Vitamin B12 | Methylcobalamin
Vitamin B12, or cobalamin, is unique among vitamins because it contains a metal ion, cobalt, from which the term cobalamin derived. Methylcobalamin is one of the two coenzyme forms of vitamin B12 (the other is adenosylcobalamin). These are the forms used in enzymes in the human body. Methylcobalamin is used in only one enzyme, methionine synthase, which is required to make the purines and pyrimidines needed for DNA. Methionine synthase also links the folate cycle and the S-adenosylmethionine cycle, converting methyltetrahydrofolate into tetrahydrofolate, and subsequently homocysteine into methionine (this acts to support healthy homocysteine levels). Methylcobalamin is a central player in a process called methylation or methyl donation. This process has wide spread interactions with metabolic function. As an example, methylation is one of the main ways the expression of genes is changed to match our genes to diet, lifestyle and environment. Methylcobalamin is thought to be the best form of vitamin B12 for supporting the vitamin B12-dependent enzymes that normally use this form of vitamin B12. Vitamin B12 is essential for the healthy function of nerves. In a general sense, methylcobalamin can be thought of as more of a nootropic form of vitamin B12; it’s been used extensively in research when vitamin B12 has been needed for supporting brain, nerve, and vision functions.
Vitamin B12 can be found in different forms, including cyanocobalamin, hydroxocobalamin, adenosylcobalamin, and methylcobalamin. Adenosylcobalamin and methylcobalamin are considered to be the coenzyme forms, because they are what’s used in enzymes in the body.
The methylcobalamin form is selected when a biologically active form of vitamin B12 is desired and the formulation’s goal is to support methionine synthase, one of the two enzymes in the body that uses vitamin B12, or brain, nerve, and vision health.
Methylcobalamin sourcing is focused on ensuring it is non-GMO, gluten-free and vegan.
Methylcobalamin is dose-dependent (see Neurohacker Dosing Principles) in the range it’s commonly dosed (up to about 1 mg), with higher doses doing a better job in normalizing functional markers of vitamin B12 status than lower doses when a person is deficient. The RDA for vitamin B12 is very low. Vitamin B12 function is not always maintained at these low levels, with functional status sometimes requiring substantially higher doses to normalize.  Relative insufficiencies are more common with older age and in persons eating a vegetarian or vegan diet (vitamin B12 is found in animal products but not plants). Methylcobalamin has been the preferred form of vitamin B12 in research studies on the brain and the nervous system function dating back to the 1990's, so it's the form of vitamin B12 we include for products intended to support brain and vision health.
Methionine Synthase Activity
Methylcobalamin is required as a cofactor for the activity of the cytosolic enzyme methionine synthase [2,3]
Methionine synthase transfers the methyl group from methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate [2,3]
Methionine is required for the synthesis of S-adenosylmethionine (SAMe), a methyl group donor used in many biological methylation reactions [2,3]
Methionine synthase is essential for the methylation of nucleic acids (DNA and RNA) for DNA synthesis and protein synthesis [2,3]
Cardiovascular and cerebrovascular function
Downregulates homocysteine levels (protects cardiovascular function); complementary to vitamin B6 and folic acid (vitamin B9) [4–6]
Supports accommodation (i.e., focusing of eyes) when using devices with screen [7,8]
Supports retinal circadian rhythms 
Supports healthy retinal function [10–12]
Supports healthy optic nerve function [10,13–21]
Supports retinal nerve fiber layer thickness [22,23]
Supports normal activity of ciliary muscles of the lens 
Supports healthy function of eye ocular surfaces and corneal nerve [24,25]
Supports healthy gut microbiome flora and function [26,27]
Folate - Insufficient methylcobalamin slows the regeneration of tetrahydrofolate and traps folate in a form that is not usable by the body. This can often be corrected with higher doses of folate but can mask a vitamin B12 deficiency, so vitamin B12 is almost always given when folates are supplemented.
Methyl Donors - Key methyl donor nutrients include trimethylglycine (betaine), folates, vitamin B6, vitamin B12, and S-adenosylmethionine: One or more of these nutrients are often given together.
Adenosylcobalamin (another coenzyme form of vitamin B12) 
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