Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: ethnic and sex differences in cobalamin and metabolite abnormalities.
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BACKGROUND: Low cobalamin concentrations and mild hyperhomocysteinemia are common in the elderly but ethnic differences have not been defined. OBJECTIVE: Our objective was to determine the demographic characteristics of cobalamin deficiency in the elderly and its role in their hyperhomocysteinemia. DESIGN: We measured serum cobalamin, total homocysteine (Hcys), and methylmalonic acid (MMA) concentrations in 725 subjects >60 y old, and folate concentrations in 520 subjects. RESULTS: After exclusion of subjects taking cobalamin supplements or with renal insufficiency, high prevalences of low cobalamin (11.8%), high MMA (16.6%), and high Hcys (26.1%) concentrations were seen. Most cobalamin concentrations <140 pmol/L appeared to reflect deficiency because 78. 3% of them were accompanied by abnormal metabolites. Subjects with cobalamin concentrations of 140-258 pmol/L had significantly fewer metabolic abnormalities. A low cobalamin concentration and renal insufficiency were the strongest predictors of abnormal Hcys concentrations. Elderly men had higher Hcys concentrations than did women (P = 0.0001). Whites and Latin Americans had lower cobalamin concentrations than did blacks and Asian Americans (P < 0.005). Whites also had higher Hcys concentrations than all the other groups (P < 0.05). When included in the analysis, renal insufficiency in subjects was associated with 23.8% of all high Hcys and 25.5% of all high MMA concentrations; most with renal insufficiency were Asian American and black men. CONCLUSIONS: Mild cobalamin deficiency is most common in elderly white men and least common in black and Asian American women. Hyperhomocysteinemia, which is most strongly associated with low cobalamin concentrations, is also most common in elderly whites, whereas that associated with renal insufficiency is more common in blacks and Asian Americans. Ethnic differences in cobalamin deficiency and the Hcys patterns associated with it or with renal insufficiency warrant consideration in supplementation strategies. Extending suspicion of deficiency to persons with cobalamin concentrations of 140-258 pmol/L appears to provide more disadvantages than advantages. (+info)
Racial differences in prevalence of cobalamin and folate deficiencies in disabled elderly women.
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BACKGROUND: Many previous investigations of cobalamin and folate status were performed in white populations. OBJECTIVE: Our objective was to determine whether there are racial differences in the prevalence of cobalamin and folate deficiency. DESIGN: The study was a cross-sectional comparison of baseline serum cobalamin, folate, methylmalonic acid (MMA), total homocysteine (tHcy), and creatinine concentrations, complete blood count, and vitamin supplementation in 550 white and 212 African American subjects from a cohort of physically disabled older women. RESULTS: The mean (+/-SD) serum MMA concentration was significantly higher in whites than in African Americans: 284 +/- 229 compared with 218 +/- 158 nmol/L (P = 0.0001). tHcy concentration was higher in African Americans than in whites: 12.4 +/- 7.0 compared with 10.9 +/- 4.6 micromol/L (P = 0.001). Serum cobalamin was lower in whites (P = 0.0002). Cobalamin deficiency (serum cobalamin <258 pmol/L and MMA >271 nmol/L) was more frequent in the white women (19% compared with 8%; P < 0.0003). Folate deficiency (serum folate <11.4 nmol/L, tHcy >13.9 micromol/L, and MMA <271 nmol/L) was more prevalent in African Americans than in whites (5% compared with 2%; P = 0.01). Multivitamin use was associated with lower tHcy but not with MMA concentrations. Regression models showed that age >85 y, African American race, serum creatinine >90 micromol/L, and high MMA concentration were all significantly correlated with higher tHcy. Creatinine > 90 micromol/L, white race, and folate concentration were positively associated with MMA concentration. CONCLUSIONS: Cobalamin deficiency with elevated serum MMA concentration is more prevalent in elderly white than in African American women and elevated serum tHcy and folate deficiency are more prevalent in elderly African American than in white women. (+info)
Epidermal growth factor as a local mediator of the neurotrophic action of vitamin B(12) (cobalamin) in the rat central nervous system.
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We have recently demonstrated that the myelinolytic lesions in the spinal cord (SC) of rats made deficient in vitamin B(12) (cobalamin) (Cbl) through total gastrectomy (TG) are tumor necrosis factor-alpha (TNF-alpha)-mediated. We investigate whether or not permanent Cbl deficiency, induced in the rat either through TG or by chronic feeding of a Cbl-deficient diet, might modify the levels of three physiological neurotrophic factors-epidermal growth factor (EGF), vasoactive intestinal peptide (VIP), and somatostatin (SS)-in the cerebrospinal fluid (CSF) of these rats. We also investigated the ability of the central nervous system (CNS) in these Cbl-deficient rats to synthesize EGF mRNA and of the SC to take up labeled Cbl in vivo. Cbl-deficient rats, however the vitamin deficiency is induced, show a selective decrease in EGF CSF levels and an absence of EGF mRNA in neurons and glia in various CNS areas. In contrast, radiolabeled Cbl is almost exclusively taken up by the SC white matter, but to a much higher degree in totally gastrectomized (TGX) rats. Chronic administration of Cbl to TGX rats restores to normal both the EGF CSF level and EGF mRNA expression in the various CNS areas examined. This in vivo study presents the first evidence that the neurotrophic action of Cbl in the CNS of TGX rats is mediated by stimulation of the EGF synthesis in the CNS itself. It thus appears that Cbl inversely regulates the expression of EGF and TNF-alpha genes in the CNS of TGX rats. (+info)
Comparison of serum and plasma methylmalonic acid measurements in 13 laboratories: An international study.
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BACKGROUND: Detection of cobalamin deficiency is increasingly important, and methylmalonic acid (MMA) appears to be a useful marker. Information on interlaboratory variation and on methodological differences for MMA in serum and plasma is limited. METHODS: Using gas chromatography/mass spectrometry, 13 laboratories participated in a 2-day analysis of 8 serum and 11 EDTA-plasma specimens. Results were analyzed for imprecision, recovery, and differences among laboratories and methods. RESULTS: The mean among-laboratory imprecision (CV) was 19% and 21% for serum and plasma samples, respectively, and 9.3% and 7.8% for serum and plasma samples with added MMA, respectively. The mean within-laboratory (among-run) CV was 13% for both serum and plasma samples and 5.2% and 4.9% for serum and plasma samples with added MMA. Within-method imprecision was the same or higher than among-method imprecision. The mean among-laboratory recovery of MMA was 105% and 95% in serum and plasma, respectively. Most laboratories showed a proportional bias relative to the consensus mean of up to 15%. Two laboratories reported results that on average were almost 30% higher than the consensus mean. CONCLUSIONS: No method differences were found, but significant among-laboratory imprecision was found in the present study. Improvements are needed to reduce the analytical imprecision of most laboratories, and attention must be focused on calibration issues. Differences among laboratories can be improved by introducing high-quality reference materials and by instituting external quality assessment programs. (+info)
Evaluation of low serum vitamin B(12) in the non-anaemic pregnant patient.
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Low serum vitamin B(12) concentrations in pregnancy may not indicate true megaloblastic anaemia. In the present study we compared biochemical indices of vitamin B(12) deficiency (serum homocysteine and urine methylmalonic acid) in non-anaemic pregnant women with and without low serum vitamin B(12) concentrations. The groups were matched for age, parity and gestational age. No differences were found, and all values were within normal range. These results suggest that the measurement of low serum B(12) concentrations in pregnant women should be followed by analysis at the biochemical level before vitamin B(12) injections are started. (+info)
Relationship between methylmalonic acid and cobalamin in uremia.
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Relationship between methylmalonic acid and cobalamin in uremia. BACKGROUND: To evaluate the requirement for routine supplementation with vitamin B12 and to study the effect of a change from injection to oral B12 supplementation, we examined the relationship between cobalamin and methylmalonic acid in plasma from 67 patients on chronic hemodialysis, all in regular therapy with intramuscular cobalamin injections (1 mg) every third month. METHODS: Starting just before one cobalamin injection, blood samples were collected once a month during a nine-month withdrawal from regular cobalamin substitution to a final three-month period with cyanocobalamin tablets (1 mg) administered once daily. RESULTS: Plasma cobalamin was above the lower reference limit in all subjects, and from a peak value one month after the regular injection, the cobalamin concentration during the withdrawal period decreased to a level below the point of origin, followed by a significant rise after cyanocobalamin tablets. The methylmalonic acid concentrations were above the reference interval. In the withdrawal period, the concentrations significantly increased further, followed by a significant decrease after oral cyanocobalamin substitution. CONCLUSION: We demonstrated a within-patient inverse relationship between the concentrations of methylmalonic acid and cobalamin in plasma from these uremic patients. Despite the fact that only two of the patients developed subnormal plasma cobalamin values, we demonstrated a B12 depletion during the withdrawal period. Treatment with cyanocobalamin tablets once daily was found efficient, but the oral doses should possibly be increased. (+info)
Non-compressive myelopathy: clinical and radiological study.
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Fifty seven patients (42 males and 15 females) with non-compressive myelopathy were studied from 1997 to 1999. Acute transverse myelitis (ATM) was the commonest (31) followed by Vit B12 deficiency myelopathy (8), primary progressive multiple sclerosis (5), hereditary spastic paraplegia (3), tropical spastic paraplegia (2), subacute necrotising myelitis (1), radiation myelitis (1), syphilitic myelitis (1) and herpes zoster myelitis (1). 4 cases remained unclassified. In the ATM group, mean age was 30.35 years, antecedent event was observed in 41.9% case, 25 cases had symmetrical involvement and most of the cases had severe deficit at onset. CSF study carried out in 23 patients of ATM revealed rise in proteins (mean 147.95mg%, range 20-1200 mg/dL) and pleocytosis (mean 20.78/cumm, range 0-200 mm3). Oligoclonal band (OCB) was present in 28% of cases of ATM. The most common abnormality detected was a multisegment hyperintense lesion on T2W images, that occupied the central area on cross section. In 6 patients hyperintense signal was eccentric in location. MRI was normal in 4 cases of ATM. Thus ATM is the leading cause of non-compressive myelopathy. Clinical features combined with MRI findings are helpful in defining the cause of ATM. (+info)
Brain function in the elderly: role of vitamin B12 and folate.
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Vitamin B12 (cobalamin) deficiency associated neuropathy, originally called subacute combined degeneration, is particularly common in the elderly. The potential danger today is that with supplementation with folic acid of dietary staples such as flour, that the incidence of this disease could rise as folic acid, as opposed to natural folate (N5CH3HFGlu1), enters the cell and the metabolic cycle by a cobalamin independent pathway. This chapter briefly describes the clinical presentation of the disease, which unless treated will induce permanent CNS damage. The biochemical basis of the interrelationship between folate and cobalamin is the maintenance of two functions, nucleic acid synthesis and the methylation reactions. The latter is particularly important in the brain and relies especially on maintaining the concentration of S-adenosylmethionine (SAM) which, in turn, maintains the methylation reactions whose inhibition is considered to cause cobalamin deficiency associated neuropathy. SAM mediated methylation reactions are inhibited by its product S-adenosylhomocysteine (SAH). This occurs when cobalamin is deficient and, as a result, methionine synthase is inhibited causing a rise of both homocysteine and SAH. Other potential pathogenic processes related to the toxic effects of homocysteine are direct damage to the vascular endothelium and inhibition of N-methyl-D-aspartate receptors. (+info)