[2][6] Vitamin B12 deficiencies have a greater effect on young children, pregnant and elderly people, and are more common in middle and lower-developed countries due to malnutrition.

[2] This can result in fatigue, decreased ability to think, lightheadedness, shortness of breath, frequent infections, poor appetite, numbness in the hands and feet, depression, memory loss, confusion, difficulty walking, blurred vision, irreversible nerve damage, and many others.

Vitamin B12 deficiency in pregnant women is strongly associated with an increased risk of spontaneous abortion, congenital malformations such as neural tube defects, and problems with brain development growth in the unborn child.

[6][24] Deficiency at levels only slightly lower than normal can cause a range of symptoms such as fatigue, feeling weak, lightheadedness, dizziness, breathlessness, headaches, mouth ulcers, upset stomach, decreased appetite, difficulty walking (staggering balance problems),[15][25] muscle weakness, depression, poor memory, poor reflexes, confusion, and pale skin, feeling abnormal sensations, among others, especially in people over age 60.

As with vegetarians, vegans can avoid this by consuming a dietary supplement or eating B12 fortified food such as cereal, plant-based milks, and nutritional yeast as a regular part of their diet.

[46] What the nursing mother consumes is more important than her liver tissue content, as it is recently absorbed vitamin that more effectively reaches breast milk.

[39]: 974–975  Signs of low vitamin levels in infants and young children can include anemia, poor physical growth, and neurodevelopmental delays.

"[50] The vitamin deficiency is typically suspected when a routine complete blood count shows anemia with an elevated mean corpuscular volume (MCV).

[59][60] The mechanism of action is straightforward: the hydroxycobalamin hydroxide ligand is displaced by the toxic cyanide ion, and the resulting non-toxic cyanocobalamin is excreted in urine.

[6][62] Since there are few non-animal sources of the vitamin, vegans are advised to consume a dietary supplement or fortified foods for B12 intake, or risk serious health consequences.

[6] Children in some regions of developing countries are at particular risk due to increased requirements during growth coupled with diets low in animal-sourced foods.

[73][74] Other mammalian species (examples: rabbits, pikas, beaver, guinea pigs) consume high-fiber plants which pass through the gastrointestinal tract and undergo bacterial fermentation in the cecum and large intestine.

[74] Non-ruminant, non-hindgut herbivores may have an enlarged forestomach and/or small intestine to provide a place for bacterial fermentation and B-vitamin production, including B12.

However, the Academy of Nutrition and Dietetics considers plant and algae sources "unreliable", stating that vegans should turn to fortified foods and supplements instead.

Microbial fermentation yields adenosylcobalamin, which is then converted to cyanocobalamin by the addition of potassium cyanide or thiocyanate in the presence of sodium nitrite and heat.

[22] Most cyanobacteria, including Spirulina, and some algae, such as Porphyra tenera (used to make a dried seaweed food called nori in Japan), have been found to contain mostly pseudovitamin-B12 instead of biologically active B12.

[23][100] These pseudo-vitamin compounds can be found in some types of shellfish,[22] in edible insects,[101] and at times as metabolic breakdown products of cyanocobalamin added to dietary supplements and fortified foods.

Clinically significant vitamin B12 deficiency and megaloblastic anemia are unlikely, unless these drug therapies are prolonged for two or more years, or if in addition, the person's dietary intake is below recommended levels.

Symptomatic vitamin deficiency is more likely if the person is rendered achlorhydric (a complete absence of gastric acid secretion), which occurs more frequently with proton pump inhibitors than H2 blockers.

[107] Certain medications can decrease the absorption of orally consumed vitamin B12, including colchicine, extended-release potassium products, and antibiotics such as gentamicin, neomycin and tobramycin.

The vitamin is then transferred to TC2, which serves as the circulating plasma transporter, hereditary defects in the production of TC2 and its receptor may produce functional deficiencies in B12 and infantile megaloblastic anemia, and abnormal B12 related biochemistry, even in some cases with normal blood B12 levels.

[124] Other causes of B12 malabsorption include intrinsic factor deficiency, pernicious anemia, bariatric surgery pancreatic insufficiency, obstructive jaundice, tropical sprue and celiac disease, and radiation enteritis of the distal ileum.

[127][128] Vitamin B12 is derived from a tetrapyrrolic structural framework created by the enzymes deaminase and cosynthetase which transform aminolevulinic acid via porphobilinogen and hydroxymethylbilane to uroporphyrinogen III.

It was not until a genetically engineered strain of Pseudomonas denitrificans was used, in which eight of the genes involved in the biosynthesis of the vitamin had been overexpressed, that the complete sequence of methylation and other steps could be determined, thus fully establishing all the intermediates in the pathway.

[137] Propionibacterium, the other commonly used bacteria, produce no exotoxins or endotoxins and are generally recognized as safe (have been granted GRAS status) by the Food and Drug Administration of the United States.

William Castle demonstrated that gastric juice contained an "intrinsic factor" which when combined with meat ingestion resulted in absorption of the vitamin in this condition.

Shorb knew that the same liver extract was used to treat pernicious anemia (her father-in-law had died from the disease), and concluded that LLD could be developed as an assay method to identify the active compound.

[135] As noted above, the completely synthetic laboratory synthesis of B12 was achieved by Robert Burns Woodward and Albert Eschenmoser in 1972, though this process has no commercial potential, requiring more than 70 steps and having a yield well below 0.01%.

After he died in 1984, other physicians and naturopaths took up prescribing "intravenous micronutrient therapy" with unsubstantiated health claims for treating fatigue, low energy, stress, anxiety, migraine, depression, immunocompromised, promoting weight loss, and more.

A Mayo Clinic review concluded that there is no solid evidence that vitamin B12 injections provide an energy boost or aid weight loss.