Low Serum Vitamin B12 Research Articles

Frequency of intrinsic factor antibody in megaloblastic anaemia.

To evaluate the presence of intrinsic factor antibody in vitamin B12 deficient patients. Cross-sectional, observational study. Fauji Foundation Hospital, Foundation University Medical College and Armed Forces Institute of Pathology, Rawalpindi, from January 2011 to June 2012. A total of 120 patients of megaloblastic anaemia were selected on the basis of low serum vitamin B12 level. The intrinsic factor antibody tests were performed by ELISA method. The patients were considered positive or negative on the basis of presence or absence of intrinsic factor antibody respectively. The data was analyzed by using SPSS version 14. Pernicious anaemia with intrinsic factor deficiency was found in 13.3% in 120 vitamin B12 deficient patients. The mean age of patients of pernicious anaemia was 41.5 years, with a male to female ratio of 1:2.5. It was relatively more common in older age (17% in age more than 60 years) as compared to other age groups. Frequency of pernicious anaemia in megaloblastic anaemia was 13.3%. The male to female ratio was 1:2.5 and it was relatively more common in age group of more than 60 years.

Low serum vitamin B12 levels among psychiatric patients admitted in Butabika mental hospital in Uganda

BackgroundPsychiatric manifestations have been noted in patients with low serum vitamin B12 levels even in the absence of other neurologic and/or haematologic abnormalities. There is no literature on low serum B12 prevalence among Ugandans with psychiatric illnesses. The aim of this study was to establish the prevalence, risk factors, and clinical manifestations of low serum vitamin B12 among psychiatric patients admitted in a Mental Health Hospital in Uganda.MethodUsing a cross sectional descriptive study design, 280 in-patients selected by systematic sampling were studied using a standardized protocol. Low serum vitamin B12 was defined as a level < 240 pg /mL.ResultsWe found a prevalence of low serum B12 in 28.6% of the participants. Absent vibration sense which was significantly associated (58.3% Vs. 26.7%: OR = 3.84 (95% C.I. 1.18, 12.49); p-value = 0.025) with low vitamin B12 was observed among 12 participants. Macro-ovalocytes present among 23 participants on peripheral film were significantly associated with low serum levels (73.9% Vs. 26.2%: OR = 7.99 (95% C.I. 3.01, 21.19) p-value < 0.0001). Factors significantly associated with low serum B12 levels included psychiatric diagnosis of schizophrenia (AOR 1.74 (95% C.I. 1.00, 3.02); p-value = 0.049), duration of psychiatric illness > or = 3 years (AOR 2.27 (95% C.I. 1.29, 3.98); p-value = 0.004), and hospitalization < 3 weeks (AOR 4.01 (95% C.I. 1.02, 15.79); p-value = 0.047). Female participants were associated with protection from low serum levels (AOR 0.4 (95% C.I. 0.22, 0.73); p-value = 0.003).ConclusionLow serum B12 is common among hospitalized psychiatric patients with the majority having no haematological findings. Associated risk factors included having a psychiatric diagnosis of schizophrenia, a shorter duration of hospitalization and longer duration of psychiatric illness. Female participants were less likely to have low serum vitamin B12 levels. Routine screening for serum vitamin B12 levels should be adopted by all hospitals for admitted psychiatric patients.

Among Vitamin B12 Deficient Older People, High Folate Levels are Associated with Worse Cognitive Function: Combined Data from Three Cohorts

Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed. To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment. Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer's disease were excluded. A Mini-Mental State Examination score of <24 was used to define impaired cognitive function. Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60-7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance (AOR 1.74, 95% CI: 1.03-2.95, p = 0.04). High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority.

Evaluation of serum vitamin B12 levels and its correlation with anti-thyroperoxidase antibody in patients with autoimmune thyroid disorders.

Vitamin B12 deficiency has been reported in patients with Autoimmune thyroid disorders. However there is limited data on exact prevalence of low B12 and its correlation with anti-thyroperoxidase antibody (anti-TPO) levels in these patients. The aim of our study was to estimate serum vitamin B12 levels in autoimmune thyroid disorders and to correlate B12 levels with anti-TPO. 350 patients were selected by convenient sampling. Vitamin B12 levels and thyroid parameters were estimated using fully automated chemiluminescence method on Access 2. Results of our study shows that using the manufacturer's cut-off of 145pg/mL, the prevalence of low serum vitamin B12 was found to be 45.50%. Higher prevalence (55%) was seen based on the published cut-off of 200pg/mL The study however did not demonstrate any significant correlation between vitamin B12 levels and anti-TPO (r=-0.11 and p value of 0.30).

Vitamin B12 Deficiency in Children

Vitamin B12 deficiency in children can rarely cause neurologic manifestations. In this series, 14 pediatric cases (median age 11 months) have been described in whom association of vitamin B12 deficiency with developmental delay or regression was observed. Severe to profound delay was present in 8 (57%) patients. All the patients were exclusively or predominantly breast-fed and 10 of 12 mothers had low serum vitamin B12 levels. Three to 6 months after treatment, a mean gain of development quotient of 38.8 points was seen in 7 follow-ups. In settings with a high prevalence of vitamin B12 deficiency, this association should be actively searched for.

Clinical, nerve conduction and nerve biopsy study in vitamin B12 deficiency neurological syndrome with a short-term follow-up

ObjectiveThe frequency and type of neuropathy in vitamin B12 deficiency neurological syndrome (VBDNS) is controversial. This study reports the frequency and type of nerve dysfunction in VBDNS using nerve conduction and sural nerve biopsy and its response to treatment.MethodSixty-six patients with VBDNS diagnosed on the basis of low serum vitamin B12 level and/or megaloblastic bone marrow were subjected to clinical evaluation, hemoglobin, mean corpuscular volume, thyroid function test, HIV serology, and vasculitic profile. Peroneal motor and sural sensory nerve conduction studies were done. Sural nerve biopsy was done in six patients. The patients were treated with cyanocobalamin injection and followed up clinically and with nerve conduction study at 3 and 6 months.ResultsThe median age of the patients was 46 (12–80) years and 11 patients were females. The duration of symptoms was 1–96 (median 7) months. Clinical features of neuropathy were present in 46 (69.7%) patients and nerve conduction was abnormal in 36 (54.5%) patients. On nerve conduction study, 8 (22.2%) patients had axonal, 4 (11.1%) had demyelinating, and 24 (66.7%) had mixed features. Nerve biopsy revealed acute axonal degeneration in early stage and chronic axonopathy with demyelination in the late stages of disease. The nerve conduction parameters improved at 6 months along with clinical recovery.ConclusionNearly 70% patients with VBDNS had evidence of neuropathy which is mainly axonal with some demyelinating features.

Low Serum Vitamin B12 With Supplement In Pernicious Anemia

Pernicious anemia is commonly associated with autoimmune disorders. This abstract will describe three cases with low serum Vitamin B12 even with 2 weeks Vitamin B12 inrtamuscular injection of 1000 micrograms. First patient is thirty nine 39 years old white male with known history of pernicious anemia and Alopecia Totalis with prior history of Methotrexate and cyclosporin treatment. The patient had low serum iron and low iron saturation at initial presentation. He was given IV Iron supplement to saturate iron stores with good result. However, his serum vitamin B12 remain border line low normal below 300 pg/ml ( patient’s level is 210, normal range 180-941 pg/ml), even with every two weeks IM injection for more than six months. Patient was also given oral supplement with no increase in the serum vitamin B12 level. The second patient is sixty eight 68 years old white female with history of colon cancer that underwent resection and history of Hashimoto’s Thyroiditis who was on Thyroid hormonal supplement. Her serum Vitamin B12 level remain borderline low below 300. The third patient is forty 40 years old white female with history of Hypothyroidism and breast cancer that had received adjuvant chemotherapy post Lumpectoy and radiation therapy. This patient was treated with IV intravenous iron supplement for iron deficency with good result. All three patients had blocking antibodies to intrinsic factor and presented with various degree of iron deficency and treated with oral as well as IV iron supplement. Peripheral blood smear were reviewed on all the three patients. Hypersegmentation of neutrophils was seen with normocytic normochromic red cell morphology. One patient had low plateletes count. All patients had white blood cell counts below ten thousands. Two patients showed excess of apoptotic neutrophils. None of the patients had enlarged spleen or adenopathy or evidence of bone marrow hypofunction. All of the above patients improved clinically interm of sense of well being and increased level of energy with vitamin B12 supplement. None of the above patients had abnormal liver or kidney function. All patients had low serum vitamin B12 with one monthly dose IM injection plus oral supplement. All patients had normal LDH level and normal Folic acid level. In conclusion The low serum vitamin B12 levels with adequate supplement that should saturate the liver reserve open an interesting question about the possiblility of Transcobalamine receptor abnormality interm of abnormal function or deficency. Antibodies blocking the receptors or rapid neutrophils turn over is another possibility. Further study needed to solve this delema. Disclosures: No relevant conflicts of interest to declare.

Do MCI patients with vitamin B12 deficiency have distinctive cognitive deficits?

BackgroundVitamin B12 deficiency is common in older people, and may be responsible for reversible dementia. Low serum vitamin B12 levels were also observed in patients with Mild Cognitive Impairment (MCI). It is not known whether patients with vitamin B12 deficiency have a distinctive profile of cognitive impairment different from the episodic memory deficit usually observed in MCI.ResultsFrom a cohort of 310 patients with MCI followed in a memory clinic in Lisbon, only 10 cases with vitamin B12 deficiency were found. From collaboration with other neurologists, 5 further patients with vitamin B12 deficiency were added. These cases were compared to MCI patients with normal vitamin B12 levels in a ratio 1:3. The duration of subjective cognitive symptoms was significantly shorter in MCI patients with B12 deficiency (1.2±1.0 years) as compared to MCI patients with normal vitamin B12 levels (3.4±3.0 years, p<0.001, Student’ t test). There were no statistically significant differences in the neuropsychological tests between MCI patients with and without vitamin B12 deficiency. Vitamin B12 was started in MCI patients with vitamin B12 deficiency, with no noticeable clinical improvement.ConclusionMCI patients with low levels of vitamin B12 had no particular profile of cognitive impairment, however vitamin B12 deficiency might have precipitated the onset of symptoms. The effect of vitamin B12 supplementation in patients with MCI and low vitamin B12 levels should be clarified by future prospective studies.

Spastic Quadreparesis - An Unusual Presentation of Sub-acute Combined Degenaration of Spinal Cord

We report a case of a 45-year-old gentleman presenting with numbness of both legs and hands. He has anemia, spastic quadriplegia with exageraterd tendon jerks with lose of vibration and position sense. Investigations revealed combined deficiency anemia with low serum vitamin B12. His MRI of cervicel spine was normal. Endoscopically he had atrophic gastritis. Ultimately he was dignosed as a case of sub-acute combined degeneration of spinal cord due to pernicious anemia. Patient was treated with injection vitamin B12 and well responded. On his followup, he had significant clinical improvement. This is a reversible condition if early diagnosis can be made and vitamin B12 therapy promptly given. Delayed treatment can result in irreversible neurological impairment.DOI: http://dx.doi.org/10.3329/jom.v14i1.14585 J MEDICINE 2013; 14 : 85-87

Pigmentation in vitamin B12 deficiency masquerading Addison′s pigmentation: A rare presentation

A 35-year-female presented with generalized weakness, weight loss, and progressive pigmentation was worked up for suspicion of Addisons disease. On examination hyper pigmentation was noted on both palmar and dorsal aspect of hands involving knuckles, creases, feet, tongue, oral mucosa and gluteal region. There was no evidence of hypocortisolemia as initially suspected, and literature search revealed a possibility of vitamin B12 deficiency. She had megaloblastic anemia with a low serum vitamin B12, mostly due to poor dietary intake. Her hyper pigmentation resolved with vitamin B12 supplementation. Skin biopsy showed increased pigmentation at stratum spinosum and basal-layer. The mechanism of hyper pigmentation in vitamin B12 deficiency was due to an increase in melanin synthesis.

Vitamin B12 in pregnancy: Maternal and fetal/neonatal effects—A review

Vitamin B12 maintains normal folate metabolism which is essential for cell multiplication during pregnancy. No good data are available on what constitutes vitamin B12 deficiency in pregnancy, nevertheless vitamin B12 deficiency is frequently reported in pregnancy due to inadequate dietary intake of vitamin B12 and a physiological decline of maternal vitamin B12 concentrations. This decline can be explained by the increased maternal metabolic rate and active transport by the placenta to the fetus. If the mother is deficient during pregnancy, the baby may have low serum vitamin B12 concentrations at birth [1]. Vitamin B12 deficiency during pregnancy is associated with preeclampsia, fetal growth restriction, preterm labor, neural tube defects, neonatal megaloblastic anemia and neonatal neurological symptoms. It has been suggested to improve vitamin B12 status of women in the periconceptional period by supplementation of vitamin B12, but no randomized studies on the outcome of such supplementation have been published.

Prevalence of vitamin B12 deficiency in Helicobacter pylori infected patients in Jordan.

Objective: The purpose of this study is to assess the frequency of vitamin B 12 deficiency in patients with Helicobacter pylori (H. pylori) infection to determine whether low serum vitamin B12 levels correlate with serological evidence of H. pylori infection. Background: An association between H. pylori infection and vitamin B12 deficiency has been recently reported. Subjects: From 200 people blood was collected. For each subject serum vitamin B12, folic acid, complete blood count and H. pylori IgG antibodies were measured. 150 subjects have H. pylori infection and 50 subjects healthy control group. The following cases were excluded, history of H. pylori eradication or antacid take, liver disease, chronic alcoholism inflammatory bowel disease, previous gastrointestinal surgery and a vegetarian diet or multivitamin supplementation. Results: Vitamin B12 deficiency was found in 87(58%) patients with seropositive H. pylori IgG antibodies (HP+) versus 9 (18%) patients with seronegative H. pylori IgG antibodies (HP).The mean±SD of serum vitamin B12 level in overall subjects (males and females) was 345.717± 215.214 and 271.254±35.234 (p < 0.01) respectively. The mean±SD of serum vitamin B12 level in H. pylori infected subjects was 295,574±71,482 versus 411,973±368,241in healthy group (p < 0.02). The mean±SD of serum vitamin B 12 level in overall H. pylori infected subjects with vitamin B12 deficiency (male and female) was 142±24.423 and 144.322±18.736 (p < 0.02) where it was 565.197±149.488 and 615.33±139.981 with normal serum vitamin B12 level in the same group. Hemoglobin and hematocrit levels were significantly lower in H. pylori positive subjects, hemoglobin (g/dL) was 13.5±0.15 mean±SD versus 14.2±0.25, p < 0.05 and hematocrit (%) 40.1±0.35 versus 42 ±0.7 p < 0.05, Mean Corpuscular Volume (MCV) (μm3) was 95±2% versus 85±2%. Folic acid levels (normal range 4.6-12.7 ng/ml) were significantly lower in H. pylori seropositive subjects (5.65±0.2 versus 9.1±0.5 p < 0.05). Conclusion: Collectible results suggest a causal relationship between H. pylori infection and vitamin B12 deficiency in Jordanians.

Níveis séricos de vitamina B12 não se relacionam com baixa densidade mineral óssea em mulheres brasileiras na pós-menopausa

Osteoporosis and vitamin B12 deficiency are conditions with an increasing prevalence over time. It has been described an association between low serum vitamin B12, osteoporosis and increased risk of bone fractures, but the studies are heterogeneous and the results are controversial. To investigate the association between plasma levels of vitamin B12 and bone mineral density in a group of asymptomatic women after menopause. Asymptomatic postmenopausal women were consecutively invited to participate in this cross-sectional study. Bone mineral density (lumbar spine and femur) was measured by DXA Lunar Prodigy Vision, and blood levels of vitamin B12, calcium, phosphorus, bone alkaline phosphatase (BAF), and parathyroid hormone were determined. For the diagnostic of osteoporosis the World Health Organization criteria were considered. Seventy women were included, mean age 62.5 ± 7 years. Eighteen (25.7%) women had normal bone mineral density, 33 (47.1%) had osteopenia and 19 (27.1%) had osteoporosis. Six (8.6%) patients had wrist fracture; two (2.8%) reported a diagnosis of vertebral fracture and only one (1.4%) patient had suffered a hip fracture. The levels of vitamin B12 (mean ± SD, pg/mL) of women with normal bone mineral density, osteopenia and osteoporosis were 590.2 ± 364.3, 536.6 ± 452.3, and 590.2 ± 497.9, respectively (P = 0.881). Multiple regression analysis showed that body mass index and BAF were the main predictors of lumbar spine bone mineral density. The results indicate that vitamin B12 serum levels are not related to bone mineral density in this group of Brazilian postmenopausal women.

Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2 diabetes

Contradictory results for concentrations of vitamin B12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) have been reported. We tested the hypothesis that the extracellular vitamin B12 markers are not reflecting the intracellular vitamin B12-dependent biochemical reactions in individuals with type 2 diabetes. The study included 92 patients with diabetes and 72 controls with similar age and sex distribution. We measured vitamin B12 markers [MMA, total serum vitamin B12, holoTC, total homocysteine (tHcy)], red blood cell (RBC)-B12, and the plasma concentrations of the methylation markers [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)]. In comparison to controls, diabetic patients showed significantly higher concentrations of plasma SAH (median 15.1 vs. 11.8nmol/L; p<0.001) and lower SAM/SAH ratio (9.1 vs. 8.2; p=0.006). Concentrations of total vitamin B12 andholoTC did not differ significantly between the groups, but plasma MMA concentrations were significantly higher in diabetics (250 vs. 206nmol/L). However, RBC-B12 was lower in diabetics compared tocontrols (median 230 vs. 260pmol/L; p=0.001). The inverse correlation between MMA and RBC-B12 was stronger in the controls compared to that in the patients (correlation coefficient in controls R=-0.446, p=0.001; in patients R=-0.289, p=0.022). Metformin treatment was associated with a lower total serum vitamin B12, but a comparable RBC-B12 and a slightly lower MMA and better methylation index. In conclusion, patients with type 2 diabetes showed normal extracellular vitamin B12, but disturbed intracellular B12-dependent biochemical reactions. Metformin treatment was associated with low serum vitamin B12 and improved intracellular vitamin B12 metabolism despite low serum vitamin B12.

Low vitamin B12 levels and gastric parietal cell antibodies in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders

In up to 80 % of patients, neuromyelitis optica (NMO, Devic’s syndrome), is associated with antibodies to aquaporin-4 (AQP4-Ab), the most abundant water channel in the central nervous system [2, 6–8, 10, 11]. However, AQP4 is also highly expressed in the basal cell membrane of gastric parietal cells (GPC) and, accordingly, serum AQP4-Ab from patients with NMO has been shown to bind to GPC [10]. The latter fact is of particular interest because humoral autoimmunity to GPC is a common cause of vitamin B12 deficiency and because low vitamin B12 levels can cause subacute combined degeneration of the spinal cord (SACD) as well as optic neuropathy and may thus aggravate neurological deficits in patients with NMO, a disease mainly characterized by spinal cord and optic nerve damage (Fig. 1) [14]. Moreover, AQP4-Ab is known to be frequently associated with other, co-existing autoantibodies; however, the frequency of gastric parietal cell antibodies (PCA) in NMO has not been systematically studied so far. We retrospectively identified 13 patients with NMO spectrum disorders (NMOSD) in whom vitamin B12 levels had been determined as part of the diagnostic workup (Table 1). All of these patients were AQP4-IgGpositive. In 6 of the 13 patients (46.2 %) vitamin B12 serum levels were low (\300 pmol/l) [12]. Levels ranged between 118 and 204 pmol/l (median, 150 pmol/l) (Table 1). Methylmalonic acid (MMA) and homocystein (HC), respectively, two markers of vitamin B12 deficiency, had been determined in two of these patients and were elevated in both (MMA: 5.19 mg/g creatinine, reference range,\2; HC: 15.4, reference range,\13.9). In three further patients, repeat testing was done and confirmed the low serum vitamin B12 status (160 pmol/l at baseline and 170 pmol/l 24 months later in patient 1; 204 at baseline and 259 64 months later in patient 2; 166 at baseline, 174 1 month later, and 139 another 18 months later in patient 3). Classical cytoplasmic PCA were present in three patients, two of whom had low vitamin B12 levels. Of these three patients, two had anti-H/K-ATPase (HKA) and none had anti-intrinsic-factor antibodies (IFA); one had classic PCA but was negative for both HKA and IFA. The remaining four patients with low vitamin B12 levels were all negative for HKA and IFA. Of note, vitamin B12 levels were also not very high in most of the remaining patients (median, 365 pmol/l; after excluding one patient with values[1500, which indicate possible vitamin B12 supplementation). Disease duration at the time of blood sampling did not differ significantly between patients with vitamin B12 levels \300 pmol/l and the remaining patients (68 vs. 42 months). Our results suggest that low vitamin B12 serum levels may be relatively common in AQP4-Abpositive NMOSD. The finding that a subgroup of patients harbors HKA is in line with a known predisposition towards humoral autoimmunity in patients with AQP4-Abpositive NMO, which has been previously reported in association with myasthenia gravis [5, 9], connective tissue disorders [4, 13, 15], or celiac disease [1, 3]. Interestingly, S. Jarius (&) B. Wildemann Division of Molecular Neuroimmunology, Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany e-mail: sven.jarius@med.uni-heidelberg.de

Sa1112 CT Attenuation Value of the Fluid Collection Site to Diagnose Infected Pancreatic Fistula After Distal Pancreatectomy

BACKGROUND: It is unclear whether serum vitamin B12 level accurately reflects its deficiency at the cellular level in the low normal range (200-400pg/ml). Serum homocysteine is a cheap, widely available and sensitive test (95.9%) which has been shown to be a reliable marker for cellular deficiency of vitamin B12. AIMS AND OBJECTIVES: To determine whether patients with low normal serum vitamin B12 levels have vitamin B12 deficiency at cellular level, using serum homocysteine as a surrogate marker MATERIALS AND METHOD: Consecutive patients attending Gastroenterology department at a tertiary care hospital in south India, and found to have serum vitamin B12 levels between 200 to 400 pg/ml, during the period from November 2009 to November 2010, were prospectively enrolled after informed consent. Patients were excluded if any of the following was present: age 1.4, serum folic acid 200pg/ml) and high performance liquid chromatography was used for serum homocysteine (normal<13μM). Data was analyzed using SPSS 16.0. The study was approved by the institutional review board. RESULTS: 50 participants (27male, 23female) with serum vitamin B12 level in low normal range(200-400pg/ml) were enrolled. 74% of the participants had hyperhomocysteinemia suggestive of cellular deficiency of vitamin B12. There was no significant correlation between serum levels of homocysteine and vitamin B12 in the study group (spearman correlation coefficient,r = -0.22, p=0.11). Further analysis was done after including 47 consecutive patients with vitamin B12 deficiency (serum vitamin B12 < 200pg/ml) which revealed a strong inverse correlation between serum vitamin B12 and serum homocysteine levels in patients with vitamin B12 deficiency, ie <200 pg/ml (Spearman correlation coefficient, r = -0.44, p<0.01), unlike the patients with low normal serum vitamin B12 levels, ie 200-400 pg/ml (figure 1). This suggests that serum vitamin B12 may not reflect its deficiency at celluar level, in the low normal range CONCLUSIONS: A majority of patients with low normal serum vitamin B12 levels (200-400pg/ml) have hyperhomocysteinemia, suggestive of vitamin B12 deficiency at cellular level. Serum homocysteine is a useful ancillary test to detect intracellular vitamin B12 deficiency in patients with low normal serum vitamin B12 levels and thereby identify a subgroup with potential benefit from vitamin B12 supplementation.

Sa1111 Serum Vitamin B12 Levels: Does it Reflect Cellular Deficiency of the Vitamin in Low Normal Range?

BACKGROUND: It is unclear whether serum vitamin B12 level accurately reflects its deficiency at the cellular level in the low normal range (200-400pg/ml). Serum homocysteine is a cheap, widely available and sensitive test (95.9%) which has been shown to be a reliable marker for cellular deficiency of vitamin B12. AIMS AND OBJECTIVES: To determine whether patients with low normal serum vitamin B12 levels have vitamin B12 deficiency at cellular level, using serum homocysteine as a surrogate marker MATERIALS AND METHOD: Consecutive patients attending Gastroenterology department at a tertiary care hospital in south India, and found to have serum vitamin B12 levels between 200 to 400 pg/ml, during the period from November 2009 to November 2010, were prospectively enrolled after informed consent. Patients were excluded if any of the following was present: age 1.4, serum folic acid 200pg/ml) and high performance liquid chromatography was used for serum homocysteine (normal<13μM). Data was analyzed using SPSS 16.0. The study was approved by the institutional review board. RESULTS: 50 participants (27male, 23female) with serum vitamin B12 level in low normal range(200-400pg/ml) were enrolled. 74% of the participants had hyperhomocysteinemia suggestive of cellular deficiency of vitamin B12. There was no significant correlation between serum levels of homocysteine and vitamin B12 in the study group (spearman correlation coefficient,r = -0.22, p=0.11). Further analysis was done after including 47 consecutive patients with vitamin B12 deficiency (serum vitamin B12 < 200pg/ml) which revealed a strong inverse correlation between serum vitamin B12 and serum homocysteine levels in patients with vitamin B12 deficiency, ie <200 pg/ml (Spearman correlation coefficient, r = -0.44, p<0.01), unlike the patients with low normal serum vitamin B12 levels, ie 200-400 pg/ml (figure 1). This suggests that serum vitamin B12 may not reflect its deficiency at celluar level, in the low normal range CONCLUSIONS: A majority of patients with low normal serum vitamin B12 levels (200-400pg/ml) have hyperhomocysteinemia, suggestive of vitamin B12 deficiency at cellular level. Serum homocysteine is a useful ancillary test to detect intracellular vitamin B12 deficiency in patients with low normal serum vitamin B12 levels and thereby identify a subgroup with potential benefit from vitamin B12 supplementation.

Cognitive impairment and vitamin B12: a review

This review examines the associations between low vitamin B12 levels, neurodegenerative disease, and cognitive impairment. The potential impact of comorbidities and medications associated with vitamin B12 derangements were also investigated. In addition, we reviewed the evidence as to whether vitamin B12 therapy is efficacious for cognitive impairment and dementia. A systematic literature search identified 43 studies investigating the association of vitamin B12 and cognitive impairment or dementia. Seventeen studies reported on the efficacy of vitamin B12 therapy for these conditions. Vitamin B12 levels in the subclinical low-normal range (<250 ρmol/L) are associated with Alzheimer's disease, vascular dementia, and Parkinson's disease. Vegetarianism and metformin use contribute to depressed vitamin B12 levels and may independently increase the risk for cognitive impairment. Vitamin B12 deficiency (<150 ρmol/L) is associated with cognitive impairment. Vitamin B12 supplements administered orally or parenterally at high dose (1 mg daily) were effective in correcting biochemical deficiency, but improved cognition only in patients with pre-existing vitamin B12 deficiency (serum vitamin B12 levels <150 ρmol/L or serum homocysteine levels >19.9 μmol/L). Low serum vitamin B12 levels are associated with neurodegenerative disease and cognitive impairment. There is a small subset of dementias that are reversible with vitamin B12 therapy and this treatment is inexpensive and safe. Vitamin B12 therapy does not improve cognition in patients without pre-existing deficiency. There is a need for large, well-resourced clinical trials to close the gaps in our current understanding of the nature of the associations of vitamin B12 insufficiency and neurodegenerative disease.

Evaluation of C677T polymorphism of the methylenetetra hydrofolate reductase gene and its association with levels of serum homocysteine, folate, and vitamin B12 as maternal risk factors for Down syndrome

AIMS AND OBJECTIVE:Evaluation of C677T polymorphisms of the methylenetetra hydrofolate reductase (MTHFR) gene and its association with level of serum homocysteine, folate, and vitamin B12 as possible maternal risk factors for Down syndrome.DESIGN:This was a case–control study.MATERIAL AND METHODSFifty-two mothers (mean age 27.6 years) with babies having free trisomy 21 of North Indian ethnicity and 52 control nonlactating mothers (mean age 24.9 years) of same ethnicity attending services of genetic lab for bloodletting for other causes were enrolled after informed written consent. Fasting blood was collected and was used for determination of plasma homocysteine, vitamin B12, and folate (serum and RBC), and for PCR amplification of the MTHFR gene.RESULTS:The prevalence of MTHFR C677T polymorphism in north Indian mothers of babies with trisomy 21 Down syndrome was 15.38% compared to 5.88 % in controls. The difference between two groups was not statistically significant (P = 0.124). Low serum folate was demonstrated in 34.62% of cases vs. 11.54% in controls, which was significant (P = 0.005). Low RBC folate was found in 30.7% of cases versus 11.53% in controls, which was not significant (P = 0.059), when analyzed independently. But on multiple regression analysis the difference was statistically significant. Low serum vitamin B12 was found in 42.31% of cases versus 34.62% in controls, which was not significant (P = 0.118). The mean serum homocysteine in cases was 10.35 ± 0.68 while controls were 9.02 ± 0.535.CONCLUSION:Serum levels of folate were low in cases. The RBC folate levels were comparable in both groups. However the combined serum folate and RBC folate were low in cases compared to control groups. Homocysteine levels in our study were higher in Down syndrome mothers compared to controls; however high-serum level of Homocysteine had no association with MTHFR polymorphism. No association of serum vitamin B12 with MTHFR polymorphism in occurrence of Down syndrome births was found. Peri- or preconceptional folate supplementation may therefore lead to a decline in DS births, if supported by larger studies.

Unilateral tremor induced by risperidone in a patient with acute mania: Vitamin B12 deficiency as possible mediating factor

Identification and management of drug-induced movement disorders is a clinical challenge, more so when the clinical presentation is atypical. A young male with acute mania was under treatment with sodium valproate and risperidone. He developed tremors of right hand and neck. These were present at rest and exacerbated by mental activity, when under observation and during voluntarily initiated activity. There were no associated extra pyramidal symptoms or cerebellar signs. Investigations for other common causes of tremors did not reveal any evidence except for low value of serum vitamin B12 levels. The tremors persisted after the withdrawal of valproate, but resolved following the withdrawal of risperidone. It is a common dictum that drug-induced tremors are bilateral. This may not be true always as we found out in our case. These movements were probably induced by risperidone. This atypical presentation could be due to concurrent use of valproate and low serum vitamin B12 levels.