available for use in metabolic processes. This can be particularly beneficial for those with impaired methylation due to MTHFR mutations.

On the other hand, cyanocobalamin is a synthetic form of B12 that must be converted to an active form within the body. This conversion process can be less efficient in individuals with MTHFR mutations, potentially leading to less effective supplementation. Some studies suggest that while cyanocobalamin is effective in raising serum B12 levels, the body's ability to use this form can be compromised in those with MTHFR mutations

Current Research Insights
Despite these considerations, current research does not conclusively show that methylcobalamin is superior to cyanocobalamin in terms of absorption and overall efficacy for individuals with MTHFR mutations. Both forms can correct B12 deficiencies, but methylcobalamin may offer advantages in terms of ease of utilization and reduced conversion requirements, which is particularly relevant for those with impaired methylation pathways.

Summary and Recommendations

In summary, while methylcobalamin is generally preferred for individuals with MTHFR gene mutations due to its direct usability by the body, both forms of B12 can be effective. The choice often depends on individual health conditions, the specific type of MTHFR mutation, and personal response to supplementation. Consulting with a healthcare provider can help determine the most suitable form of B12 for individual needs.

Efficacy and Absorption of B12 Forms

While methylcobalamin is often touted as a superior form of vitamin B12 due to its natural occurrence in foods and its role in neurological health, evidence does not conclusively demonstrate that it is better absorbed than the more commonly used synthetic form, cyanocobalamin.

Several studies and reviews have explored the absorption and efficacy of both forms. According to a meta-analysis published in the *Irish Journal of Medical Science*, no significant differences were found between various forms of vitamin B12, including methylcobalamin and cyanocobalamin, in terms of their ability to increase serum B12 levels when administered orally or through other routes. This suggests that both forms are effectively absorbed and utilized by the body when taken as supplements.

Another review highlighted that while methylcobalamin may have a slight edge in bioavailability due to its natural form, the differences in absorption rates between methylcobalamin and cyanocobalamin are generally negligible. Cyanocobalamin is often preferred in supplements due to its stability and lower cost, and it effectively maintains serum B12 levels.


Ultimately, both methylcobalamin and cyanocobalamin are effective in correcting B12 deficiencies and providing the necessary health benefits associated with adequate B12 levels. The choice between the two often comes down to personal preference, cost, and specific health conditions [oai_citation:11,Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis | Irish Journal of Medical Science.


1. [MTHFR & Vitamin B12 - What you need to know first for MTHFR](
2. [MTHFR Mutations and Vitamin B12 Deficiencies | Methyl-Life - Methyl-Life® Supplements](
3. [Vitamin B12 Deficiency: What You Should Know | Amy Myers MD](
4. [How to Choose the Right Type of B12 for the MTHFR Gene Mutation](
5. [Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis | Irish Journal of Medical Science (1971 -)](
6. [Methylcobalamin vs Cyanocobalamin: A Dietitian Explains](

June 22, 2024 — stephanie dowling

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