Vitamin B12, also known as cobalamin, is a vital nutrient that is essential for maintaining a healthy body.
B12 acts as a cofactor in many important biological reactions, including the synthesis of DNA and the formation of the myelin sheath in nerve cells.
However, a deficiency in vitamin B12 can lead to a cascade of negative effects. While there are several genes that can influence how much vitamin B12 is absorbed, transported, and required, looking at an individual’s genetic data may help to determine the optimal amount of B12 for their body.
Background Info on Vitamin B12
Vitamin B12 is found primarily in animal products, including meat, fish, eggs, and dairy. Vegetarian and vegan diets are often deficient in B12, and supplementation is recommended. Vitamin B12 as a supplement comes in four different forms: cyanocobalamin, methylcobalamin, adenosylcobalamin, and hydroxocobalamin.
Cyanocobalamin is commonly found in cheaper vitamins and processed foods, but it must be converted by the body before use. Methylcobalamin and adenosylcobalamin are active forms that are readily used by the body.
Vitamin B12 Deficiency Symptoms
Vitamin B12 deficiency or insufficiency can lead to several negative health outcomes, including mental confusion, tingling and numbness in the feet and hands, memory loss, disorientation, megaloblastic anemia, and gastrointestinal symptoms.
To absorb B12 from foods, an individual needs to have adequate intrinsic factor produced in the stomach. Unfortunately, intrinsic factor is often depleted in the elderly, leading to B12 deficiency.
MTR & MTRR: Methionine and Vitamin B12
Methionine is an essential amino acid that is used in the production of proteins. MTR (methionine synthase) and MTRR (methionine synthase reductase) code for two enzymes that work together in the methylation cycle.
The MTR gene works in the final step to regenerate homocysteine into methionine using methylcobalamin, while MTRR regenerates the methylcobalamin for MTR to use again.
Both enzymes are essential for the methylation cycle, which is your body’s way of recycling certain molecules to ensure that there are enough methyl groups available for cellular processes.
Methyl Groups
Methyl groups (one carbon plus three hydrogens) are added to organic molecules in the methylation cycle, which is used in methylation reactions such as the synthesis of some of the nucleic acid (DNA) bases, turning off genes so that they aren’t transcribed (DNA methylation), converting serotonin into melatonin, methylating arsenic so that it can be excreted, breaking down neurotransmitters, metabolizing estrogen, and regenerating methionine from homocysteine.
The balance of methylation reactions is crucial, and a deficiency in B12 or methyl folate can lead to a buildup of homocysteine and an increase in the risk of heart disease.
High Homocysteine and B12
Homocysteine levels are strongly associated with an increase in the risk of heart disease.
If an individual’s homocysteine levels are high and they carry the MTHFR or MTRR variants, supplementing with vitamin B12, methylfolate, riboflavin, and B6 may help to lower their levels.
However, clinicians often caution individuals who carry the COMT rs4680 A/A genotype (lower COMT levels) to avoid methylcobalamin and stick to adenosylcobalamin or
Resources
• Stover PJ. (2006). Physiology of folate and vitamin B12 in health and disease. Nutrition Reviews, 64(5 Pt 2), S27-S32.
• Selhub J. (1999). Homocysteine metabolism. Annual Review of Nutrition, 19, 217-246.
• Hannibal L, et al. (2016). Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency. Frontiers in Molecular Biosciences, 3, 27.
2. Glutathione synthesis and B-vitamins:
• Lu, S. C. (2013). Glutathione synthesis. Biochimica et Biophysica Acta (BBA) – General Subjects, 1830(5), 3143-3153.
• James SJ, et al. (2002). Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. The American Journal of Clinical Nutrition, 80(6), 1611-1617.
• Bottiglieri T. (2005). Homocysteine and folate metabolism in depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29(7), 1103-1112.
