Vitamin B12, cobalamin, is indispensable for humans owing to its participation in two biochemical reactions: the conversion of l-methylmalonyl coenzyme A to succinyl coenzyme A, and the formation of methionine by methylation of homocysteine. Eukaryotes, encompassing plants, fungi, animals and humans, do not synthesise vitamin B12, in contrast to prokaryotes. Humans must consume it in their diet. The most important sources include meat, milk and dairy products, fish, shellfish and eggs. Due to this, vegetarians are at risk to develop a vitamin B12 deficiency and it is recommended that they consume fortified food. Vitamin B12 behaves differently to most vitamins of the B complex in several aspects, e.g. it is more stable, has a very specific mechanism of absorption and is stored in large amounts in the organism. This review summarises all its biological aspects (including its structure and natural sources as well as its stability in food, pharmacokinetics and physiological function) as well as causes, symptoms, diagnosis (with a summary of analytical methods for its measurement), prevention and treatment of its deficiency, and its pharmacological use and potential toxicity.

As vitamin B12 is only synthesized by bacteria, ruminant products, especially dairy products, are excellent sources of this vitamin. This study aims to identify if diet and cow characteristics could affect vitamin B12 concentration in milk of dairy cows. Information on 1484 first, 1093 second and 1763 third and greater parity Holstein cows in 100 herds was collected during three consecutive milkings. During the first morning milking, all dietary ingredients given to cows were sampled and quantities offered were recorded throughout the day. Nutrient composition of ingredients was obtained by wet chemistry to reconstitute nutrient composition of the ration. Milk samples were taken with in-line milk meters during the evening milking of the 1st day and the morning milking of the 2nd day and were analyzed for vitamin B12 concentration. Milk yields were recorded and milk components were separately analyzed for each milking. Daily vitamin B12 concentration in milk was obtained using morning and evening vitamin B12 concentrations weighted with respective milk yield, then divided by daily yield. To decrease the number of interdependent variables to include in the multivariable model, a principal component analysis was carried out. Daily milk concentration of vitamin B12 averaged 3809±80 pg/ml, 4178±79 pg/ml and 4399±77 pg/ml for first, second and third, and greater lactation cows. Out of 11 principal components, six were significantly related to daily milk concentration of vitamin B12 when entered in the multivariable model. Results suggested that vitamin B12 concentration in milk was positively related to percentage of fiber and negatively related to starch as well as energy of the diet. Negative relationships were noted between vitamin B12 concentration in milk and milk yield as well as milk lactose concentration and positive relationships were observed between vitamin B12 concentration in milk and milk fat as well as protein concentrations. The percentages of chopped mixed silage and commercial energy supplement in the diet as well as cow BW were positively related to vitamin B12 in milk and percentages of baled mixed silage, corn and commercial protein supplement in the ration were negatively related to vitamin B12 concentration in milk. The pseudo-R2 of the model was low (52%) suggesting that diet and cow characteristics have moderate impact on vitamin B12 concentration in milk. Moreover, when entering solely the principal component related to milk production in the model, the pseudo-R2 was 46%. In conclusion, it suggests that studied diet characteristics have a marginal impact on vitamin B12 concentration in milk variation.

Fat digestibility is decreased in old cats for unknown reasons. Subclinical gastrointestinal diseases and pancreatic dysfunction, both related to ageing, can affect food digestibility. The aim of the present study was to elucidate the prevalence of subnormal cobalamin concentration and pancreatic disease in old cats and study the relationship between both markers and fat digestibility. A total of sixty-four cats without evident signs of gastrointestinal disease were included and grouped according to age: (1) fifteen middle-aged (MA), aged 3–7 years; and (2) forty-nine old, aged 10–17 years. All cats were tested for serum cobalamin, specific feline pancreatic lipase (fPL) and feline trypsin-like immunoreactivity. Then, sixteen of the old cats were selected and grouped according to cobalamin and fPL concentrations: control (normal cobalamin and fPL); low vitamin B12 (cobalamin <290 ng/l; normal fPL); and high fPL (normal cobalamin; fPL >4 µg/ml). A food digestibility trial with a high-fat diet (21·6 %) was performed. In the old group, cobalamin was lower and fPL higher than in MA cats. Of the old cats (n 49), 14 % had subnormal cobalamin, 8 % had a severe increase in fPL, 2 % had both alterations and 14 % had a slight increase in fPL. By contrast, MA cats did not have cobalamin deficiency or an increase in fPL concentrations. Fat digestibility was lower in low vitamin B12 cats than control cats. Decreased fat digestibility is not present in all old cats but could be a characteristic of subclinical chronic gastrointestinal disease. Cobalamin concentration, as a marker of gastrointestinal disease, could be useful for the routine evaluation of old cats.

Cobalamin (Cbl) is an essential B vitamin involved in the normal functioning of the nervous system, the formation of key components of blood, DNA synthesis and methylation, and energy production. Physiological levels of Cbl vary greatly within populations, although the basis for this variability remains largely unknown. We conducted a twin study to characterise the basis of variation in plasma Cbl levels and to test whether common genetic polymorphisms in genes known to cause defects in inborn errors of Cbl metabolism and transport are also associated with mean plasma Cbl levels in the general population. The present results showed that plasma levels of Cbl were heritable, with genetic and phenotypic variance increasing with age, and levels significantly correlated with age, BMI, exercise, alcohol consumption, smoking status, social class and folate levels, which collectively accounted for up to 15 % of Cbl variation. Of eight genes responsible for the defects of the Cbl metabolic pathway (cblA–G and mut), MMAA, MMACHC, MTRR and MUT harboured polymorphisms that showed evidence of association with Cbl levels. Characterisation of the heritable component of variation in Cbl levels can facilitate the early diagnosis and prognosis of Cbl insufficiency/deficiency in individuals at a higher risk of associated diseases.

Plasma total cysteine (tCys) concentrations are associated with BMI. To study the relationship between tCys and BMI, we monitored the changes in serum concentrations of tCys and metabolically related compounds in sixty obese patients (BMI 50–60 kg/m2) from before to 1 year after either gastric bypass surgery (mean 30 % weight loss) or duodenal switch surgery (mean 41 % weight loss). A total of fifty-eight healthy persons (BMI 17–31 kg/m2) served as controls. Before surgery, obese patients had modestly (approximately 17 %) higher mean serum tCys, and markedly (>2-fold) higher glutamate concentrations, than controls (P ≤ 0·001 for both). Serial examinations after surgery revealed that gastric bypass patients had no change in tCys concentrations (P = 0·22), while duodenal switch patients showed a modest (approximately 12 %) but significant decrease in tCys (P < 0·001). Total homocysteine concentrations increased in duodenal switch patients but not in gastric bypass patients. Independent of surgery type, serum concentrations of methionine and cystathionine decreased (P < 0·05 for both), while serum glutathione and taurine remained stable. Glutamate concentrations declined, as did γ-glutamyltransferase activity (P < 0·001 for both). These results show that despite 30 % weight loss, and decreases in methionine, cystathionine and glutamate, there was no significant change in serum tCys in patients after gastric bypass surgery. The decrease in tCys in patients undergoing duodenal switch could be related to malabsorption. The present findings do not suggest that BMI is a causal determinant of plasma tCys.

Background: The aim of this study is to determine whether B12 replacement would ameliorate cognitive and psychiatric symptoms in elderly subjects with dementia and low serum B12 levels.

Methods: A test group (n = 28) of nursing home residents with low serum B12 levels (<250 pg/mL) and a matched comparison group (n = 28) with normal serum B12 levels (>300 pg/mL) were evaluated by blinded raters while the test group received intramuscular (IM) B12 replacement therapy. All subjects were assessed at baseline, 8 weeks, and 16 weeks with the Dementia Rating Scale, Brief Psychiatric Rating Scale, and Geriatric Depression Scale.

Results: Although B12 replacement produced significant improvement in hematologic and metabolic parameters, it yielded no significant effect on cognitive or psychiatric variables. A few subjects evidenced notable individual treatment responses; however, these were not statistically more frequent than in the normal B12 group.

Conclusions: These results suggest that B12 replacement is unlikely to benefit cognitive or psychiatric symptoms in the vast majority of elderly dementia patients with low serum B12 levels.

The primary function of cobalamin (Cbl; vitamin B12) is the formation of red blood cells and the maintenance of a healthy nervous system. Before cells can utilise dietary Cbl, the vitamin must undergo cellular transport using two distinct receptor-mediated events. First, dietary Cbl bound to gastric intrinsic factor (IF) is taken up from the apical pole of ileal epithelial cells via a 460 kDa receptor, cubilin, and is transported across the cell bound to another Cbl-binding protein, transcobalamin II (TC II). Second, plasma TC II–Cbl is taken up by cells that need Cbl via the TC II receptor (TC II-R), a 62 kDa protein that is expressed as a functional dimer in cellular plasma membranes. Human Cbl deficiency can develop as a result of acquired or inherited dysfunction in either of these two transmembrane transport events. This review focuses on the biochemical, cellular and molecular aspects of IF and TC II and their cell-surface receptors.