Vitamin B12 Deficiency Masquerading as Clozapine-Resistant Psychotic Symptoms in Schizophrenia

Vitamin B₁₂Deficiency and Depression in the Elderly

To examine the effect of vitamin B12 deficiency on older veterans and its relationship to general health and cognitive impairment. Cross-sectional study. Oklahoma City Veterans Affairs Medical Center. Data for this research were obtained from 303 ambulatory, older veterans who used the outpatient laboratories of the Oklahoma City Department of Veterans Affairs Medical Center. Subjects were included in the study if they were 65 years of age and older and if they had no known diagnosis associated with B12 deficiency. The sample in this study consisted of 301 men and 2 women aged 65 to 89 years. This study used two separate measurements of vitamin B12 deficiency: (1) a strict definition of B12 deficiency (serum B12 level < laboratory norm) and (2) a broader definition of B12 deficiency (serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and methyl malonic acid (MMA) or homocysteine (HC) elevated by more than two standard deviations). The laboratory norm is 200 pg/mL. The dependent variables were measures of cognitive impairment and general health. Cognitive impairment was measured using the Folstein Mini-Mental State Examination (MMSE) and general health was measured using the RAND 36-Item Health Survey Version 1.0. The control variables for this study were the subjects' daily alcohol intake, daily intake of a vitamin/mineral supplement, annual income, and level of education. Nineteen subjects (6%) were vitamin B12-deficient as measured by the strict definition of B12 deficiency (serum B12 level < laboratory norm), and 49 subjects (16%) were vitamin B12-deficient as measured by the broader definition of B12 deficiency (serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and MMA or HC elevated by more than two standard deviations). Vitamin B12 level decreases as age increases. Of the nine general health outcomes measured by using the RAND 36-Item Health Survey, only bodily pain is associated with vitamin B12 deficiency, and only then when B12 deficiency is measured as serum B12 level < laboratory norm, the strict definition of B12 deficiency. Vitamin B12-deficient subjects experience more bodily pain than those with normal vitamin B12 levels. There is a significant difference between B12-deficient subjects and B12 normal subjects on cognitive impairment, with B12 normal subjects indicating less cognitive impairment, only when B12 deficiency is measured as B12 level < laboratory norm, the strict definition of B12 deficiency. The broader measurement of vitamin B12 deficiency (i.e., serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and MMA or HC elevated by more than two standard deviations) is not a significant correlate of cognitive impairment and general health.

Background: Clinical evidence suggests an association between vitamin B12 deficiency and vasovagal syncope (VVS) in pediatric patients. This study investigated the association of vitamin B12 and folate deficiency with VVS in adults. Methods: In this case-control study, adult patients with VVS who presented to the tertiary syncope unit for head-up tilt table testing comprised the case group. Age- and sex-matched individuals without syncope history from the population-based Tehran Cohort Study served as the control group. Exclusion criteria included but were not limited to the use of vitamin B supplements, carbamazepine, or phenobarbital, and sleeve gastrectomy. Serum vitamin B12, folate, and homocysteine levels were measured and compared. Results: From February 2020 through February 2021, 44 patients comprised the case group, matched with 44 controls (mean age, 37.9 years; 23 [52.3%] females in each group). No statistically significant difference existed between the groups in vitamin B12 or folate deficiency or serum levels. Serum vitamin B12 levels were significantly lower in patients with frequent VVS (≥3 lifetime episodes) than in patients with infrequent VVS (&lt;3 lifetime episodes) (233.8 [80.7] vs 305.2 [118.1] pg/mL; P=0.042), and the association remained significant after adjustment for confounders (P=0.026). Conclusion: No association existed between vitamin B12 or folate deficiency or serum levels and VVS. Frequent VVS was associated with lower serum vitamin B12 levels than infrequent VVS.

P2 – 2736: Vitamin B12 deficiency and neurologic findings: Retrospective analysis of 124 patients

The aim of this study was to evaluate if multiple sclerosis (MS) is associated with vitamin B12 (cobalamin) deficiency. We measured serum vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebrospinal fluid (CSF) MMA and tHcy in 72 patients with MS and 23 controls. The mean plasma tHcy level was significantly increased in MS patients (11.6 micromol/L) compared with controls (7.4 micromol/L) (P = 0.002). Seven patients showed low serum vitamin B12 levels but only one of them had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or blood folate levels did not differ between MS patients and controls. We found no significant differences in mean values or frequency of pathological tests of serum B12, serum MMA, mean corpuscular volume (MCV), haemoglobin concentration, CSF tHcy or CSF MMA between patients and healthy subjects. There were no correlations between CSF and serum/plasma levels of MMA or tHcy. Serum vitamin B12, serum MMA, plasma tHcy, CSF Hcy or CSF MMA were not correlated to disability status, activity of disease, duration of disease or age. The relevance of the increased mean value of plasma tHcy thus seems uncertain and does not indicate functional vitamin B12 deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism relevant for the development of neuroinflammation/degeneration. Our findings indicate that, regardless of a significant increase in plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B12 deficiency since we did not find any other factors indicating vitamin B12 deficiency. Analysis of CSF MMA and CSF tHcy, which probably reflects the brain vitamin B12 status better than serum, are not warranted in MS. We conclude that B12 deficiency, in general, is not associated with MS.

The authors of the much publicized though not yet published Norwegian Vitamin Study (NORVIT)1 of vitamin therapy in coronary artery disease, are widely quoted as saying that vitamin therapy for lowering plasma total homocysteine (tHcy) was harmful, and that “homocysteine is dead.” However, the slides of their presentation1 do not show the B12 status of the participants, nor do they indicate whether B12 injections were given to participants with low levels of B12. Commentators2 have called NORVIT “the largest trial to date to test the hypothesis that folate supplementation reduces risk of cardiovascular disease,” but because there were 4 treatment arms in NORVIT, each with 900 participants, the number of patients randomized to folate/B12 or folate/B12/B6 was essentially the same as that in the Vitamin Intervention for Stroke Prevention (VISP) trial3 (≈1800). They used a much higher dose of B6 than other studies and cannot exclude the possibility that their results were driven by that choice. As did VISP, they also used a dose of B12 that, as has recently become apparent, was too low for adequate absorption of B12 in elderly subjects (discussed below). In this issue of Stroke , a substudy of the Vitamins to Prevent Stroke (VITATOPS) trial4 reports that in Singapore, treatment with 2.5 mg folic acid, 0.5 mg vitamin B12, and 25 mg B6 reduced levels of tHcy by 3.8 μmol/L compared with placebo.5 The authors also studied 2 polymorphism …

The Many Faces of Cobalamin (Vitamin B12) Deficiency

Objectives: We examined the oral intake and serum concentration of vitamins B1 and B12 in patients with alcohol withdrawal syndrome to determine some risk factors leading to deficiencies of those vitamins and their impact on memory function. Methods: Data were collected from patients with alcohol withdrawal syndrome admitted to 3 addiction care clinics in Ulaanbaatar. A total of 162 subjects were selected with a ratio 1:1 in this case-control study. Nutrient intake of B1 and B12 were estimated by questioning the patients regarding their food intake during the 24 hours prior to admission. Results: Drinking while hungry resulted in inadequate oral vitamin B12 consumption (OR 9.43; 95% CI 2.42;36.64, p=.001) as did refusing food while drinking (OR 4.76; 95% CI 1.23;18.30, p=.02). Inadequate B1 intake was higher in women (OR 0.16; 95% CI 0.05;0.49, p=.001) and if the patient refused food while drinking (OR 3.38; 95% CI 1.24; 9.21, p=.01). Serum B1 and B12 deficiency were associated refusing food while drinking (OR 4.53; 95% CI 1.81; 11.31, p=.001 and OR 3.43; 95% CI 1.22; 9.61, p=.01). Short term memory impairment was associated with dietary B1 and B12 deficiency (OR 8.59; 95% CI 3.10;23.82, p=.0001 and OR 3.14; 95% CI 1.02;9.61, p=.04) and low serum B12 levels (OR 2.45; 95% CI 0.98;6.11, p=.05). Long-term memory impairment was associated with deficient B12 and B1 intake (OR 19.49; 95% CI 3.19;118.86, p=.0001 and OR 4.73; 95% CI 1.91; 11.68, p=.0001) and low serum B12 and B1 levels (OR 3.32; 95% CI 1.31;8.42, p=.01 and OR 2.64; 95% CI 1.06;6.59, p=.03.)

IntroductionVitamin B12 deficiency is characterised by haematological and neurological complications, from mild symptoms (e.g. fatigue and paraesthesia), to severe symptoms (e.g. pancytopenia and combined degeneration of the spinal cord). If treatment is delayed, irreversible neurological damage may occur. Thus, early recognition and prompt corrective therapy are essential. The vitamin B12 deficiency can be due to a variety of anomalies: the paradoxical interaction between folic acid and vitamin B12 has recently been well described.Case descriptionWe report the case of a patient who presented to the emergency department with balance disorders and a blood count indicating macrocytosis. Vitamin B12 deficiency and a high folate value were detected, supporting the hypothesis of the high-folate-low-vitamin B12 interaction as a cause of vitamin B12 depletion.DiscussionAn excessive oral intake of folic acid leads to a reduction in the active fraction of vitamin B12 and this decrease exacerbates the deficiency itself. The neurological signs and symptoms of vitamin B12 deficiency are due to demyelination of the posterior and lateral columns of the spinal cord. This patient had been taking folic acid for 30 years and the serum folate value was high. We hypothesise that the high-folate-low-vitamin B12 interaction represents the cause of vitamin B12 depletion in this patient.ConclusionAll the patients with neurological signs and symptoms should be tested for possible vitamin B12 deficiency: early diagnosis and treatment could stop the progression of the disease and allow the regression of the neurological deficit. It is important not to rely on blood count values to diagnose a vitamin B12 deficiency as the neurological and haematological outlook may be inversely proportional. This study is the first to report a case of combined sclerosis and high-folate-low-vitamin B12 interaction from Italy and is therefore of interest to public health decision makers and clinical practice.LEARNING POINTSVitamin B12 and folate should be measured in all patients with neurological symptoms.In case of vitamin B12 deficiency, folate levels should always be measured as well.Vitamin blood levels should be checked periodically while taking vitamin supplements.

Background In today's busy world, health is often neglectedespecially among full-time workers.Consequently, lifestyle disorders such as vitamin deficiencies are increasing, perhaps because of inadequate nutrition and lack of sunlight due to long hours working indoors. These deficiencies can lead to various short-term and long-term complications. Objective To estimate serum levels of vitamin B12 and vitamin D3 among vegetarian employees. Methods and materials A questionnaire about dietary and exercise habits was administered to participants who fulfilled the inclusion criteria and provided informed written consent. Participants also were asked about drug and supplement intake, history of smoking and alcohol, specific symptoms of vitamin B12 and D3 deficiency, and sociodemographic status. Blood samples were collected to estimate serum B12 and D3 levels. Results The results indicated that 14.00% of participants were vitamin B12 deficient and 82.00% were D3 deficient. Differences by gender were not statistically significant; vitamin B12 deficiency was identified in 10.00% of women and 14.44% of men, and vitamin D3 deficiency occurred in 100.00% of the women and 80.00% of men. Among 71 participants aged 35-45 years, 15.49% and 91.55% were deficient in B12 and D3, respectively; among 25 participants aged 46-55, 12.00% and 64.00% were deficient in B12 and D3, respectively; among four participants older than 55, no vitamin B12 deficiency was observed, but 25.00% were deficient in vitamin D3 (p=0.00002). Nearly all (96.15%) participants who reported never exercising were found to be vitamin D3 deficient, compared to 77.02% of those who exercised (OR=0.13, p=0.043). No significant association was found between alcohol consumption and vitamin B12 (p=1) or D3 (p=0.713) deficiency. Conclusions The results revealed a prevalence of both vitamin B12 and D3 deficiencies among corporate employees who identified as vegetarians. Increased awareness, dietary modifications, conscious physical activity, and most importantly, attention to one's health may help improve vitamin sufficiency. Women over age 45 should pay particular attention due to their increased risk of vitamin D3 deficiency. Further research is needed to assess nutrition profiles among other populations to better understand vitamin deficiencies and design adequate preventive measures.

Vitamin B12 deficiency in infants secondary to maternal deficiency: A case series of seven infants

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

High frequencies of vitamin B12 and folic acid deficiencies and hyperhomocysteinemia in Taiwanese male patients with oral submucous fibrosis

A vitamin B12 deficiency in infants is rare, but may sometimes be seen in breastfed babies of strict vegetarian mothers. Vitamin B12, also known as cobalamin, is only found in meat and other animal products. Most babies have a sufficient supply as long as the mother was not deficient herself. Symptoms and signs of vitamin B12 deficiency appear between the ages of 2 to 12 months and include vomiting, lethargy, failure to thrive, hypotonia, and arrest or regression of developmental skills. Urinary concentrations of methylmalonic acid and homocystine are characteristically elevated in vitamin B12 deficiency. Early treatment for a vitamin B12 deficiency in an infant involves immediate administration of vitamin B12 to the baby and the breastfeeding mother. The infant and mother will each receive an injection of vitamin B12 containing 1,000 mcg or more of the vitamin, and the mother will continue to receive injections every month to raise her own stores. After the initial injection, the baby will often receive future vitamin B12 through food sources. We present a case of vitamin B12 deficiency in a 9-month-old girl presented with psychomotor regression, hypotonia and lethargy. The child was exclusively breast-fed from birth by a mother who was on strict vegetarian diet and belong to a low socio-economic status. Laboratory data revealed bicytopenia with macrocytic anemia and methylmalonic acid in the urine, consistent with vitamin B12 deficient anemia. The Brain CT revealed a cerebral atrophy and delayed myelination. Vitamin B12 supply was effective on anaemia and psychomotor delay. This case figures out the importance of an early diagnosis in front of psychomoteur regression and hypotonia, given the risk of incomplete neurologic recovery due to vitamin B12 deficiency mainly in the setting of maternal nutritional deficiency.

Vitamin B12 deficiency in childhood and adolescence