Haemoglobin A2 levels in vitamin B12 and folate deficiency.

Haemoglobin A2 levels were measured in 50 patients with vitamin B12 deficiency, 50 patients with folate deficiency, and six patients with combined deficiencies of these vitamins. All were normal except for three patients with vitamin B12 deficiency, who had a slightly elevated Hb A2 level; this fell to normal after vitamin B12 therapy. It is concluded that haemoglobin A2 levels are usually normal in vitamin B12 or folate deficiency. However, raised levels of haemoglobin A2 may be found, but these are not as high as is found in beta thalassaemia trait and should not cause difficutly in diagnosis.     

Experiences with dual protein bound aqueous vitamin B12 absorption test in subjects with low serum vitamin B12 concentrations.

A dual isotope vitamin B12 absorption test in which vitamin B12 is given both in aqueous solution and bound to protein (chicken serum), was evaluated in 26 controls and 68 patients with subnormal serum vitamin B12 concentrations (19 with pernicious anaemia, 13 with iron deficiency, seven after partial gastrectomy, seven with malabsorptive states, five with folate deficiency, four with chronic alcoholism and 13 in whom no cause was apparent). In control patients protein bound absorption decreased with age; isotope excretion was 1.0% or over in those aged under 60 and 0.5% or over in those aged 60 and above. Malabsorption of protein bound vitamin B12 with normal aqueous absorption occurred in five patients with iron deficiency, three with alcoholism, two after partial gastrectomy, two with folate deficiency and in one with a malabsorptive state. In alcoholics abstinence produced an improvement in protein bound absorption. All patients in the group for whom no cause could be found for the subnormal serum vitamin B12 concentration had normal aqueous absorption but four had malabsorption of protein bound vitamin. Although the dual isotope test gave reproducible results and was consistent with the standard Schilling test some anomalies were detected; nine patients had reduced aqueous absorption with normal protein bound absorption. Despite this the dual test may prove useful in determining the importance of a subnormal vitamin B12 concentration where the cause is not clinically apparent. Further development is needed before it can be considered for routine use.     

Vitamin B12 absorption studies: effect of parenteral non-radioactive vitamin B12 on serum level of 57Co vitamin B12

The intestinal absorption of (57)Co vitamin B(12) has been measured by counting the radioactivity in the serum, and the effect of the parenteral administration of 1 mg. non-radioactive vitamin B(12) two hours after the oral dose has been studied. When parenteral vitamin B(12) was not given, the mean radioactivity in the serum was lower in both patients with pernicious anaemia and in control subjects, and the results in the patients with pernicious anaemia were more definitive. There was no significant difference between the results obtained with an Ekco scaler and those with an I.D.L. scaler.This is the simplest and most convenient method of measuring vitamin B(12) absorption. It is suggested that the test be standardized by giving 0.5 mug. (57)Co vitamin B(12) with a maximal histamine stimulation of intrinsic factor secretion, but without a parenteral dose of non-radioactive vitamin B(12). The results are expressed most usefully as a percentage of the administered dose per litre of serum or plasma.     

Dietary vitamin B12 deficiency in an adolescent white boy

Dietary deficiency of cobalamin resulting in tissue deficiency in white individuals is unusual. However, several patients with dietary deficiency who were neither vegan nor Hindu have been described. This report describes the case of a 14 year old boy who was a white non-Hindu with a very low intake of cobalamin, which was not apparent until a detailed dietary assessment was performed. The patient responded rapidly to a combination of oral and parenteral B12. This case illustrates the fact that severe dietary vitamin B12 deficiency can occur in non-Hindu white individuals. Inadequate dietary content of B12 may not be apparent until a detailed dietary assessment is performed. This patient is likely to have had subclinical vitamin B12 deficiency for several years. Increased vitamin B12 requirements associated with the adolescent growth spurt may have provoked overt tissue deficiency.     

Vitamin B12 and folic acid deficiency in chronic pancreatitis: a relevant disorder?

Summary Vitamin B12 malabsorption was reported earlier to occur in patients with exocrine pancreatic insufficiency, and pancreatic extracts were shown to improve the absorption of vitamin B12. We investigated serum levels of vitamin B12 and serum folate in patients with chronic pancreatitis and different degrees of pancreatic insufficiency.137 patients (84 males, 53 females, age 34–72 years) with chronic pancreatitis (C.P.) were included in the study. 123 of 137 (89.8%) patients had a pathologic pancreatic function test result, classified into mild (n=24), moderate (n=61) or severe (n=38) insufficiency. The normal range of serum vitamin B12 and folic acid was established in 58 healthy controls and was found to be 190–1020 pg/ml for serum vitamin B12 and 2.4–16.1 ng/ml for folic acid. 7 patients (5.7%) with C.P. had vitamin B12 serum levels below 190 pg/ml; 4 of these had severe and 3 had mild or moderate exocrine pancreatic insufficiency. However there was no overall correlation between the degree of pancreatic insufficiency and vitamin B12 values. Serum levels of Vitamin B12 were 512±48 pg/ml in mild, 493±52 pg/ml in moderate and 428±45 pg/ml in severe exocrine insufficiency. Serum folic acid below 2.4 ng/ml were present in 5 patients (3.6%). Folic acid serum levels were 8.34±0.76 ng/ml in mild, 6.34±0.52 ng/ml in moderate and 7.45±0.53 ng/ml in severe exocrine insufficiency. We conclude that vitamin B12 deficiency is a rare finding in chronic pancreatitis and does not strictly depend on the degree of exocrine pancreatic insufficiency. In clinical practice enzyme supplementation in patients with severe pancreatic insufficiency is obviously sufficient for normal vitamin B12 absorption. Folic acid deficiency is also unfrequently found in chronic pancreatitis.     

Effect of vitamin B12 and folic acid deficiency on small intestinal absorption

Three patients are described, and they provide further evidence that deficiency of folic acid and vitamin B(12) may sometimes affect small intestinal function. Malabsorption of both xylose and vitamin B(12) returned to normal in one patient after treatment of a megaloblastic anaemia due to dietary deficiency of folic acid. Impaired absorption of vitamin B(12) was corrected by vitamin B(12) therapy in the other two patients. The initial cause of the vitamin B(12) deficiency in one patient was not apparent, but she was taking Gynovlar 21, which may have been an aetiological factor. In the third patient the small intestinal defect was secondary to pernicious anaemia, and in a group of 98 other patients with pernicious anaemia intrinsic factor did not improve vitamin B(12) absorption in six, and only partially corrected absorption in 30. The significance of these observations is discussed.     

Relationship between megadose vitamin supplementation and immunological function in a healthy elderly population.

We studied the immunological effects of 'megadose' vitamin or mineral supplementation by comparing the immunological functions of healthy elderly subjects taking large amounts of specific nutrients to similar subjects not on supplements. There was a non-significant trend for those subjects taking megadoses of vitamin C to have increased cell-mediated immune responses as measured in vivo by skin test reactivity but not by in vitro mitogen responses. In addition, subjects taking megadoses of vitamin E or any of several B vitamins (B1, B2, B6, folate and niacin) had lower absolute circulating lymphocyte counts than did the rest of the population. The relative lack of effect of megadose vitamins on immunological function in this population compared to reports of short term trials of mega nutrients raises the possibility that some of the previously reported immuno-enhancing properties of megadose vitamins may be due to a non-specific adjuvant effect that disappears with time.     

Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin B12).

Two adolescent patients suffering from persistent sleep-wake schedule disorders appear to have responded to treatment with vitamin B12 (methylcobalamin). A 15-year-old girl with delayed sleep phase syndrome (DSPS) and a 17-year-old boy with hypernychthemeral syndrome complained of not being able to attend school despite many trials of medication. The improvement of the sleep-wake rhythm disorders appeared immediately after the administration of high doses (3,000 micrograms/day) of methylcobalamin. Neither patient showed any laboratory or clinical evidence of vitamin B12 deficiency or hypothyroidism (which can cause B12 deficiency). Serum concentrations of vitamin B12 during treatment were in the high range of normal or above normal. The duration of the sleep period of the DSPS patient decreased gradually from 10 hours to 7 hours, and the time of sleep onset advanced from 2 a.m. to midnight. The period of the sleep-wake cycle of the hypernychthemeral patient was 24.6 hours before treatment and 24.0 hours after treatment. The relationship between the circadian basis of these disorders and vitamin B12 and its metabolites is discussed.     

Adverse effect of metformin therapy on serum vitamin B12 and folate: Short-term treatment causes disadvantages?

Diabetes is a global public health challenge that imposes heavy burdens on communities and individuals. Metformin, the first-line medication for diabetes, has the superiority of reducing risk of macrovascular diseases, all-cause mortality and even possibly cancers. Recent observational studies, however, have demonstrated that long-term metformin therapy increases the probability of vitamin B12 and folate deficiency, and might contribute to the progression of diabetic peripheral neuropathy. Despite metformin is widely used and extensively studied, randomized controlled trials performed to explore the effects of metformin on vitamin B12 and folate are limited. Besides, whether short-term treatment causes vitamin deficiency is a pending issue. We postulate that even a few-month treatment with metformin results in the decrease of vitamin B12 and folate. However, supplementation of vitamin B12 rather than the combination of vitamin B12 and folate might be profitable based on the mechanism of metformin on vitamins in patients with type 2 diabetes. This viewpoint differs from those of majority that a combined supplementation of vitamin B12 and folate is inclined to be advised.     

Influence of water and sodium diuresis and furosemide on urinary excretion of vitamin B(6), oxalic acid and vitamin C in chronic renal failure

Urinary excretion of vitamin B(6), oxalic acid and vitamin C was investigated in 15 healthy subjects during maximal water diuresis and in the group of 12 patients in polyuric stage of chronic renal failure without dialysis treatment receiving a diet containing high sodium chloride (15g/day). Urinary excretions of the same parameters were investigated in another group of 15 patients in polyuric stage of chronic renal failure without dialysis treatment after i.v. administration of 20 mg furosemide. Urinary excretion of vitamin B(6), oxalic acid and vitamin C significantly increased during maximal water diuresis while during high intake of sodium chloride the urinary excretions of these substances were not affected. The results suggest that urinary excretion of vitamin B(6), oxalic acid and vitamin C depends on the urinary excretion of water. Intravenous administration of 20 mg furosemide led to an increase of urinary excretion of vitamin B(6), oxalic acid and vitamin C in patients with chronic renal failure. The increased urinary excretion of vitamin B(6) and vitamin C is a new negative side effect of furosemide and increased urinary excretion of oxalic acid is a new positive side effect in patients with chronic renal failure.     

Racial differences in vitamin B12 levels in the United States

Studies from Africa have demonstrated that black people have higher vitamin B12 (cobalamin) levels than do white people. The authors compared healthy white people, black people, and Latin-Americans in the United States. Their study is also the largest in which the effect of race and sex on the cobalamin levels has been examined. Analysis of 233 healthy subjects showed that black people had significantly higher (P less than 0.0001) vitamin B12 levels than did white people. Latin-Americans had levels intermediate between those of white and black people, although their levels were significantly different only in comparison with white people (P = 0.0029). Based on the study of 305 healthy subjects, no sex difference in vitamin B12 levels was noted. Conflicting claims have been made on sex difference in the past. The authors conclude that there is a racial but not a sex difference in vitamin B12 levels in the United States. Like African black people, black people and Latin-Americans in this country have significantly higher vitamin B12 levels than do white people. This finding supports the thesis that genetic factors contribute to the racial differences in vitamin B12 levels.     

Vitamin B12 deficiency: a clinical and electrophysiological profile

OBJECTIVE: The present study was conducted to evaluate the clinical and electrophysiological profile of vitamin B12 deficiency syndrome and whether a correlation exists between the disease process and the various electrophysiological parameters. METHODS: 40 patients with vitamin B12 deficiency neurological syndromes with low serum vitamin B12 and high homocysteine levels were subjected to a detailed motor and sensory nerve conduction studies and pattern reversal VER (P100), SSEP (P37) after stimulation of the posterior tibial nerve and median nerve (N 20) were obtained bilaterally. MR cervical spine was done in all the patients and MR brain in those who presented with neuro-psychiatric symptoms. The patients were followed up at three months, six months and one year after treatment. RESULTS: On the basis of clinico-electrophysiological profile, 31 patients had myeloneuropathy, 5 isolated myelopathy, 4 isolated neuropathy. Four of the patients with myeloneuropathy, had concomitant dementia. MR imaging revealed abnormality in 12.5% of cases. Prolongation of P37 latency was observed in 39 (97.5%) patients, N 20 latency in 22 (55%), and P100 latency in 19 (47.5%) patients. Peripheral neuropathy was seen in 18 patients; optic neuropathy in 8; and combination of peripheral and optic neuropathy in 9 patients. The peripheral neuropathy was axonal in 19, and demyelinating in 6 patients. There was a significant correlation of the duration of the disease with N 20 latency (P < 0.04). Serum vitamin B12 level correlated well with the latencies of P37 (P < 0.005) and sural SNAP (P < 0.006). On treatment, normalization of P100, MRI signal, N 20 and partial recovery of P37 latencies was seen at 6 months, 9 months and one year respectively. CONCLUSION: Differential recovery of central and peripheral syndromes was seen. This correlated with the underlying demyelinating and axonal processes, which was well reflected by the electrophysiological studies, and has an important bearing on the outcome.     

Vitamin B12 deficiency neurological syndromes: a clinical,MRI and electrodiagnostic study

BACKGROUND: Vegetarianism is an important cause of vitamin B12 deficiency, especially in countries like India. We managed 17 patients with neurological syndrome due to vitamin B12 deficiency in a tertiary care referral teaching hospital which caters to relatively affluent population. AIM: To evaluate neurophysiological and MRI changes in patients presenting with vitamin B12 deficiency neurological syndrome and interpret these is the light of reported autopsy findings. SETTING: Tertiary care referral teaching hospital. METHODS: Patients with vitamin B12 deficiency neurological syndrome diagnosed by low serum vitamin B12 and/or megaloblastic bone marrow were subjected to clinical evaluation and spinal MRI. The neurophysiological tests included nerve conduction studies, tibial somatosensory evoked potential (SEP), motor evoked potential (MEP) and visual evoked potential (VEP) studies. The recovery was defined on the basis of 6 months Barthel Index score into complete, partial or poor. RESULTS: There were 17 patients with vitamin B12 deficiency neurological syndrome, 3 were females and 12 lactovegetarian. The clinical syndrome was that of myelopathy in 8, myeloneuropathy in 5, dementia myelopathy in 3 and neuropathy in 1 patient. All the patients had impaired joint position and vibration sensation in the lower limbs and 4 had in upper limbs as well. Lower limbs were spastic in 13 and upper limbs in 2 patients. Spinal MRI revealed T2 hyperintensity in cervicodorsal region in 6 and cord atrophy in 3 patients. Sural nerve conduction was abnormal in 8 and peroneal conduction in 5 patients. In one patient all sensory nerve conductions were unrecordable but motor conductions were normal. Tibial SEP was abnormal in 12 out of 15 and lower limb MEP in 8 out of 12 patients. P100 latency of VEP was prolonged in 7 out of 13 patients. Right to left asymmetry was present in tibial SEP in 4 and VEP in 2 patients. At 6 months followup 2 patients improved completely, 7 partially and 3 had poor recovery. Clinical recovery correlated with MEP but not with SEP or MRI changes. CONCLUSION: The evoked potential and MRI changes in vitamin B12 deficiency neurological syndrome are consistent with focal demyelination of white matter in spinal cord and optic nerve. Myelopathic presentation is commoner and SEP is more frequently abnormal. The outcome at 6 months correlated with MEP changes.     

Measurement of intestinal absorption of 57Co vitamin B12 by serum counting

The results of the measurement of vitamin B(12) absorption by counting the radioactivity of 5 ml. serum obtained eight to 10 hours after the ingestion of an oral dose of 0.5 mug. vitamin B(12) labelled with 0.5 muc. (57)Co are compared with those obtained with the urinary excretion (Schilling) test. Inadequate urine collection and impaired renal function were responsible for low results in the Schilling test in four of the 12 control subjects, and an incomplete urine collection in four patients with pernicious anaemia could have led to doubt about the validity of the low result.The measurement of serum radioactivity for 1,000 seconds gave conclusive results, the range in the patients with malabsorption of vitamin B(12) being between 0 and 24 counts per minute, and in the control subjects and other patients with megaloblastic anaemia between 28 and 64 counts per minute. The highest serum radioactivity level in a patient with pernicious anaemia was 19 counts per minute.Serum counting is simpler than the Schilling test and may be done alone when the patient's renal function is known to be poor, when urine collection is expected to be unreliable, or when the flushing dose of vitamin B(12) should be avoided. Otherwise there is an advantage in doing both tests together for confirmation.     

Economic and laboratory considerations in screening for vitamin B12 deficiency in psychiatric practice

Two alternative methods for detecting vitamin B(12) deficiency in a psychiatric population have been compared: the ;direct' approach by microbiological assay of serum vitamin B(12) levels in all patients, and the ;indirect' approach where all patients are first screened for antigastric parietal cell antibodies and thereafter all positive reactors and other ;high-risk' patients have serum vitamin B(12) assayed. The indirect approach was found to be cheaper.     

Importance of low serum vitamin B12 and red cell folate concentrations in elderly hospital inpatients.

To determine the functional importance of the low B12 and red cell folate concentrations repeatedly observed in the elderly 200 consecutive patients admitted to a geriatric unit were studied. Forty six of the patients had low serum concentrations of B12 (15), red cell folate (26), or both (five). Serum B12 and red cell folate concentrations correlated with mean cell volume, and serum B12 correlated with the neutrophil lobe count. Bone marrow deoxyuridine suppression was abnormal in 35% of the patients with low vitamin concentrations, but 55% of those with abnormal deoxyuridine suppression had morphologically normal bone marrow, and 73% had a normal mean cell volume. In patients with low vitamin values the deoxyuridine suppressed value correlated with the haemoglobin concentration and neutrophil lobe count. Thus synthesis of thymidylate was impaired by vitamin B12 or folate deficiency in at least 8% of newly admitted elderly patients, many of whom had normal blood counts despite the biochemical disturbance affecting haemopoiesis. A nutritionally depleted diet may have been responsible for many of the low vitamin values.     

Serum levels of folic acid and vitamin B12 in Korean patients with vitiligo.

The association of vitiligo and pernicious anemia has been previously documented. The low levels of folic acid and vitamin B12 were thought to be related to vitiligo. To date, there have been very few reports about the serum levels of folic acid and vitamin B12 in patients with vitiligo. Using radioimmunoassay, we measured the serum levels of folic acid and vitamin B12 in 100 Korean patients with vitiligo. The mean serum levels of folic acid and vitamin B12 were 6.31 +/- 2.82 ng/ml and 630.25 +/- 230.94 pg/ml, respectively, in patients with vitiligo. These levels showed no significant difference compared to the normal control group, suggesting that folic acid and vitamin B12 do not appear to play a role in the pathogenesis of vitiligo.     

Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment

It has been suggested that vitamin B12 (vit.B12) plays an important role in immune system regulation, but the details are still obscure. In order to examine the action of vit.B12 on cells of the human immune system, lymphocyte subpopulations and NK cell activity were evaluated in 11 patients with vit.B12 deficiency anaemia and in 13 control subjects. Decreases in the number of lymphocytes and CD8+ cells and in the proportion of CD4+ cells, an abnormally high CD4/CD8 ratio, and suppressed NK cell activity were noted in patients compared with control subjects. In all 11 patients and eight control subjects, these immune parameters were evaluated before and after methyl-B12 injection. The lymphocyte counts and number of CD8+ cells increased both in patients and in control subjects. The high CD4/CD8 ratio and suppressed NK cell activity were improved by methyl-B12 treatment. Augmentation of CD3-CD16+ cells occurred in patients after methyl-B12 treatment. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) activity, lectin-stimulated lymphocyte blast formation, and serum levels of immunoglobulins were not changed by methyl-B12 treatment. These results indicate that vit.B12 might play an important role in cellular immunity, especially relativing to CD8+ cells and the NK cell system, which suggests effects on cytotoxic cells. We conclude that vit.B12 acts as an immunomodulator for cellular immunity.     

Malabsorption of vitamin B12 in dermatitis herpetiformis and its association with pernicious anaemia

Serum vitamin B12 concentrations were determined in 129 patients and a pentagastrin test performed in 116 patients with dermatitis herpetiformis (DH). Low serum vitamin B12 levels were found in 27 patients (21%) and achlorhydria in 30. Forty-two patients with achlorhydria and/or vitamin B12 deficiency were subjected to further haematological and gastrointestinal investigations. Functional or morphological involvement of the small intestine was seen in almost all patients with vitamin B12 deficiency but, in addition, atrophic gastritis resulting in defective secretion of intrinsic factor (pernicious anaemia) was found in 8 cases (7% of all DH patients). Thus, a low vitamin B12 level in DH patients should result in a careful gastrointestinal examination as both an atrophic gastritis and a coeliac-like enteropathy have further clinical implications.     

The role of vitamin B 12 and its transport globulins in the production of antibodies.

Immunological functions were repeatedly tested in a patient with hereditary deficiency of transcobalamin II (TC II): he was unable to synthesize immunoglobulins and specific antibodies, but was able to do so normally after injection of high doses of vitamin B 12 (1000 mug per week). Lymphocytes (B and T) were present in normal numbers prior to therapy, thus indicating normal differentiation of stem cells. In contrast, clonal expansion, necessary for immunoglobulin production, was possible only after vitamin B 12 administration. These observations, as well as the well known disturbances in haemopoiesis, indicate that vitamin B 12 is indispensable to rapidly replicating tissues, and that a severe deficiency of this vitamin in the cells can result from the absence of TC II.