This report consists of a brief summary of experimental studies which emphasize (a) the dominant role played by vitamin B₁₂ in the utilization of carbohydrates, (b) interrelationships between vitamin B₁₂ absorption and endocrine function, and (c) some relationships of vitamin B₁₂ to diabetes mellitus.

(1) Weanling rats fed a diet, rich in carbohydrate and low in fat require more vitamin B₁₂ for growth.

(2) The fat content of the carcass of vitamin B₁₂-deficient rats is abnormally low but can be elevated by injection of this vitamin.

(3) The administration of glucose to rats results in a decrease in the vitamin B₁₂levels of plasma or liver.

(4) Deficiency of vitamin B₁₂ causes hyperglycemia correctable with vitamin B₁₂. In vitro experiments indicate that the red cells of vitamin B₁₂-deficient animals are low in glutathione content as well as enzyme activity essential for the degradation of glucose. Other enzyme systems involved in carbohydrate metabolism such as coenzyme A in liver or DPN in liver are also deranged due to this deficiency.

(5) The effect of cortisone and thyroid on absorption of orally administered vitamin B₁₂ and retention of injected vitamin B₁₂ was re-emphasized. It was found that corticotropin (ACTH) or cortisone causes hyperglycemia, destruction of vitamin B₁₂-binding substances in muscles as well as an elevation of the vitamin B₁₂serum level. Thyroidectomy decreases absorption of vitamin B₁₂.

(6) Some evidence of adrenal hyperactivity in diabetic patients with diabetic retinopathy, (as gathered by other investigators), has been reviewed. We caution against a premature interpretation that adrenal hyperactivity is causally or pathogenetically related to diabetic retinopathy; it may turn out to be a mere associated phenomenon.

(7) Diabetic patients without retinopathy excrete in their urines a significantly smaller amount of an orally administered radioactive vitamin B₁₂-test dose than do non-diabetic subjects or diabetic patients with retinopathy. Fecal excretion tests confirm the above findings.

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Vitamin B₁₂, also called cobalamin, is a water-soluble vitamin that has a key role in the normal functioning of the brain and nervous system, and the formation of red blood cells. It is one of eight B vitamins. It is involved in the metabolism of every cell of the human body, especially affecting DNA synthesis, fatty acid and amino acid metabolism.^[1] No fungi, plants, or animals (including humans) are capable of producing vitamin B₁₂. Only bacteria and archaea have the enzymes needed for its synthesis. Some substantial sources of B₁₂ include animal products (shellfish, meat), fortified food products, and dietary supplements.^[2][3] B₁₂ is the largest and most structurally complicated vitamin and can be produced industrially only through bacterial fermentation synthesis, typically used to manufacture B₁₂ for fortified foods and supplements.

Vitamin B₁₂ consists of a class of chemically related compounds (vitamers), all of which show pharmacological activity. It contains the biochemically rare element cobalt (chemical symbol Co) positioned in the center of a planar tetra-pyrrole ring called a corrin ring. The vitamer is produced by bacteria as hydroxocobalamin, but conversion between different forms of the vitamin occurs in the body after consumption.

Vitamin B₁₂ was discovered^[4] as a result of its relationship to the disease pernicious anemia, an autoimmune disease in which parietal cells of the stomach responsible for secreting intrinsic factor are destroyed; these cells are also responsible for secreting acid in the stomach. Because intrinsic factor is crucial for the normal absorption of B₁₂, its lack in the presence of pernicious anemia causes a vitamin B₁₂ deficiency. Many other subtler kinds of vitamin B₁₂ deficiency and their biochemical effects have since been elucidated.^[5] Due to impairment of vitamin B₁₂ absorption during aging, people over age 60 are at risk of deficiency.

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Vitamin B₁₂ deficiency can potentially cause severe and irreversible damage, especially to the brain and nervous system.^[8] At levels only slightly lower than normal, a range of symptoms such as fatigue, lethargy, depression, poor memory, breathlessness, headaches, and pale skin, among others, may be experienced, especially in elderly people (over age 60)^[2][9] who produce less stomach acid as they age, thereby increasing their probability of B₁₂deficiencies.^[5] Vitamin B₁₂ deficiency can also cause symptoms of mania and psychosis.^[10][11]

Vitamin B₁₂ deficiency is most commonly caused by low intakes, but can also result from malabsorption, certain intestinal disorders, low presence of binding proteins, and use of certain medications. Vitamin B₁₂ is rare from plant sources, so vegetarians are most likely to suffer from vitamin B₁₂ deficiency. Infants are at a higher risk of vitamin B₁₂ deficiency if they were born to vegetarian mothers. The elderly who have diets with limited meat or animal products are vulnerable populations as well. Vitamin B₁₂ deficiency may occur in between 40% to 80% of the vegetarian population.^[12] In Hong Kong and India, vitamin B₁₂ deficiency has been found in roughly 80% of the vegan population as well.^[13]

Vitamin B₁₂ is a co-substrate of various cell reactions involved in methylation synthesis of nucleic acid and neurotransmitters. Synthesis of the trimonoamine neurotransmitters can enhance the effects of a traditional antidepressant.^[14] The intracellular concentrations of vitamin B₁₂ can be inferred through the total plasma concentration of homocysteine, which can be converted to methionine through an enzymatic reaction that uses 5-methyltetrahydrofolate as the methyl donor group. Consequently, the plasma concentration of homocysteine falls as the intracellular concentration of vitamin B₁₂ rises. The active metabolite of vitamin B₁₂ is required for the methylation of homocysteine in the production of methionine, which is involved in a number of biochemical processes including the monoamine neurotransmitters metabolism. Thus, a deficiency in vitamin B₁₂ may impact the production and function of those neurotransmitters.