Sleep Disturbances: The use of MetCbl in the treatment of a variety of sleep-wake disorders is very promising. Although the exact mechanism of action is not yet elucidated, it is possible MetCbl is needed for the synthesis of melatonin, since the biosynthetic formation of melatonin requires the donation of a methyl group. Based on available information, MetCbl appears to be capable of modulating melatonin secretion, enhancing light-sensitivity, and normalizing circadian rhythm.

AdeCbl and MetCbl are the coenzyme forms of vitamin B12 utilized in the vitamin B12-dependent enzymes in humans. Because the coenzyme forms bypass several of the enzymatic reactions required for the formation of the functional forms of vitamin B12, they offer a theoretical advantage in cobalamin supplementation. Both AdeCbl and MetCbl are retained in the body better and increase tissue concentrations of cobalamin better than CN-Cbl. Additionally, the coenzyme forms of vitamin B12 demonstrate a range of activity and clinical results not shown by the other supplemental forms of vitamin B12.

It is important to remember that circulating levels of vitamin B12 are not always a reflection of tissue levels, and that even if an adequate supply of cobalamin appears in the circulation, a functional deficiency of the coenzyme forms might coexist in tissues and other body fluids. Although CN-Cbl will usually increase circulating levels of cobalamin, its ability to increase tissue levels of the active forms of vitamin B12 can be limited in a range of sub-clinical and clinical conditions. Even in a best case scenario, the activation of CN-Cbl to either AdeCbl or MetCbl does not occur instantly, possibly occurring over 1-2 months, and requires the interaction of GSH, reducing agents, possibly alpha-tocopherol, and in the case of MetCbl, SAM and the active form of folic acid.

The use of either AdeCbl and/or MetCbl offers a significant biochemical and therapeutic advantage over other existing forms of vitamin B12, and should be considered as a first-line choice for correcting vitamin B12 deficiency and treating conditions shown to benefit from cobalamin administration.