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[Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences].

The increasing number of older people is characteristic for most industrialised nations and implicates the known psychosocial and economic consequences. Therefore, an optimal nutrient supply that promotes continuing mental and physical well-being is particularly important. In this respect, vitamin B(12) and folic acid play a major role, since deficiency of both vitamins is associated with the pathogenesis of different diseases such as declining neurocognitive function and atherosclerotic lesions. Vitamin B(12) and folic acid act as coenzymes and show a close molecular interaction on the basis of the homocysteine metabolism. In addition to the serum concentrations of the vitamins, the metabolites homocysteine and methylmalonic acid are sensitive markers of cobalamin and folate status. Depending on the used marker, 3-60% of the elderly are classified as vitamin B(12) deficient and about 29% as folate deficient. Predominantly, this high prevalence of poor cobalamin status is caused by the increasing prevalence of atrophic gastritis type B, which occurs with a frequency of approximately 20-50% in elderly subjects. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal digestion and absorption of both B vitamins. This is the reason why an insufficient vitamin B(12) status in the elderly is rarely due to low dietary intake. In contrast, folic acid intake among elderly subjects is generally well below the recommended dietary reference values. Even moderately increased homocysteine levels or poor folate and vitamin B(12) status are associated with vascular disease and neurocognitive disorders. Results of a meta-analysis of prospective studies revealed that a 25% lower homocysteine level (about 3 micromol/L) was associated with an 11% lower ischemic heart disease risk and 19% lower stroke risk. It is still discussed, whether hyperhomocysteinemia is causally related to vascular disease or whether it is a consequence of atherosclerosis. Estimated risk reduction is based on cohort studies, not on clinical trials. Homocysteine initiates different proatherogenetic mechanisms such as the formation of reactive oxygen species and an enhanced fibrin synthesis. Supplementation of folic acid (0.5-5 mg/d) reduces the homocysteine concentration by 25%. Additional vitamin B(12) (0.5 mg/d) induces further reduction by 7%. In secondary prevention, supplementation already led to clinical improvements (reduction of restenosis rate and plaques). Depression, dementia, and mental impairment are often associated with folate and vitamin B(12) deficiency. The biochemical reason of this finding may be the importance of folic acid and vitamin B(12) for the transmethylation of neuroactive substances (myelin, neurotransmitters) which is impaired in vitamin deficiency ("hypomethylation hypothesis"). In recent years, there is increasing evidence for a role of folic acid in cancer prevention. As a molecular mechanism of a preventive effect of folic acid the hypomethylation of certain DNA sections in folate deficiency has been suggested. Since folate and vitamin B(12) intake and status are mostly insufficient in elderly subjects, a supplementation can generally be recommended.

Aged↗

Are children with cystic fibrosis who are treated with a proton-pump inhibitor at risk for vitamin B(12) deficiency?

BACKGROUND: In a recent study, the authors demonstrated the beneficial effect of proton-pump inhibitors (PPI) on fat malabsorption and bone mineral content in children with cystic fibrosis (CF). Prolonged use of PPI could result in vitamin B(12) deficiency as a consequence of impaired release of vitamin B(12) from food in a nonacid environment. The aim of this study was to evaluate the vitamin B 12 status of CF patients either treated with a PPI or not by measuring vitamin B(12) and homocysteine blood levels, the latter being a sensitive indicator of vitamin B(12) deficiency. METHODS: The study population consisted of 20 CF patients, 11 patients treated with a PPI for at least 2 years and 9 patients not treated with a PPI, and 10 healthy, age-matched control participants. Homocysteine blood levels were measured by high-performance liquid chromatography, and vitamin B(12) levels were measured by a competitive protein-binding assay. RESULTS: Vitamin B(12) levels were significantly higher in both CF groups compared with the control participants (PPI+, P = 0.02; PPI-, P = 0.009). There was no significant difference in vitamin B(12) levels between both CF groups. Homocysteine levels were normal and similar in all groups. CONCLUSIONS: Cystic fibrosis patients treated with a PPI for at least 2 years show no signs of vitamin B(12) deficiency.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Dried green and purple lavers (Nori) contain substantial amounts of biologically active vitamin B(12) but less of dietary iodine relative to other edible seaweeds.

Vitamin B(12) concentrations of dried green (Enteromorpha sp.) and purple (Porphyra sp.) lavers (nori) were determined by both Lactobacillus leichmannii ATCC 7830 microbiological and intrinsic factor chemiluminescence methods. The values determined by using the microbiological method (63.58 +/- 2.90 and 32.26 +/- 1.61 microg/100 g of dry weight) were identical to those found by using the chemiluminescence method (69.20 +/- 2.21 and 25.07 +/- 0.54 microg/100 g of dry weight) in both dried green and purple lavers, respectively. A silica gel 60 thin-layer chromatography of both laver extracts shows that non-coenzyme forms (hydroxo and cyano forms) of vitamin B(12) predominate in both dried lavers. The dried lavers contained lesser amounts of dietary iodine ( approximately 4-6 mg/100 g of dry weight) relative to other seaweeds, suggesting that excessive intake of the dried lavers is unlikely to result in harmful intake of dietary iodine. These results indicate that the dried lavers (nori) are the most excellent source of vitamin B(12) among edible seaweeds, especially for strict vegetarians.

Iodine↗

Plasma homocysteine, folate and vitamin B(12) compared between rural Gambian and UK adults.

The disease risk indicator plasma total homocysteine (tHcy) is influenced by genetic and environmental factors, including folate and vitamin B(12) status. Little is known about the determinants of tHcy in rural West Africa. We explored the hypothesis that tHcy in rural Gambian adults might vary between the sexes and physiological groups, and/or with folate and vitamin B(12) status. Comparisons were made with a British national survey. Non-pregnant Gambian women (n 158) had tHcy concentrations (geometric mean 9.0 micromol/l) similar to those of non-pregnant UK women (n 449; 9.4 micromol/l), whereas pregnant Gambian women (n 12) had significantly lower values (6.2 micromol/l). Gambian men (n 22) had significantly higher values (14.7 micromol/l) than British men (n 354; 10.8 micromol/l). Gambian lactating women and British men and women exhibited significant inverse relationships between log(e)(tHcy) and folate status; however, only the British subjects exhibited significant inverse relationships between loge(tHcy) and vitamin B(12) status. In the British sample, and in Gambian lactating women, folate and vitamin B(12) status variations together accounted for 20-25 % of the variation in log(e)(tHcy). Within the UK, black-skinned adults had folate and tHcy levels similar to those of their white-skinned counterparts, but significantly higher vitamin B(12) values. We conclude that, whereas folate and vitamin B(12) status are similar between British and rural Gambian populations, tHcy is higher in Gambian men and lower in pregnant Gambian women, and that serum vitamin B(12) values appear to be higher in black-skinned than white-skinned British subjects. Possible reasons are discussed.

Adult↗

[Investigation of relationship between pregnancy induced hypertension syndrome and homocysteine, folic acid and vitamin B(12)].

OBJECTIVE: To investigate the relationship between pregnancy induced hypertension syndrome (PIH) and homocysteine, folic acid and vitamin B(12). METHODS: There were 59 cases of PIH (group A) and 60 cases of normal late pregnancy were enrolled (group B). The serum homocysteine level was detected with fluorescence polarization immunoassay (FPIA), serum folic acid and vitamin B(12) levels were detected with microparticle enzyme immunoassay (MEIA). RESULTS: There was significant difference (P < 0.05) of serum homocysteine levels between group A [(13.1 +/- 3.7) micromol/L] and group B [(10.4 +/- 3.9) micromol/L]. Although, the level of folic acid and vitamin B(12) in group A were lower than those of group B, there was no statistical differences between the two groups (P > 0.05). CONCLUSION: It was concluded that the disorder of homocysteine metabolism may play an important role in the pathogenesis of PIH, and no direct evidence to prove that folic acid and vitamin B(12) were related with PIH.

Adult↗

Cardiovascular risk factors in vegetarians. Normalization of hyperhomocysteinemia with vitamin B(12) and reduction of platelet aggregation with n-3 fatty acids.

Hyperhomocysteinemia in association with vitamin B(12) deficiency, and increased platelet aggregation, probably due to dietary lack of n-3 fatty acids, constitute cardiovascular risk factors frequently observed in vegetarians. We tested if administration of vitamin B(12) normalizes the concentration of total plasma homocysteine, and if intake of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) fatty acids modulates platelet function in a population of lactoovovegetarians. One week after a single intramuscular injection of cyanocobalamin (10000 microg) in 18 individuals, serum vitamin B(12) increased from 149+/-63 pg/mL to 532+/-204 pg/mL (p<0.0001) and total tHcy dropped from 12.4+/-4.7 to 7.9+/-3.1 micromol/L (p<0. 0001). Ten of fourteen of these vegetarians completed an 8-week supplementation with 700 mg/day of each eicosapentaenoic and docosahexaenoic acids. Increased incorporation of these fatty acids into plasma lipids was observed in all of them, together with a significant reduction in maximum percentage or slope of platelet aggregation with all the agonists tested (ADP, epinephrin, collagen, arachidonic acid). No significant change in bleeding time was observed after n-3 fatty acid trial. Supplementation with vitamin B(12) and n-3 fatty acids corrects hyperhomocysteinemia and reduces platelet reactivity to agonists in vegetarians. Whether this supplementation improves the already reduced cardiovascular morbidity and mortality associated with vegetarian diet has yet to be demonstrated.

Adult↗

Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women's Health and Aging Study.

OBJECTIVE: It has been hypothesized that adequate concentrations of vitamin B(12) and folate are essential to maintain the integrity of the neurological systems involved in mood regulation, but epidemiologic evidence for such a link in the general population is unavailable. This study examined whether community-dwelling older women with metabolically significant vitamin B(12) or folate deficiency are particularly prone to depression. METHOD: Serum levels of vitamin B(12), folate, methylmalonic acid, and total homocysteine were assayed in 700 disabled, nondemented women aged 65 years and over living in the community. Depressive symptoms were measured by means of the Geriatric Depression Scale and categorized as no depression, mild depression, and severe depression. RESULTS: Serum homocysteine levels, serum folate levels, and the prevalences of folate deficiency and anemia were not associated with depression status. The depressed subjects, especially those with severe depression, had a significantly higher serum methylmalonic acid level and a nonsignificantly lower serum vitamin B(12) level than the nondepressed subjects. Metabolically significant vitamin B(12) deficiency was present in 14.9% of the 478 nondepressed subjects, 17. 0% of the 100 mildly depressed subjects, and 27.0% of the 122 severely depressed women. After adjustment for sociodemographic characteristics and health status, the subjects with vitamin B(12) deficiency were 2.05 times as likely to be severely depressed as were nondeficient subjects. CONCLUSIONS: In community-dwelling older women, metabolically significant vitamin B(12)deficiency is associated with a twofold risk of severe depression.

Age Factors↗

The biosynthesis of vitamin B 12 : a study by 13 C magnetic resonance spectroscopy.

The origin of the methyl group on C-1 of Ring A of the corrin ring of vitamin B(12) was investigated by (13)C magnetic resonance spectroscopy. The proton-decoupled (13)C spectra of vitamin B(12) synthesized from [5-(13)C]delta-aminolevulinic acid by Propionibacteria were obtained by Fourier-transform nuclear magnetic resonance of high resolution, and spectra of high-resolution proton magnetic resonance of the (13)C-labeled B(12) were also taken. The delta-carbon atom of delta-aminolevulinic acid is the source of seven or eight known positions of vitamin B(12), depending on whether the C-1 methyl group is also derived from the labeled substrate. We have found seven resonances whose chemical shifts enable us to identify the position of the (13)C atoms in the molecule from the assignment of Dodderell and Allerhand. We observed no (13)C resonance corresponding to the C-1 methyl group of Ring A. Furthermore, the proton magnetic resonance spectrum showed no spin-spin splitting of the proton peak at the tau values assigned for the H atoms in this methyl group. It would thus appear that the methyl group at C-1, which has been considered to have the same origin as the delta-methine bridge of porphyrins, does not originate from the delta-carbon atom of delta-aminolevulinic acid. This finding may aid in elucidation of the mechanism of synthesis of the functional isomer of vitamin B(12) and porphyrins. The (13)C-labeled vitamin B(12) enabled us to make further assignments to the (13)C magnetic resonance of the vitamin.

Carbon Isotopes↗

Isolation of vitamin B 12 transport mutants of Escherichia coli.

Escherichia coli KBT001, a methionine-vitamin B(12) auxotroph, was found to require a minimum of 20 molecules of vitamin B(12) (CN-B(12)) per cell for aerobic growth in the absence of methionine. After mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine and penicillin selection, two kinds of B(12) transport mutant were isolated from this strain. Mutants of class I, such as KBT069, were defective in the initial rapid binding of CN-B(12) to the cell and were unable to grow in the absence of methionine even with CN-B(12) concentrations as high as 100 ng/ml. The class II mutants possessed intact initial phases of CN-B(12) uptake but were defective in the secondary energy-dependent phase. These strains were also unable to convert the CN-B(12) taken up into other cobalamins. In the absence of methionine, some of these strains (e.g., KBT103) were able to grow on media containing 1 ng of CN-B(12)/ml, whereas others (e.g., KBT041) were unable to grow with any of the CN-B(12) concentrations used. Osmotic shock treatment did not affect the initial rate of uptake of CN-B(12) but gave a substantial decrease in the secondary rate. Trace amounts of B(12)-binding macromolecules were released from the cells by the osmotic shock, but only from strains such as KBT001 and KBT041 which possessed an active initial phase of CN-B(12) uptake. These results are interpreted as being consistent with the view that the initial CN-B(12) binding site which functions in this transport system is probably bound to the cell membrane.

Aerobiosis↗