Compared with cyanocobalamin, it appears that both methylcobalamin and adenosylcobalamin are better absorbed and retained in higher amounts within your tissues. In simple terms, they are used much more effectively. In general, methylcobalamin is used primarily in your liver, brain and nervous system, while adenosylcobalamin is used mostly in the liver and for hemoglobin (blood cell) production
One of the classic indications of B12 deficiency is a specialized form of anemia called macrocytic anemia. This usually shows up on a lab test as an increased mean corpuscular volume (in other words your blood cells are a bit larger than they should be). While iron is often the only thing given for anemia, this form of anemia usually has nothing to do with a lack of iron. B12 and folic acid are the nutrients you would need, but you need them to be plugged into enzymes. Because of this, the active forms of B12 are often much more effective. Even with other forms of anemia, it is usually much more effective to combine iron supplementation with folic acid + either or both of the active forms of vitamin B12.
In animals, a significant body of experimental evidence suggests that a deficiency of vitamin B12 can enhance the activity of various carcinogens. Animal experiments have also demonstrated that both methylcobalamin and adenosylcobalamin increase survival time and reduce tumor growth in some forms of cancer. Amazingly, methylcobalamin has also been shown to enhance the effectiveness of methotrexate, a drug sometimes used in the treatment of cancer. The active forms of B12 also appear to be very important in supporting proper immune system health. While this information should not be presumed to apply to human cancer, and their is currently no available evidence indicating that any form of vitamin B12 has any benefit in preventing or treating cancer, it certainly seems that this nutrient would be worthy of some future research.
Methylcobalamin is the specific form of B12 needed for nervous system health. Because of this it should be the first form of this vitamin thought of when interested in attempting to optimize the health of the nervous system with vitamin supplementation. Indications of a potential deficiency of B12 in the nervous system might include numbness, tingling, loss of feeling sensation, burning sensations, muscle cramps, nerve pain and slowness of reflexes.
The relative balance of the nervous system is also of critical importance in your overall sense of health and well being. In essence we have a fight or flight nervous system and a relaxation nervous system. Methylcobalamin has been shown to be an important vitamin in helping to establish and maintain an appropriate balance between these two opposing nervous systems.
Because of methylcobalamin's importance in nervous system health, it is also an important nutrient for vision. In fact, continued visual work (like work on a computer) often leads to a reduction in something called "visual accommodation". Methylcobalamin can significantly improve visual accommodation, while cyanocobalamin appears to be ineffective.
An elevated level of homocysteine is a metabolic indication of decreased levels of the coenzyme forms of vitamin B12, especially methylcobalamin. Homocysteine has received a tremendous amount of emphasis in the scientific literature because of its associations with heart disease and a variety of other specific health conditions. I have even seen advertisements on television promoting folic acid, as a vitamin needed to lower homocysteine. While this is true, and folic acid does lower homocysteine levels, the combination of methylcobalamin and folic acid appears to work much better.
In people with liver disease, although high blood levels of vitamin B12 are common, it is not unusual to actually have a correspondingly low liver tissue concentration of vitamin B12 and its enzymes. In effect your locksmith can't make keys anymore so the functions that depend on a complete and working B12 enzymes often suffer. Because of this, methylcobalamin and adenosylcobalamin should be the forms of B12 used under these circumstances. In fact, even under normal circumstances, the active forms of B12 help the liver function much more efficiently. Liver detoxification and antioxidant systems work much more effectively when methylcobalamin and adenosylcobalamin are supplied (as opposed to cyanocobalamin). Since our livers tend to be over worked due to the varieties of pollution and other environmental factors we are exposed to, these active forms of B12 can be valuable forms of additional nutritional support for the liver.
The most well studied use of methylcobalamin has to do with sleep. Although the exact mechanism of action is not yet clear, it is possible that methylcobalamin is needed for the synthesis of melatonin. Available information indicates that methylcobalamin can modulate melatonin secretion, enhance light-sensitivity, and normalize circadian rhythm (your 24-hour clock). Because of this, individuals supplementing this form of B12 often have improved quality of sleep, often will require slightly less sleep, and will not uncommonly report that they feel a bit more refreshed when waking in the morning. Methylcobalamin is particularly effective when your 24-hour clock is not running smoothly. This may be indicated by a need for excessive sleep, changing sleep-wake cycles, or a tendency to have altered sleep wake patterns. As examples, you might require 10-12 hours of sleep, or you might not feel tired until 2-3 am and you might wake at noon, or you might find that you wake a bit later every day and go to be a bit later every night. Under all of these circumstances the combination of methylcobalamin (about 3000 mcg daily) and exposure to bright light in the morning can help reestablish your 24-hour clock.
Because of methylcobalamin's impact on 24-hour clock and the cycles that feed of this, it is also an important vitamin to regulate your 24-hour release of the stress hormone cortisol. This seems to be particularly important for blood types A and AB. Methylcobalamin also seems to result in a better 24-hour maintenance of body temperature. Typically individuals supplementing this coenzyme form of B12 have higher temperatures in the later hours of the daytime. This usually corresponds with improved alertness at the same time of the day. While this can be of importance to all blood types, low body temperatures seems to be an area of greater challenge for A's and B's.