Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new b12 research articles will be listed here shortly after becoming available to us.
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Medical research on b12
Menopause modulates homocysteine levels in diabetic and non-diabetic women.
J Endocrinol Invest. 2008 Jun; 31(6): 546-51
Russo GT, Di Benedetto A, Alessi E, Giandalia A, Gaudio A, Ientile R, Horvath KV, Asztalos B, Raimondo G, Cucinotta D
High total homocysteine (tHcy) plasma levels may contribute to the increased cardiovascular risk of Type 2 diabetic women. However, to date, data on factors modulating tHcy concentration in this population are scarce. Fasting tHcy, vitamin B12, folate plasma levels, and the methylene tetrahydrofolate reductase (MTHFR) C677T genotype as well as clinical, biochemical, and lifestyle variables were compared in 91 Type 2 diabetic and 91 matched non-diabetic women (40 pre- and 51 post-menopausal, in each group). Fasting tHcy concentration did not differ between diabetic and control women, even after multivariable adjustment. In both groups, tHcy levels increased after menopause, but the differences were weakened after multivariable adjustment. The MTHFR genotype distribution was in accordance with the Hardy-Weinberg equilibrium, with a similar TT frequency in diabetic (22.2 %) and control women (19.8%). Overall, tHcy plasma concentration was higher in TT homozygous compared to other genotypes. We found a menopause-genotype interaction on tHcy levels (p=0.068 for menopause*genotype interaction); overall, the increase of tHcy concentration in TT subjects was limited to pre-menopause (p
A cost-effectiveness analysis of folic acid fortification policy in the United States.
Public Health Nutr. 2008 Jul 1; 1-13
Bentley TG, Weinstein MC, Willett WC, Kuntz KM
OBJECTIVE: To quantify the health and economic outcomes associated with changes in folic acid consumption following the fortification of enriched grain products in the USA. DESIGN: Cost-effectiveness analysis. SETTING: Annual burden of disease, quality-adjusted life years (QALY) and costs were projected for four steady-state strategies: no fortification, or fortifying with 140, 350 or 700 mug folic acid per 100 g enriched grain. The analysis considered four health outcomes: neural tube defects (NTD), myocardial infarctions (MI), colon cancers and B12 deficiency maskings. SUBJECTS: The US adult population subgroups defined by age, gender and race/ethnicity, with folate intake distributions from the National Health and Nutrition Examination Surveys (1988-1992 and 1999-2000), and reference sources for disease incidence, utility and economic estimates. RESULTS: The greatest benefits from fortification were predicted in MI prevention, with 16 862 and 88 172 cases averted per year in steady state for the 140 and 700 mug fortification levels, respectively. These projections were between 6261 and 38 805 for colon cancer and 182 and 1423 for NTD, while 15-820 additional B12 cases were predicted. Compared with no fortification, all post-fortification strategies provided QALY gains and cost savings for all subgroups, with predicted population benefits of 266 649 QALY gained and $3.6 billion saved in the long run by changing the fortification level from 140 mug/100 g enriched grain to 700 mug/100 g. CONCLUSIONS: The present study indicates that the health and economic gains of folic acid fortification far outweigh the losses for the US population, and that increasing the level of fortification deserves further consideration to maximise net gains.
Altern Med Rev. 2008 Jun; 13(2): 85-115
Kidd PM
Alzheimer's disease, AD, is the most common form of dementia. AD initially targets memory and progressively destroys the mind. The brain atrophies as the neocortex suffers neuronal, synaptic, and dendritic losses, and the hallmark amyloid plaques and neurofibrillary tangles proliferate. Pharmacological management, at best, is palliative and transiently effective, with marked adverse effects. Certain nutrients intrinsic to human biochemistry (orthomolecules) match or exceed pharmacological drug benefits in double-blind, randomized, controlled trials, with superior safety. Early intervention is feasible because its heritability is typically minimal and pathological deterioration is detectable years prior to diagnosis. The syndrome amnestic mild cognitive impairment exhibits AD pathology and to date has frustrated attempts at intervention. The condition age-associated memory impairment is a nonpathological extreme of normal brain aging, but with less severe cognitive impairment than amnestic mild cognitive impairment. Age-associated memory impairment is a feasible target for early intervention against AD, beginning with the modifiable AD risk factors - smoking, hypertension, homocysteine, type 2 diabetes, insulin resistance, and obesity. Stress reduction, avoidance of toxins, and mental and physical exercise are important aspects of prevention. The diet should emphasize omega-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid; flavonoids and other antioxidant nutrients; and B vitamins, especially folate, B6 and B12. Dietary supplementation is best focused on those proven from randomized, controlled trials: the phospholipids phosphatidylserine and glycerophosphocholine, the energy nutrient acetyl-L-carnitine, vitamins C and E, and other antioxidants. A comprehensive integrative strategy initiated early in cognitive decline is the most pragmatic approach to controlling progression to Alzheimer's disease.
Arch Latinoam Nutr. 2008 Mar; 58(1): 12-8
García-Casal MN, Leets I, Bracho C, Hidalgo M, Bastidas G, Gomez A, Peña A, Pérez H
The objective of this work was to determine the prevalence of anemia and deficiencies of iron, folic acid and vitamin B12 in Betania del Topocho, a Piaroa community from Estado Amazonas, Venezuela, a zone with a high incidence of malaria. The group studied included 184 subjects of all ages that assisted to the local health center for malaria diagnosis. Analysis performed included hematology by coulter counter, ferritin quantification by ELISA with monoclonal antibodies and folic acid and vitamin B12 determinations by an immunoradiometric assay. It was found that the prevalence of anemia was 89.6% and deficiencies of iron, folic acid and vitamin B12 affected 37.1,70.3 and 12.4% of the population studied, respectively. Plasmodium infection was detected by molecular diagnosis in 53.2% of the cases, and 86% of them were anemic. The highest incidence of anemia was found in children, with a prevalence of 100% in infants of both sexes. The high prevalence of anemia, iron and folic acid deficiencies found, indicates an important health and nutrition problem that should be immediately and properly addressed. The number of cases of anemia due to iron deficiency could be underestimated, since ferritin concentration increased as a acute phase protein, although prevalence data was also analyzed with a cutoff point of 30 microg/L for ferritin concentration.
Neural tube defects and disturbed maternal folate- and homocysteine-mediated one-carbon metabolism.
Exp Neurol. 2008 May 20;
Zhang HY, Luo GA, Liang QL, Wang Y, Yang HH, Wang YM, Zheng XY, Song XM, Chen G, Zhang T, Wu JX
Disturbances in maternal folate and homocysteine metabolism are associated with neural tube defects (NTDs). However, the role played by specific components in the one-carbon metabolic pathways leading to NTDs remains unclear. Here, we conducted a case-control study to investigate the relationship between the disturbed one-carbon metabolism and the risk of NTD-affected pregnancies. Major components were examined in population-based samples of women who had NTD-affected pregnancies (case subjects, n=46) or unaffected by any birth defects (control subjects, n=44). We used the newly developed high-performance liquid chromatography tandem mass spectrometry along with a routine chemiluminescent assay, to measure serum concentrations of 5-methyltetrahydrofolate (5-MeTHF), 5-formyltetrahydrofolate (5-FoTHF), folic acid, serine, histidine, homocysteine, cystathionine, methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), total folate and vitamin B12 in both groups adjusting for lifestyle and sociodemographic variables. We found significantly lower serum concentrations of 5-MeTHF (P
Structure and function of SirC from Bacillus megaterium - a metal binding precorrin-2 dehydrogenase.
Biochem J. 2008 Jun 26;
Schubert HL, Rose RS, Leech HK, Brindley AA, Hill CP, Rigby SE, Warren MJ
In Bacillus megaterium, the synthesis of vitamin B12 (cobalamin) and siroheme diverge at sirohydrochlorin along the branched modified tetrapyrrole biosynthetic pathway. This key intermediate is made by the action of SirC, a precorrin-2 dehydrogenase that requires NAD+ as a cofactor. The structure of SirC has now been solved by X-ray crystallography to 2.8 A resolution. The protein is shown to consist of three domains and has a similar topology to the multifunctional siroheme synthases Met8p and the N-terminal region of CysG, both of which catalyse not only the dehydrogenation of precorrin-2 but also the ferrochelation of sirohydrochlorin to give siroheme. Guided by the structure, a number of active site residues within SirC were investigated by site-directed mutagenesis. No active site general base was identified, although surprisingly some of the resulting protein variants were found to have significantly enhanced catalytic activity. Unexpectedly, SirC was found to bind metal ions such as cobalt and copper, and to bind them in an identical fashion to that observed in Met8p. It is suggested that SirC may have evolved from a Met8p-like protein by loss of its chelatase activity. It is proposed that the ability of SirC to act as a single monofunctional enzyme, in conjunction with an independent chelatase, may provide greater control over the intermediate at this branchpoint in the synthesis of siroheme and cobalamin.
J Biochem. 2008 Jun 27;
Toraya T, Tamura N, Watanabe T, Yamanishi M, Hieda N, Mori K
Summary The reactions of diol dehydratase with 3-unsaturated 1,2-diols and thioglycerol were investigated. Holodiol dehydratase underwent rapid and irreversible inactivation by either 3-butene-1,2-diol, 3-butyne-1,2-diol, or thioglycerol without catalytic turnovers. In the inactivation, the Co-C bond of adenosylcobalamin underwent irreversible cleavage forming unidentified radicals and cob(II)alamin that resisted oxidation even in the presence of oxygen. Two mol of 5'-deoxyadenosine per mol of enzyme was formed as an inactivation product from the coenzyme adenosyl group. Inactivated holoenzymes underwent reactivation by diol dehydratase-reactivating factor in the presence of ATP, Mg2+, and adenosylcobalamin. It was thus concluded that these substrate analogues served as mechanism-based inactivators or pseudosubstrates, and that the coenzyme was damaged in the inactivation, whereas apoenzyme was not damaged. In the inactivation by 3-unsaturated 1,2-diols, product radicals stabilized by neighboring unsaturated bonds might be unable to back-abstract the hydrogen atom from 5'-deoxyadenosine and then converted to unidentified products. In the inactivation by thioglycerol, a product radical may be lost by the elimination of sulfhydryl group producing acrolein and unidentified sulfur compound(s). H2S or sulfide ion was not formed. The loss or stabilization of product radicals would result in the inactivation of holoenzyme, because the regeneration of the coenzyme becomes impossible.
Clin Appl Thromb Hemost. 2008 Jul; 14(3): 365-8
Küpeli E, Cengiz C, Cila A, Karnak D
Pulmonary thromboembolism is a life-threatening condition resulting mostly from lower extremity deep-vein or pelvic-vein thrombosis. A 46-year-old woman was admitted to hospital with pain on the right side of the chest and hemoptysis. On laboratory analysis, D-dimer level was elevated. Computed tomographic pulmonary angiography revealed intravascular filling defects due to thrombi in right lower lobe pulmonary segmental arteries. Screening for thrombophilic states was normal except for heterozygous mutations of both prothrombin and methylene tetrahydrofolate reductase (MTHFR 677) genes. Homocysteine level was high, and vitamin B12 level and serum ferritin level were reduced. Serum antiparietal antibody was positive, and therefore, pernicious anemia was diagnosed along with iron-deficiency anemia. After the diagnoses were established, enoxaparin followed by warfarin was started in addition to oral vitamin B12, pyridoxine, thiamine, folic acid, and ferroglycine sulfate supplementation. At the end of 8 weeks of the replacement therapy, vitamin B12, folate, and homocysteine levels and red cell volume were found to be normal, with complete resolution of the thrombus confirmed by repeat computed tomographic pulmonary angiography. We conclude that hyperhomocysteinemia due to vitamin B12 deficiency associated with pernicious anemia might have decreased the threshold for thrombosis. In addition, the presence of heterozygous prothrombin and methylene tetrahydrofolate reductase mutations might serve as synergistic cofactors triggering pulmonary thromboembolism.
Association between C677T/MTHFR genotype and homocysteine concentration in a Kazakh population.
Asia Pac J Clin Nutr. 2008; 17(2): 325-9
Akilzhanova A, Takamura N, Kusano Y, Karazhanova L, Yamashita S, Saito H, Aoyagi K
We recently suggested that due to insufficient intake of vegetables, low folate status and mild homocysteinemia might exist in the Kazakh population. To clarify the determinants of homocysteine concentrations among this population, we determined concentrations of serum folate, albumin, creatinine, vitamin B12, and the C677T/ MTHFR genotype in 110 Kazakh individuals and compared these with plasma total homocysteine. In Kazakh, after adjustment for age and sex, folate was correlated with plasma total homocysteine, whereas concentrations in those with the TT genotype was almost twice as high as in those with the CC and CT genotypes (19.7+/-1.8 mumol/L vs. 10.7+/-0.5 mumol/L, p
Cancer Invest. 2008 Jul; 26(6): 583-9
Jensen LH, Lindebjerg J, Crüger DG, Brandslund I, Jakobsen A, Kolvraa S, Nielsen JN
The possible associations between microsatellite instability, homocysteine and thymidylate synthase were investigated in tumors and plasma from 130 patients with colorectal cancer. Other analyses included thymidylate synthase and 5,10-methylene-tetrahydrofolate reductase gene polymorphisms, carcinoembryonic antigen, vitamin B12, and folate. Microsatellite instability of tumors was associated with higher levels of plasma homocysteine (p = 0.008) and higher protein expression of thymidylate synthase (p < 0.001). Supplemental analyses ruled out that the finding could be explained by the other analyzed factors. CEA was not associated with neither homocysteine nor microsatellite instability. The data suggests that there is a more pronounced methyl unit deficiency in microsatellite instable tumors.