Supplements cobalamins

Dietary deficiency in the absence of absorption defects can be effectively reversed with oral supplementation of 1 p.m of vitamin B 2 daily. If deficiency is related to a defect in vitamin absorption, daily doses of 1 pg adininistered subcutaneously or intramuscularly are effective (33). However, a single intramuscular dose of 100 pg of cobalamin once per month is adequate in patients with chronic gastric or ileal damage. Larger doses are generally rapidly cleared from the plasma into the urine and are not effective unless the patient demonstrates poor vitamin retention. 

Cobalamin (vitamin B12) Streptomyces olivaceus Food supplements... 

The fibroblasts do not convert cyanocobalamin or hydroxocobalamin to methylcobalamin or adenosyl-cobalamin, resulting in diminished activity of both N5-methyltetrahydrofolate homocysteine methyltransferase and methylmalonyl-CoA mutase. Supplementation with hydroxocobalamin rectifies the aberrant biochemistry. The precise nature of the underlying defect remains obscure. Diagnosis should be suspected in a child with homocystinuria, methylmalonic aciduria, megaloblastic anemia, hypomethioninemia and normal blood levels of folate and vitamin B12. A definitive diagnosis requires demonstration of these abnormalities in fibroblasts. Prenatal diagnosis is possible. 

Oral vitamin B12 supplementation appears to be as effective as parenteral, even in patients with pernicious anemia, because the alternate vitamin B12 absorption pathway is independent of intrinsic factor. Oral cobalamin is initiated at 1 to 2 mg daily for 1 to 2 weeks, followed by 1 mg daily. 

The ligand attached to the cobalt atom determines the activity of vitamin B12 in human enzymatic reactions. The two active coenzyme forms are methyl-cobalamin and 5 -adenosylcobalamin, the primary form of vitamin B12 in tissues. Cyanocobalamin, the therapeutic form of vitamin B12 contained in vitamin supplements, is produced by the cleavage of the unstable fink... 

Vitamin B12, cobalamin or cyanocobaltamin, C63H88CoN14Oi4P, has the most complicated structure of the B vitamins. It contains one atom of cobalt in its molecule. It is required in minute amounts but without it the manufacture of proteins and red blood cells is affected. A diet which is deficient in liver, eggs, meat, fish or milk can lead to pernicious anaemia. Vegetarians are often advised to take vitamin B12 supplements. 

Vitamin B12 (cyancobali-min, cobalamin) Protein and fatty acid metabolism production of red blood cells maintenance of nervous system, concentration and memory. Clams, oysters, beef, eggs and dairy products. Not found in many plant products strict vegetarians may need to consider Bi2 supplements. 2 mg No... 

Oral vitamin Bj2 supplementation appears to be as effective as parenteral, even in patients with pernicious anemia, because the alternate vitamin Bj2 absorption pathway is independent of intrinsic factor. Oral cobalamin is initiated at 1 to 2 mg daily for 1 to 2 weeks, followed by 1 mg daUy. Parenteral therapy is more rapid acting than oral therapy and should be used if neurologic symptoms are present. A popular regimen is cyanocobalamin 1,000 meg daily for 1 week, then weekly for 1 month, and then monthly. When symptoms resolve, daily oral administration can be initiated. 

Cobalmin Deficiency. Pernicious anemia is the disease associated with vitamin Bi2 deficiency. It is usually caused by the inability to produce intrinsic factor. Indeed, many times the vitamin must be administered by injection. The blood picture, a megaloblastic anemia, is indistinguishable from that caused by folic acid deficiency. Indeed folic acid supplements can mask the blood picture. This is illustrated in Fig. 8.53. Removal of ad-enosyl cobalamin eliminates the regeneration of tetrahydrofolate during the methylation of homocysteine to methionine. Folic acid supplements provide a fresh source of tetrahydrofolate coenzymes. DNA synthesis can continue and new erythrocytes form. Excess folic acid also may compete for the available vitamin, further exacerbating vitamin deficiency. 

One often-overlooked major factor that may contribute to anemia in the older population is nutritional status. Cross-sectional studies demonstrate a higher prevalence of anemia in low socioeconomic populations, as well as a high prevalence of other nutritional deficiencies. Thus nutritional deficiencies not usually severe enough to affect the hematopoietic system in the younger population may account for anemia in the aged. Edentulous or infirm elderly who may be too ill to prepare their meals are at risk for nutritional folate deficiency. However, unlike cobalamin levels, it has been demonstrated that folate levels increase rather than decline with age. This may be due to the dramatic increase in folate supplements used by the elderly, especially in white women, as well as the fortification of the American diet with folic acid. ... 

Homocysteine is an intermediate in biosynthesis of cysteine, methionine, and in the breakdown of methionine. Recent research has indicated that elevated levels of homocysteine may correlate with increased incidence of vasuclar disease. Supplementation of diets with folic acid, cobalamin and pyridoxine appear to provide protection by lowering homocysteine levels in the blood. 

If folate is given without cobalamin to a B 12-deficient patient, the drug only partially corrects the megaloblastic anemia because it will bypass the methyl-folate trap and provide adequate FH4 coenzyme for the conversion of dUMP to dTMP and for a resurgence of purine synthesis. As a result, normal DNA synthesis, DNA repair, and cell division occur. However, the neurologic syndrome, resulting from hypomethylation in nervous tissue, may progress unless the physician realizes that B12 supplementation is required. In Jean Ann s case, in which the serum B12 concentration was borderline low and in which the dietary history supported the possibility of a B12 deficiency, a combination of folate and B12 supplements is required to avoid this potential therapeutic trap. 

Description. Vitamin B12 is the largest and most complex of all the vitamins. It is unique among vitamins in that it contains a metal ion, cobalt. For this reason cobalamin is the term used to refer to compounds having B12 activity. Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of vitamin B12 used in the human body. The form of cobalamin used in most supplements, cyano-cobalamin, is readily converted to 5-deoxyadenosyl and methylcobalamin. 

Some forms of MMA may be responsive to vitamin Bjj. Responsiveness can be determined by administration of 1.0 mg hydroxocobalamin (IM or IV) for 5 days. A reduction in serum methylmalonic acid concentrations of 50 % or greater suggests responsiveness [14]. For those with cobalamin-responsive forms of MMA, intramuscular (IM) hydroxocobalamin injections of 1.0-2.0 mg are often administered daily. A decreased frequency of IM injections or use of oral supplements may be appropriate for older individuals. The hydroxocobalamin form rather than the standard cyanocobalamin form must be used [15]. 

Vitamin B12 (cobalamine) is needed to metabolize fatty adds and amino acids and to synthesize DNA in cells. Vitamin C also has several functions. It is needed to synthesize collagen, the most abundant protein in the body, but it also acts as an antioxidant, helping to reduce the risk of developing chronic diseases like heart disease and cancer. Water-soluble vitamins are not stored in the body. Because they are eliminated in urine, a continuous daily support through diet is required. However, even foods that contain the necessary vitamins can have reduced vitamin content after storage, processing, or cooking. Therefore, many people take a multivitamin tablet to supplement their diet. To ensure that these tablets contain the labeled amounts of vitamins, there must be a quality control assay for these tablets. 

Coverage includes B vitamins and folate in the context of a historical background, disease, cardiovascular effects and the importance of vitamins in biochemistry as illustrated by a single vitamin. Thereafter there are chapters on the chemistry and biochemistry of thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folate and cobalamin. Methodical aspects include characterization and assays of B vitamins and folate in foods of all kinds, dietary supplements, biological fluids and tissues. The techniques cover solid-phase extraction, spectrofluorimetry, mass spectrometry, HPLC, enzymatic assay, biosensor and chemiluminescence. In terms of fimction and effects or... 

Coronary heart disease Folic acid Cobalamin (vitamin B12) Pyridoxine (vitamin Be) Homocysteine reduction MA of RCTs supplementation in patients does not affect risk of a recurrent event Clarke et al. (2010)... 

Chen, J.H., and Jiang, S.J. 2008. Determination of cobalamin in nutritive supplements and chlorella foods by capillary electrophoresis-inductively coupled plasma mass spectrometry. Journal of Agricultural and Food Chemistry. 56(4) 1210-1215. 

Kwok, T., Tang, C., Woo, J., Lai, W.K., Law, L.K., and Pang, C.P., 1998. Randomised trial of the effect of supplementation on the cognitive fimction of older people with subnormal cobalamin levels. International Journal of Geriatrics Psychiatry. 13 611-616. 

Vitamin B12 must be converted into its coenzyme forms, adenosylcobalamin and methylcobalamin, in the cell. These coenzymes function as cofactors of methylmalonyl-CoA mutase and methionine synthase, respectively. Chronic kidney disease (CKD) may affect the conversion from vitamin B12 to the coenzyme forms. This section describes the intracellular metabolism of cyanocobalamin, which is included in many dietary supplements, in particular, referring to a recently discovered trafficking chaperone called methylmalonic aciduria cdlC type with homocystinuria (MMACHC). Cyanocobalamin is first converted to cob(II)alamin, which has no cyanogen group on the ligand occupying the upper axial position of the cobalamin structure. Cob(II)alamin is further reduced to cob(I)alamin, which can function as a coenzyme in the body. 

Impairment of remethylation is strongly implicated as the cause of hyper-homocysteinemia in patients with CKD, which has been demonstrated in a radioisotope study in patients with CKD (Van Guldener et al. 1999), although reduced clearance of homocysteine has been suggested as the possible cause in some reports. We reported that supplementation with folic add and methyl-cobalamin normalized the remethylation pathway (Koyama et al. 2002). Compared with the decreases in homocysteine of 17.3 8.4% after supplementation with folic add alone and 18.7 7.5% after that with methylcoba-lamin alone, a combination of foUc acid and methyleobalamin decreased homocysteine by approximately 60% and normalized the findings of the methionine loading test Table 47.1. This result suggest that both coenzymes, folic acid and methyleobalamin, were insufficient due to reduced availability of these coenzymes in patients with CKD. There is also a report that increased MMA in dialysis patients was reduced by the administration of methylcoba-lamin (Nakamura et al. 2002). 

Table 47.3 Methionine loading on patients with CKD Stage V. Group A was treated with folic acid 15 mg/day orally, methylcobamain 500 pg intravenously after each hemodialysis session and vitamin Bg 60 mg/day orally. Group B was treated with folic acid and methyl-cobalamin (without vitamin Bg). All patients were treated for three weeks. A methionine-loading test was conducted before and after supplementation. Amino acid level was measured at fasting and two hours and four hours after methionine load (0.05 g/kg orally). Both groups showed normal findings of homocysteine profile during the methionine loading test after treatment whether with vitamin Bg or not. However, profiles of methionine and cysteine were not normalized. Reproduced with permission from Koyama (2011).

Livestock supplementation. Cobalt-deficient fodder such as grasses (contain less than 0.08 ppm) may cause serious losses of livestock and lead to vitamin Bn deficiency in humans consuming animal products. Farm animals utilize relatively small amounts of vitamin Bn, ranging from 0.05 to 0.5 mg per kg of their weight, but its content in animal feed is also very low. An effective utilization of the vitamin is due to the high affinity binding proteins. Low yields of cobalamins in the rumen of animals result from a relatively short period of bacterial transit and anaerobic conditions, unfavorable for the synthesis of the cobalamin precursor DMB. When DMB... 

A connection between folic acid and Bi displayed in pernicious anemia was also revealed in Shive s (1950) studies of the reversal of sulfanilamide inhibition, as mentioned earlier in the discussion of E. coli 313-3. A more direct approach to folic-Bij relations seems available in certain p-aminobenzoic acid (PAB)-deficient strains of Bacillus stearothermophilus which respond with equal sensitivities, on a molar basis, to pteroic acid and pteroylglutamic acid (Baker et al., 1956). This PAB-folic requirement is satisfied by a combination of thymine, xanthine, and cyanocobalamin. The concentration of cyanocobalamin required under these conditions was high (10 ug. %) as contrasted with the requirement (0.01 ug-%) of a Bi2-requiring strain of B. stearothermophilus. The cobalamin supplement for the PAB-deficient strain was not replaceable by methionine on the other hand, cyanocobalamin for the B 12 deficient strain ivas replaceable by methionine. XTnexpectedly, cyanocobalamin did not reverse inhibition by sulfanilamide of the PAB-deficient strain in the presence of methionine, xanthine, thymine, glycine, serine, threonine, and leucine—the combination found effective by Shive in reversing sulfanilamide inhibition of wild-type E. coli. 

Vitamin Bj2 is used for the enrichment of some foods (such as breakfast cereals, soy products, energy bars and yeast extract spread) and which maybe the source of corrinoids for strict vegetarians and vegans. Along with other vitamins, vitamin Bjj is added to many multivitamin preparations and to food supplements. Cyanocobal-amin, which is used in most supplements, is readily converted into the coenzyme forms of cobalamin (methylcobalamin and 5 -deoxyadenosylcobalamin) in the human body. 

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