B12-deficient Subjects Research Articles

Etiology and treatment response of macrocytic anemia among patients admitted at a tertiary care setup: A prospective study

Abstract Background: Macrocytic anemia is a prevalent hematologic disorder characterized by the presence of larger than normal red blood cells in the peripheral blood. Overall, about 40% of patients also have associated anemia, macrocytosis often precedes anemia, it may be the early sign of Vitamin B12 deficiency, and mild macrocytic anemia is maintained for a long period before a rapid worsening occurs. Objective: The objective of this study was to investigate the etiology and treatment response of macrocytic anemia among patients admitted at a tertiary care setup. Materials and Methods: Adult patients admitted at the facility having macrocytic anemia were included and their demographic, clinical history, and physical examination were noted. All patients were investigated for peripheral blood smear, complete blood count, liver function test, Vitamin B12, folate, and thyroid profile. Bone marrow examination and upper gastrointestinal endoscopy were done among Vitamin B12 deficient subjects. Results: At baseline, severe anemia was noted in 31.48% of patients, and moderate anemia was noted in 68.51%. Bilirubin was raised in 51.85% of patients. The etiological profile suggested the majority of the cases were due to nutritional causes (22.23%), followed by 20.37% (n = 11) cases of drug-induced and 16.66% (n = 9) cases owing to chronic alcoholism. The mean baseline hemoglobin was 8.83, which raised to 10.92 after 6 months of treatment (P < 0.001). Mean corpuscular volume at baseline was 108.85 which reduced to 97.32 after treatment of 6 months (P < 0.001). About 18.52% of patients were deficient in only Vitamin B12, 35.17% in only folate, and 18.52% in both Vitamin B12 and folate. No significant association was observed between deficiency and severity of anemia (P = 0.642). Conclusion: Macrocytic anemia poses a significant health burden among patients admitted to tertiary care facilities. Understanding the diverse etiological factors and treatment responses is crucial for effective management and improved patient outcomes.

There is a positive association between vitamin B12 deficiency and serum total cholesterol in Iranian type 2 diabetic patients on Metformin

Abstract Introduction Considering the low level of vitamin B12 in diabetic patients on Metformin and also the importance of this vitamin in lipid metabolism , the aim of the present study was assessing the possible relationship between vitamin B 12 deficiency, lipid profile and atherogenic indices in Iranian diabetic patients. Method In the present cross-sectional study, a sample of 200 patients with type 2 diabetes was selected. Serum level of lipid profile was measured using enzymatic colorimetric method. LDL-C was calculated by Friedewald equation and atherogenic indices including total cholesterol to HDL-C and Log Triglyceride to HDL-C ratio were calculated. Serum level of vitamin B 12 was measured photometrically using commercial kit. Results The prevalence of vitamin B12 deficiency was about 14%. There was a significant difference between normal participants and vitamin B12 deficient subjects in the case of total cholesterol (P = 0.04). The results of the regression analysis showed that in adjusted model, there was significant association between total cholesterol and vitamin B12 deficiency (OR: 16.46 [95% CI: 0.27, 33.19], P = 0.04). Conclusion The results of the present study showed the relatively high prevalence of the vitamin B12 deficiency in type 2 diabetic patients who were on Metformin. Moreover, there was a significant association between vitamin B12 deficiency and total cholesterol level in diabetic patients. Further studies with larger sample size and considering dietary information and duration of Metformin consumption are needed to confirm these preliminary results.

Study of vitamin B12 status and the consequential clinico-hematological profile in healthy vegetarian population in Nepal

Background: A strict vegetarian diet has been associated with an increased risk of vitamin B12 deficiency. Clinical manifestations of cobalamin deficiency are hematologic and neurological symptoms. The purpose of this study was to determine the prevalence of vitamin B12 deficiency in healthy vegetarian population and to study the clinical and hematological profile of vitamin B12 deficient subjects.Methods: A community based cross-sectional observational study was conducted through preplanned camps in Kathmandu Nepal. 166 vegetarian people were investigated for serum vitamin B12 level and their hematological profile was done. They were examined for neurological manifestation of vitamin B12 deficiency.Results: The mean serum vitamin B12 level of the vegetarian in this study was 271.34 ±241.74 pg/ml (mean ± SD)., 53.6 % had serum vitamin B12 deficiency. 56.5 % of male and 47.1 % of female had vitamin B12 deficiency. The risk of vitamin B12 deficiency is more in males than females with odds ratio 1.201 (CI=95%) which is not statistically significant with p-value 0.312. There was no significant difference in vitamin B12 level in different age group.The study population had mean hemoglobin of 13.12 ± 1.72 gm/dl. Anemia was present in 34.9 % of study population. 33.9 % of male and 37.3 % of female had anemia. There was no significant difference in anemia in male and female vegetarian (p-value 0.72). 40% of patient who had vitamin B12 deficiency had anemia.A significant low hemoglobin level and higher MCV were found as level of serum vitamin B12 decreased. Only one patient had macrocytic anemia.There were few symptoms but not specific to vitamin B12 deficiency.Conclusion: The result of present study show that prevalence of vitamin B12 deficiency among healthy vegetarian was 53.6% with higher prevalence in male and elder age group.Prevalence of anemia was 34.9% in this study with elderly group and females being more affected.There was significant correlation between vitamin B12 and hemoglobin level and significant negative correlation with MCV. Although, not significant, leucocytes count, lymphocyte count and platelets were low in vitamin B12 deficient population.Few clinical features were present in vitamin B12 deficient subjects but neurological features specific to vitamin B12 deficiency were not seen.

Status of Vitamin B12 Deficiency in the Elderly Chinese Community People

This study was aimed to investigate the vitamin B12 deficiency prevalence and symptoms in elderly people lived in a community of Shanghai, China. A total number of 962 elderly people resided in Shanghai community were recruited in the present study. They were 60 years and older, and the average age was 76.38 ± 13.68 years old. Information on previous and present diseases, currently prescribed and over-the-counter medication, and the presence or absence of symptoms relating to vitamin B12 deficiency were obtained by questionnaire. The levels of serum vitamin B12, folate and homocysteine (Hcy) were estimated. The patients with vitamin B12 deficiency were screened. The results of symptoms and positive signs of neurological examination were compared between subjects with or without vitamin B12 deficiency. The results showed that vitamin B12 deficiency was found in 130 persons (13.53% of the total subjects), with an increase in incidence with aging, only 10% of the vitamin B12 deficient subjects had megaloblastic anemia. The reported symptoms of vitamin B12 deficient subjects included fatigue, memory decline, dizziness, unsteadily walking in the darkness and hypopallesthesia. In conclusion, vitamin B12 deficiency was remarkably common in Chinese elderly people, with various and atypical clinical manifestations, and the neurological symptoms were more common than those of megaloblastic anemia.

Low vitamin B12 status and less response to vitamin B12 treatment in Chilean B12‐deficient elderly with high serum folate (135.8)

Few data are available on the relationship between folate and B12 status in B12 deficient, but asymptomatic, free-living populations. The objective was to determine the effect of a single i.m. dose of 10,000 µg cbl on B12 status in B12 deficient subjects with high (>45.3 nmol/L) and normal (蠄45.3 nmol/L) serum folate. 51 elderly participants (73 ± 2.5y, 49% women) with sB12 <148 pmol/L received treatment. sB12, tHcy, MMA, holo-TC and folate status biomarkers were assessed 4 mo after treatment. B12 status was defined based on Fedosov’s criterion: w=log_10 [(holoTC*sB12)/(MMA*tHcy)-age factor)]. At baseline (Fig 1), subjects with high sfolate (n=14) presented low B12 status (w= -3.3 ± 0.2), as compared to subjects with normal folate levels (n=37, w= -2.9 ± 0.5) (p<0.001). B12 status improved in both groups after treatment (p<0.001). However, subjects with high folate status at baseline remained severely deficient (w= -2.7 ± 0.7). On the other hand, participants with normal folate values at baseline were classified as moderately deficient (w= -1.8 ± 1.1) after treatment. B12 deficiency, as defined by Fedosov’s criteria, was highly prevalent both at baseline and after treatment. Chilean B12 deficient older people with high sfolate presented low B12 status and less response to B12 treatment as compared to those B12 deficient with normal folate status. Figure 1. Vitamin B12 status before and after treatment depending on folate status. Grant Funding Source: Funding: Chilean FONDECYT #10700592

Gastrointestinal abnormalities in vitamin B12 deficient patients with megaloblastic anemia.

In a retrospective cohort study, hospital records of 220 patients (119 males and 101 females, age 1 year-80 years) with megaloblastic anemia were examined to find out any relationship of gastrointestinal abnormalities with vitamin B12 and folate deficiencies in these patients. Forty three percent of the patients were folate-deficient (serum folate levels < 3.5 ng/ml), while 79% were vitamin B12-deficient (serum B12 levels < 200 pg/ml). Gastrointestinal abnormalities (gastritis, malabsorption and infection) in B12-deficient patients were marginally significant (p=0.05) compared to the abnormalities in B12-normal patients. Severe dyserythropoiesis was more common in vitamin B12-deficient and folate-deficient patients compared to B12-normal and folate-normal patients. However, the proportions were not statistically significant. Marginally significant occurrence of gastrointestinal abnormalities in vitamin B12-deficient subjects points towards the notion that poor dietary intake along with poor gut absorption could be contributing to the high prevalence of vitamin B12 deficiency in this population.

Low vitamin B12 status is negatively associated with global DNA methylation in young Chinese women

Vitamin B12 is a required coenzyme for homocysteine remethylation, essential for the generation of S‐adenosylmethionine, the source of methyl groups for DNA methylation. The objective of this study was to assess the association of low vitamin B12 status on global DNA methylation in reproductive age Chinese women. Global DNA methylation was assessed in two groups of women whose plasma vitamin B12 concentration was either deficient (&lt;148 pmol/L) (n=24) or normal (&gt;148 pmol/L)(n=128). To correct for the possible effects of RBC folate on DNA methylation, a subset (n= 24) of the vitamin B12 normal subjects were further matched for RBC folate concentration with the vitamin B12 deficient subjects. DNA methylation was expressed as a percent of methylated cytosines (as measured by a novel LC‐MS/MS assay). The mean±SD % methylcytosine for the B12‐deficient group (3.51±0.57) was lower (p&lt;0.001) than the total normal group (4.42± 0.18), and the RBC folate‐matched group (4.40±0.17). These data suggest that impaired vitamin B12 status might reduce global DNA methylation and provide a rationale for future investigations. This work was supported by a collaborative CDC agreement and the GCRC Grant # MO1‐RR00082.

The Usefulness of Holotranscobalamin in Predicting Vitamin B12 Status in Different Clinical Settings

Serum concentrations of homocysteine (Hcy) and methylmalonic acid (MMA) become increased in B12-deficient subjects and are therefore, considered specific markers of B12 deficiency. Serum level of holotranscobalamin (holoTC) becomes decreased before the development of the metabolic dysfunction. We investigated the usefulness of holoTC in diagnosing B12 deficiency in some clinical settings. We measured serum concentrations of holoTC, MMA, Hcy and total B12 in omnivores, vegetarians, elderly people and haemodialysis patients. Our results indicated that the incidence of holoTC <35 pmol/L was highest in the vegans (76%). Low holoTC and elevated MMA were detected in 64% of the vegans and 43% of the lacto- and lacto-ovovegetarians. An elevated MMA and a low holoTC were found in subjects with total serum B12 as high as 300 pmol/L. The distribution of holoTC in elderly people was similar to that in younger adults (median holoTC 55 pmol/L in both groups). A low holoTC and an elevated MMA were found in 16% of the elderly group. An elevated MMA and a normal holoTC were found in 20% of the elderly group who had a relatively high median serum concentration of creatinine (106.1 micromol/L). Serum concentrations of holoTC in dialysis patients were considerably higher than all other groups (median 100 pmol/L). This was also associated with severely increased serum levels of MMA (median 987 nmol/L). From these results it can be concluded that serum concentration of holoTC is a much better predictor of B12 status than total B12. This was particularly evident in case of dietary B12 deficiency. Serum concentrations of holoTC as well as MMA can be affected by renal dysfunction. Elevated MMA and normal holoTC in patients with renal insufficiency may not exclude vitamin B12 deficiency. HoloTC seems not to be a promising marker in predicting B12 status in renal patients.

The role of histidine in the anemia of folate deficiency.

The amino acid histidine is metabolized to glutamic acid in mammalian tissue. Formiminoglutamic acid (FIGLU) is an intermediary in this reaction, and tetrahydrofolic acid is the coenzyme that converts it to glutamic acid. A test for folate deficiency concerns the measurement of urinary FIGLU excretion after a histidine load. It was observed that folate-deficient individuals receiving the histidine for the FIGLU test made hematological response that alleviated the anemia associated with this deficiency. This was unusual in that a biochemical test to determine the deficiency results in a beneficial effect for one aspect of the deficiency. The studies reported in this paper give a metabolic explanation for this phenomenon. Urine was collected for 24 hr from 25 folate-deficient subjects, 10 vitamin B(12)-deficient subjects, and 15 normal controls. Urinary excretion of histidine was a mean of 203 mg with a range of 130-360 mg for the folate-deficient subjects; 51.5 mg with a range of 30-76.6 mg for normal subjects; and 60.0 mg with a range of 32.3-93.0 mg for the vitamin B(12)-deficient subjects. All the folate-deficient subjects subsequently made a hematological response to the histidine administered for the FIGLU test. No hematological response was observed in the vitamin B(12)-deficient individuals. When folic acid was given to folate-deficient subjects who received no histidine, urinary histidine levels returned to normal levels rapidly and this was followed by a hematological response. Others have shown that volunteers fed a histidine-free diet developed anemia. In normal subjects, histidine is excreted much more in the urine than other essential amino acids are. Hemoglobin protein contains 10% histidine. Under normal conditions, dietary histidine can supply sufficient histidine to prevent anemia. When the dietary intake is diminished or the urinary excretion is greatly increased, anemia results. It is concluded that folate deficiency causes histidine depletion through increased urinary excretion of this amino acid. Feeding histidine replenishes tissue levels of histidine, resulting in hemoglobin regeneration. Folic acid administration results in return of histidine to normal urinary levels. Thus, a combination of folic acid histidine would be beneficial for folate deficient individuals.

The impact of vegetarianism on some haematological parameters.

Subjects adopting a vegetarian diet are liable to vitamin B12 and iron deficiencies. Co-existing vitamin B12 and iron deficiencies may give an equivocal haematological picture, which may, in turn, delay making an early diagnosis. The current work was undertaken to investigate some haematological parameters in relation to vitamin B12 and iron status in vegetarians. Twenty-nine vegans, 64 lacto- and lacto-ovo-vegetarians, in addition to 20 occasional meat eaters, were enrolled for this study. The total group included 49 males and 64 females aged [mean (SD) = 46(15) yr]. Complete blood count, methylmalonic acid (MMA), homocysteine (HCY), ferritin, and transferrin concentrations and percentage transferrin saturation were assayed, using conventional methods. Vegans displayed the highest MMA and HCY levels (median MMA = 708 nmol L(-1); HCY = 12.8 micromol L(-1)). A lower lymphocyte count and a higher mean corpuscular volume (MCV) were found in vegans compared with lacto- or lacto-ovo-vegetarians (median = 1.51 x 10(9) vs. 1.83 x 10(9) L(-1); 92 vs. 89 fL, respectively). Vitamin B12-deficient subjects in the higher range of transferrin saturation percentage had higher MCV than vitamin B12-deficient subjects in the lower transferrin saturation range (mean MCV = 92 vs. 89 fL). A lower platelet count was found in the highest quartile of MMA (mean = 211 x 10(9) L(-1)) and in the highest quartile of HCY (mean = 215 x 10(9) L(-1)), compared with the other quartiles. Lower lymphocyte and platelet counts and higher MCV were found in subjects with elevated MMA and HCY, compared to those with normal metabolites. Factors that explained the variations in MCV were red blood cell count, ferritin, transferrin saturation, and methylmalonic acid levels. vitamin B12 and iron status were compromised by a vegetarian diet. Variations in mean corpuscular volume were determined by iron and vitamin B12 status. Lower lymphocyte and platelet count were accompanied by metabolic evidence that indicated vitamin B12 deficiency.

Clinical correlates of subnormal vitamin B12 levels in patients infected with the human immunodeficiency virus.

To determine the prevalence and describe the clinical correlates of subnormal cobalamin levels in subjects infected with the human immunodeficiency virus (HIV), and to assess its relationship to virus-mediated immunosuppression and/or anti-viral therapy. Outpatient referral clinic in tertiary care hospital. 200 HIV infected individuals. Descriptive cross sectional survey, with prospective follow-up in a subgroup of patients before and after initiation of zidovudine therapy. Routine complete blood count, serum B12 assay, CD4 counts. Serum homocysteine levels, and Schilling tests were performed on subgroups of study subjects. Subnormal serum B12 levels were found in 61 subjects (30.5%). B12 deficient subjects were more likely to be taking zidovudine. (P = .007). Serum homocysteine levels were significantly higher in patients with subnormal cobalamin levels but were unrelated to CD4 counts or zidovudine use, and were rarely outside of the normal range. Malabsorption of vitamin B12 as evidenced by abnormal Schilling tests was more likely among patients with more advanced HIV disease, or gastrointestinal symptoms but was not necessarily associated with low B12 levels. Decreased cobalamin levels are found frequently in HIV disease, especially among those treated with zidovudine. Evidence of B12 malabsorption is found among those with more advanced disease and gastrointestinal symptoms.

Is nitrous oxide a dangerous anesthetic for vitamin B12-deficient subjects?

Is nitrous oxide a dangerous anesthetic for vitamin B12-deficient subjects?

Is nitrous oxide a dangerous anesthetic for vitamin B12-deficient subjects?

Two women developed significant neurologic dysfunction, consistent with subacute combined degeneration of the spinal cord, within eight weeks of being anesthetized with nitrous oxide. Investigation revealed that each had preclinical or masked vitamin B₁₂deficiency. The first patient had two previous ileal resections for Crohn's disease and the other had pernicious anemia. It is postulated that nitrous oxide anesthesia may precipitate neurologic disease in people with unrecognized deficiency of vitamin B₁₂. (<i>JAMA</i>1986;255:1605-1606)

Impaired chemiluminescence and bactericidal killing by neutrophils from patients with severe cobalamin deficiency.

Neutrophil function was examined in 24 patients with megaloblastic haemopoiesis due to vitamin B12-or folate deficiency. Defective bactericidal activity was demonstrated in the B12-deficient group only and was associated with normal phagocytic activity but impaired intracellular killing. Luminol amplified luminescence was consistently low in B12-deficient subjects with RBC counts of less than 2 X 10(12)/l. These defects were not seen in the folate-deficient cases although isolated abnormalities were present in those who were also alcoholic.

Leukocyte methylmalonyl-CoA mutase. I. Vitamin B12 deficiency

The leukocyte activity of the 5’ deoxyadenosyl B12-linked enzyme, methylmalonyl-CoA mutase, was measured in vitro in seven patients with vitamin B12 deficiency (group I), six patients with anemia not due to vitamin B12 lack (group II), and nine normal healthy adult controls (group III). Assay was based on the rate of utilization of enzymatically prepared, chromatographically purified 14C carboxy-labeled racemic methylmalonyl-CoA. The time course of the assay as described was linear over a 1-hr period at activities of 0.013 to 0.34 nmole/hr of methylmalonyl-CoA utilized. Leukocyte mutase activities were measured without (basal) and with added dAB12. Mutase activities were: group I basal, mean 0.034 (0.005 to 0.099); group II, mean 0.114 (0.017 to 0.309); group III, mean 0.286 ± 0.079 (0.170 to 0.459) nmole/mg leukocyte protein per hr. In the presence of added dAB12 (100 to 500 ng) activities were: group I, 0.091 (0.018 to 0.190), group II, 0.093 (0.005 to 0.308), and group III, 0.232 ± 0.135 (0.090 to 0.510) nmole/mg leukocyte protein per hr. All seven vitamin B12-deficient subjects showed enhanced leukocyte methylmalonyl-CoA mutase activity in the presence of added dAB12. No correlation was apparent between leukocyte mutase ativities of the vitamin B12-deficient subjects and the excretion of urinary methylmalonate, the severity of the anemia, or the presence of neurological impairment of the vitamin B12-deficiency state.

Identification of an Immunoreactive Folate in Serum Extracts by Radioimmunoassay*

Summary. A radioimmunoassay for folic acid using antibodies with binding determinants specific for this vitamin has been used to identify an immunoreactive folate in serum and serum extracts. Because reduced folates such as methyltetra‐hydrofolate, formyltetrahydrofolate and dihydrofolate did not inhibit the antibody binding of [3H]folic acid while unreduced folates did, the immunoreactive folate in serum and serum extracts was most likely an unreduced folate. Serum extracted by boiling in the absence of ascorbate had a significantly higher concentration of immunoreactive folate than did whole serum. The extraction procedure apparently released or converted endogenous folate to an immunoreactive form because serum extracted with ascorbate contained very low concentrations of the immunoreactive form. The range of recovery of crystalline folic acid added to serum and assayed in extracts prepared without ascorbate was 82‐132%, with a mean of 104%.Subjects taking oral folic acid had significantly elevated levels of serum immunoreactive folate. Following intravenous administration of folic acid, the immunoreactive folate concentration did not rise as high and it decreased more rapidly in folate deficient patients than in normal subjects. Serum extracted without ascorbate from normal, vitamin B12 and folate deficient subjects had immunoreactive folate levels (mean ± SEM) of 1350 ± 110, 949 ± 152 and 525 ± 72 pg/ml, respectively.