From the Guidelines
Vitamin B12 metabolism is not directly affected by the MFCKR gene, as there is no evidence of the existence of this gene, but it is indirectly connected to the MTHFR gene through the methionine cycle. The MTHFR gene produces an enzyme that plays a crucial role in processing folate, which is connected to B12 metabolism 1. When someone has certain MTHFR gene variants, their ability to convert folate to its active form may be reduced, affecting the B12-dependent methylation pathway. Some key points to consider include:
- The connection between MTHFR and B12 is important because they work together in several biochemical processes, including DNA synthesis and homocysteine metabolism 1.
- People with MTHFR variants may benefit from taking methylated forms of B vitamins, including methylcobalamin rather than cyanocobalamin, though individual responses vary.
- If you suspect MTHFR-related issues, consulting with a healthcare provider for appropriate testing and personalized recommendations is advisable before starting any supplementation regimen. The study by the European Heart Journal 1 highlights the importance of considering homocysteine and atherosclerosis, and how treatment of moderate homocysteinaemia would reduce cardiovascular risk, which is relevant to B12 metabolism. Key aspects of B12 metabolism and MTHFR include:
- Intermediate homocysteinaemia is usually the result of moderate/severe cobalamin or folate deficiency or renal failure 1.
- Severe cobalamin deficiency and homocystinuria are the main causes of severe homocysteinaemia, and it should definitely be treated accordingly (cobalamin 0.02–1 mg/day) 1.
From the Research
Association between MFCKR Gene and Vitamin B12
- There is no direct evidence in the provided studies to suggest an association between the MFCKR gene and vitamin B12 levels 2, 3, 4, 5, 6.
- However, studies have identified associations between other genes and vitamin B12 levels, such as the CUBN gene 2 and the FUT2 gene 6.
- The CUBN gene has been associated with vitamin B12 levels, with a non-synonymous SNP located in the CUBN gene showing a strong association with baseline vitamin B12 levels 2.
- The FUT2 gene has also been associated with vitamin B12 serum levels, with a polymorphism in the FUT2 gene interfering with the absorption of vitamin B12 6.
Genetic Associations with Vitamin B12 Levels
- Genome-wide association studies have identified several genetic variants associated with vitamin B12 levels, including variants in the CUBN, TCN1, and FUT2 genes 2, 6.
- These genetic variants may influence the absorption, transport, or metabolism of vitamin B12, leading to variations in vitamin B12 levels 2, 6.
- Further research is needed to fully understand the genetic factors that contribute to vitamin B12 levels and to identify potential therapeutic targets for vitamin B12 deficiency 2, 6.
Vitamin B12 and Disease Risk
- Vitamin B12 deficiency has been associated with an increased risk of various diseases, including cardiovascular disease, stroke, and neurological disorders 3, 4, 5.
- Homocysteine levels, which are influenced by vitamin B12 levels, have also been associated with disease risk, including cardiovascular disease and neurological disorders 3, 4, 5.
- Understanding the genetic factors that contribute to vitamin B12 levels and homocysteine levels may help identify individuals at increased risk of disease and inform strategies for disease prevention and treatment 2, 3, 4, 5, 6.