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Vitamin B12 (cobalamin) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. The role of B12 deficiency in hyperhomocysteinemia and the promotion of atherosclerosis is only now being explored. Diagnosis of vitamin B12 deficiency is typically based on measurement of serum vitamin B12 levels; however, about 50 percent of patients with subclinical disease have normal B12 levels. A more sensitive method of screening for vitamin B12 deficiency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B12 deficiency. Use of the Schilling test for detection of pernicious anemia has been supplanted for the most part by serologic testing for parietal cell and intrinsic factor antibodies. Contrary to prevailing medical practice, studies show that supplementation with oral vitamin B12 is a safe and effective treatment for the B12 deficiency state. Even when intrinsic factor is not present to aid in the absorption of vitamin B12 (pernicious anemia) or in other diseases that affect the usual absorption sites in the terminal ileum, oral therapy remains effective.
Vitamin B12 is implicated in methylation processes. Myelin basic protein is methylated on one arginine group. A defect in methylation could produce an unstable protein, leading to neurological disorders. In order to study myelin basic protein, we have developed the cultures of newborn rat oligodendrocytes in vitamin B12-depleted medium. As these cells do not grow without serum, vitamin B12 is always present. We overcame this problem by using OH-cobalamin c-lactam, an antagonist of B12. To ensure that the system was vitamin B12 deficient, we measured the concentrations of homocysteine and methylmalonic acid whose accumulations reflect a vitamin B12 deficiency. Methylmalonic acid was measured by mass spectrometry and homocysteine by HPLC. We obtained a powerful model for studying the influence of B12 deficiency on the synthesis of myelin compounds.
Vitamin B12 (cyanocobalamin) is an integral component of two biochemical reactions in man: the conversion of L-methylmalonyl coenzyme A into succinyl coenzyme A and the formation of methionine by methylation of homocysteine. The transmethylation reaction is essential to DNA synthesis and to the maintenance of the myelin sheath by the methylation of myelin basic protein. Active vitamin B12 contains cobalt in its reduced form (Co+). Nitrous oxide produces irreversible oxidation to the Co++ and Co forms that renders vitamin B12 inactive. Five cases (four from the literature and one new case) are presented in which patients unsuspected of having vitamin B12 deficiency developed subacute combined degeneration of the spinal cord following nitrous oxide anesthesia. Patients with vitamin B12 deficiency are exceedingly sensitive to neurologic deterioration following nitrous oxide anesthesia. If unrecognized, the neurologic deterioration becomes irreversible and may result in death.
Vitamin B12 deficiency is common, with most patients lacking classic features of advanced severe deficiency. Early diagnosis and treatment prevent severe anemia and irreversible damage to the nervous system. We describe a 34-year-old man with pernicious anemia who presented with clinical and radiologic features of early myelopathy and borderline low serum levels of vitamin B12. Prompt diagnosis based on the measurement of serum methylmalonic acid and treatment with cyanocobalamin injections led to rapid resolution of clinical manifestations and magnetic resonance imaging abnormalities. We review the literature of magnetic resonance imaging in vitamin B12 deficiency myelopathy and discuss the issues relating to diagnosis and early treatment of this potentially reversible condition.
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Vitamin B12 deficiency causes decreased Methionine Synthase and L-Methylmalonyl-CoA Mutase activity and results in accumulation of Homocysteine, Methylmalonic acid and Propionylcarnitine. Propionylcarnitine is included in tandem mass spectrometry-based newborn screening programs for detection of certain inborn errors of metabolism. We report two asymptomatic newborns with Vitamin B12 deficiency due to maternal deficiencies. One was detected incidentally at 3 weeks of age; the second on supplemental newborn screening based on elevated Propionylcarnitine at 2 days of age. This illustrates the potential for false negative results for Vitamin B12 deficiency screening by acylcarnitine profiling in newborn screening. Homocysteine and Methylmalonic acid may be better markers of Vitamin B12 deficiency. In conclusion, we suggest measuring Methylmalonic acid, Propionylcarnitine and Homocysteine levels in blood spots in expanded newborn screening in order to detect asymptomatic newborns with Vitamin B12 deficiency. Further studies are needed to establish the sensitivity of these three markers in screening for Vitamin B12 deficiency.
BACKGROUND: Vitamin B12 deficiency in infancy may cause failure to thrive, severe neurological disorders and megaloblastic pancytopenia. It is well known that infants born with deficient vitamin B12 storage have increased the risk of vitamin B12 deficiency. Vitamin B12 deficiency is more prevalent in infancy in Sanliurfa province (at the southeast region of Turkey). AIM OF THE STUDY: The aim of this study was to determine the frequencies of vitamin B12, folic acid and iron deficiencies in pregnants and their babies at birth and to what extend the mothers' deficiency becomes effective on babies' deficiencies. METHODS: The study groups were constituted by 180 pregnant women and their single and term babies. Venous blood samples of pregnants were obtained 1-3 h before delivery and babies' cord bloods were collected at birth. Vitamin B12 and folic acid levels were measured with electro chemiluminiscence method; serum iron and iron binding capacities were measured by colorimetric method and complete blood counts were performed by automatic blood counter. RESULTS: Mean vitamin B12 levels in maternal and cord blood serum were 130 +/- 61.7 pg/ml and 207 +/- 141 pg/ml; mean folic acid levels were 8.91 +/- 6.46 ng/ml and 17.8 +/- 11.8 ng/ml; mean serum iron levels were 56.9 +/- 37.5 microg/dl and 147 +/- 43.2 microg/dl; and mean transferrin saturations were 11.8 +/- 8% and 65.6 +/- 24%, respectively. There were vitamin B12 deficiency (<160 pg/ml) in 72% of the mothers and 41% of the babies, and severe deficiency (<120 pg/ml) in 48% of the mothers and 23% of the babies. Folic acid deficiency was found in 12% of the mothers, but was not found in the babies. There were iron deficiency in 62% of the mothers and 1% of the babies. There were statistically significant correlation between maternal and cord blood serum vitamin B12 levels (r = 0.395, P < 0.001) and folic acid levels (r = 0.227, P = 0.017), while there were no correlation between maternal and cord blood iron levels and transferrin saturations. CONCLUSION: The study results showed that vitamin B12 deficiency is prevalent in pregnants in this region and that 41% of infants have born with deficient vitamin B12 storages. Therefore, prophylactic use of vitamin B12 by pregnant women in Sanliurfa and other poor communities could have considerable benefits to prevent vitamin B12 deficiency and its complications in infants.
BACKGROUND: Vitamin B12 deficiency is common and rises with age. Most people with vitamin B12 deficiency are treated in primary care with intramuscular vitamin B12 which is a considerable source of work for health care professionals. Several case control and case series studies have reported equal efficacy of oral administration of vitamin B12 but it is rarely prescribed in this form, other than in Sweden and Canada. Doctors may not be prescribing oral formulations because they are unaware of this option or have concerns regarding effectiveness. OBJECTIVES: To assess the effectiveness of oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. SEARCH STRATEGY: Searches were undertaken of The Cochrane Library, MEDLINE, EMBASE and Lilacs in early 2005. The bibliographies of all relevant papers identified using this strategy were searched. In addition we contacted authors of relevant identified studies and Vitamin B12 research and pharmaceutical companies to enquire about other published or unpublished studies and ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) examining the use of oral or intramuscular vitamin B12 to treat vitamin B12 deficiency. DATA COLLECTION AND ANALYSIS: All abstracts or titles identified by the electronic searches were independently scrutinised by two reviewers. When a difference between reviewers arose, we obtained and reviewed a hard copy of the papers and made decisions by consensus. We obtained a copy of all pre-selected papers and two researchers independently extracted the data from these studies using piloted data extraction forms. The whole group checked whether inclusion and exclusion criteria were met, and disagreement was decided by consensus. The methodological quality of the included studies was independently assessed by two researchers and disagreements were brought back to the whole group and resolved by consensus. MAIN RESULTS: Two RCT's comparing oral with intramuscular administration of vitamin B12 met our inclusion criteria. The trials recruited a total of 108 participants and followed up 93 of these from 90 days to four months. High oral doses of B12 (1000 mcg and 2000 mcg) were as effective as intramuscular administration in achieving haematological and neurological responses. AUTHORS' CONCLUSIONS: The evidence derived from these limited studies suggests that 2000 mcg doses of oral vitamin B12 daily and 1000 mcg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short term haematological and neurological responses in vitamin B12 deficient patients.
The effect of a vitamin B12 and folic acid deficient diet on juvenile and adolescent baboons (Papio cynocephalus anubis) was studied. The baboons developed clinical and hematological signs characteristics of folacin deficiency, although they were less severe in juvenile baboons. The signs disappeared when folic acid was replaced in the diet. The serum vitamin B12 levels increased in all baboons fed the vitamin B12 and folic acid deficient diet. When folic acid was added to the diet, the levels gradually decreased in adolescent baboons, liver vitamin B12 levels decreased to a lesser extent when fed a vitamin B12 and folic acid deficient diet than when fed a vitamin B12 deficient diet. In juvenile baboons fed a vitamin B12 and folic acid deficient diet, for 7 months and a vitamin B12 deficient diet for a further 11 months, liver vitamin B12 levels did not decrease at any time but were similar to those in baboons fed a vitamin B12 and folic acid supplemented diet.
Vitamin B12 (cobalamin) deficiency is a common disorder with potential irreversible haematological and neurological consequences. Currently used diagnostic tests such as the evaluation of serum vitamin B12 and the Schilling test are insufficient, e.g. the positive predictive value of a low serum vitamin B12 level for actual vitamin B12 deficiency (i.e. tissue deficiency) is low. Insufficient availability of vitamin B12 will lead to the accumulation of methylmalonic acid and homocysteine in the body. Nearly all patients with vitamin B12 deficiency also have substantially increased levels of methylmalonic acid and homocysteine. New tests of serum methylmalonic acid and homocysteine are highly sensitive for vitamin B12 deficiency and may obviate the need for the somewhat cumbersome Schilling test.
PURPOSE: Neurological symptoms of B12 vitamin deficiency are polymorph. Causes are dominated by Biermer's disease and B12 vitamin non dissociation that is frequent in the elderly. METHODS: We realized a retrospective study during 11 years. Patients with neurological symptoms associated to megaloblastosis were included. Treatment with B12 vitamin lead to haematological manifestation regression. RESULTS: 26 cases were analyzed. Mean age was 50+/-14.5 years and there were 11 women and 15 men. Neurological signs included combined medullar sclerosis (N = 10), peripheral neuropathy (N = 10), isolated paresthesia (N = 5) and inferior limb pyramidal syndrome (N = 1). Neurological signs revealed vitamin B12 deficiency in 4 cases. Mean haemoglobin rate was 6.2+/-2.6 g/dl, mean MCV was 109+/-56 fl. Eight patients had macrocytic anaemia, nine bi-cytopenia and eight deep pancytopenia. Electromyography (N = 8) confirmed neuropathy and medullar MRI (N = 2) showed antero-posterior cordonal demyelinisation of cervico-dorsal medulla. Causes of B12 vitamin deficiency were Biermer's disease (N = 11), non dissociation of B12 vitamin's syndrome (N = 8) and partial gastrectomy (N = 1). In 6 patients, no aetiology was found. Treatment with parenteral vitamin B12 induced neurological symptoms regression in 14 cases. Patient with neurological disorder had significantly higher platelet count and haemoglobin level as compared with patients without neurological disorder. Reticulocyte crisis was more precocious in patients with neurological disorders. CONCLUSION: Neurological symptoms in vitamin B12 deficiency are frequent. We insist on isolated forms, inaugural forms and on the interest of medullar MRI for early diagnosis.
Since vitamin B12 serves as a cofactor in the synthesis of methyl precursors for biological methylation and enables methylfolate to be recycled for nucleotide synthesis, B12 deficiency has been known to induce hyperhomocysteinemia and inadequate DNA synthesis, along with "methylfolate trap". Even though depletion of B12, a common B-vitamin deficiency in the elderly, has not often been invoked as a causative factor in carcinogenesis, a recent animal study demonstrated that a B12-deficient diet, which was of insufficient severity to cause anemia or illness, disturbed normal homeostasis of one-carbon metabolism in the colonic mucosa and resulted in diminished genomic DNA methylation and increased uracil misincorporation in DNA, both of which are purported mechanisms for one-carbon metabolism-related colonic carcinogenesis.
Orthostatic hypotension (OH) and vitamin B12 deficiency are common disorders in older people. Several case series have reported an association between vitamin B12 deficiency and OH. The effect of vitamin B12 replacement on this dysfunction has not been studied. We prospectively studied responses to head up tilt in patients over 70 years with vitamin B12 deficiency (intervention group) and compared their responses after replacement to those of matched patients with idiopathic OH and normal serum vitamin B12 concentrations (control group). Blood pressure (BP), heart rate (HR) and systemic vascular resistance (SVR) changes during orthostatic stress were evaluated using digital artery photoplethysmography. Eight patients and eight controls were studied. Initial head up tilt produced a mean BP decrease of 44/29 mmHg (s.e.m. 4/4 mmHg) in the intervention group and 33/12 mmHg (s.e.m. 3/2 mmHg) in the control group. Repeat head up tilt 6 months after vitamin B12 replacement produced a mean BP decrease of 15/9 mmHg (s.e.m. 5/2 mmHg) in the intervention group. The mean decrease in the control group was 30/12 mmHg (s.e.m. 2/2 mmHg). The difference in BP decreases between groups was statistically significant for both systolic and diastolic BP (p < 0.001 for both systolic BP and diastolic BP). Mean SVR in the intervention group decreased by 658 dynes/cm5/sec (s.e.m. 74 dynes/cm5/sec) during initial head up tilt. Mean SVR during repeat head up tilt decreased by 79 dynes/cm5/sec (s. e. m. 12 dynes/cm5/sec). Mean SVR in the control group decreased by 158 dynes/cm5/sec (s. e. m. 10 dynes/cm5/sec) during initial head up tilt and by 258 dynes/cm5/sec (s. e. m. 31 dynes/cm5/sec). The difference in SVR changes between groups was statistically significant (p = 0.02). We conclude that replacing vitamin B12 in older patients with vitamin B12 deficiency is associated with improved orthostatic tolerance to head up tilt.
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Low serum vitamin B12 levels are not uncommon in the elderly. Patients with vitamin B12 deficiency manifest a spectrum of clinical findings. Pernicious anemia and malabsorption syndrome are the usual causes of vitamin B12 deficiency. Pernicious anemia is confirmed by the presence of intrinsic factor blocking antibody or abnormal results on the Schilling test. Patients with neuropsychiatric symptoms of vitamin B12 deficiency may have a normal Schilling test and no evidence of macrocytic anemia. In such patients, vitamin B12 deficiency is confirmed by determining serum levels of homocysteine and methylmalonic acid.
Vitamin B12 deficiency has been shown to result in an increase in content and activity of the hepatic cytosolic enzymes of fatty acid synthesis. The present study demonstrated that ATP citrate lyase, an enzyme whose activity has been positively correlated with rates of fatty acid biosynthesis, also increased in the livers of B12-deficient animals. Total and specific activity of hepatic citrate synthase, an enzyme whose activity is unaffected by a variety of dietary and hormonal changes, also was found to be increased in the B12-deprived state. By contrast, the activity of hepatic succinate-cytochrome c reductase, a portion of a multicomponent enzyme complex synthesized in part within the mitochondria, was unchanged in B12 deficiency. Vitamin B12 deprivation resulted in an increase in hepatic mitochondrial cristae membranes in both animals and man. Histochemical and chemical analysis demonstrated increased glycogen in the liver cells from B12-deficient animals and man. Thus, in the livers from vitamin B12-deficient animals there is an increased activity of the otherwise highly constant Krebs cycle enzyme citrate synthase, and in both animals and man there are increased mitochondrial cristae membranes.
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