High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia

2007 ◽  
Vol 293 (1) ◽  
pp. H860-H865 ◽  
Author(s):  
E. Zittan ◽  
M. Preis ◽  
I. Asmir ◽  
A. Cassel ◽  
N. Lindenfeld ◽  
...  
Keyword(s):  
Folic Acid ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vitamin B12 ◽  
Acid Treatment ◽  
Vitamin B12 Deficiency ◽  
Mthfr C677t ◽  
C677t Mutation ◽  
B12 Deficiency ◽  
Asymptomatic Individuals

The aim of this study was to examine the association of homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and vitamin B12 deficiency in 360 asymptomatic individuals and to investigate forearm endothelial function in C677T homozygotes. MTHFR C677T mutation and levels of vitamin B12, folic acid, and homocysteine were measured in study participants. Frequency of homozygosity for the C677T mutation was 67/360 (18.6%). Homocysteine levels were elevated in homozygous compared with heterozygous subjects or those without the mutation (20.6 ± 18.8 vs. 9.4 ± 3.2 μmol/l; P < 0.0001). The number of subjects with vitamin B12 deficiency (<150 pmol/l) was significantly higher among the homozygote than the heterozygote subjects or subjects without mutation [20/67 (29.8%) vs. 27/293 (9.2%); P < 0.0001]. Homozygote subjects had 4.2 times higher probability of having B12 deficiency (95% confidence interval = 2.1–8.3). Forearm endothelial function was assessed in 33 homozygote and 12 control subjects. Abnormal endothelial function was observed in homozygous subjects and was worse in homozygote subjects with vitamin B12 deficiency. Endothelial function was normalized after B12 and folic acid treatment. We found that homozygosity for the C677T mutation is strongly associated with B12 deficiency. Coexistence of homozygosity for the C677T mutation and B12 deficiency is associated with endothelial dysfunction and can be corrected with vitamin B12 and folic acid treatment.

C677T Methylenetetrahydrofolate Reductase and Plasma Homocysteine Levels among Thai Vegans and Omnivores

2013 ◽  
Vol 83 (2) ◽  
pp. 86-91 ◽  
Author(s):  
Saowanee Kajanachumpol ◽  
Kalayanee Atamasirikul ◽  
Phieuvit Tantibhedhyangkul
Keyword(s):  
Vitamin B12 ◽  
Methylenetetrahydrofolate Reductase ◽  
Vitamin B12 Deficiency ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Serum Folate ◽  
Geometric Means ◽  
C677t Mutation ◽  
B12 Deficiency ◽  
Mthfr Mutation

Hyperhomocysteinemia among vegetarians and vegans is caused mostly by vitamin B12 deficiency. A C-to-T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene results in a thermolabile MTHFR, which may affect homocysteine (Hcy) levels. The importance of this gene mutation among populations depends on the T allele frequency. Blood Hcy, vitamin B12, folate, vitamin B6, and MTHFR C677T mutation status were determined in 109 vegans and 86 omnivores aged 30 - 50 years. The vegans had significantly higher Hcy levels than the omnivores, geometric means (95 % CI) 19.2 (17.0 - 21.7) µmol/L vs. 8.53 (8.12 - 8.95) µmol/L, p < 0.001. A C-to-T mutation in the vegans increased plasma Hcy, albeit insignificantly; geometric means 18.2 µmol/L, 20.4 µmol/L, and 30.0 µmol/L respectively in CC, CT, and TT MTHFR genotypes. There was also a significant decrease in serum folate; geometric means 12.1 ng/mL, 9.33 ng/mL, and 7.20 ng/mL respectively, in the CC, CT, and TT mutants, p = 0.006, and particularly, in the TT mutant compared with the CC wild type, 7.20 ng/mL vs. 12.1 ng/mL, p = 0.023. These findings were not seen in the omnivores. It was concluded that hyperhomocysteinemia is prevalent among Thai vegans due to vitamin B12 deficiency. C-to-T MTHFR mutation contributes only modestly to the hyperhomocysteinemia.

scholarly journals Prevalence of Iron, Folic Acid and Vitamin B12 Deficiency in Patients with Thalassemia Minor

2013 ◽  
Vol 7 (4) ◽  
pp. 83 ◽  
Author(s):  
Suheyl Asma ◽  
Cigdem Gereklioglu ◽  
Ahmet Erdogan ◽  
Mahmut Yeral ◽  
Mutlu Kasar ◽  
...  
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Thalassemia Minor ◽  
B12 Deficiency ◽  
Iron Folic Acid

Brief Report: Observations on Conjugated and Unconjugated Blood Folate Levels in Megaloblastic Anemia and the Effects of Vitamin B12

Blood ◽  
1965 ◽  
Vol 26 (3) ◽  
pp. 354-359 ◽  
Author(s):  
K. N. JEEJEEBHOY ◽  
S. M. PATHARE ◽  
J. M. NORONHA
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Cellular Level ◽  
B12 Deficiency

Abstract Vitamin B12 deficiency was associated with a rise in unconjugated folates and marked depletion of intracellular conjugated folates. The changes could be reversed by giving vitamin B12. These results probably indicate a way by which vitamin B12 and folic acid are interrelated at the cellular level.

The Effect of Vitamin B12 Deficiency on Methylfolate Metabolism and Pteroylpolyglutamate Synthesis in Human Cells

1974 ◽  
Vol 47 (6) ◽  
pp. 617-630
Author(s):  
A. Lavoie ◽  
E. Tripp ◽  
A. V. Hoffbrand
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Direct Effect ◽  
Vitamin B12 Deficiency ◽  
Pernicious Anaemia ◽  
Normal Subjects ◽  
Normal Cells ◽  
Methyl Group ◽  
Consistent Effect ◽  
B12 Deficiency

1. The uptake of 14C from [methyl-14C]methyItetrahydrofolate was significantly reduced in the phytohaemagglutinin (PHA)-stimulated lymphocytes from nine patients with untreated pernicious anaemia compared with the uptake in seven normal subjects. 2. The uptake of 14C from [14C]methyltetrahydrofolate by the lymphocytes from seven of the patients with pernicious anaemia was consistently increased by addition of vitamin B12in vitro. 3. The proportion of 14C taken up from [14C]methyltetrahydrofolate transferred to non-folate compounds was found to be significantly reduced in the PHA-stimulated lymphocytes from nine patients with untreated pernicious anaemia compared with the proportion transferred in the PHA-stimulated lymphocytes from seven normal subjects. Addition of vitamin B12in vitro consistently increased the transfer in vitamin B12-deficient cells but had no consistent effect in normal cells. 4. Normal and vitamin B12-deficient PHA-stimulated lymphocytes took up [3H]folic acid and after 72 h incubation converted this largely into pteroylpolyglutamate forms. 5. The proportion of labelled lymphocyte folate as pteroylpolyglutamate after incubation with [3H]folic acid was the same in vitamin B12-deficient as in normal lymphocytes and the proportion of pteroylpolyglutamates formed in vitamin B12-deficient lymphocytes was unaffected by addition of vitamin B12in vitro. 6. No radioactivity could be decteted in pteroylpolyglutamates after incubating normal PHA-stimulated lymphocytes with [14C]methyltetrahydrofolate for 72 h, suggesting that pteroylpolyglutamate forms of folate cannot be made directly from methyltetrahydrofolate. 7. These results are consistent with the ‘methyltetrahydrofolate trap’ hypothesis in vitamin B12 deficiency. It is suggested that reduced synthesis of pteroylpolyglutamates reported by others in vitamin B12-deficient cells may be secondary to the failure of removal of the methyl group from methyltetrahydrofolate rather than to a direct effect of vitamin B12 deficiency on the enzyme responsible for pteroylpolyglutamate synthesis. 8. Reduced entry of methyltetrahydrofolate into vitamin B12-deficient cells may be secondary to failure of conversion of this compound into tetrahydrofolate.

scholarly journals Differentiation between Vitamin B12—deficient and Folic Acid—deficient Megaloblastic Anemias with C14—Histidine

Blood ◽  
1963 ◽  
Vol 21 (4) ◽  
pp. 447-461 ◽  
Author(s):  
MATHEWS B. FISH ◽  
MYRON POLLYCOVE ◽  
THOMAS V. FEICHTMEIR
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Specific Activity ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Intermediary Metabolism ◽  
Folic Acid Deficiency ◽  
Acid Deficiency ◽  
B12 Deficiency

Abstract Intermediary metabolism of the monocarbon pool and histidine in normal subjects and patients with megaloblastic anemia was studied by continuous measurement of pulmonary excretion of C14O2 and urinary excretion of C14 after injection of L-histidine-2(ring)-C14. Cumulative pulmonary and renal excretion of C14 for 1 month by two normal subjects approximates 45 per cent of the amount injected. Within 4 months after injection of the dose used in this study, the resultant average tissue radiation decreases below the average natural terrestrial and cosmic radiation level. Simultaneous determination of two parameters, (1) cumulative 1-hour pulmonary C14 excretion and (2) the time of occurrence of maximum C14O2specific activity (Tmax), may permit rapid and unequivocal differentiation between folic acid deficiency and vitamin B12 deficiency in the pathogenesis of megaloblastic anemia. Folio acid deficiency results in marked diminution of pulmonary C14 excretion (approximately 0.1 per cent of injection C14 in 1 hour) and marked prolongation of C14O2-specific activity Tmax (approximately 3 hours), while both parameters are normal (approximately 1 per cent and less than 1 hour, respectively) in patients with vitamin B12 deficiency and megaloblastic anemia. Measurement during periods of reticulocyte response to either folio acid or vitamin B12 demonstrate normal C14O2-specific activity Tmax but decreased pulmonary C14 excretion. These observations suggest that prolongation of C14O2-specific activity Tmax is a sensitive index of folic acid deficiency or block and that if Tmax is normal, pulmonary C14 excretion is a sensitive index of the relative partition of the active monocarbon pool between pathways for oxidation and pathways for nucleic acid synthesis. This type of breath analysis seems to provide a quantitative dynamic representation of metabolic function which may be particularly useful in differentiating between the alterations of intermediary metabolism that occur in patients with folic acid-deficient megaloblastic anemia and in patients with vitamin B12-deficient megaloblastic anemia.

scholarly journals Effect of vitamin B12 and folic acid deficiencies on neutrophil function

Blood ◽  
1976 ◽  
Vol 47 (5) ◽  
pp. 801-805 ◽  
Author(s):  
SS Kaplan ◽  
RE Basford
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Cell Function ◽  
Vitamin B12 Deficiency ◽  
Folic Acid Deficiency ◽  
Specific Therapy ◽  
Bacterial Killing ◽  
Leukocyte Function ◽  
Acid Deficiency ◽  
B12 Deficiency

Abstract Morphological and quantitative neutrophil abnormalities are common in the megaloblastic anemias of vitamin B12 and folic acid deficiency. Little is known, however, about the role of these vitamins in normal leukocyte function. Seven patients with megaloblastic bone marrows, four with vitamin B12 deficiency and three with folic acid deficiency, were studied to determine the effect, if any, of these deficiencies on leukocyte function. Phagocytosis of staphylococci, hexose monophosphate shunt activation with phagocytosis, and microbicidal capacity against Staphylococcus aureus were determined prior to the institution of specific therapy. In two instances, these studies were repeated following treatment. There was no impairment of phagocytosis per se, and resting metabolism was not significantly decreased. With phagocytosis, however, metabolic activation was decreased to 35%-36% of control values in the leukocytes of patients with vitamin B12 deficiency but not in the leukocytes of patients with folic acid deficiency. Bacterial killing was slightly decreased in vitamin B12 but not in folic acid deficiency. These abnormalities of function were reversed after specific therapy. These findings suggested a specific role for vitamin B12 in the production of intermediates necessary for normal cell function.

Vitamin B12 and folic acid associated megaloblastic anemia: Could it mislead the diagnosis of breast cancer?

2019 ◽  
Vol 89 (5-6) ◽  
pp. 255-260
Author(s):  
Inanc Karakoyun ◽  
Can Duman ◽  
Fatma Demet Arslan ◽  
Anil Baysoy ◽  
Banu Isbilen Basok
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Normal Group ◽  
Ca 125 ◽  
Folic Acid Deficiency ◽  
Acid Deficiency ◽  
B12 Deficiency

Abstract. CA 15-3 is a tumor-associated antigen and is overexpressed in breast tumors, and may also be high in some other non-cancerous conditions. The aim of this study was to investigate the effect of megaloblastic anemia due to vitamin B12 or folic acid deficiency on the levels of tumor markers. Five-year patient data were retrospectively analyzed. The associations between megaloblastic anemia due to vitamin B12 deficiency and CA 15-3, CA 125, CA 19-9, CEA, and AFP levels were analyzed. Furthermore, association between CA 15-3 level and megaloblastic anemia due to folic acid deficiency was evaluated. Median CA 15-3 level was 38.1 U/mL in the group with megaloblastic anemia due to vitamin B12 deficiency(n = 15), 46.7 U/mL in the group with megaloblastic anemia related to folic acid deficiency (n = 3), and 17.8 U/mL in the normal group(n = 1724). CA 15-3 levels were significantly higher among patients with vitamin B12- and folic acid-associated megaloblastic anemia compared to the normal group (p = 0.001 and p = 0.005, respectively). Megaloblastic anemia due to vitamin B12 deficiency was not associated with any significant differences in CA 125, CA 19-9, CEA, or AFP levels compared to the normal group (p = 0.777, p = 0.327, p = 0.577, and p = 0.197, respectively). The numbers of anemic and normal subjects compared in these tests were 12 vs. 1501, 17 vs. 1827, 4 vs. 897, and 8 vs. 1041, respectively. In conclusion, megaloblastic anemia results in ineffective erythropoiesis, and increased levels of CA 15-3 may be associated with this issue. Clinicians should take this into account when evaluating for a pre-diagnosis of breast cancer.

Hyperhomocysteinaemia, low folate concentrations and MTHFR C677T mutation in abdominal aortic aneurysm

VASA ◽  
2014 ◽  
Vol 43 (3) ◽  
pp. 181-188 ◽  
Author(s):  
Hui Cao ◽  
Xinhua Hu ◽  
Qiang Zhang ◽  
Jun Li ◽  
Bing Liu ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Folic Acid ◽  
Aortic Aneurysm ◽  
Vitamin B12 ◽  
Gene Mutation ◽  
Plasma Levels ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Abdominal Aortic ◽  
C677t Mutation

Background: Homocysteine (Hcy) has been implicated in abdominal aortic aneurysm (AAA). However, the association of Hcy, vitamin B12, and folate in patients with AAA has not been studied in China. This study was conducted with the aim to evaluate the relationship of vitamin B12, folic acid, and Hcy levels in AAA. Patients and methods: 463 patients who had AAA were included in this study. 463 control subjects were age- and sex-matched with the patients. In all of the subjects, we evaluated total plasma levels Hcy, vitamin B12, folic acid and the distribution of the C677T methylenetetrahydrofolate reductase (MTHFR) gene mutation. Results: The mean plasma Hcy levels were significantly higher in patients with AAA compared with controls (18.37 ± 6.97 vs. 12.89 ± 4.08 μmol/L, P < 0.001). The frequency of homozygous (TT) genotype in MTHFR C677T mutation was significantly higher in patients with AAA than that in control subjects (19.4 % vs. 11.9 %, P = 0.002). The fasting Hcy correlated negatively with folate (A r = - 0.311, P < 0.01; Control: r = - 0.348, P < 0.01). The aneurysm size was significantly greater (P < 0.001) in patients with hyperhomocysteinemia than that in patients with normal Hcy plasma levels. The size of the AAA had a linear correlation with the plasma Hcy level (r = 0.286; P< 0.001). Conclusions: Serum folate deficiency and hyperhomocysteinemia were associated with an increased risk of AAA in Northeast China. The homozygous (TT) genotype of MTHFR gene mutation may be a crucial hereditary risk factor in AAA.

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