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[The influence of vitamin B 12 premedication on the result of the Schilling test (author's transl)].

The effect of previous administration of vitamin B 12 on the Schilling test was examined in 10 patients, repeating the test during and 10 days after vitamin B 12 treatment. Under vitamin B 12 medication, the patients showed a significantly decreased vitamin B 12 urinary excretion. Ten days after vitamin B 12, repeat Schilling test demonstrated comparable results with baseline values except for one patient, who persistently had a low value.

Cobalt Radioisotopes↗

Low Vitamin B(12) level as a risk factor for very early recurrent abortion.

OBJECTIVE: To examine the relationship between Vitamin B(12) deficiency and early recurrent abortion (ERA) or very early recurrent abortion (VERA) abortion around 5 weeks of amenorrhea. STUDY DESIGN: Serum B(12), folate and homocysteine levels were carried out in 110 consecutive women with unexplained ERA or VERA and in 96 women with one or more children and no abortion history. RESULTS: Ten women were found to have low serum B(12) levels versus one in the control group. A total of 50% of these had raised homocysteine. No difference was noticed between cases and controls for folate. Among women with low serum B(12) level and ERA, 87.5% of the abortions were VERA. Vitamin B(12) supplementation led to four normal pregnancies in five women who became pregnant again. In a statistical analysis performed on five studies in which serum B(12) was assayed in ERA, including ours, a significant relationship was found between ERA and Vitamin B(12) deficiency. CONCLUSION: Vitamin B(12) deficiency may be involved in ERA. Vitamin B(12) assay should be done in ERA women whether or not hematological abnormalities are present.

Abortion, Habitual↗

Vitamin B(12) and Folate Status in Head and Neck Cancer.

Deficiency of vitamin B(12) and folate is associated with causation of certain precancerous conditions and cancer. The present study was carried out on 56 controls, 167 patients with oral precancerous conditions (OPC) and 214 head and neck cancer patients, to evaluate the plasma vitamin B(12) and folate levels to determine their association with tobacco habits and vegetarianism and several sociodemographic factors. The subjects were interviewed using a health habit and diet questionnaire at the time of blood collection. Simultaneous estimations of plasma vitamin B(12) and folate were done by Dual Count Radioassay. It was found that the habit of tobacco consumption, lower education and low income were among the risk factors. A decrease in the plasma vitamin B(12) and folate levels with respect to tobacco habits, disease progression, and vegetarian diet was also observed. The individuals in the ower quartile for vitamin B(12) and folate were at a higher risk of developing OPC, as compared to those in higher quartiles. Similarly, the patients with OPC in lower quartiles were found to be at a higher risk of developing cancer than their counterparts. There was a significant positive correlation between vitamin B(12) and folate levels in the subjects consuming tobacco, and more so in patients with OPC (r=0.4330, p=0.000). Folate levels were significantly lower in patients with advanced as compared with early disease (ANOVA p=0.006 and Spearman's Rho = -0.211 and p=0.01). The results suggest, potential significance of plasma vitamin B(12) and folate levels in head and neck malignancies which needs to be confirmed by further studies on a large population.

Journal Article↗

Risk factors of vitamin B(12) deficiency in patients receiving metformin.

BACKGROUND: Identification of risk factors for metformin-related vitamin B(12) deficiency has major potential implications regarding the management of diabetes mellitus. METHODS: We conducted a nested case-control study from a database in which the source population consisted of subjects who had levels of both serum vitamin B(12) and hemoglobin A(1c) checked in a central laboratory. We identified 155 cases of diabetes mellitus and vitamin B(12) deficiency secondary to metformin treatment. Another 310 controls were selected from the cohort who did not have vitamin B(12) deficiency while taking metformin. RESULTS: A total of 155 patients with metformin-related vitamin B(12) deficiency (mean +/- SD serum vitamin B(12) concentration, 148.6 +/- 40.4 pg/mL [110 +/- 30 pmol/L]) were compared with 310 matched controls (466.1 +/- 330.4 pg/mL [344 +/- 244 pmol/L]). After adjusting for confounders, we found clinically important and statistically significant association of vitamin B(12) deficiency with dose and duration of metformin use. Each 1-g/d metformin dose increment conferred an odds ratio of 2.88 (95% confidence interval, 2.15-3.87) for developing vitamin B(12) deficiency (P<.001). Among those using metformin for 3 years or more, the adjusted odds ratio was 2.39 (95% confidence interval, 1.46-3.91) (P = .001) compared with those receiving metformin for less than 3 years. After exclusion of 113 subjects with borderline vitamin B(12) concentration, dose of metformin remained the strongest independent predictor of vitamin B(12) deficiency. CONCLUSIONS: Our results indicate an increased risk of vitamin B(12) deficiency associated with current dose and duration of metformin use despite adjustment for many potential confounders. The risk factors identified have implications for planning screening or prevention strategies in metformin-treated patients.

Age Factors↗

Folate, vitamin B(6), and vitamin B(12) intake and the risk of breast cancer among Mexican women.

BACKGROUND: High intake of folate, vitamin B(6), and vitamin B(12) have been hypothesized to lower the risk for breast cancer. We conducted a population-based case-control study to evaluate the risk for breast cancer among Mexican women with relatively low vitamin intakes. METHODS: We included 475 women (median age, 53 years; range, 23-87 years) diagnosed with incident breast cancer through six hospitals in Mexico City and interviewed them to obtain data on breast cancer risk factors and their usual diet using a food frequency questionnaire. We selected 1,391 (median age, 49 years; range, 18-82 years) controls from the Mexico City population using a national sampling frame. RESULTS: Compared with women in the lowest quartile, the odds ratio for breast cancer for women in the highest quartile of folate intake was 0.64 [95% confidence intervals (CI), 0.45-0.90; P, test for trend = 0.009] and 0.32 (95% CI, 0.22-0.49; P, test for trend < 0.0001) for vitamin B(12) intake. Among postmenopausal women, intakes of folate and vitamin B(12) were associated with a lower risk of breast cancer and those associations were stronger than among premenopausal women. The inverse association of folate and breast cancer was stronger among women who consumed a high level of vitamin B(12) as compared with women consuming diets low in vitamin B(12). No association was observed for vitamin B(6) intake. CONCLUSIONS: In this population, high intakes of folate and vitamin B(12) were independently associated with decreased breast cancer risk, particularly among postmenopausal women.

Adult↗

Synthesis and characterization of chlorinated alkenylcobaloximes to probe the mechanism of vitamin B(12)-catalyzed dechlorination of priority pollutants.

Vitamin B(12) catalyzes the reductive dechlorination of several ubiquitous pollutants such as perchloroethylene (PCE) and trichloroethylene (TCE). Several mechanisms have been proposed for these transformations, some of which involve the intermediacy of chlorinated vinylcobalamins. To evaluate the currently unknown chemical and physical properties of such species, various chlorinated vinylcobaloxime complexes [cobaloxime = bis(dimethylglyoximato)(pyridine)cobalt(III)] were prepared and characterized. X-ray structures are reported for (cis-1,2-dichloroethenyl)cobaloxime (4), (cis-monochloroethenyl)cobaloxime (5), (alpha-chloroethenyl)cobaloxime (6), and vinylcobaloxime (7), and the reactivities of these isolated complexes were investigated. They were stable in the presence of ethanolic NaBH(4) unless external cobaloximes were added. The cob(I)aloxime formed under the latter conditions promoted the conversion of 4 to 5 and 6, and of 5 and 6 into 7. Mechanistic studies of these transformations are consistent with a pathway in which the conversion of 4 into 5 and 6 takes place via chloroacetylene as an intermediate, and the conversion of 6 to 7 involves vinyl chloride as an intermediate. Cyclic voltammetry on the chlorinated vinylcobaloximes resulted in irreversible reduction waves, with 4 displaying the least negative and 7 the most negative peak potential. These results are discussed in the context of the B(12)-catalyzed reductive dechlorination of PCE and TCE.

Air Pollutants↗

Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor.

OBJECTIVE: To report a case of vitamin B(12) deficiency associated with long-term use (approximately 4 1/2 y) of histamine(2) (H(2))-receptor antagonists and a proton-pump inhibitor (PPI) in a patient with gastroesophageal reflux. CASE SUMMARY: A 78-year-old nonvegetarian white woman with symptomatic gastroesophageal reflux (GER) was started on cimetidine 300 mg 4 times daily in February 1990 and took various other antisecretory medications over the course of the next 4 1/2 years. She had a normal serum vitamin B(12) concentration of 413 pg/mL in August 1992. In June 1994, her serum vitamin B(12) concentration was found to be in the low normal range at 256 pg/mL. Biochemical markers of vitamin B(12)-dependent enzyme activity were measured at that time, and methylmalonic acid (MMA) and homocysteine (HCYS) were elevated at 757 nmol/L and 27.3 micromol/L, respectively. Serum folate was within the normal range at 4.9 ng/mL, and serum creatinine was slightly elevated at 1.4 mg/dL. MMA and HCYS concentrations decreased dramatically with oral replacement of vitamin B(12) 1000 microg/d, which confirmed vitamin B(12) deficiency. Oral replacement also demonstrated that the woman was able to adequately absorb nonprotein-bound vitamin B(12) from the gastrointestinal tract, suggesting that her deficiency was a result of food-cobalamin malabsorption. The accumulation of MMA and HCYS was not a consequence of renal dysfunction, since both metabolites dramatically decreased with vitamin B(12) replacement. DISCUSSION: Malabsorption of dietary protein-bound vitamin B(12) has been demonstrated with the use of H(2)-receptor antagonists and PPIs. One previous case report of vitamin B(12) deficiency resulting from long-term use of omeprazole has been published. The malabsorption of dietary vitamin B(12) is thought to be a result of its impaired release from food protein, which requires gastric acid and pepsin as the initial step in the absorption process. CONCLUSIONS: The use of H(2)-receptor antagonists and/or PPIs may impair the absorption of protein-bound dietary vitamin B(12) and could contribute to the development of vitamin B(12) deficiency with prolonged use. Patients taking these medications for extended periods of time, particularly >4 years, should be monitored for vitamin B(12) status.

Aged↗

Total homocysteine, vitamin B(12), and total antioxidant status in vegetarians.

BACKGROUND: Decreasing or eliminating animal products from the diet decreases the intake of some essential nutrients, such as vitamin B(12), which may lead to hyperhomocysteinemia. We investigated vitamin B(12)-dependent metabolism and oxidative stress in groups with various or no intake of meat or animal products. METHODS: We investigated 44 high meat eaters, 19 low meat eaters, 34 lacto-ovo/lacto vegetarians, and 7 vegan vegetarians. Homocysteine (HCY) was assayed by HPLC, methylmalonic acid (MMA) by capillary gas chromatography-mass spectrometry, serum folate and vitamin B(12) with a chemiluminescence immunoassay, and total antioxidant status (TAS) by a Randox method. RESULTS: The mean serum HCY concentration of vegetarians was significantly increased, and in vegans the median concentration exceeded 15 micromol/L. Vegetarians had a higher serum concentration of MMA but a lower TAS. Vitamin B(12) and folate did not differ significantly between vegetarian and omnivorous subjects. Overall, HCY and MMA were significantly correlated. Vitamin B(12) correlated negatively with MMA, HCY, and folate, whereas the correlation with TAS was positive. Backward regression analysis revealed an independent influence of MMA on HCY, of HCY and vitamin B(12) on MMA, and of vitamin B(12) on TAS. The increased MMA concentration suggested a 25% frequency of functional vitamin B(12) deficiency in all vegetarians. Serum vitamin B(12) was below the lower reference limit in only five subjects. CONCLUSIONS: Functional vitamin B(12) deficiency in vegetarians may contribute to hyperhomocysteinemia and decreased TAS, which may partly counteract the beneficial lifestyle of vegetarians. However, increased serum HCY is most likely not responsible for the lower TAS values in vegetarians. We recommend assaying of MMA and HCY to investigate functional vitamin B(12) status.

Adult↗

Effects of moderate alcohol consumption on folate and vitamin B(12) status in postmenopausal women.

BACKGROUND: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, a causal relationship has not been established, and the mechanisms mediating this association are speculative. Alcohol may act through altered status of folate and vitamin B(12), two vitamins required for DNA methylation and nucleotide synthesis, and thus cell integrity. Although the effects of heavy alcohol intake on folate and vitamin B(12) status have been well-documented, few studies have addressed the effects of moderate alcohol intake in a controlled setting. OBJECTIVE: The objective of this study was to determine the effects of moderate alcohol intake on folate and vitamin B(12) status in healthy, well-nourished, postmenopausal women. DESIGN: The study design was a randomized, diet-controlled crossover intervention. Postmenopausal women (n=53) received three 8-week alcohol treatments in random order: 0, 15, and 30 g/day. Treatment periods were preceded by 2-5-week washout periods. Blood collected at baseline and week 8 of each treatment period was analyzed for serum folate, vitamin B(12), homocysteine (HCY), and methylmalonic acid (MMA) concentrations. RESULTS: After adjusting for body mass index (BMI), a significant 5% decrease was observed in mean serum vitamin B(12) concentrations from 0 to 30 g of alcohol/day (461.45+/-30.26 vs 440.25+/-30.24 pg/ml; P=0.03). Mean serum HCY concentrations tended to increase by 3% from 0 to 30 g of alcohol/day (9.44+/-0.37 vs 9.73+/-0.37 micromol/l; P=0.05). Alcohol intake had no significant effects on serum folate or MMA concentrations. CONCLUSIONS: Among healthy, well-nourished, postmenopausal women, moderate alcohol intake may diminish vitamin B(12) status.

Aged↗

The response to prednisolone in atrophic gastritis: a possible effect on non-intrinsic factor-mediated vitamin B 12 absorption.

The administration of prednisolone did not affect absorption of vitamin B(12) and gastric secretion of intrinsic factor in nine subjects with normal gastric mucosa, or in five with chronic superficial gastritis. No gastric morphological changes were observed in either group. In contrast, four of seven patients with pernicious anaemia showed improvement in absorption of vitamin B(12) during prednisolone administration for periods of two to 10 months. No consistent changes in gastric mucosal morphology were noted. An additional five patients were studied intensively during one month of prednisolone administration. In three, absorption of vitamin B(12) was restored to within the normal range between eight and 13 days after the commencement of the drug. The improvement was not paralleled by enhancement of secretion of intrinsic factor or other vitamin B(12) binders. Suppression of intrinsic factor antibodies in serum and gastric juice did not occur consistently in those patients showing a functional response.

Anemia, Pernicious↗

Smoking in pregnancy and vitamin B 12 metabolism.

In pregnancy the level of serum vitamin B(12) is lower in women who smoke than in non-smokers. This finding occurs independently of social class, parity, or level of haemoglobin. In addition, the mean serum B(12) level tends to be less in women who are anaemic and is less in those women who have smaller babies. These findings may be an effect of the cyanide content of tobacco smoke, since cyanide may be detoxified by a mechanism which depletes the stores of vitamin B(12) in the body.

Anemia↗

A water channel in the core of the vitamin B(12) RNA aptamer.

BACKGROUND: The 3.0 A crystal structure of the vitamin B(12) RNA aptamer revealed an unusual tertiary structure that is rich in novel RNA structural motifs. Important details of the interactions that stabilize noncanonical base pairing and the role of solvent in the structure were not apparent owing to the limited resolution. RESULTS: The structure of the vitamin B(12) RNA aptamer in complex with its ligand has been determined at 2.3 A resolution by X-ray crystallography. The crystallographic asymmetric unit contains five independent copies of the aptamer-vitamin B(12) complex, making it possible to accurately define well-conserved features. The core of the aptamer contains an unusual water-filled channel that is buried between the three strands of an RNA triplex. Well-ordered water molecules positioned within this channel form bridging hydrogen bonds and stabilize planar base triples that otherwise lack significant direct base-base contacts. The water channel terminates at the interface between the RNA and the bound ligand, leaving a pair of water molecules appropriately positioned to hydrogen bond with the highly polarized cyanide nitrogen of vitamin B(12). Analysis of the general solvation patterns for each nucleotide suggests that water molecules are not precisely positioned, as observed in previous RNA duplex structures, but instead might adjust in response to the varying local environment. Unusual intermolecular base pairing contributes to the formation of three different dimerization contacts that drive formation of the crystal lattice. CONCLUSIONS: The structure demonstrates the important role of water molecules and noncanonical base pairing in driving the formation of RNA tertiary structure and facilitating specific interactions of RNAs with other molecules.

Computer Simulation↗

VITAMIN B 12 CONTENT OF CIRCULATING LEUKOCYTES AS AN AID IN THE DIFFERENTIATION OF THE ACUTE LEUKEMIAS.

From 25 patients with acute leukemia 116 specimens of leukocytes were assayed microbiologically for total vitamin B(12) to determine if variation in vitamin B(12) content would help in differentiating the acute leukemias. The mean cell vitamin B(12) levels (mumug./10(8) cells) in the different types of leukemia were: lymphoblastic 464, myeloblastic 1058 and monocytic 200. Cell vitamin B(12) levels above the normal range (100-800 mumug./10(8) cells) are suggestive of myeloblastic leukemia. The only elevated cell vitamin B(12) levels comparable to those found in myeloblastic leukemia were in reticulum cell leukemia, and this type of leukemia was not difficult to diagnose morphologically. Blast cells contained more vitamin B(12) than mature cells of the same series; there was a significant positive correlation between the percentage of blast cells and cell levels of total vitamin B(12) in both lymphoblastic and myeloblastic leukemia.

Acute Disease↗

DNA methylation, cancer susceptibility, and nutrient interactions.

DNA methylation is an important epigenetic mechanism of transcriptional control. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of cancer. Aberrant methylation of DNA (global hypomethylation accompanied by region-specific hypermethylation) is frequently found in tumor cells. Global hypomethylation can result in chromosome instability, and hypermethylation has been associated with the inaction of tumor suppressor genes. Preclinical and clinical studies suggest that part of the cancer-protective effects associated with several bioactive food components may relate to DNA methylation patterns. Dietary factors that are involved in one-carbon metabolism provide the most compelling data for the interaction of nutrients and DNA methylation because they influence the supply of methyl groups, and therefore the biochemical pathways of methylation processes. These nutrients include folate, vitamin B(12), vitamin B(6), methionine, and choline. However, looking at individual nutrients may be too simplistic. Dietary methyl (folate, choline, and methionine) deficiency in combination causes decreased tissue S-adeno-sylmethionine, global DNA hypomethylation, hepatic steatosis, cirrhosis, and ultimately hepatic tumorigenesis in rodents in the absence of carcinogen treatment. Other dietary components such as vitamin B(12), alcohol, and selenium may modify the response to inadequate dietary folate.

Animals↗

Vitamin B(12) and folate in relation to the development of Alzheimer's disease.

OBJECTIVE: To explore the associations of low serum levels of vitamin B(12) and folate with AD occurrence. METHODS: A population-based longitudinal study in Sweden, the Kungsholmen PROJECT: A random sample of 370 nondemented persons, aged 75 years and older and not treated with B(12) and folate, was followed for 3 years to detect incident AD cases. Two cut-off points were used to define low levels of vitamin B(12) (< or =150 and < or =250 pmol/L) and folate (< or =10 and < or =12 nmol/L), and all analyses were performed using both definitions. AD and other types of dementia were diagnosed by specialists according to DSM-III-R criteria. RESULTS: When using B(12) < or =150 pmol/L and folate < or =10 nmol/L to define low levels, compared with people with normal levels of both vitamins, subjects with low levels of B(12) or folate had twice higher risks of developing AD (relative risk [RR] = 2.1, 95% CI = 1.2 to 3.5). These associations were even stronger in subjects with good baseline cognition (RR = 3.1, 95% CI = 1.1 to 8.4). Similar relative risks of AD were found in subjects with low levels of B(12) or folate and among those with both vitamins at low levels. A comparable pattern was detected when low vitamin levels were defined as B(12) < or =250 pmol/L and folate < or =12 nmol/L. CONCLUSIONS: This study suggests that vitamin B(12) and folate may be involved in the development of AD. A clear association was detected only when both vitamins were taken into account, especially among the cognitively intact subjects. No interaction was found between the two vitamins. Monitoring serum B(12) and folate concentration in the elderly may be relevant for prevention of AD.

Aged↗

Dementia associated with vitamin B(12) deficiency: presentation of two cases and review of the literature.

Vitamin B(12) deficiency has long been associated with a wide variety of hematological, neurological, and psychiatric disorders. The role of vitamin B(12) deficiency as one of the few treatable causes of dementia, however, is still controversial. The authors report on 2 elderly patients suffering from cognitive impairment and psychotic symptomatology probably related to cobalamin deficiency, who showed improvement after parenteral vitamin B(12) substitution. The literature concerning the pathophysiology and the diagnostic and therapeutic aspects of cobalamin deficiency is reviewed.

Aged↗