Macro-B12 and Unexpectedly High Levels of Plasma B12: A Critical Review.

A low total plasma vitamin B12 supports a clinical suspicion of B12 deficiency, while the interpretation of an unexpectedly normal/high level is marred by controversies. Here, we critically review current knowledge on B12 in blood plasma, including the presence of the so-called "macro-B12". The latter form is most often defined as the fraction of B12 that can be removed by precipitation with polyethylene glycol (PEG), a nonspecific procedure that also removes protein polymers and antibody-bound analytes.

Kinetics of Cellular Cobalamin Uptake and Conversion: Comparison of Aquo/Hydroxocobalamin to Cyanocobalamin.

Cyanocobalamin (CNCbl) and aquo/hydroxocobalamin (HOCbl) are the forms of vitamin B that are most commonly used for supplementation. They are both converted to methylcobalamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl), which metabolize homocysteine and methylmalonic acid, respectively. Here, we compare the kinetics of uptake and the intracellular transformations of radiolabeled CNCbl vs.

Protein binding assays for an accurate differentiation of vitamin B12 from its inactive analogue. A study on edible cricket powder.

Inactive analogues of vitamin B12 (cobalamin, Cbl) can mimic the active Cbl in food if using the traditional microbiological measurements. Thus, overestimated Cbl was recently revealed in edible insects employing immunoaffinity adsorption, HPLC-separation and mass spectrometry (https://doi.org/10.

Low methylcobalamin in liver tissues is an artifact as shown by a revised extraction procedure.

Background: Vitamin B12 (cobalamin, Cbl) is represented by several molecular variants distinguished by the exchangeable ligand X coordinated to cobalt ion (XCbl). The most typical XCbl-forms are cyanocobalamin (CNCbl), hydroxocobalamin (HOCbl), methylcobalamin (MeCbl) and 5'-deoxydeoxyadenosylcobalamin (AdoCbl). Cells convert the "inactive" vitamins CNCbl and HOCbl to the two critically important coenzymes AdoCbl or MeCbl.

The avian retroviral receptor Tva mediates the uptake of transcobalamin bound vitamin B12 (cobalamin).

The Avian sarcoma and leukosis viruses (ASLVs) are important chicken pathogens. Some of the virus subgroups, including ASLV-A and K, utilize the Tva receptor for cell entrance. Though Tva was identified three decades ago, its physiological function remains unknown.

Elevated Plasma Vitamin B in Patients with Hepatic Glycogen Storage Diseases.

: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B status in a large cohort of hepatic GSD patients. : Plasma vitamin B, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls.

Cyano-B12 or Whey Powder with Endogenous Hydroxo-B12 for Supplementation in B12 Deficient Lactovegetarians.

Lactovegetarians ( = 35) with low vitamin B12 (B12) status were intervened for eight weeks capsules containing cyano-B12 (CN-B12), (2 × 2.8 µg/day), or equivalent doses of endogenous B12 (mainly hydroxo-B12 (HO-B12)) in whey powder. Blood samples were examined at baseline, every second week during the intervention, and two weeks post-intervention.

Vitamin B and its binding proteins in milk from cow and buffalo in relation to bioavailability of B.

Milk is an important source of highly bioavailable vitamin B (cobalamin) in human nutrition. In most animal products, vitamin B is strongly bound to various specific protein carriers. The 2 vitamin B-specific proteins, predominantly transcobalamin (TC) and haptocorrin (HC), were earlier found in milk from Holstein Friesian cows and in human or sow milk, respectively.

Comparative Bioavailability of Synthetic B12 and Dietary Vitamin B12 Present in Cow and Buffalo Milk: A Prospective Study in Lactovegetarian Indians.

We assessed improvements in the vitamin B12 status of Indian lactovegetarians receiving four weeks supplementation with natural B12 in milk versus cyano-B12 in capsules. Three groups ( = 22, 23, 22) received daily oral doses of cyano-B12 (2 × 0.76 µg) or milk (2 × 200 mL) from a cow or buffalo (amounting to B12 ≈ 2 × 0.

Kinetic analysis of transcellular passage of the cobalamin-transcobalamin complex in Caco-2 monolayers.

We suggest a novel kinetic approach to quantifying receptor-ligand interactions via the cellular transport and/or accumulation of the ligand. The system of cobalamin (Cbl, vitamin B12) transport was used as a model, because Cbl is an obligatory cofactor, taken up by animal cells with the help of a transport protein and a membrane receptor. Bovine transcobalamin (bTC) stimulated the cellular accumulation and transcytosis of radioactive [Co]Cbl in polarized monolayers of Caco-2 cells.

Differences in Tissue Distribution of Cyano⁻B12 and Hydroxo⁻B12 One Week after Oral Intake: An Experimental Study in Male Wistar Rats.

Foods contain natural vitamin B12 forms, such as hydroxo⁻B12 (HO⁻B12), whereas vitamin pills contain the synthetic cyano⁻B12 (CN⁻B12). Recent studies in rats showed different tissue distributions of CN⁻B12 and HO⁻B12 24 h after oral administration. Here, we investigate whether these differences are sustained or leveled out with time in both B12-deplete and -replete rats, thereby assessing if the two forms are equally good at maintaining a normal B12 status.

Dietary Intake of Vitamin B12 is Better for Restoring a Low B12 Status Than a Daily High-Dose Vitamin Pill: An Experimental Study in Rats.

Vitamin B12 (B12) is present in foods of animal origin, and vegans are encouraged to take supplements with synthetic B12 in order to ensure a sufficient uptake. Recent rat studies suggest that natural (hydroxo-B12, HO-B12) and synthetic (cyano-B12, CN-B12) B12 behave differently in the body. Here, we test if a daily vitamin pill matches dietary B12 in ability to restore a low B12 status in rats.

The tissue profile of metabolically active coenzyme forms of vitamin B12 differs in vitamin B12-depleted rats treated with hydroxo-B12 or cyano-B12.

Recent rat studies show different tissue distributions of vitamin B12 (B12), administered orally as hydroxo-B12 (HO-B12) (predominant in food) and cyano-B12 (CN-B12) (common in supplements). Here we examine male Wistar rats kept on a low-B12 diet for 4 weeks followed by a 2-week period on diets with HO-B12 (n 9) or CN-B12 (n 9), or maintained on a low-B12 diet (n 9). Plasma B12 was analysed before, during and after the study.

The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults.

Background: The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized.

Objective: We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion.

Methods: A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin.

Tissue distribution of oral vitamin B12 is influenced by B12 status and B12 form: an experimental study in rats.

Purpose: Hydroxocobalamin (HOCbl) is the dominating Cbl form in food, whereas cyanocobalamin (CNCbl) is common in vitamin pills and oral supplements. This study compares single-dose absorption and distribution of oral HO[Co]Cbl and CN[Co]Cbl in Cbl-deficient and normal rats.

Methods: Male Wistar rats (7 weeks) were fed a 14-day diet with (n = 15) or without (n = 15) Cbl.

False low holotranscobalamin levels in a patient with a novel TCN2 mutation.

Background: Measurement of holotranscobalamin (holoTC) is increasingly used as a screening test for cobalamin (Cbl) deficiency. A level well below the reference interval strongly supports a deficient state. We examined a 21-year-old woman diagnosed as Cbl deficient because of an extremely low holoTC level as measured by the Abbott Architect Assay.

Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated peripheral nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of vitamin B-12 status.

Background: It is uncertain whether vitamin B-12 supplementation can improve neurophysiologic function in asymptomatic elderly with low vitamin B-12 status or whether folate status affects responses to vitamin B-12 supplementation.

Objective: We assessed the effects of a single intramuscular injection of 10 mg vitamin B-12 (which also contained 100 mg vitamin B-6 and 100 mg vitamin B-1) on vitamin B-12 status and neurophysiologic function in elderly community-dwelling Chileans with low serum vitamin B-12 concentrations who were consuming bread fortified with folic acid.

Design: A pretreatment and posttreatment study was conducted in 51 participants (median ± SD age: 73 ± 3 y; women: 47%) with serum vitamin B-12 concentrations <120 pmol/L at screening.

Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency.

Methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) are coenzymes for methionine synthase and methylmalonyl-CoA mutase, respectively. Hydroxylcobalamin (HOCbl) and cyanocobalamin (CNCbl) are frequently used for supplementation. MeCbl and AdoCbl have recently emerged as alternative forms in supplements.

Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points.

Background: A novel approach to determine vitamin B12 status is to combine four blood markers: total B12 (B12), holotranscobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy). This combined indicator of B12 status is expressed as cB12=log10[(holoTC·B12)/(MMA·Hcy)]-(age factor). Here we calculate cB12 in datasets with missing biomarkers, examine the influence of folate status, and revise diagnostic cut-points.

The extracellular heme-binding protein HbpS from the soil bacterium Streptomyces reticuli is an aquo-cobalamin binder.

The extracellular protein HbpS from Streptomyces reticuli interacts with iron ions and heme. It also acts in concert with the two-component sensing system SenS-SenR in response to oxidative stress. Sequence comparisons suggested that the protein may bind a cobalamin.

Analysis of oil-biodiesel samples by high performance liquid chromatography using the normal phase column of new generation and the evaporative light scattering detector.

Conversion of vegetable oil to biodiesel is usually monitored by gas chromatography. This is not always convenient because of (i) an elaborate derivatization of the samples; (ii) inhibition of this process by methanol and water; (iii) low stability of the derivatives under storage. HPLC methods are apparently more convenient, but none of the described variants had won a wide recognition so far.

Biochemical markers of vitamin B12 deficiency combined in one diagnostic parameter: the age-dependence and association with cognitive function and blood hemoglobin.

Background: Vitamin B12 deficiency is diagnosed by measurements of total B12, holo-transcobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (Hcy) in blood. Results of the individual biochemical tests are often contradictory. Here the four markers are combined to achieve a more reliable indication of the B12 status.