Vitamin B12 Therapy Research Articles

Successful treatment of recurrent aphthous stomatitis of any origin with vitamin B12 (irrespective of its blood level)

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal lesions seen in primary care. Over the past four years we have treated 15 RAS patients with vitamin B12. Of these, 11 patients reported a rapid and complete recovery from RAS during treatment and the other four reported pronounced reduction in the frequency and severity of RAS episodes. We suppose that a treatment with vitamin B12 can be effective for patients suffering from RAS any origin, regardless of their serum vitamin B12 level. Now we are doing double-blind, placebo-controlled, randomized clinical trial addressing the issue. It's supposed to confirm the safety and effectiveness of vitamin B12 therapy for RAS.

Imerslund-Grasbeck Syndrome Associated With Recurrent Aphthous Stomatitis and Defective Neutrophil Function

Vitamin B(12) deficiency is a well-known cause of recurrent aphthous stomatitis (RAS). However, the mechanism by which this deficiency causes the stomatitis is not well understood. Imerslund-Grasbeck syndrome (IGS) causes vitamin B(12) deficiency and proteinuria due to a defect in the vitamin B(12) receptor. We sought to determine whether the RAS observed in IGS patients is associated with neutrophil dysfunction. We report 3 infants with vitamin B(12) deficiency due to IGS, who presented with borderline or normal hemoglobin concentrations, RAS, and a neutrophil function defect. All 3 patients were homozygous for a splice site mutation affecting exon 4 of the AMN gene. A direct correlation was observed between low serum vitamin B12 levels and defective neutrophil function (low chemotaxis and elevated superoxide production) in the patients. Vitamin B(12) therapy led to an immediate resolution of aphthous stomatitis and full correction of neutrophil function. We demonstrated that serum vitamin B(12) deficiency is associated with a neutrophil chemotactic defect and RAS in IGS patients. We suggest that the RAS observed in these patients is due to this defect.

Abnormally High Plasma Levels of Vitamin B6 in Children with Autism Not Taking Supplements Compared to Controls Not Taking Supplements

There have been many studies of the effect of high-dose supplementation of vitamin B6 on children and adults with autism, with all but one reporting benefits. The aim of this study was to investigate the biochemical basis for vitamin B6 therapy by measuring the level of total vitamin B6 in the plasma of unsupplemented children with autism spectrum disorder compared to unsupplemented control subjects. Children with autism spectrum disorders (n = 35, age 3-9 years) and unrelated typical children (n = 11, age 6-9 years), all from Arizona, were studied. (This includes the data from 24 children with autism from our previous study.) A microbiologic assay was used to measure the level of total vitamin B6 (including phosphorylated and unphosphorylated forms), in a blinded fashion. Children with autism had a 75% higher level of total vitamin B6 than the controls (medians of 56 versus 32 ng/mL, respectively, p = 0.00002). Most of the autistic children (77%) had levels that were more than 2 standard deviations above the median value of the controls. The autistic girls (n = 5) also had elevated levels (mean of 54.6 ng/mL, median of 60 ng/mL). These results are consistent with previous studies that found that: (1) pyridoxal kinase had a very low activity in children with autism and (2) pyridoxal 5 phosphate (PLP) levels are unusually low in children with autism. Thus, it appears that the low conversion of pyridoxal and pyridoxine to PLP results in low levels of PLP, which is the active cofactor for 113 known enzymatic reactions, including the formation of many key neurotransmitters. Total vitamin B6 is abnormally high in autism, consistent with previous reports of an impaired pyridoxal kinase for the conversion of pyridoxine and pyridoxal to PLP. This may explain the many published studies of benefits of high-dose vitamin B6 supplementation in some children and adults with autism.

Food-cobalamin malabsorption in elderly patients: Clinical manifestations and treatment

Purpose Approximately 15% of people aged more than 60 years old have a cobalamin (vitamin B12) deficiency, mainly in relation with food-cobalamin malabsorption (FCM). To date, no study has documented this disorder in the elderly. There is also little information on clinical consequences. Subjects and methods We studied 92 elderly patients with well-established FCM who were extracted from an observational cohort study (1995-2004) of 172 consecutive elderly patients with documented cobalamin deficiency. Results The median patient age was 76 ± 8 years; 60 patients were women. The most common clinical manifestations were neurologic or psychologic: mild sensory polyneuropathy (44.6%), confusion or impaired mental functioning (22.8%), and physical asthenia (20.7%). Hematologic abnormalities were reported in at least one third of the patients: anemia (21%), leukopenia (10.9%), thrombopenia (8.7%), and pancytopenia (6.5%). All patients had low serum vitamin B12 levels (<200 pg/mL), with a mean value (± standard deviation) of 131 ± 38 pg/mL and total serum homocysteine level of 22.1 ± 9.3 μmol/L. The mean hemoglobin level was 10.9 ± 2.5 g/dL and the mean erythrocyte cell volume 95.7 ± 12.7 fL. Correction of the serum vitamin B12 levels and hematologic abnormalities was achieved equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. Conclusions This study suggests that in elderly patients, FCM may be associated with significant neurologic, psychologic, and hematologic abnormalities, which seem to respond equally well to either oral or parenteral vitamin B12 therapy.

Medical intelligence in Sweden. Vitamin B12: oral compared with parenteral?

Background: Sweden is the only country in which oral high dose vitamin B12 has gained widespread use in the treatment of deficiency states. Objective: The aim of the study was...

Oral vitamin B12therapy in the primary care setting: a qualitative and quantitative study of patient perspectives

BackgroundAlthough oral replacement with high doses of vitamin B12 is both effective and safe for the treatment of B12 deficiency, little is known about patients' views concerning the acceptability and effectiveness of oral B12. We investigated patient perspectives on switching from injection to oral B12 therapy.MethodsThis study involved a quantitative arm using questionnaires and a qualitative arm using semi-structured interviews, both to assess patient views on injection and oral therapy. Patients were also offered a six-month trial of oral B12 therapy. One hundred and thirty-three patients who receive regular B12 injections were included from three family practice units (two hospital-based academic clinics and one community health centre clinic) in Toronto.ResultsSeventy-three percent (63/86) of respondents were willing to try oral B12. In a multivariate analysis, patient factors associated with a "willingness to switch" to oral B12 included being able to get to the clinic in less than 30 minutes (OR 9.3, 95% CI 2.2–40.0), and believing that frequent visits to the health care provider (OR 5.4, 95% CI 1.1–26.6) or the increased costs to the health care system (OR 16.7, 95% CI 1.5–184.2) were disadvantages of injection B12. Fifty-five patients attempted oral therapy and 52 patients returned the final questionnaire. Of those who tried oral therapy, 76% (39/51) were satisfied and 71% (39/55) wished to permanently switch. Factors associated with permanently switching to oral therapy included believing that the frequent visits to the health care provider (OR 35.4, 95% CI 2.9–432.7) and travel/parking costs (OR 8.7, 95% CI 1.2–65.3) were disadvantages of injection B12. Interview participants consistently cited convenience as an advantage of oral therapy.ConclusionSwitching patients from injection to oral B12 is both feasible and acceptable to patients. Oral B12 supplementation is well received largely due to increased convenience. Clinicians should offer oral B12 therapy to their patients who are currently receiving injections, and newly diagnosed B12-deficient patients who can tolerate and are compliant with oral medications should be offered oral supplementation.

Development and Validation of an Automated Chemiluminometric Immunoassay for Human Intrinsic Factor Antibodies in Serum

The cobalamins, also referred to as vitamin B12, are a group of closely related enzymatic cofactors involved in the conversion of methylmalonyl-coenzyme A to succinyl-coenzyme A and in the synthesis of methionine from homocysteine (1)(2)(3). Vitamin B12 deficiency can lead to megaloblastic anemia and neurologic deficits (4). The latter may exist without anemia or precede it. Adequate replacement therapy will generally improve or cure cobalamin deficiency. Unfortunately, many other conditions, which require different interventions, can mimic the symptoms and signs of vitamin B12 deficiency (4). Moreover, even when cobalamin deficiency has been established, clinical improvement may require different dosages or routes of vitamin B12 replacement, depending on the underlying cause (3)(4). In particular, patients with pernicious anemia, possibly the commonest type of cobalamin deficiency in developed countries, require either massive doses of oral vitamin B12 or parenteral replacement therapy (3)(4)(5). The reason is that in pernicious anemia, patients suffer from gastric mucosal atrophy, which leads to diminished or absent gastric acid, pepsin, and intrinsic factor (IF) production. Because gastric acid, pepsin, and IF are required for liberation of cobalamin from binding proteins and efficient cobalamin absorption in the gut, respectively, vitamin B12 deficiency ensues (3)(4). Most of these patients have autoantibodies against gastric parietal cells or IF, with the latter being very specific but present in only ∼50% of cases (1). The aim of the work-up of patients with suspected vitamin B12 deficiency is therefore to confirm the presence of deficiency and to establish its most likely etiology. Many different testing algorithms have been proposed to achieve maximum sensitivity and specificity for both tasks, but almost all involve measurement of serum vitamin B12 and IF antibodies (IFABs) at …

Variations in the lipid profile of patients with chronic renal failure treated with pyridoxine

BackgroundHyperhomocysteinemia and lipid abnormalities are commonly found in patients with chronic renal failure; both are recognized as risk factors for atherosclerosis. The homocysteine-lowering effect of pyridoxine is controversial. This study was performed to determine the effect of a high dose of pyridoxine (300 mg i.v. three times a week) on plasma and red blood cell lipid profile and plasma homocysteine concentration in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (basal 1), after 30 and 60 days of treatment and 4 months after withdrawal (basal 2).ResultsPyridoxine supplementation induced a significant decrease in total plasma homocysteine level and also a lowering effect in plasma total cholesterol and triglycerides. These biochemical data increased when the samples were taken at basal 2, reaching the levels obtained at the beginning of the experiment. LDL cholesterol increased whereas HDL cholesterol was reduced during the treatment. In erythrocyte membranes vitamin B6 therapy enhanced the cholesterol/phospholipid ratio as well as the fluorescence anisotropy of diphenyl-hexatriene.ConclusionsWe conclude that high doses of pyridoxine represent an effective strategy to ameliorate both plasma homocysteine levels and lipid profiles in chronic renal failure patients, protecting them from atherosclerosis. Further research using a long-term treatment would be necessary in an attempt to restore the fatty acid pattern and the fluidity of red cell membranes.

Vitamin B12 and folate after 5-12 years of continent ileal urostomy (Kock reservoir) in children and adolescents.

To assess B12 and folate deficiency after continent urinary diversion via a Kock continent urinary reservoir in children and adolescents. Ten boys and 10 girls (10.8-18 years old at surgery) were operated with a Kock reservoir and followed for 5-12 years (mean 8.5). The follow-up period was divided into early (3 months-5 years, EFU) and late (5-12 years, LFU) follow-up. Patients were investigated for haemoglobin, serum iron, total iron binding capacity (TIBC), serum Vitamin B12, serum and blood folate, methylmalonic acid (MMA), homocystine and glomerular filtration rate. Two patients developed subnormal B12 values (median 107.5 pmol/l), one at the EFU, and the other at LFW. The B12 value decreased during the LFU compared to the EFU in nine patients, but it was still within the normal range. Two patients with renal impairment had elevated MMA with normal B12 values. Five patients had high values of homocystine with folate deficiency and/or B12 deficiency and renal impairment. Plasma folate mean value was normal during the whole follow-up. Blood folate was below normal in five patients at the EFU. Two of these five patients, in addition to three patients, had low values at the LFU. Three of four patients with remaining short terminal ileum (20-45 cm) had normal B12 values at both the EFU & LFU and one had low values at the LFU. Six patients had subnormal GFR at the LFU. To a similar degree as in adults, Vitamin B12, folate and iron deficiency can occur in children and adolescents after continent urinary diversion using an ileal segment. Therefore, Vitamin B12 and folate should be monitored regularly in these patients. Serum MMA and homocystine may offer increased detection of Vitamin B12 deficiency, especially in the patients with normal renal function. Vitamin B12 deficiency is neither correlated with the time elapsed since surgery, nor with the ileum length. Patients are usually asymptomatic, so patients with true B12 deficiency should be identified and placed on life-long Vitamin B12 therapy. An adequate synthetic folic acid as supplements or fortified food is recommended for patients with folate deficiency.

Vitamin B6 Therapy During Childbearing Years: Cause for Caution?

Vitamin B6, or pyridoxine, is either prescribed or recommended in large doses for a variety of ailments. These ailments include morning sickness and premenstrual syndrome, despite the fact that the effect of large doses of vitamin B6 on developing human fetuses is currently unknown. Both clinical reports and recent experimental evidence indicate, however, that large doses of vitamin B6 can have adverse affects on proprioceptive neuron function, and these deficits may be permanent if caused during development. This evidence suggests that ingestion of large quantities of vitamin B6 should be viewed with caution by pregnant women and women of childbearing potential.

Hyperhomocysteinemia and inflammatory bowel disease: prevalence and predictors in a cross-sectional study.

Homocysteine is a sulfur-containing amino acid formed during the demethylation of methionine. Vitamin B12 and folate deficiency and therapy with antifolate drugs may predispose patients with inflammatory bowel disease (IBD) to hyperhomocysteinemia. The known associations between hyperhomocysteinemia and smoking, osteoporosis, and thrombosis make it an interesting candidate as a pathogenetic link in IBD. The aim of this study was to identify the prevalence and risk factors of hyperhomocysteinemia in patients with IBD. Sixty-five consecutive IBD patients were recruited from a tertiary outpatient gastroenterology practice. Fasting plasma homocysteine levels were measured, along with vitamin B12 and folate. Data regarding medication use, multivitamin use, disease location and severity, and extraintestinal manifestations of IBD were gathered. Homocysteine levels in 138 healthy control subjects were compared with the IBD cohort, and adjustments for age and sex were made using logistic regression. Multivariate analysis was performed to seek predictors of homocysteine levels. The mean age in the IBD cohort was 42+/-13.4 yr (+/-SD), and 43% were male. The mean disease duration was 13.8+/-9.4 yr, and 32% had used steroids within the last 3 months. Immunomodulator therapy had been used in 32%, and 75% had had an intestinal resection. Osteoporosis was present in 33% of patients. Five patients had experienced venous thrombosis or stroke, but only one of these had hyperhomocysteinemia. Of the 10 IBD patients (15.4%) with hyperhomocysteinemia, only two had vitamin B12 deficiency. The homocysteine levels in the IBD cohort cases and controls were 8.7 and 6.6 micromol/L, respectively (p < 0.05). IBD significantly increased the risk of hyperhomocysteinemia (adjusted odds ratio = 5.9 [95% CI: 1.5-24]). Advanced age, male sex, vitamin B12 deficiency or lower vitamin B12 serum levels, and multivitamin therapy were independently associated with higher homocysteine levels in the multivariate analysis (R2 = 0.55; p = 0.001). Hyperhomocysteinemia is significantly more common in patients with IBD compared with healthy controls, and is associated with lower (but not necessarily deficient) vitamin B12 levels.

Homocysteine, vascular dementia and Alzheimer's disease.

There is some evidence from recent observational studies that hyperhomocysteinemia is a risk factor for cognitive dysfunction, including Alzheimer's disease and vascular dementia. There are only a few intervention studies, and the results are disappointing for such a frequent disease. Prospective double-blind and placebo-controlled intervention studies are not available. If homocysteine-lowering therapy will be in the running for the prevention and treatment of dementia, we must be able to diagnose the disease at a preclinical stage (i.e. 5 or 10 or 20 years before the disease becomes clinically overt for Alzheimer's disease). At the moment, there are insufficient data to support a vitamin B12, B6 or folate therapy in the prevention or treatment of patients with dementia.

Vitamin B6 Therapy Does Not Improve Hematocrit in Hemodialysis Patients Supplemented with Iron and Erythropoietin

Background/Aim: Pyridoxine deficiency may be the cause of failure to respond appropriately to iron and erythropoietin (EPO) administration in hemodialysis patients. Method: We studied 36 patients on chronic hemodialysis amply supplemented with iron and EPO, who failed to raise hematocrit levels >33%. Patients were divided into three equal groups and evaluated for 6 months as follows: Group A – no additional therapy; group B – supplemented with oral pyridoxine 50 mg/day, and group C received 100 mg/day pyridoxine orally. Results: In all our patients, erythrocyte pyridoxine levels were initially within reference range for a healthy population and did not vary significantly during the study period. Likewise, ferritin levels and iron saturation values remained normal and constant. Hemoglobin and/or hematocrit levels remained practically unchanged in all three groups. Conclusions: The results indicate that in hemodialysis patients with normal pyridoxine status who, despite appropriate supplementation of iron and EPO, fail to reach optimal hematocrit levels, additional pyridoxine treatment does not produce any hematocrit elevation.

Is Vitamin B

Patients with severe depression have been shown to benefit from vitamin B12 and folate replacement therapy. It is not known whether adequate

A tale of two homocysteines—and two hemodialysis units

Pharmacologic doses of folic acid are commonly used to reduce the hyperhomocysteinemia of end-stage renal disease (ESRD). Vitamin B12 acts at the same metabolic locus as folic acid, but information is lacking about the specific effects of high doses of this vitamin on homocysteine levels in renal failure. We therefore compared the plasma homocysteine concentrations of maintenance hemodialysis patients in two McGill University-affiliated urban tertiary-care medical centers that differed in the use of vitamin B12 and folic acid therapy. Patients in the first hemodialysis unit are routinely prescribed high-dose folic acid (HI-F, 6 mg/d), whereas those in the second unit receive high-dose vitamin B12 in the form of a monthly 1-mg intravenous injection, along with conventional oral folic acid (HI-B12, 1 mg/d). Predialysis homocysteine was 23.4 +/- 6.8 micromol/L (mean +/- SD) in the HI-F unit and 18.2 +/- 6.1 micromol/L in the HI-B12 unit (P < .002). Postdialysis homocysteine was 14.5 +/- 4.1 in the HI-F unit and 10.6 +/- 3.4 micromol/L in the HI-B12 unit (P = .0001). Multiple regression analysis indicated that high-dose parenteral vitamin B12 was associated with a lower homocysteine concentration even after controlling for the potential confounders of sex, serum urea, serum creatinine, urea reduction ratio, and plasma cysteine. Because this was a cross-sectional observational study, we cannot exclude the possibility that unidentified factors, rather than the different vitamin therapies, account for the different homocysteine levels in the two units. Careful prospective studies of the homocysteine-lowering effect of high-dose parenteral vitamin B12 in ESRD should be undertaken.

MRI Findings of the Subacute Combined Degeneration of the Spinal Cord: A Case Report

Subacute combined degeneration (SCD) of the spinal cord is a neurological complication arising from vitamin B12 deficiency. Typical findings are demyelination and axonal loss of the posterior and lateral columns of the thoracic and cervical spinal cord, leading to sensory ataxia and paresthesia. Clinical and neurological features and MRI findings all contribute to the diagnosis of this entity. In the Korean medical literature, only one case of SCD involving pre-treatment MRI has been reported. We describe one case of SCD in a post-gastrectomy patient who initially presented with progressive sensory abnormality in both upper and lower extremities and showed T2 hyperintensity in the posterior and lateral columns of the spinal cord; this diminished, with clinical improvement, after vitamin B12 therapy. Our report includes the MR images obtained during follow up.

Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications

BACKGROUNDInflammatory bowel disease (IBD) is associated with an increased incidence of thromboembolic disease. Hyperhomocysteinaemia (hyper-tHcy), a condition associated with the C677T variant of 5,10-methylenetetrahydrofolate reductase (MTHFR), is linked with an...

Canine Calcium Oxalate Urolithiasis: Case-Based Applications of Therapeutic Principles

The case study presented here illustrates the diagnosis and management of calcium oxalate urolithiasis in a Bichon Frise, a breed at increased risk for this type of stone. If the Bichon Frise had persistent hypercalcemia, we would have evaluated serum concentrations of ionized calcium, parathyroid hormone, and vitamin D to identify an underlying cause. Because his urine was alkaline, additional potassium citrate was not provided. Likewise, as a fortified diet was fed to him, vitamin B6 therapy was not considered. This case study illustrates the benefits of radiographic evaluation immediately following surgery and during follow-up examinations. If we had postponed radiographs until the patient developed clinical signs, additional surgical procedures may have been required.

Clinical features of circadian rhythm sleep disorders in outpatients

The clinical data of 86 cases of primary circadian rhythm sleep disorder (primary CRSD) were retrospectively examined and compared to 40 cases of secondary circadian rhythm sleep disorder (secondary CRSD), who had presented with some kind of psychiatric or medical disorder, and had exhibited sleep-wake rhythm disorders that were judged to be secondary CRSD based on sleep logs. The comparison of cases found that: (i) the mean age at first presentation to the clinic was significantly younger for primary CRSD compared to secondary CRSD; (ii) more secondary CRSD cases were unemployed than were Primary CRSD cases; (iii) more cases in the secondary CRSD group had a clear trigger for sleep-wake rhythm disorder onset than cases in the primary CRSD group; and (iv) the types of sleep-wake rhythm disorders in the primary CRSD group consisted of delayed sleep phase syndrome (DSPS), 72 (83.7%), non-24 pattern, 11 (12.8%), and irregular, 3 (3.5%). In the secondary CRSD group there were 25 (62.5%) cases of DSPS pattern, 1 (2.5%) of non-24 pattern and 14 (35.0%) with irregular pattern. The 56 (65.1%) cases with primary CRSD showed good response to vitamin B12 and bright light therapy; however, 28 (70.0%) cases with secondary CRSD did not respond to such therapies.

Atypical vitamin B12-unresponsive methylmalonic aciduria in a sibship with severe progressive encephalomyelopathy: A new genetic disease?

We report on two siblings, a girl of 7 years and a boy of 2 years, who presented in infancy with hypotonia, athetoid movements, myopathy and severe developmental delay. The progressive clinical course was characterized by ophthalmoplegia, pyramidal tract signs, loss of visual contact and failure to thrive. The older sister died at the age of 7 years. The younger brother followed an almost identical clinical course. MRI of the brain revealed bilateral hypodensities and atrophy of the putamen. Neurophysiological investigations were consistent with peripheral neuropathy. Investigations for neurometabolic disorders in urine, plasma and CSF of both patients revealed a consistent increase of methylmalonic acid in urine, plasma and CSF as well as borderline low free GABA in CSF. Except for an inconstant elevation of lactate in the boy, metabolic acidosis, hypoglycaemia, episodic ketoacidosis, or hyperammonaemia, the usual concomitants of organoacidopathies, were absent in both children. Homocystinuria was excluded. Methylmalonic aciduria did not respond to antibiotic treatment, vitamin B12 therapy nor dietary protein restriction. Incorporation of [14C]propionate into protein in cultured fibroblasts was pathologically but inconsistently decreased. Both patients' cell lines showed only minimal response to hydroxocobalamin and normal methylmalonyl-CoA mutase activity. Even though the definitive underlying enzymatic defect in this sibship remains obscure our results suggest a new genetic disorder. This report illustrates that hitherto undescribed metabolic disorders remain to be elucidated even in long investigated areas of intermediary metabolism such as methylmalonic aciduria.