Relationship Between the Levels of Holotranscobalamin and Vitamin B<Subscript>12</Subscript> in Children

The purpose of this study was to evaluate the relationship between the plasma holoTC and serum vitamin B₁₂ in children and to identify a cutoff cobalamin values according to holoTC. One hundred and fifty-five children were enrolled into the study. All children were evaluated for hemoglobin, vitamin B₁₂, folate, ferritin and holoTC levels. Children were grouped as with low vitamin B₁₂ level (≤200 pg/mL, group I) and normal vitamin B₁₂ (>200 pg/mL, group II). Serum vitamin B₁₂, and holoTC levels were performed in each patient in the study. In 101 patients with low vitamin B₁₂ (group I) the mean holoTC was 21.74 ± 1.14 pmol/L. In 54 children with normal vitamin B₁₂ (group II) mean holoTC was 44.0 ± 2.7 pmol/L (p < 0.01). A ROC curve analysis was performed to delineate the optimum cut-off point for vitamin B₁₂ level and it was found to be 165 pg/mL with a sensitivity of 70% and specificity of 74%; the area under curve was 0.783 (p < 0.01). Our study displayed a positive correlation between vitamin B₁₂ and holoTC, and defined an optimum cutoff value for vitamin B₁₂ as 165 pg/mL. Further studies using the markers both MMA, tHcy and holoTC to confirm the findings are needed.     

The deoxyuridine suppression test in HIV-1 positive patients: the role of azydothymidine (AZT)

The deoxyuridine suppression test (dUST) was used to evaluate human immunodeficiency virus type 1 positive (HIV-1) patients with low serum levels of vitamin B₁₂ and/or low red cell folate and to assess any possible interferences of azydothymidine (AZT) in this test. The dUST was studied in 29 HIV-1 positive patients, 18 without low serum vitamin B₁₂ or low red cell folate and 11 with low serum vitamin B₁₂ (6 patients), low red cell folate (4 patients) and 1 case with both. The role of AZT was studied using different concentrations (0.2, 2.5 and 10 μM/ml) in 2 groups: 1 group of 5 patients with vitamin B₁₂ and/or folate deficiency and another group consisting of 13 healthy subjects. Methotrexate (MTX) (50 μg/ml) was added to induce a folate megaloblastic pattern in the latter group. Results of the dUST in the HIV-1 group without low levels of serum vitamin B₁₂ fell within the health-related reference interval values. A vitamin B₁₂ deficiency was only detected in 1 case in the HIV-1 group with low serum vitamin B₁₂, although a folate deficiency pattern was observed in the 4 patients with low red cell folate. In the healthy subjects AZT induced a dose-dependent decrease of the MTX-induced folate megaloblastic pattern. The pattern was also observed in the group of patients with vitamin B₁₂ or folate deficiency, although AZT did not entirely interfere with the dUST. The effect of AZT on the dUST was attributed to a decrease in the incorporation of the isotope in the absence of deoxyuridine. The dUST is useful in differentiating vitamin B₁₂ deficient patients from HIV-1 infected patients with low levels of serum vitamin B₁₂.     

The lymphocyte as a marker of past nutritional status: persistence of abnormal lymphocyte deoxyuridine (dU) suppression test and chromosomes in patients with past deficiency of folate and vitamin B12

In short-term suspension cultures of bone marrow cells or PHA-stimulated lymphocytes from normal subjects, non-radioactive deoxyuridine (dU) suppresses the incorporation of radioactive thymidine ([³H]TdR) or its analogue, [¹²⁵I]deoxyuridine ([¹²⁵I]Udr), into DNA. This normal suppression by deoxyuridine (dU) is impaired in both of these cell systems from patients with deficiency of folate or vitamin B₁₂, and corrected by the appropriate vitamin. Patients with megaloblastic anaemia due to deficiency of vitamin B₁₂ or folate were studied before and after treatment. When treatment had returned to normal the bone marrow morphology and the serum and red cell vitamin levels, then the dU suppression test and chromosomal changes in the bone marrow were also corrected. However, the dU suppression test and chromosomal changes remained abnormal in lymphocytes as long as 84 d after therapy. These abnormal lymphocyte dU suppression tests were corrected by the appropriate in vitro additions of folic acid, methylfolate and vitamin B₁₂, depending on the vitamin deficiency present before therapy. These studies suggest that an abnormal lymphocyte dU suppression test corrected by the appropriate vitamin in vitro, and characteristic chromosome abnormalities in lymphocytes, when these are absent in the bone marrow, indicate past deficiency of vitamin B₁₂ or folate. These changes can be used for retrospective diagnosis of these deficiencies in patients treated by ‘shotgun’ therapy. They further support the concepts that circulating unstimulated lymphocytes: (1) do not incorporate appreciable amounts of vitamin B₁₂ or folic acid; (2) reflect the vitamin status of the patient at the time the lymphocytes were generated; and (3) cannot replace bone marrow in dU suppression tests aimed at diagnosis of current marrow and other non-lymphocyte cell line nutrient status. These studies add to the evidence that selective nutrient deficiency may occur in one but not another cell line in the same person, and point to the need for more studies on factors affecting nutrient delivery, uptake, and utilization by various human cell lines. These studies also provide a new approach to evaluation of circulating lymphocyte age.     

Serum Ferritin,Vitamin B<Subscript>12</Subscript>, Folate,and Zinc Levels in Children Infected with <Emphasis Type="Italic">Helicobacter pylori</Emphasis>

We sought to explore the relationship between Helicobacter pylori infection and serum ferritin, vitamin B₁₂, folate, and zinc status among children. Fifty patients aged 5–18 years who underwent upper gastrointestinal endoscopy because of dyspeptic symptoms, were studied, prospectively. Patients were grouped as H. pylori positive (group 1, n=32) or H. pylori negative (group 2, n=18) by histopathologic examination and rapid urease test. Fasting serum ferritin, vitamin B₁₂, folate, and zinc levels of patients were measured. Both groups were indifferent according to age, gender, height standard deviation score (H_SDS), and weight standard deviation score (W_SDS). Serum ferritin levels were 33±26 and 50±46 ng/mL (P=.098), vitamin B₁₂ levels were 303±135 and 393±166 pg/mL (P=.042), folate levels were 9.64±3.2 and 9.61±2.8 ng/mL (P=.979), and zinc levels were 95±48 and 87±31 μg/dL (P=.538), in groups 1 and 2, respectively. Ferritin levels of 14 (43.8%) patients in group 1 and 6 (33.3%) patients in group 2 were below the normal range (P=.470). Serum vitamin B₁₂ levels of 9 children (28%) in group 1 and 2 children (11%) in group 2 were below the normal range (P=.287). The findings of the present study suggest that H. pylori infection has a negative effect on serum ferritin and vitamin B₁₂ levels in children. This negative effect on vitamin B₁₂ levels is rather marked in contrast to that on ferritin levels. H. pylori infection has no significant effect on serum folate or zinc levels among children.     

Elevated homocysteine levels indicate suboptimal folate status in pediatric sickle cell patients

We investigated whether pediatric patients with sickle cell disease (SCD) (9 + 4 years; 27 homozygous SCD [HbSS]; 19 sickle-C disease [HbSC]) have different folate status compared with age-, sex-, and race-matched normal hemoglobin (HbAA) controls (n = 20), and whether their folate status can be improved by folate supplementation. The patients were supplemented with vitamins B₆ and B₁₂ during one week and with folate during the following week. Circulating folate, homocysteine, vitamin B₆ and vitamin B₁₂ levels were measured at baseline (patients and controls), after one week and after two weeks (patients). The patients had similar folate, vitamin B₆, and vitamin B₁₂, but higher homocysteine levels compared with HbAA controls (12.7 + 4.5 vs. 10.9 + 3.5 μmol/l; P = 0.04). Vitamin B₆ and B₁₂ supplementation did not change their homocysteine levels, but folate supplementation caused a 53% reduction (to 5.7 + 1.6). We conclude that patients with SCD have adequate vitamin B₆ and B₁₂ status, but suboptimal folate status, leading to elevated plasma homocysteine levels. They may therefore benefit from folate supplementation to reduce their high risk for endothelial damage. Am. J. Hematol. 59:192–198, 1998. © 1998 Wiley-Liss, Inc.     

Randomized, placebo-controlled trial of intramuscular vitamin B12 for the treatment of hyperhomocysteinaemia in dialysis patients

Abstract Background: Plasma homocysteine is elevated in patients with end‐stage renal disease (ESRD) and is a risk factor for cardiovascular disease. Folic acid has been shown to partially reduce homocysteine levels in dialysis patients. It is not known whether vitamin B₁₂ reduces homocysteine independent of folic acid in patients who are not vitamin B₁₂ deficient. Aim: To determine whether 1 mg vitamin B₁₂ lowers homocysteine in stable, chronic, haemodialysis patients independent of folic acid. Methods: Twenty‐eight haemodialysis patients were randomized to receive three doses of 1 mg vitamin B₁₂ or 1 mL saline placebo in a double‐blind fashion at 1‐month intervals. Fasting plasma total homocysteine, folic acid, red‐cell folate, vitamin B₁₂ and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection. The study was powered to detect a 30% reduction in homocysteine over the 3 months. Results: Both the two groups were well matched with respect to total homocysteine levels, folic acid, red‐cell folate and vitamin B₁₂ levels. Serum vitamin B₁₂ levels were significantly higher in the treatment group compared to placebo (217.7 pmol/L; 95% confidence interval (CI) 103.0?332.5; P < 0.001) at the end of the trial but homocysteine levels were not significantly different (3.08 µmol/L; 95% CI ?4.44?10.61; P= 0.406). Conclusions: The administration of intramuscular vitamin B₁₂ over a 3‐month period does not result in any reduction of plasma homocysteine levels in haemo­dialysis patients independent of folate status, however reductions of <30% cannot be excluded by the present study. High‐dose folic acid remains the treatment of choice in reducing homocysteine, but whether this results in a reduction in cardiovascular events remains to be determined. (Intern Med J 2003; 33: 489?494)     

Correlations between the Deoxyuridine-Suppressed Value and Some Conventional Haematological Parameters in Patients with Folate or Vitamin B12 Deficiency

The correlations between the deoxyuridine-suppressed value and some conventional haematological parameters (Hb concentration, red cell count, MCV, total white cell count, red cell folate level and serum vitamin B₁₂ level) have been investigated in 40 patients with megaloblastic haemopoiesis due to folate or vitamin B₁₂ deficiency. The only statistically significant correlations found were (a) an inverse correlation between the deoxyuridine-suppressed value and the Hb level or red cell count in both the folate- and vitamin B₁₂-deficient groups and (b) a direct correlation between the deoxyuridine-suppressed value and MCV in the vitamin B₁₂-deficient group. The results indicated that the deoxyuridine-suppressed value was a better index of the magnitude of the disturbance in red cell production induced by folate or vitamin B₁₂ deficiency than either the red cell folate or serum vitamin B₁₂ levels.     

Hyperhomocysteinaemia and Risk of Thrombosis in Systemic Lupus Erythematosus Patients

Hyperhomocysteinaemia is strongly associated with increased relative risk of occlusive vascular disease, mainly of the carotid and coronary arteries. The aim of our study was to assess whether raised plasma homocysteine is a risk factor for thrombotic events in patients with systemic lupus erythematosus (SLE), a condition known to be associated with premature atherothrombotic complications. The study included 34 consecutive consenting SLE patients who were seen in the Rheumatology Unit of Al-Amiri hospital, one of the main teaching hospitals in Kuwait. Twenty consenting healthy subjects were included in the control group. Twenty-four patients were grouped as SLE without thrombosis and 10 had different types of thromboses. Vitamin B₁₂, folate, anticardiolipin antibodies (IgG and IgM), activated partial thromboplastin time (APTT) and total homocysteine level were measured for both patients and controls. A raised homocysteine concentration was defined as plasma homocysteine level above 9.4 mmol/l. Hyperhomocysteinaemia was found in 21 (61.8%) SLE patients. Low levels of folate and vitamin B₁₂ were significantly associated with high concentrations of plasma homocysteine (r = −0.35 and −0.39, respectively, P<0.01). SLE patients with elevated homocysteine concentration have a threefold increase in odds ratio of thrombotic events after adjusting for other risk factors (male sex, shortened APTT, treatment with prednisone, low folate and vitamin B₁₂ levels). We concluded that homocysteine is an independent risk factor for thrombosis in patients with SLE and is potentially modifiable. Received: 27 December 2001 / Accepted: 14 April 2002 Correspondence and offprint requests to: Dr I. H. Al-Salem, PO Box 16434, Al-Qadeseyah 35855, Kuwait. Tel: 965 2532025; Fax: 965 2666205; E-mail: driqbalham@hotmail.com     

Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study

Aims/hypothesis Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B₁₂, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years. Methods In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B₁₂, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years. Results Two-thirds of mothers had low vitamin B₁₂ (<150 pmol/l), 90% had high MMA (>0.26 μmol/l) and 30% had raised tHcy concentrations (>10 μmol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B₁₂ (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B₁₂ concentrations were the most insulin resistant. Conclusions/interpretation Low maternal vitamin B₁₂ and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Vitamin B12 level in peripheral arterial disease

Hyperhomocysteinemia is considered a risk factor for atherosclerosis. Methyltetrahydrofolate reductase (MTHFR) gene mutation and low level of plasma vitamin B₁₂ and folate could take part in the etiology of peripheral arterial disease (PAD). We examined whether plasma vitamin B₁₂ and folate levels and MTHFR-C677T polymorphism are associated with the risk of PAD. The study comprised 293 patients (107 females, 186 males, mean age of 66 ± SEM0.7 years) and 293 sex-matched control subjects (mean age of 62 ± SEM0.8 years). We also determined plasma lipid profile, hs-CRP, creatinine, vitamin B₁₂, folate and total homocysteine (tHcy) for all patients and controls. Odds ratios were non-significant for different genotypes of MTHFR-C677T polymorphism. There was a significant lower level of vitamin B₁₂ in PAD patients. 43 and 25 % of patient and control populations were in the lowest quartile of vitamin B₁₂ (<188 pmol/L), respectively. Plasma level of vitamin B₁₂ in the lowest quartile significantly increased tHcy level in PAD patients, and it was independent of plasma folate level. Low level of plasma vitamin B₁₂ was independently associated with hyperhomocysteinemia in PAD patients. The prevalence of the MTHFR-C677T mutation was not significantly different in patients with PAD compared with controls.     

Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects

Abstract. Objectives. Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. We explored possible determinants of plasma homocysteine and cysteine concentrations amongst middle-aged and elderly subjects. Design and subjects. Of 501 35–95-year-old randomly selected residents of Lund and Malmö, Sweden, 244 (49%; 131 men, 113 women) were investigated. Results. Total plasma homocysteine concentrations were higher in men than in women (mean ± SD: 13.9 ± 4.1 and 12.3 ± 4.1 μmol L^?1; P < 0.001), increased markedly with age (Spearman's p = 0.488; P < 0.001), and were correlated (P < 0.001) to concentrations of blood folate, serum vitamin B₁₂, and serum creatine (p = ?0.366, ?0.338, and 0.463). Users of multivitamins had lower homocysteine levels than nonusers [10.5 ± 3.3 μmol L^?1 (n = 31) and 13.5 ± 4.2 μmol L^?1 (n = 213), respectively; P < 0.001]. Total plasma cysteine concentrations also increased significantly with age and increasing serum creatinine, but were unrelated to gender, blood folate, serum vitamin B₁₂ and use of multivitamins. Conclusions. Age, gender, folate, serum vitamin B₁₂, serum creatinine and multivitamin usage are all important determinants of the plasma homocysteine concentration, whereas only age and serum creatinine are determinants of the plasma cysteine concentration. The age-related increase in homocysteine and cysteine may be linked to the age-related impairment of renal function, whereas the sex difference in plasma homocysteine may be because of the fact that more homocysteine is formed in men than in women in conjunction with creatine-creatinine synthesis.     

Crohn's disease and vitamin B12 metabolism

The concentrations of vitamin B₁₂, its analogs, and the haptocorrin and transcobalamin carriers in 21 patients suffering from Crohn's disease and a group of controls (20 adults) were measured. There were no significant differences in the mean values for vitamin B₁₂, total corrinoids (vitamin B₁₂ + analogs), or vitamin B₁₂ or total corrinoids bound to haptocorrin or transcobalamin of the Crohn's and control patients. There was a significant increase in the binding capacity of transcobalamin in the Crohn's patients compared to the controls (P<0.001), but there was no difference in the binding capacities of haptocorrin. The serum concentrations of the markers of vitamin B₁₂ status, homocysteine and methylmalonic acid, showed an increase (P<0.01) in homocysteine in the Crohn's disease patients, but no change in methylmalonic acid. As the hyperhomocysteinemia was associated with normal folate concentrations, there may have been a defect in the activation of the enzyme due to altered intracellular vitamin B₁₂ status.     

Genetic polymorphism of methylenetetrahydrofolate reductase G1793A,hyperhomocysteinemia, and folate deficiency correlate with ulcerative colitis in central China

Background and Aims: Methylenetetrahydrofolate reductase (MTHFR) encoding genes were associated with ulcerative colitis in Chinese in our previous study. We further studied association of a new polymorphism of MTHFR G1793A with ulcerative colitis and assessed relationship of this polymorphism with hyperhomocysteinemia (HHcy, ≥ 15 mmol/L) and deficiency of folate (≤ 7 nmol/L) and vitamin B₁₂ (≤ 150 pmol/L) in a cohort of patients with ulcerative colitis in central China. Methods: A total of 252 patients and 654 healthy controls were recruited. Polymorphism of MTHFR G1793A was examined using a polymerase chain reaction‐restriction fragment length polymorphism method. Plasma levels of homocysteine (Hcy), folate and vitamin B₁₂ were determined by enzymatic cycling assay and corpuscle immune chemiluminescence assay, respectively. Results: Frequencies of alleles and genotypes in MTHFR G1793A gene differed significantly between ulcerative colitis patients and the healthy controls (20.83% vs 10.47%, 95% confidence interval [CI]: 1.703–2.972, P = 0.0006; 40.48% vs 19.88%, 95% CI: 1.997–3.761, P = 0.0002, respectively). Plasma Hcy levels were higher and folate and vitamin B₁₂ concentrations were lower in the patients than in the healthy controls (21.72 ± 6.59 vs 12.47 ± 5.02, 95% CI: ?10.93–?7.58, P < 0.0001; 11.25 ± 6.19 vs 15.28 ± 7.72, 95% CI: 2.03–6.04; P < 0.001; 322.81 ± 128.47 vs 442.59 ± 129.36, 95% CI: 62.61–136.95, P < 0.0001, respectively). HHcy and folate deficiency were more prevalent in patients with ulcerative colitis (45.32% vs 26.17%, 95% CI: 1.285–4.378, P = 0.005; 30.68% vs 13.0%, 95% CI: 1.416–6.197, P = 0.003, respectively). Conclusions: MTHFR G1793A gene polymorphism, HHcy, folate deficiency and low vitamin B₁₂ concentration were associated with ulcerative colitis in central China. Our findings demonstrate that the Hcy‐related gene and metabolites are involved in pathogenesis of ulcerative colitis.     

Serum vitamin B12 and transcobalamin levels in early HIV disease

A cohort of asymptomatic human immunodeficiency virus (HIV) seropositive patients was followed over a 2 1/2-year period, to establish changes in serum vitamin B₁₂ (B₁₂) concentrations. Serum B₁₂, CD4 count, and clinical progression to acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) were measured. The unsaturated B12 binding capacities of the transcobalamins were also determined at the start of the study and compared to those from a homosexual HIV seronegative control group. The geometric mean of serum B₁₂ in 218 asymptomatic HIV seropositive patients was significantly lower than of a homosexual HIV seronegative control group (P = 0.02) and the unsaturated B₁₂ binding capacities of transcobalamins I and II were significantly higher in the asymptomatic patients compared with the same control group (P < 0.03, P < 0.0001, respectively). Fifty-nine of the asymptomatic HIV seropositive patients were followed over a 2 1/2-year period during which most had falling serum B₁₂ levels (64%). Twelve patients progressed clinically to ARC or AIDS, of which nine had repeat serum B₁₂ estimation prior to progression. All nine patients had or developed falling serum B₁₂ levels without any evidence of an HIV-related bowel disorder. All patients progressing had falling CD4 counts. Subnormal serum B₁₂ levels are common in HIV disease and occur at an early stage. B₁₂ levels fall in most patients with time and may help predict those patients whose disease will progress the most rapidly. © 1994 Wiley-Liss, Inc.     

Abnormal vitamin b6 status in rheumatoid cachexia association with spontaneous tumor necrosis factor α production and markers of inflammation

Objective. To compare vitamin B₆ levels in rheumatoid arthritis (RA) patients and healthy control subjects. Methods. We measured levels of vitamin B₆ in 23 adults with well-controlled RA, and in 23 healthy control subjects matched for age, sex, race, and weight. Results. Although plasma folate and vitamin B₁₂ concentrations and erythrocyte B₆ activity coefficients were similar in the patients and controls, plasma levels of pyridoxal-5′-phosphate (PLP) were lower in the RA patient group (mean ± SD 46.1 ± 48.1 versus 69.3 ± 58.4 nmoles/liter; P ≤ 0.004). In multivariate analyses, PLP was inversely associated with tumor necrosis factor α (TNFα) production by peripheral blood mononuclear cells (PBMC) (P < 0.001), after adjustment for age, pain score, erythrocyte sedimentation rate, and use of nonsteroidal antiinflammatory drugs. Conclusion. PLP levels are reduced in patients with RA. This reduction is associated with TNFα production by PBMC.     

Elevated serum homocysteine as a predictor for vitamin B12 or folate deficiency

Abstract: Tissue deficiency of vitamin B₁₂ and folate results in an increase in serum homocysteine (sHcy). We have measured sHcy in patients with reduced serum vitamin B₁₂ and/or red cell folate (RCF) to determine its usefulness as a discriminant for the diagnostic interpretation of reduced vitamin levels. Of 3846 patients who had serum vitamin B₁₂ and RCF assayed, 335 (9%) had reduced vitamin levels. Multivariate analysis showed a significant association between sHcy and serum creatinine (p = 0.0001), positive intrinsic factor (IF) antibody or neutrophil hypersegmentation (NHS) (p = 0.001), increased MCV (p = 0.014) and low RCF (p = 0.025) but no relationship with the level of serum vitamin B₁₂ or haemoglobin. After censoring the patients with renal impairment (n = 54), the distribution of the remaining 72 patients with elevated sHcy was 37/151 (25%) with low serum vitamin B₁₂ with or without low RCF and 35/130 (27%) with low RCF alone. sHcy correctly identified response to vitamin therapy in 33/35 (94%) patients who had adequate parameters to assess response. The positive predictive values of IF antibody/NHS, macrocytosis and/or low RCF for elevated sHcy were 100% and 34% respectively. Twenty-four percent of patients with a low serum vitamin B₁₂ and elevated sHcy had no abnormal haematologic parameters as determined by the routine laboratory staff. These data suggest that the usefulness of measuring sHcy in a routine diagnostic setting is limited and a careful review of the peripheral blood for macrocytosis and NHS plus determination of RCF may be a more cost-effective process than sHcy assay in most instances to determine the presence of tissue deficiency.     

The Excretion of Methylmalonic Acid and Succinic Acid in Vitamin B12 and Folate Deficiency

The excretion of methylmalonic acid (MMA) and of succinic acid was measured in 18 control subjects and in 58 patients with vitamin B₁₂ and/or folate deficiency. The 18 control subjects excreted from 0.0 to 3·5 mg. MMA in 24 hours. MMA excretion was raised in 27 of 41 patients (Group I) with conditions associated primarily with B₁₂ deficiency. These 27 patients included 15 patients with Addisonian pernicious anaemia, two patients following total gastrectomy, two patients with anatomical lesions of the small intestine and eight patients following partial gastrectomy, whereas MMA excretion was normal in four patients with atrophic gastritis and in a further 10 patients following partial gastrectomy. In Group I, MMA excretion was raised in all but one of the patients with serum B₁₂ levels less than 100 pg./ml. due to uncomplicated B₁₂ deficiency, but was invariably normal in patients with borderline serum B₁₂ levels (from 100 to 160 pg./ml.). In the patients with serum B₁₂ levels less than 100 pg./ml., with associated iron and/or folate deficiency, the excretion of MMA tended to be lower than in patients with uncomplicated B₁₂ deficiency, and was often normal. MMA excretion was slightly raised in one of 17 patients with megaloblastic anaemia, primarily due to folate deficiency (Group II), although six of them had serum B₁₂ levels less than 100 pg./ml. The patient with a raised MMA excretion needed B₁₂ therapy for a full haematological remission. The 18 control subjects excreted from 2.0 to 12.5 mg. succinic acid in 24 hours. Succinic acid excretion was subnormal in nine and raised in five patients in Group I. These 14 patients all had serum B₁₂ levels less than 100 pg./ml. None of the Group II patients excreted subnormal amounts of succinic acid but three, including two patients with serum B₁₂ levels less than 100 pg./ml., excreted raised amounts of succinic acid.     

Relationship of homocysteine and homocysteine‐related vitamins to bone mineral density in Japanese patients with type 2 diabetes

Aims/Introduction: To estimate nutritional risk factors for osteoporosis in patients with type 2 diabetes, bone mineral density, homocysteine level, and intakes and levels of Hcy‐related vitamins including folate, vitamin B₆ and vitamin B₁₂ were analyzed in a cross‐sectional study. Materials and Methods: Lumbar spine and femoral neck bone mineral density, serum concentrations of vitamin B₆, vitamin B₁₂, and folate and plasma homocysteine levels were measured in 125 Japanese patients with type 2 diabetes. Nutrient intake values were evaluated using a food frequency questionnaire. Results: Homocysteine was inversely correlated with bone mineral density, and with both dietary intake and serum concentration of folate. Intake of green vegetables was correlated with intake and level of folate and homocysteine levels. When the population was analyzed across the quartiles, bone mineral density, serum folate concentration, folate intake and intake of green vegetables were lowest in the highest homocysteine group. Conclusions: In patients with type 2 diabetes, the nutritional status of folate might affect the homocysteine level, a putative risk factor for osteoporosis. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00088.x, 2011)     

Vitamin B12 Metabolism in Myelomatosis

In 38 patients with myelomatosis the serum cobalamin varied from 34 pmol/l to 404 pmol/l, median 181.5 pmol/l, which is significantly lower than the levels in 22 control persons with range 173–535 pmol/l, median 265 pmol/l. In spite of low serum cobalamin no symptoms of vitamin B₁₂ deficiency could be demonstrated in any of the patients, except for the one patient who had a serum cobalamin of 34 pmol/l. Mean values for Hb, MCV, PCV, serum lactate-dehydrogenase, adjusted red cell folate and nucleated neutrophil count were similar in a group of patients with a serum cobalamin below 160 pmol/l and a group of patients with higher serum cobalamin values. The decrease in serum cobalamin is due in part to a reduction in the major cobalamin binder (TC-I) in serum. Measuring serum cobalamin in relationship to gastric acid secretion, we found a significantly higher frequency of hypo- and achlorhydria in patients with serum cobalamin below 160 pmol/l although the intestinal absorption of vitamin B₁₂ was normal by a Schilling test. Although our finding of low saturation of TC-I in serum seems to demonstrate decreased vitamin B₁₂ content in the body in myelomatosis, the lack of evidence for a functional vitamin B₁₂ deficiency speaks against giving a supplement to patients with myelomatosis.     

Vitamin B12 and vitamin B6 supplementation is needed among adults with phenylketonuria (PKU)

Summary Phenylketonuria (PKU) is caused by an autosomal recessive deficiency of the enzyme phelnylalanine hydroxylase leading to a failure to convert phenylalanine to tyrosine. To avoid irreversible neurological damage because of increased phenylalanine, treatment is instituted rapidly after birth. We examined 31 adult PKU patients living on a less protein-restricted diet. Theoretically, these PKU patients had an increased risk of developing vitamin B₁₂ and B₆ deficiency because of a limited intake of animal products. Besides laboratory tests (n = 31) we obtained clinical information (n = 30) and detailed information on food consumption (n = 28). Three-quarters of the patients had early biochemical signs of vitamin B₁₂ deficiency. In spite of a normal folate status, 9 (29%) had a plasma homocysteine above 12 μmol/L. In accord with these findings, the food questionnaires indicated that 11 (39%) patients received less than the recommended daily vitamin B₁₂, and 20 (71%) received less vitamin B₆ than recommended. A significant association was found between reduced vitamin B₁₂ intake and both reduced serum cobalamins (p = 0.04) and reduced serum transcobalamin saturation (p = 0.03). Eleven patients took a vitamin pill daily, and these patients had a significantly lower plasma homocysteine compared to the rest. The present study suggests that adult PKU patients were at increased risk of developing vitamin B₁₂ deficiency, and their intake of vitamin B₆ was below the recommended daily intake. In conclusion PKU patients need continuing dietary guidance throughout adult life, and considering the risks, costs and potential benefits, daily vitamin supplementation seems justified in these patients.