Bioavailability Of B12 Research Articles

Effect of calcium supplementation on reversing metformin-based inhibition of vitamin B12 bioavailability in healthy adults using a [13C] cyanocobalamin tracer – A pilot study

Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated with a decrease in vitamin B12 (B12) levels in patients with DM. Few studies have shown that this effect could be mitigated with calcium supplementation. In the present study, we quantified the effect of metformin, and metformin co-administered with calcium on B12 absorption using a novel stable isotope [13C] cyanocobalamin tracer. A pilot crossover study was conducted to estimate the bioavailability of B12 in healthy subjects, using [13C] cyanocobalamin as a tracer. In the study, [13C] cyanocobalamin was administered orally to the participants followed by hourly venous sampling to measure the concentration of the tracer and estimate bioavailability. This protocol was followed for three experiment days, each separated by a one month wash out period. As part of the study, all participants received the tracer alone for the control day (C), metformin 850mg along with the tracer for the metformin day (M) and metformin 850mg with calcium 500mg and the tracer for the metformin calcium day (MC). Seven participants completed all three experiment days. The mean B12 bioavailability (±SD, n=7) was 42.6±10.2% for the control day (C), 30.8±15.3% for the metformin day (M) and 46.4±8.6% for the metformin-calcium day (MC). Repeated measures ANOVA was done and the pairwise comparison showed a significant difference in the B12 bioavailability between control and metformin day (C vs M p=0.010), and between the metformin and metformin with calcium day (M vs MC p=0.003). B12 bioavailability reduced significantly from baseline (C) when metformin (M) was administered and this reduction was reversed when calcium was co-administered (MC) in healthy participants. In patients using metformin, calcium supplementation as a strategy to prevent B12 deficiency needs to be further studied.

Bioavailability and daily requirement of vitamin B12 in adult humans: an observational study of its colonic absorption and daily excretion as measured by [13C]-cyanocobalamin kinetics

BackgroundClinical and biochemical vitamin B12 (B12) deficiency is lower than anticipated in vegetarians. Extraileal absorption, such as from the colon, as well as reduced daily excretion, may be adaptive mechanisms to maintain B12 homeostasis with marginal intakes. ObjectiveTo measure the absorption of B12 from the small and large intestine, and its daily rate of excretion from the body, using a [13C]-cyanocobalamin tracer. MethodsOral B12 bioavailability was measured over 12 h after administration of [13C]-cyanocobalamin tracer (2.5 μg) in normal participants. The colonic B12 bioavailability was evaluated by direct instillation of [13C]-cyanocobalamin (5 μg) into the ascending colon. Bioavailability was calculated from 2-compartmental modeling of the tracer appearance in plasma. The excretion rate of B12 was measured from [13C]-cyanocobalamin elimination from the body over 4 wk after oral dosing (5 μg). ResultsThe oral B12 bioavailability (n = 11) was 63% ± 10% measured over 12 h. A late absorption peak, accounting for 12% of the absorption, was observed after an average lag time of 8.7 h from dosing. The colonic B12 bioavailability (n = 10) was 7% ± 5% over 4 h. The daily B12 excretion rate (n = 4) was 0.7 ± 0.2 μg/d. The minimum daily requirement of B12 in these participants was derived at 1 μg /d. ConclusionsB12 is absorbed in the human colon. This observation confirms the potential contribution of the colon in daily B12 nutriture, and along with a possible lower requirement, could explain the absence of clinical deficiency in populations with marginal B12 intakes. Trial Registration NumberThis study was registered in Clinical Trials Registry of India (CTRI) with the registration number CTRI/2018/04/012957, available from https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49319&EncHid=&userName=029108.

Propiyonik Asit Bakterileri ile B12 Vitamini Üretimi ve Etkili Parametrelerin İncelenmesi

Propionic acid bacteria (PAB) are extremely important because of the metabolites they produce (vitamins, propionic acid, conjugated linoleic acid, and bioactive peptides). Nowadays, the increasing interest in healthy nutrition has led to the formation of the concepts of probiotics, postbiotics and functionality with studies. Vitamin B12 is one of the postbiotics produced by PAB and is known to be beneficial for human health. Due to its coenzyme feature, it plays a key role in the body process, as well as shows anti-inflammatory properties. The recommended dietary intake of vitamin B12 for adults is 4 μg/day. Although it is highly found in meat products, it is known that the bioavailability of B12 in dairy products is higher. Fermented dairy products, especially products that contain PAB in their natural microflora, are good tools for the production and intake of vitamin B12. In this study, the factors affecting the microbial production of vitamin B12 were examined.

Investigation of the potential of Glycyrrhiza glabra as a bioavailability enhancer of Vitamin B12.

Vitamin B12 deficiency is prevalent among individuals globally. Inadequate consumption of B12 rich diet and low bioavailability (due to diet based/physiological factors) are linked to the deficiency of Vitamin B12 inside the body. Bioavailability enhancers augment the bioavailability of an ingested substance (drug/nutrient) thus increasing their concentration inside the body and maximizing their therapeutic benefits. In traditional medicine, Licorice (Glycyrrhiza glabra) finds utility in the treatment of various health conditions. Thus, the present study aimed to examine the potential of ethanolic extract obtained from G. glabra roots to enhance the bioavailability of Vitamin B12. The effect of ethanolic extract of G. glabra (GgEtOH) on intestinal absorption enhancement of B12 was assessed in vitro on Caco-2 and ex-vivo everted gut sac models. The influence of extract on the pharmacokinetics of Vitamin B12 was determined in vivo in Swiss albino mice. GgEtOH significantly enhanced the permeation (Papp) of B12 by 2-5 fold in vitro (25, 50, and 100 μg/ml concentrations) and ex-vivo (250 and 500 μg/ml concentrations). The pharmacokinetic parameters of B12 such as Cmax, AUC, Tmax, etc. were also significantly elevated in vivo upon oral administration of B12 (1 mg/kg dose) in combination with GgEtOH (100 and 1,000 mg/kg dose). These preliminary findings indicate that the ethanolic extract of G. glabra is capable of enhancing the bioavailability of Vitamin B12. To the best of our knowledge, this is the first report to demonstrate herbal extract-mediated enhancement of Vitamin B12 bioavailability through in vitro, ex vivo, and in vivo assays.

Measuring Oral Vitamin B12 Bioavailability Using [13C]-cyanocobalamin in Humans

Abstract Objectives To biosynthesize a stable-isotope labeled [13C]-cyanocobalamin and to measure its bioavailability in humans. Methods Salmonella enterica was precultured in Luria-Bertani medium and single-cell colonies were grown in No carbon E medium, supplemented with [13C]-ethanolamine as a sole-carbon source along with other precursors (dicyanocobinamide and dimethylbenzimidazole) and incubated for 48 h at 30°C and centrifuged. The pellets were resuspended in methanol/sodium cyanide and incubated overnight and extracts were purified by HPLC. The peaks corresponding to standard cyanocobalamin were collected and characterized by MALDI-MS. After animal testing, healthy young subjects were orally administered with [13C]-cyanocobalamin in a protocol that included hourly blood sampling for 12 h post-dose, and daily sampling for the next 5 days, to characterize its kinetics at a higher dose than the daily requirement (∼10x, n = 4, 2 males and females) and its appearance was modeled using a two-compartment model with early and late absorption phases. The same model was applied for lower dose at daily requirement (∼2.5 μg, n = 11 males), with sampling for 12 h post-dose. In addition, the effect of co-ingested food (n = 1, male) and the effect of parenteral replenishment of existing body vitamin B12 stores by intramuscular injection of 1 mg hydroxocobalamin, (n = 3, males) on bioavailability was also studied. The appearance of tracer in plasma was quantified by Q-Exactive-Orbitrap-MS. Results Biosynthesized [13C]-cyanocobalamin was labeled with up to 7–13[C] atoms and at a daily requirement dose (∼2.5 μg), its mean bioavailability was 50.4 ± 8.2%, but this was also dependent on the existing body store of vitamin B12. Two-weeks after replenishing the body stores, bioavailability increased by 1.5-fold (from 45.6 ± 0.02% to 67.8 ± 0.06%). At a higher dose (∼20 μg), its bioavailability was 6.0 ± 1.2% but the absolute amount absorbed was similar to that with the low dose. Conclusions A novel stable isotope-based vitamin B12 bioavailability assessment is described at low and high doses. This has implications toward rationalizing dosages used in clinical supplementation and public health fortification programs. Funding Sources Department of Biotechnology, India (to SD and AVK) and by the Wellcome Trust/DBT India Alliance Margdarshi Fellowship [No. IA/M/14/1/501,681] awarded to AVK.

Alzheimer's Amyloidopathy: An Alternative Aspect.

The ‘amyloid hypothesis’ dominates Alzheimer’s disease (AD) research but has failed to deliver effective therapies. Amyloid precursor protein (APP) and presenilin-1 (PSEN1) genetic mutations are undoubtedly pathogenic, albeit by unclear mechanisms. Conversely, high dose B-vitamins convincingly slow brain atrophy in a pre-stage state of sporadic AD. Here we suggest a link between sporadic and genetic AD: 1) Increased serum homocysteine, a marker of B-vitamin deficiencies, is a significant risk factor for sporadic AD. It also correlates with elevated levels of antichymotrypsin, a serine protease inhibitor. 2) Family members with codon 717 APP mutations and dementia have low serum vitamin B12 values. Overexpression of the APP domain coding for a Kunitz type serine protease inhibitor might explain this. 3) PSEN1 mutations disrupt lysosomal function due to reduced proteolytic activity. They also trap cobalamin (B12) within lysosomes, leading to intracellular deficiency of the vitamin. In summary, APP and PSEN1 mutations both confer a risk for reduced protease activity and B12 bio-availability. Comparably, sporadic AD features a constellation of increased protease inhibition and B-vitamin deficiencies, the central part of which is believed to be B12. These concordant observations in three disparate AD etiologies suggest a common neuropathogenic pathway. This hypothesis is evaluable in laboratory and clinical trials.

Vitamin B12 and its binding proteins in milk from cow and buffalo in relation to bioavailability of B12

Milk is an important source of highly bioavailable vitamin B12 (cobalamin) in human nutrition. In most animal products, vitamin B12 is strongly bound to various specific protein carriers. The 2 vitamin B12-specific proteins, predominantly transcobalamin (TC) and haptocorrin (HC), were earlier found in milk from Holstein Friesian cows and in human or sow milk, respectively. As the type of vitamin B12 binders may influence bioavailability of the vitamin, we examined vitamin B12 carriers in pooled milk specimens derived from European and Indian cow and buffalo herds. The total endogenous vitamin B12 concentration was comparable in all milk pools (≈3 nM), but the vitamin carriers varied considerably: TC + caseins in Danish cows, TC + HC in Indian cows and buffaloes, and mainly HC in Italian buffaloes. Danish cow milk contained half as much TC as vitamin B12, and the surplus vitamin was all attached via a single coordination bond to abundantly available histidine residues of casein. The specific binding proteins in Indian cow milk (TC + HC) approximately matched the molar content of vitamin B12. Milk from the 2 buffalo breeds contained more specific binders than vitamin B12, and the surplus proteins included the unsaturated TC ≈ 3 nM (Indian stock), or both TC ≈ 4 nM and HC ≈ 23 nM (Italian stock). The abundant HC of the latter sample bound nearly all endogenous vitamin B12. We tested (in vitro) the transfer of vitamin B12 from milk proteins to human carriers, involved in the intestinal uptake. The bovine TC-vitamin B12 complex rapidly dissociated at pH 2 (time of half reaction, τ1/2 < 1 min, 37°C) and was susceptible to digestion with trypsin + chymotrypsin (pH 7.5). Transfer of vitamin B12 from the precipitated bovine casein (pH 2) to human carriers proceeded with τ1/2 ≈ 7 min (37°C) and τ1/2 ≈ 35 min (20°C). Liberation of vitamin B12 from buffalo HC was hampered because of its pH stability and slow proteolysis. Nutritional availability of vitamin B12 is expected to be high in cow milk (with TC-vitamin B12 and casein-vitamin B12 complexes) but potentially constrained in buffalo milk (with HC-vitamin B12). This especially concerns the Italian buffalo milk, where a high excess of HC was found. We speculate whether the isolated stock of Italian buffalo maintained the ancestral secretion of carriers (HC ≫ vitamin B12, TC ≈ 0), whereas intensive crossbreeding of cows and buffaloes from other regions caused a change to TC ≤ vitamin B12, with low or absent HC. The substitution of HC by less sturdy carriers is apparently more beneficial to human consumers as far as vitamin B12 bioavailability is concerned.

Vitamin B12 buccoadhesive tablets: auspicious non-invasive substitute for intra muscular injection: formulation, in vitro and in vivo appraisal

Attempting to prepare a convenient bioavailable formulation of vitamin B12 (cyanocobalamin), 17 tablet formulations were prepared by direct compression. Different concentrations of hydroxypropyl methyl cellulose (HPMC), carbopol 971p (CP971p), and chitosan (Cs) were used. The tablets were characterized for thickness, weight, drug content, hardness, friability, surface pH, in vitro drug release, and mucoadhesion. Kinetic analysis of the release data was conducted. Vitamin B12 bioavailability from the optimized formulations was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neurotone® I.M. injection was used for comparison. HPMC (F1-F4), CP971p (F5-F8), and HPMC/CP971p (F12-F15)-based formulations showed acceptable mechanical properties. The formulated tablets showed maximum swelling indices of 232 ± 0.13. The surface pH values ranged from 5.3 ± 0.03 to 6.6 ± 0.02. Bioadhesive force ranged from 66 ± 0.6 to 150 ± 0.5 mN. Results showed that CP971p-based tablets had superior in vitro drug release, mechanical, and mucoadhesive properties. In vitro release date of selected formulations were fitted well to Peppas model. HPMC/CP971p-based formulations showed bioavailability up to 2.7-folds that of Neurotone® I.M. injection.

Methods to assess vitamin B12 bioavailability and technologies to enhance its absorption.

Vitamin B12 (B-12) deficiency is still relatively common in low-, medium-, and high-income countries, mainly because of dietary inadequacy and, to a lesser extent, malabsorption. This narrative review is based on a systematic search of evidence on methods to assess B-12 bioavailability and technologies to enhance its absorption. A total of 2523 scientific articles identified in PubMed and 1572 patents identified in Orbit Intelligence were prescreened. Among the reviewed methods, Schilling's test and/or its food-based version (using cobalamin-labeled egg yolk) were used for decades but have been discontinued, largely because they required radioactive cobalt. The qualitative CobaSorb test, based on changes in circulating holo-transcobalamin before and after B-12 administration, and the 14C-labeled B-12 test for quantitative measurement of absorption of a low-dose radioactive tracer are currently the best available methods. Various forms of B-12 co-formulated with chemical enhancers (ie, salcaprozate sodium, 8-amino caprylate) or supplied via biotechnological methods (ie, microbiological techniques, plant cells expressing cobalamin binding proteins), encapsulation techniques (ie, emulsions, use of chitosan particles), and alternative routes of administration (ie, intranasal, transdermal administration) were identified as potential technologies to enhance B-12 absorption in humans. However, in most cases the evidence of absorption enhancement is limited.

Vitamin B12 deficiency and impaired expression of amnionless during aging.

BackgroundPhysical frailty and loss of mobility in elderly individuals lead to reduced independence, quality of life, and increased mortality. Vitamin B12 deficiency has been linked to several age‐related chronic diseases, including in the musculo‐skeletal system, where vitamin B12 deficiency is generally believed to be linked to poor nutritional intake. In the present study, we asked whether aging and frailty associate with altered vitamin B12 homeostasis in humans and investigated the underlying molecular mechanisms using preclinical models.MethodsWe analysed a subset of the Singapore Longitudinal Aging Study and stratified 238 participants based on age and Fried frailty criteria. Levels of methyl‐malonic acid (MMA), a marker for vitamin B12 deficiency, and amnionless, the vitamin B12 co‐receptor that anchors the vitamin B12 transport complex to the membrane of epithelial cells, were measured in plasma. In addition, vitamin B12 levels and the molecular mechanisms of vitamin B12 uptake and excretion were analysed in ileum, kidney, liver, and blood using a rat model of natural aging where nutritional intake is fully controlled.ResultsWe demonstrate that aging and frailty are associated with a higher prevalence of functional vitamin B12 deficiency that can be detected by increased levels of MMA in blood (ρ = 0.25; P = 0.00013). The decline in circulating vitamin B12 levels is recapitulated in a rat model of natural aging where food composition and intake are stable. At the molecular level, these perturbations involve altered expression of amnionless in the ileum and kidney. Interestingly, we demonstrate that amnionless can be detected in serum where its levels increase during aging in both rodents and human (P = 3.3e‐07 and 9.2e‐07, respectively). Blood amnionless levels negatively correlate with vitamin B12 in rats (r2 = 0.305; P = 0.0042) and positively correlate with the vitamin B12 deficiency marker MMA in humans (ρ = 0.22; P = 0.00068).ConclusionsOur results demonstrate that aging and frailty cause intrinsic vitamin B12 deficiencies, which can occur independently of nutritional intake. Mechanistically, vitamin B12 deficiency involves the physio‐pathological decline of both the intestinal uptake and the renal reabsorption system for vitamin B12. Finally, amnionless is a novel biomarker which can detect perturbed vitamin B12 bioavailability during aging and physical frailty.

Vitamin B12–Loaded Buccoadhesive Films as a Noninvasive Supplement in Vitamin B12 Deficiency: In Vitro Evaluation and In Vivo Comparative Study With Intramuscular Injection

This study aimed to formulate and evaluate vitamin B12–loaded buccal mucoadhesive hydrogel films. Various film formulations were prepared using chitosan and polyvinyl alcohol. The prepared films were characterized for thickness, weight variation, drug content, percentage moisture uptake and moisture content, surface pH, mechanical properties, in vitro release, and mucoadhesion. Vitamin B12 bioavailability from the optimized formulation was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neuroton® I.M. injection was used for comparison. The films had acceptable mechanical and mucoadhesion properties. The percentages of moisture content of the optimized formulation were 3.2 ± 0.95, whereas the percentage drug released was 98.59 ± 1.41% at the end of 40 min. FTIR revealed the incidence of drug/polymer interaction. Differential scanning calorimetry revealed the possibility of the dispersion of cyanocobalamin in a molecular state with complete amorphization in the polymers. The estimated AUC0-8h showed 1.5-fold increases in the bioavailability of cyanocobalamin from the optimized formulation compared with the marketed I.M. injection. These findings warrant that vitamin B12 buccal film formulation can be considered as an effective alternative portal with noninvasive and more convenient characteristics compared with the I.M. injection dosage form.

Methylfolate Trap Promotes Bacterial Thymineless Death by Sulfa Drugs.

The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer’s dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis. Genetic mutagenesis, chemical complementation, and metabolomic profiling revealed trap-mediated metabolic imbalances, which induced thymineless death, a phenomenon in which rapidly growing cells succumb to thymine starvation. Restriction of B12 bioavailability, required for preventing trap formation, using an “antivitamin B12” molecule, sensitized intracellular bacteria to sulfonamides. Since boosting the bactericidal activity of sulfonamides through methylfolate trap induction can be achieved in Gram-negative bacteria and mycobacteria, it represents a novel strategy to render these pathogens more susceptible to existing sulfonamides.

Nutritional profile of Indian vegetarian diets--the Indian Migration Study (IMS).

BackgroundThe cardiovascular and other health benefits and potential harms of protein and micronutrient deficiency of vegetarian diets continue to be debated.MethodsStudy participants included urban migrants, their rural siblings and urban residents (n = 6555, mean age - 40.9 yrs) of the Indian Migration Study from Lucknow, Nagpur, Hyderabad and Bangalore. Information on diet (validated interviewer-administered semi-quantitative food frequency questionnaire), tobacco, alcohol, physical activity, medical histories, as well as blood pressure, fasting blood and anthropometric measurements were collected. Nutrient databases were used to calculate nutrient content of regional recipes. Vegetarians ate no eggs, fish, poultry and meat. Using multivariate linear regression with robust standard error model, we compared the macro- and micro-nutrient profile of vegetarian and non-vegetarian diets.ResultsVegetarians, (32.8% of the population), consumed greater amounts of legumes, vegetables, roots and tubers, dairy and sugar, while non-vegetarians had a greater intake of cereals, fruits, spices, salt (p < 0.01), fats and oils. Vegetarians had a higher socioeconomic status, and were less likely to smoke, drink alcohol (p < 0.0001) and engage in less physical activity (p = 0.04). On multivariate analysis, vegetarians consumed more carbohydrates (β = 7.0 g/day (95% CI: 9.9 to 4.0), p < 0.0001), vitamin C (β = 8.7 mg/day (95% CI: 4.3 to13.0), p < 0.0001) and folate (β = 8.0 mcg/day (95% CI: 3.3 to 12.7), p = 0.001) and lower levels of fat (β = −1.6 g/day (95% CI: −0.62 to −2.7), p = 0.002), protein (β = −6.4 g/day (95% CI: −5.8 to −7.0), p < 0.0001), vitamin B12 (β = −1.4 mcg/day (95% CI: −1.2 to −1.5), p < 0.0001) and zinc (β = −0.6 mg/day (95% CI: −0.4 to −0.7), p < 0.0001).ConclusionOverall, Indian vegetarian diets were found to be adequate to sustain nutritional demands according to recommended dietary allowances with less fat. Lower vitamin B12 bio-availability remains a concern and requires exploration of acceptable dietary sources for vegetarians.

OVERCOMING VITAMIN B12 DEFICIENCY IN VEGAN DIET

Abstract:Vitamin B12 is a crystalline compound essential to a number of micro-organisms and animals, including humans. So far as is known it is not present in higher plants. Pure vegetarian food is nearly free from vit. B12. It is a nutrient that needs attention in vegan diet. Vegetarians are at risk for vitamin B(12) (B12) deficiency due to suboptimal intake. Dietary deficiency of vitamin B12 due to vegetarianism is increasing and causes hyperhomocysteinemia Areas for research include intermittent vitamin B12 supplement dosing and better measurements of the bioavailability of B12 in fermented vegetarian foods and algae. The goal of the present literature review was to create an awareness among the vegans to identify the vegetarian sources of Vitamin B12 and to incorporate them into their daily diet.

Bioavailability of Vitamin B12

Vitamin B12 deficiency is common in people of all ages who consume a low intake of animal-source foods, including populations in developing countries. It is also prevalent among the elderly, even in wealthier countries, due to their malabsorption of B12 from food. Several methods have been applied to diagnose vitamin B12 malabsorption, including Schilling’s test, which is now used rarely, but these do not quantify percent bioavailability. Most of the information on B12 bioavailability from foods was collected 40 to 50 years ago, using radioactive isotopes of cobalt to label the corrinoid ring. The data are sparse, and the level of radioactivity required for in vivo labeling of animal tissues can be prohibitive. A newer method under development uses a low dose of radioactivity as (14)C-labeled B12, with measurement of the isotope excreted in urine and feces by accelerator mass spectrometry. This test has revealed that the unabsorbed vitamin is degraded in the intestine. The percent bioavailability is inversely proportional to the dose consumed due to saturation of the active absorption process, even within the range of usual intake from foods. This has important implications for the assessment and interpretation of bioavailability values, setting dietary requirements, and interpreting relationships between intake and status of the vitamin.

In vivo enrichment of chicken eggs with 14C‐B12 for determining vitamin B12 bioavailability in humans

Animal source foods such as eggs are the only natural dietary source of vitamin B12 but there is limited information on its bioavailability from these sources. The objective was to test the feasibility of enriching eggs in vivo with sufficient 14C‐B12 for use in human bioavailability studies. 14C‐B12 was biosynthesized using Salmonella enterica, purified and injected into the thigh muscle of a laying hen. Eggs were collected 21 d, pooled, scrambled and cooked. A serving of egg containing ~0.7 μg 14C‐B12 (~30 nCi) was fed to each of 10 healthy humans after an overnight fast. 14C, detected by accelerator mass spectrometry, first appeared in plasma at 3–4 h after dose and peaked at 7–10 h, with 5–40% appearing in urine in the first 24 h. Fecal 14C analyses in progress will enable calculation of % bioavailability of B12. We conclude that this protocol can be used for human B12 bioavailability studies. Funded by the American Egg Board.

The status of vitamins B6, B12, folate, and of homocysteine in geriatric home residents receiving laxatives or dietary fiber.

Vitamin B12 deficiency as a digestive disorder and constipation as a gastro motility disorder are common in the elderly. Laxative treatment is often chosen without regard for gut health. To investigate whether the addition of oat-bran to the common oral diet for 12 weeks is able to reduce constipation and laxative use and improve gut health. It is assumed that this will lead to improved plasma levels of vitamins B6, B12, folate, and of homocysteine in nursing home residents. A controlled, parallel intervention trial. 30 frail patients with multiple chronic diseases, aged 57-98 years, receiving laxative therapy were included. Patients were randomized into a fiber (n=15) and a control group (n=15). The intervention group received 5.2g/d oat-bran for 84 days mixed into the daily common meals. The control group received the ward's habitual diet. Food intake and laxative use were documented and blood samples (on day 01, day 42 and day 84) were collected. Vitamin B12 and folate were analyzed by radioimmunoassay, B6 and homocysteine by RP-HPLC with fluorescence detection, in addition to the routine lab test of albumin and CRP. In the fiber group, the intervention was well tolerated and laxative use decreased significantly (p < 0.001). In the control group, plasma B12 decreased faster (p < 0.05). In both groups, B6 and folate status remained unchanged. Plasma homocysteine decreased in both groups (p < 0.05). General mean energy intake was low (4861.4 kJ/d). Oat-bran helps to improve constipation management and B12 bioavailability in elderly, with multiple chronic diseases who live in nursing homes.

Evidence that physiological doses of vitamin B12 are metabolized or degraded in the gastrointestinal tract: implications for vitamin B12 bioavailability and fortification

Much of our understanding of vitamin B12 derives from radiocobalt tracer studies conducted decades ago. With new technologies, we can now study B12 absorption and metabolism with unprecedented resolution using almost ambient levels of 14C biosynthetically incorporated into the B12 molecule (14C‐B12). In on‐going studies, a dose of 14C‐B12 (1.3 µg, 50 nCi) in water is administered orally and blood, urine, and feces analyzed for 14C by accelerator mass spectrometry. In 6 subjects, the plasma response was consistent with the expected behavior of peroral B12: 14C‐B12 first appeared in the plasma 3h post‐dose with a peak level within 6‐8h. Urinary and fecal excretion was maximal in the first 24h. The amount of 14C found in the urine (10‐50% of the dose) was 100‐fold greater than in previous reports (0.1‐0.5%), and fecal excretion was lower than expected (&lt;10% vs 30‐70%). Most of the urinary 14C was not associated with intact B12. These results are consistent with metabolism or degradation of the vitamin in the GI tract prior to absorption. The discrepancy between the present and previous findings may be due to the form of radioactive B12 used: 14C labeling the 5,6‐dimethylbenzimidazole moiety in the present study and radiocobalt labeling the corrin ring in previous studies. These findings provide valuable information on the fate of B12 after oral consumption that will inform considerations to fortify the food supply with B12.

Vitamin B12 Sources and Bioavailability

The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.

Vitamin B12 deficiency as a worldwide problem.

Pernicious anemia is a common cause of megaloblastic anemia throughout the world and especially in persons of European or African descent. Dietary deficiency of vitamin B12 due to vegetarianism is increasing and causes hyperhomocysteinemia. The breast-fed infant of a vitamin B12-deficient mother is at risk for severe developmental abnormalities, growth failure, and anemia. Elevated methylmalonic acid and/or total homocysteine are sensitive indicators of vitamin B12-deficient diets and correlate with clinical abnormalities. Dietary vitamin B12 deficiency is a severe problem in the Indian subcontinent, Mexico, Central and South America, and selected areas in Africa. Dietary vitamin B12 deficiency is not prevalent in Asia, except in vegetarians. Areas for research include intermittent vitamin B12 supplement dosing and better measurements of the bioavailability of B12 in fermented vegetarian foods and algae.