Liver Vitamin B12 Concentrations Research Articles

Effects of dietary supplementation of different levels of vitamin B12 on the liver metabolism of laying hens.

Vitamin B12 plays an important role in lipid, protein, carbohydrate and nucleic acid metabolism. We investigated the effect of supplementing layers' diets with different vitamin B12 levels on liver metabolism using a liquid chromatography-mass spectrometry-based metabolomic approach to observe and analyse wide-target metabolomics in the liver. We assigned hens to three groups, namely blank control group without vitamin B12 diet (BCG), normal control group with 25 μg kg-1 vitamin B12 (NCG) and vitamin B12 supplement group I with 100 μg kg-1 vitamin (VBSG I). The VBSG I group layers had higher (P < 0.05) vitamin B12 concentration than those from other groups. The egg yolk vitamin B12 concentration increased (P < 0.01) with the increasing vitamin B12 dietary supplemental level. Between the NCG versus BCG, VBSG I versus BCG, and VBSG I versus NCG groups, 11, 20 and 11 metabolites were significantly changed, respectively. The KEGG pathway of vitamin B6 metabolism was significantly impacted in the NCG layers than those from BCG; seven and five pathways were significantly impacted in the VBSG I layers compared with those from BCG and NCG, including pyrimidine metabolism, vitamin B6 metabolism, glycerophospholipid metabolism, etc. CONCLUSION: We concluded that 25 μg kg-1 vitamin B12 supplementation in corn-soybean meal-based layer diet increased the egg yolk vitamin B12 concentration and impacted the vitamin B6 metabolic pathway, and 100 μg kg-1 of it increased the egg yolk and liver vitamin B12 concentrations and impacted vitamin B6 , lipid, nucleic acid and amino acid metabolic pathways. © 2022 Society of Chemical Industry.

Lack of production response in grazing dairy cows supplemented withlong-acting injectable vitamin B12

AIM: To determine the concentrations of vitamin B12 in serum, liver and milk that identify adequate vitamin B12 status in grazing lactating cows, based on no change in milk production in response to supplementation with vitamin B12. METHODS: In October 2005, in early lactation, Friesian cows from one herd were injected S/C with 60 or 90 mg long-acting vitamin B12, or no injection (Control; n=39 per group, Day0). Pasture samples were collected for Co determination at monthly intervals over 82 days. Concentrations of vitamin B12 in milk and serum (n=10 per group) and in liver (n=5 per group) were assessed over 124 days. Milk production and composition were determined on four occasions for all cows. RESULTS: Mean concentrations of Co in pasture ranged from 0.11 to 0.34 mg/kg dry matter (DM). Mean initial concentrations of vitamin B12 in milk, serum and liver were 1,520, 128 pmol/L and 1,092 nmol/kg fresh tissue, respectively. Administration of 60 and 90 mg vitamin B12 had similar effects and increased concentrations of vitamin B12 in milk by 3-fold over controls on Day 50 (7,410 vs. 2,350 pmol/L; p<0.001) and 1.6-fold on Day 124 (3,470 vs. 2,210 pmol/L; p=0.011). Treatment with 60 and 90 mg vitamin B12 increased concentrations of vitamin B12 in serum, by at least 5-fold over controls on Day 50 (880 and 1,040 vs. 160 pmol/L; p<0.001). The two treatments increased concentrations of vitamin B12 inliver by only 1.5 fold over controls on Day 50 (1,660 and 1,900 vs. 1,200 nmol/kg fresh tissue; p<0.005). Treatment had no effect at any sampling time on daily milk volume or milk solids, fat or protein percentages. CONCLUSIONS: Concentrations of vitamin B12 in serum >128 pmol/L indicated adequate vitamin B12 status in grazing lactating cows. Supplementation with 60 or 90 mg vitamin B12 increased and maintained concentrations of vitamin B12 in serum for up to 124 days, but there was no effect on milk production. Milk was enriched in its vitamin B12 content, which would provide enhanced nutrition for calves or humans. Compared with 60 mg, the larger dose provided little additional benefit. CLINICAL RELEVANCE: Long-acting injectable vitamin B12 used to treat and prevent vitamin B12 deficiency is unlikely to improve the milk production of grazing cows when concentrations of vitamin B12 in serum are >128 pmol/L.

Growth response to increasing doses of microencapsulated vitamin B12 and related changes in tissue vitamin B12 concentrations in cobalt-de cient lambs

AIM: To investigate growth responses of cobalt-deficient lambs to increasing doses of microencapsulated vitamin B12, and to measure associated changes in serum and liver vitamin B12 concentrations over 243 days. METHODS: From a flock grazing pastures that had low cobalt (Co) levels (about 0.06 mg Co/kg dry matter), 4-6-week-old lambs (n=137) were assigned to four groups and received either no treatment or a subcutaneous injection of 3.0, 4.5 or 6.0 mg of microencapsulated vitamin B12 on Day 1. At approximately monthly intervals, all lambs were weighed and blood samples were collected from a selection (n=10) of monitor animals, up to Day 243. Liver biopsies were also carried out on the monitor lambs (n=8) on Days 1, 124 and 215. RESULTS: The vitamin B12-treated lambs grew significantly faster (p<0.001) than untreated animals. Liveweights after 243 days were 28, 45, 45 and 47 kg for the untreated, 3.0, 4.5 and 6.0 mg vitamin B12-treated lambs, respectively. Of the initial group of untreated lambs, 68% had to be removed before the end of the trial because of substantial weight loss, but none of the treated animals were similarly afflicted. Serum vitamin B12 concentrations increased in all vitamin B12-treated lambs, reaching a peak at Day 25, and those of the 4.5 and 6.0 mg vitamin B12-treated lambs remained significantly higher (except at Day 124) than the untreated lambs to Day 187. However, at Day 124, but not Day 215, the liver vitamin B12 concentrations of treated lambs were two to three times higher than those of controls. CONCLUSIONS: The growth rates of Co-deficient lambs were markedly improved by injection of 3.0, 4.5 or 6.0 mg of microencapsulated vitamin B12, and liveweights were maintained for at least 243 days. Serum vitamin B12 concentrations were related to this growth response; concentrations of <220 pmol vitamin B12/l were associated with a 95% probability that lambs were Co-deficient and would thus respond to Co/vitamin B12 supplementation. Based on these data, the current New Zealand reference criteria for Co deficiency should be reviewed. CLINICAL SIGNIFICANCE: An injection of 3 mg microencapsulated vitamin B122 given to lambs at tailing will treat Co deficiency and will increase and maintain liveweights in a flock for up to 8 months.

Liver copper, selenium and vitamin B12 concentrations in farmed and feral red deer (Cervus elaphus)

AIM: To compare liver copper, selenium and vitamin B12 concentrations in red deer of farmed and feral origin. METHODS: Liver samples were collected from red deer at a South Island deer slaughter premise and a game packing house in November 2000. The site of origin and age of each animal were recorded. A subsample of 107 livers was selected (n=5-10 per site of origin and age category) from farmed deer from central Canterbury, Nelson and Westland, and from feral deer from north, central and south Westland. Samples were analysed for copper, selenium and vitamin B12 concentrations and reported on a wet-matter basis. RESULTS: Mean liver copper concentrations for farmed and feral yearlings were 267 and 889 µmol/kg, respectively, and for farmed and feral adults were 206 and 677 µmol/kg, respectively. Liver copper concentrations were lower for farmed than for feral deer (p<0.001) and for feral adults than for feral yearlings (p=0.002). Mean liver selenium concentrations in farmed and feral yearlings were 2050 and 1539 nmol/kg, respectively, and in farmed and feral adults were 1938 and 1625 nmol/kg, respectively. Liver selenium concentrations varied significantly between regions and overall, farmed deer had higher liver selenium concentrations than feral deer (p=0.04). Mean liver vitamin B12 concentrations in farmed and feral yearlings were 456 and 742 nmol/kg, and for farmed and feral adults were 428 and 869 nmol/kg, respectively. Liver vitamin B12 concentrations were lower for farmed than for feral deer (p<0.001). CONCLUSION: Feral deer had higher liver copper and vitamin B12 concentrations and lower liver selenium concentrations than farmed deer in the regions studied.

Effect of an injectable microencapsulated Vitamin B12 on serum and liver Vitamin B12 concentrations in calves

dAim: To evaluate the efficacy of a long-acting injectable microencapsulated formulation ofVitamin B12 in dairy calves. dMethod: Fifty calves, average liveweight 110kg, were randomly allocated to 5 groups of 10 animals and injected subcutaneously in the anterior neck with 0.12, 0.18, 0.24 and 0.3 mg Vitamin B12/kg liveweight using a formulation of microencapsulated Vitamin B12 in a lactide : glycolide copolymer. The untreated calves were injected with the same vehicle, without Vitamin B12. Subsequent changes in serum and liver Vitamin B12 concentrations were followed for 244 days. dResults: The microencapsulated Vitamin B12 significantly increased, then maintained serum and liver Vitamin B12 concentrations higher than those of untreated controls for at least 110 days. dConclusions: Injection of the microencapsulated Vitamin B12 at dose rates of 0.12 to 0.24 mg/kg liveweight will increase and maintain the Vitamin B12 status of calves for at least 110 days.

Absence of a weight gain response to Vitamin B12 supplementation in weaned dairy heifers grazing pastures of marginal cobalt content

Aim. To obtain information on serum and liver vitamin B12 and urinary methylmalonic acid concentrations as diagnostic tests to predict a weight gain response to supplementation with vitamin B12 in young dairy cattle when grazing pasture of low cobalt content. Methodology. Forty dairy cattle (12 Friesian, 14 Friesian × Jersey and 14 Jersey) were allocated to two equal sized groups, treated and untreated, based on liveweight. At monthly intervals for 14 months, all animals were weighed, their serum and urine sampled, their liver biopsied and the pasture sampled from the paddocks they were grazing and going to graze. Serum and liver were assayed for Vitamin B12 concentrations. For the first 5 months of the trial, urine was assayed for methylmalonic acid concentrations. Both washed and unwashed pasture samples were assayed for cobalt concentrations. Results. No weight gain response occurred to Vitamin B12 supplementation in young growing cattle grazing pasture with a cobalt concentration of 0.04-0.06 mg/kg DM. For 5 months of the trial, liver Vitamin B12 concentrations from untreated calves were in the range 75-220 nmol/kg and serum vitamin B12 concentrations were as low as 72 pmol/1. There was no associated growth response to supplementation. Conclusion. Further trials involving young cattle grazing pastures with cobalt concentrations less than 0.04 mg/kg DM are required to reliably determine liver and serum Vitamin B12 concentrations at which growth responses to Vitamin B12 or cobalt supplementation are likely under New Zealand pastoral grazing conditions.

The effect of increasing the Vitamin B12 status of Romney ewes on foetal liver Vitamin B12, milk Vitamin B12 and liver Vitamin B12 concentrations in suckling lambs

Aim. To determine the effect of increasing the Vitamin B12 status of the ewe on the Vitamin B12 supply to the suckling lamb. Methods. The Vitamin B12 status of the ewe was increased during gestation and lactation by three injections of a long- acting preparation of Vitamin B12 microencapsulated in an organic acid polymer. The Vitamin B12 status of the ewes and suckling lambs was assessed from changes in serum and liver Vitamin B12 concentrations. Results. Compared to untreated animals, serum and liver Vitamin B12 concentrations of the treated ewes were increased at least 70% during gestation. Foetal liver Vitamin B12 concentrations were increased 270%. Over the lactation, ewe serum and milk Vitamin B12 concentrations were increased at least 200% and 44%, respectively. The liver Vitamin B12 stores of the new born lambs from Vitamin B,,-treated ewes were depleted within 58 days. There were no significant differences in the serum vitamin B12 concentrations of suckling lambs from vitamin B12-treated and untreated ewes. Conclusion. Ewes with a high vitamin B12 status will ensure an adequate supply of vitamin B12 to their lambs for at least the first 30 days of life. Clinical significance. In flocks grazing Co-deficient pastures, treating ewes with a long-acting vitamin B12 supplement at mating will prevent Vitamin B12 (Co) deficiency in ewes, as well as their lambs, until they can be treated at tailing at 4-6 weeks of age.

An evaluation of the efficacy of injectable microencapsulated Vitamin B12 in increasing and maintaining the serum and liver Vitamin B12 concentrations of lambs

Aim. To develop a long-acting vitamin B, injection to prevent Co deficiency in sheep. Methods. Formulations of microencapsulated Vitamin B12 in lactide-glycolide polymers were injected intramuscularly or subcutaneously into the anterior neck region of groups of 10 lambs and their efficacy determined from changes in serum and liver Vitamin B12 concentrations. Results. The 955 lactide glycolide and the 100 lactide formulations containing more than 12.5% Vitamin B12 w/w significantly increased and maintained serum Vitamin B12 concentrations for at least 210 days as well as liver Vitamin B12 concentrations in treated lambs when compared with untreated controls. Conclusions. Injections of microencapsulated Vitamin B12 in lactide-glycolide copolymers are able to increase and maintain the Vitamin B12 status of lambs for at least 210 days. Clinical significance. Another option for the prevention of Co deficiency in sheep is now available using a long acting injectable Vitamin B12.

The efficacy of a subcutaneous injection of soluble Vitamirn B12 in lambs

Aims. To assess the efficacy of a soluble Vitamin B12 injection in lambs by measuring changes in the serum and liver Vitamin B12 concentrations. Methods. Thirty-six lambs were injected subcutaneously with 2 mg of soluble Vitamin B12 while another group of 36 served as untreated controls. Blood and liver biopsy samples for Vitamin B12 determinations were collected just before the injection and at days 1, 2, 5, 8, 16, 24, 30 and 45. Results. The serum Vitamin B12 concentrations of the Vitamin B12 treated lambs increased rapidly compared to the untreated lambs. Concentrations peaked at day 2, decreased rapidly to day 8, and then decreased more slowly until day 24 when there were no longer differences between the groups. Liver Vitamin B12 concentrations of the Vitamin B12 treated lambs were significantly greater over days 8-24. Conclusion. A subcutaneous injection of 2 mg of soluble Vitamin B12 was effective in increasing and maintaining the Vitamin B12 status of lambs for about 24 days. Clinical significance. This Vitamin B12 product is only effective for preventing cobalt deficiency in lambs for about 4 weeks.

Evaluation of cobalt pellets for sheep

Vitamin B12 concentrations were measured in plasma and liver, and cobalt (Co) concentrations determined in faeces, of sheep given intraruminal Co pellets with or without steel grub screws (grinders). The Co pellets contained 30 or 60% by weight Co oxide (Co3O4). Sheep were maintained on pasture at 2 sites in the South East of South Australia in an area where sheep have been shown to respond to Co supplementation. All pellets, apart from one given without a grinder, maintained above-adequate vitamin B12 concentrations in liver (&gt;200 nmol/kg wet weight) and plasma (&gt;400 �mol/L) for 1 year. In the second year, some pellets containing 30% Co3O4 failed to maintain adequate vitamin B12 concentrations in the liver of sheep at 1 site when untreated sheep were at risk of seasonal Co deficiency (liver vitamin B12 concentrations &lt;100 nmol/kg wet weight). Under these circumstances, a more recently formulated pellet containing 30% Co3O4, when given with a grinder, maintained adequate vitamin B,? status of sheep for 3 years. The 'traditional' pellet containing 60% Co3O4 increased vitamin B12 concentrations to high normal values (in plasma &gt;I500 pmol/L, in liver &gt;200 nmol/kg wet weight) for at least 3 years. Pellets containing 30% Co3P4 may only prevent Co deficiency for 1 year, depending on the source of the pellets.

An assessment of the efficacy and safety of selenium and cobalt included in an anthelmintic for sheep.

A trial was devised to assess whether the administration of selenium and cobalt together with the anthelmintic mebendazole (Ovitelmin S&C) was safe and could improve the supplies of selenium and cobalt for adult sheep fed a whole grain diet, low in both elements, which produced a steady decrease in blood glutathione peroxidase (GSHPx) and plasma vitamin B12 concentrations. Ovitelmin S&C, when given orally in a single dose as a suspension containing 0.34 mg selenium/ml, and 0.44 mg cobalt/ml (to provide 0.11 mg selenium and 0.15 mg cobalt/kg liveweight) significantly increased the GSHPx activity in blood. After a second dose given 28 days later the rate of change increased from 2.5 to 3.5 u/g haemoglobin/day. The responses in GSHPx were similar for a preparation which contained twice the concentration of selenium. Ovitelmin S&C increased the concentration of vitamin B12 in the plasma by about 1000 pg/ml for four to seven days after each dose and the increases were similar to those observed in sheep treated with an Ovitelmin preparation containing 45 times more cobalt (providing 6.7 mg cobalt/kg liveweight). After 63 days, liver vitamin B12 concentrations were 43 per cent higher in the cobalt treated than in the untreated groups (P less than 0.01) with no differences among the groups given cobalt. Neither adverse reactions nor signs of toxicity followed the administration of Ovitelmin S&C or Ovitelmin containing the higher concentrations of selenium and cobalt.

Boluses of controlled release glass for supplementing ruminants with cobalt.

Boluses of controlled release glass containing cobalt and weighing approximately either 60 g or 14.5 g were administered to 22 steers and 21 sheep respectively. The steers were housed and slaughtered at intervals between 17 and 145 days after dosing. The boluses released more than 0.85 mg cobalt daily. In both untreated and dosed animals serum and liver vitamin B12 concentrations were at the upper end of the normal range. Two types of glass were administered to sheep. In five wethers one glass released 0.07 mg cobalt per day, and in 16 grazing lambs a second glass released more than 0.15 mg cobalt per day. Fourteen of the boluses were recovered from the lambs up to 276 days after dosing. The concentration of B12 in serum of lambs increased significantly from a mean +/- sd of 1.64 +/- 0.47 to 2.02 +/- 0.04 ng/ml serum and the concentration in liver from 3.84 +/- 0.85 to 4.99 +/- 0.72 micrograms/g dry weight liver.

Urinary methylmalonic acid as an indicator of the vitamin B12status of grazing sheep

Abstract Lambs grazing cobalt-deficient pastures and injected with hydroxocobalamine gained significantly more weight and excreted significantly less methylmalonic acid in the urine than untreated controls. Lambs with liver vitamin B12 levels in the range 0.1–0.2ώg/g excreted less than 25 ώg of methylmalonic acid per ml of urine, whereas lambs with liver vitamin B12 concentrations of less than 0.1 ώg/g excreted greater amounts. Lambs in both groups had serum vitamin B12 concentrations less than 500 pg/ml. No consistent diurnal variation in urinary methylmalonic acid concentrations was found for four lambs studied. There was a decrease in the methylmalonic acid levels of urine after storage for more than 24 hours which could be prevented by acidification of the urine. A mean urinary methylmalonic acid concentration greater than 30 ώg/ml for 10 animals randomly selected from a flock would indicate a cobalt deficiency in the flock as a whole.

Lipid composition and metabolism in liver and brain of vitamin B12-deficient rat sucklings

1. Rat sucklings (18-d-old) bred from vitamin B12-deprived dams were compared with vitamin B12-supplemented dams' offspring, which were considered normal rat sucklings. 2. The vitamin B12-deficient rat sucklings had lower body-weight, liver weight and brain weight. 3. Vitamin B12 deficiency was also evident from the tenfold lower concentrations of vitamin B12 in liver and cerebellum. 4. The concentration of liver lipid was markedly increased in vitamin B12-deficient rats; triacylglycerol accounted for most of the increase. In brain the lipid concentration was slightly decreased (less than 0.05). 5. The methylation of ethanolamine phosphoglyceride to choline phosphoglyceride was reduced in both liver and brain in vitamin B12-deficient rats, as measured after the administration of [14C]ethanolamine. A slight decrease in choline phosphoglyceride concentration could be a consequence of this finding. The composition of phospholipids was otherwise normal. 6. Odd-chain fatty acids (pentadecanoate and heptadecanoate) accumulated in both liver and brain of the vitamin B12-deficient rat sucklings and constituted approximately 1% of total fatty acid. 7. The biosynthesis of fatty acid and cholesterol from intraperitoneally-injected 3H2O and [14C]propionate was unchanged in vitamin B12 deficiency.

Changes in folate metabolism in baboons Papio cynocephalus treated with 2-methyl-2-aminopropanol-B12.

After the intramuscular administration of the vitamin B12 analogue, 2-methyl-2-aminopropanol-B12, to vitamin B12-depleted baboons (Papio cynocephalus) the effects on vitamin B12 and folate metabolism have been studied. The 'apparent' serum vitamin B12 and the serum folate concentrations increased, the liver folate concentrations decreased, and the liver vitamin B12 concentrations were unchanged. The analogue caused a marked increase in the amount of formiminoglutamic acid excreted after a histidine load whereas the amount of methylmalonic acid excreted after a valine load decreased. The rate of red blood cell regeneration after venesection was normal in baboons treated with the analogue and there was no evidence of megaloblastic haemopoiesis. Two baboons given the analogue developed a partial loss of utilization and lack of co-ordination in the hind limbs.

Changes in the metabolism of vitamin B12 and methionine in rats fed unheated soya-bean flour.

1. Young rats were fed on diets containing heated or unheated soya-bean flour.2. Feeding unheated soya-bean flour decreased concentrations of vitamin B12in liver, kidneys and blood serum, urinary excretion of sulphate and concentration of reduced glutathione in liver. Blood glutathione level and urinary excretion of methylmalonic acid and formimino-glutamic acid following loads of propionate and histidine, respectively, were increased.3. Supplementing a diet of unheated soya-bean flour with vitamin B12, had no effect on the level of reduced glutathione in the liver. Adding methionine to this diet decreased excretion of methylmalonic acid and the level of glutathione in blood.4. The activity of liver methyl-tetrahydrofolate: L-homocysteine S-methyltransferase was not affected by the nature of dietary soya-bean flour nor by supplementation with vitamin B125. It is concluded that heat-labile substances present in soya-bean flour induce metabolic changes which can bring about an increased requirement for vitamin B12, and a deficiency of sulphur-containing amino acids.

Folic acid deficiency and urinary formimino-glutamic acid excretion in the rat.

SUMMARYRats fed on a folic acid‐deficient diet regularly excrete formiminoglutamic acid in the urine. The vitamin B12 and folic acid status of such rats was estimated by assay of liver tissue for these vitamins. Formiminoglutamic acid excretion occurs in the presence of normal liver vitamin B12 concentrations. There appears to be a critical level of liver folic acid below which there is excretion of formiminoglutamic acid.

Vitamin B12and cobalt in livers from grazing cobalt-deficient lambs and from others given Various Cobalt Supplements

Summary Vitamin B12 and cobalt concentrations were determined in the livers of 4 groups of lambs. Three groups were grazed on cobalt-deficient pastures. Of these groups one received no cobalt treatment and developed marked cobalt deficiency disease. Of the other two groups on cobalt-deficient pastures, one received oral doses of cobalt and the other cobaltic oxide pellets. The fourth group was grazed on cobalttopdressed pastures. Vitamin B12 concentrations in the livers of markedly cobalt-deficient lambs ranged from 0.026 to 0.097 μg/g of wet tissue, with a mean of 0.062 μg/g. Cobalt dosing and cobaltic oxide pellets increased liver vitamin B12 concentrations about fourfold and sevenfold respectively. Vitamin B12 concentrations in the livers of animals from cobalt-top-dressed pasture were of an order similar to those for lambs given cobaltic oxide pellets. Effects of cobalt deficiency disease and of cobalt treatments on B12 Co/total Co ratios are discussed. From all the information available it is conclud...