Vitamin B12 is a water-soluble vitamin needed for normal nerve cell activity, DNA replication, and production of the mood-affecting substance SAMe (S-adenosyl-L-methionine). Vitamin B12 acts with folic acid and vitamin B6 to control homocysteine levels. An excess of homocysteine has been linked to an increased risk of coronary disease, stroke, and other diseases such as osteoporosis and Alzheimer's.

Vitamin B12 deficiency causes fatigue. A small trial reported that even some people who are not deficient in B12 showed a marked increase in energy after vitamin B12 injections. However, the relationship between B12 injections and the energy level of people who are not vitamin B12-deficient has been rarely studied. Oral B12 supplements are unlikely to achieve the same results as injectable B12, because the body has a relatively poor absorption rate for this vitamin.