B12 Status Research Articles

A cross-sectional study of nutritional status in healthy, young, physically-active German omnivores, vegetarians and vegans reveals adequate vitamin B12 status in supplemented vegans

Background/Objective Plant-based diets reduce the risk of cardiovascular disease but also increase the risk of certain micronutrient deficiencies, particularly, of vitamin B12 (B12). The extent to which the unsupervised use of oral nutrient supplements is sufficient to prevent these deficiencies is not well established. We analyzed nutrient intake, laboratory biomarkers, supplementation behavior, and B12 status adequacy amongst young, healthy, physically active omnivores, lacto-ovo-vegetarians and vegans from Germany. Methods We recruited 115 participants (n = 40 omnivores; n = 37 lacto-ovo-vegetarians, and n = 38 vegans) with comparable age, sex, marital status, physical activity and educational levels through online advertisements and local newspapers in Freiburg, Germany. Results Energy intake and macronutrient distribution were comparable across diets. Major differences included intake of fiber, cholesterol, and several vitamins. Vegans had the lowest intake of B12 from foods (0.43 (0.58) µg/d), compared to omnivores (2.14 (2.29) µg/d) and lacto-ovo-vegetarians (0.98 (1.34) µg/day). Multivariate analysis of 36 blood biomarkers revealed that three major classes of biomarkers contributed the most to the clustering of individuals by dietary group, namely, biomarkers of B12 status (B12, holoTC, Hcy), iron (iron, ferritin, transferrin) and lipid metabolism (vitamin A, HDL, LDL, total cholesterol, TAG). This suggests that nutrients that modify the metabolic pathways represented by these biomarkers have the most penetrating effect on health status across diets. Analysis of B12 status (including 4cB12) revealed adequacy in omnivores and vegans, and a poorer B12 status amongst lacto-ovo-vegetarians. Fewer lacto-ovo-vegetarians used B12 supplements compared to vegans (51% versus 92%). Conclusions Even amongst homogeneously healthy Germans, each diet manifested with measurable differences in dietary intakes and biomarkers of health. Plant-based diets, in particular the vegan diet, exhibited the most favorable patterns of lipid metabolism and glycemic control, but the lowest food intake of B12. Supplementation of healthy vegans with B12 (median 250 µg B12/day, over 1 year) secured an adequate B12 status that was comparable to that of healthy omnivores. Clinical Trial Registry: German Clinical Trial register number: DRKS00027425

Vitamin B12 and Folate Status in Pregnant Females and Their Infants in Norway: Secondary Analysis from the Mommy’s Food Study

BackgroundVitamin B12 and folate are essential micronutrients important for normal infant growth and development. ObjectivesThe aims were to describe vitamin B12 and folate status in pregnant females and their infants according to commonly used status cutoffs and examine the associations between maternal status, maternal supplement use, and breastfeeding and infant status. MethodsPregnant females were recruited at 18 wk gestation in Bergen, Norway. Maternal vitamin B12 and folate status were measured at gestational weeks 18 (n = 136) and 36 (n = 116), and infant status was measured at ages 3 (n = 73) and 6 (n = 74) mo. ResultsAt gestational weeks 18 and 36, respectively, 4.4% and 2.6% of the mothers had plasma cobalamin concentrations <148 pmol/L, 0.7% and 6.9% had methylmalonic acid (MMA) concentrations >0.26 μmol/L, and 3.7% and 30% had folate concentrations <10 nmol/L. None of the females had total homocysteine (t-Hcy) concentrations >13 μmol/L or 3 combined indicator of vitamin B12 (cB12) < −0.5. At 3 and 6 mo, respectively, 4.1% and 5.4% of the infants had cobalamin concentrations <148 pmol/L, 63% and 74% had t-Hcy concentrations >6.5 μmol/L, 59% and 66% had MMA concentrations >0.26 μmol/L, and 47% and 60% had cB12 > −0.5. None of the infants had folate concentrations <10 nmol/L. Several of the vitamin B12 biomarkers in infants were associated with maternal vitamin B12 status during pregnancy. Breastfed infants had lower vitamin B12 status (as indicated by plasma cobalamin, t-Hcy, and cB12) than nonbreastfed infants at both 3 and 6 mo. Use of supplements during pregnancy was associated with better vitamin B12 status among infants at 3 and 6 mo, as indicated by infants’ cobalamin and t-Hcy concentrations. ConclusionsSubclinical vitamin B12 deficiency among infants was common and associated with maternal vitamin B12 status during pregnancy and breastfeeding. Among the mothers, an increase in biochemical folate deficiency was discovered toward the end of gestation. Further studies are needed to investigate clinical consequences.This trial was registered at clinicaltrials.gov as NCT02610959.

The Association Between the Imbalance of Single-Carbon Nutrients in Early Pregnancy and Gestational Diabetes Mellitus Risk is Influenced by Serum Selenium Status: A Cohort Study.

The role of imbalanced one-carbon nutrients in gestational diabetes mellitus (GDM) risk has garnered significant interest, yet existing studies yield inconsistent results. Our objective was to assess whether the association between an unbalanced ratio of folate to vitamin B12 and GDM risk is influenced by the status of other micronutrients. This cohort study included 366 singleton-pregnancy Han women enrolled at the Shunyi District Maternal and Child Health Hospital in Beijing, China. During the first trimester of pregnancy, we measured red blood cell (RBC) folate, serum levels of vitamin B12, vitamin D, and selenium. We examined the association between the imbalanced status of RBC folate and vitamin B12 and GDM risk using logistic regression, stratified by serum selenium or vitamin D status. Among the 366 women, 67 (18.3%) were diagnosed with GDM, 201 (54.9%) had vitamin D deficiency, and 245 (66.9%) had selenium deficiency. Overall, women with higher RBC folate/vitamin B12 ratios did not exhibit a significantly higher risk of GDM compared to those in reference tertile (all P > 0.05). Subsequently, we divided women into deficient and non-deficient groups based on serum selenium or vitamin D levels. In women with selenium deficiency, those in the highest tertile of the RBC folate/vitamin B12 ratio had the highest odds of GDM [OR: 3.40 (1.16-9.97), P=0.026] after adjusting for covariates. However, similar findings were not observed in pregnancies with normal selenium status. Irrespective of vitamin D status, women with higher RBC folate/vitamin B12 ratios did not exhibit a significantly increased risk of GDM. Micronutrient deficiencies are common in early pregnancy. Women with a higher folate/vitamin B12 ratio coupled with selenium deficiency in early pregnancy have a higher GDM risk. These findings underscore the importance of micronutrient assessment in early pregnancy and subsequent interventions for micronutrient deficiencies.

Lower levels of the neuroprotective tryptophan metabolite, kynurenic acid, in users of estrogen contraceptives

Changes in kynurenine metabolites are reported in users of estrogen containing contraception. We have assessed kynurenines, vitamin B6, vitamin B2 and the inflammation markers, C-reactive protein (CRP) and neopterin, in healthy, never-pregnant women between 18 and 40 years (n = 123) and related this to their use of hormonal contraception. The population included 58 women, who did not use hormonal contraceptives (non-users), 51 users of estrogen-containing contraceptives (EC-users), and 14 users of progestin only contraceptives (PC-users). EC-users had significantly lower plasma kynurenic acid (KA) and higher xanthurenic acid (XA) levels compared to non-users. Serum CRP was significantly higher and negatively associated with both vitamin B6 and B2 status in EC-user compared to non-users. No significant differences in any parameters were seen between PC-users and non-users (p > 0.1). The low KA and high XA concentration in users of estrogen containing contraception resemble the biochemical profile observed in vitamin B6 deficiency. The hormonal effect may result from interference with the coenzyme function of vitamin B6 and B2 for particular enzymes in the kynurenine metabolism. KA has been suggested to be neuroprotective and the significantly reduced concentration in EC-users may be of importance in the observed increased risk of mood disorders among users of oral contraceptives.

Vitamin B12 reference intervals on Beckman, Roche and Siemens analytical platforms.

Vitamin B12 status is assessed primarily by measuring total serum B12 using competitive binding methods. The lack of availability of a standard material and high-level reference measurement procedure affect the trueness of B12 results; this results in variation between methods. This study aimed to determine the reference intervals for vitamin B12 on three routine analytical platforms. A prospective reference population of healthy individuals was recruited according to the IFCC CRIDL criteria. Vitamin B12 samples were measured on Roche, Beckman and Siemens analytical platforms. In total, 300 adult subjects were recruited; the central 95th centile values for B12 for Roche (190-678ng/mL) and Siemens (181-562ng/mL) analytical platforms were in a close agreement. Beckman DXi, however, showed a significantly lower reference limit (110-562ng/mL). All reference intervals are in keeping with previously published data but some are not in agreement with manufacturer provided reference interval. As the quality of the reference intervals plays a significant role in clinical outcome, it is of great importance that laboratories use a method-specific reference interval and if possible, locally derived reference intervals until further method standardization occurs.

Nonlinear Relationship Between Maternal and Cord Blood Vitamin B12 and Folate from a Chinese Population-Based Study.

There remains a data gap on vitamin B12 and folate level in maternal and child populations. This study aimed to assess the status of vitamin B12 and folate in maternal serum (MS) and umbilical cord serum (UCS). This was a planned secondary analysis of a case-control study. A total of 858 pregnant women during late pregnancy and their newborns in the hospitals of China were included. Maternal peripheral venous blood and neonatal umbilical cord blood were collected to determine serum vitamin B12 and folate concentration. Relationship of vitamin B12 or folate concentration between MS and UCS was assessed by a quantile regression model and the non-linear relationship between them was examined. Nutritional status of serum folate was better than that of vitamin B12. Prevalence of deficiency in MS vitamin B12 and folate was 73.4% and 14.2%, respectively and these figures were about 17.8% and 0.1% in UCS. Both vitamin B12 and folate levels in UCS were significantly higher than those in MS (vitamin B12: 321.0 pg/mL vs 158.3 pg/mL, folate: 16.5 ng/mL vs 7.0 ng/mL, P <0.001). The median UCS-MS ratio of vitamin B12 and folate was 2.0 (95% CI: 1.94-2.06) and 2.4 (95% CI: 2.30-2.53), respectively. The levels of folate and vitamin B12 in UCS increased nonlinearly with their increase in MS which presented an inverted U-shaped curve. Deficiency in vitamin B12 and folate in the women during late pregnancy in China is prevalent. Nutritional status of the two vitamins in umbilical cord serum is correlated nonlinearly with that in maternal serum. Folic acid supplementation may be accompanied with vitamin B12 to improve status of vitamin B12 and folate during pregnancy.

The association between methylmalonic acid, a biomarker of mitochondria dysfunction, and phenotypic age acceleration: A population-based study

Phenotypic age acceleration (PAA) is a sensitive marker of biological aging. Circulating methylmalonic acid (MMA) is a novel biomarker of mitochondrial dysfunction and has been associated with age-related disorders. Our study aimed to investigate to what extent circulating MMA was associated with PAA, and whether the association was independent of vitamin B12 status and renal function in the general population. We analyzed cross-sectional data from 13,023 participants across a wide age range (mean age: 38.9 years, range: 12 – 85 years, 51.1% women) from the US National Health and Nutrition Examination Survey (NHANES). PAA was calculated based on the published algorithm. Linear regression models were performed to assess the association between circulating MAA and PAA. Only 31% of the variation in MMA levels was explained by age, sex, race/ethnicity, social economic status, vitamin B12 status, and renal function. Per unit increase in circulating MAA (1.0 nmol/L) was associated with 1.59 years increase in PAA (β = 1.59, 95% CI: 1.17, 2.00, p < 0.001) after adjusting for multiple confounders. Importantly, PAA increased with circulating MMA levels independent of vitamin B12, creatine, and homocysteine levels. The association was more pronounced in subgroups of age ≥ 65 years, women, underweight, vitamin B12 < 400 μmol/L, and homocysteine ≥ 10 μmol/L. The association was much stronger among participants with cardiovascular diseases (CVDs) than without CVDs. In conclusion, our current population-based study showed that mitochondria-derived circulating MMA was associated with increased phenotypic age acceleration in the general population.

A retrospective analysis of vitamin B6 deficiency and associated changes of gut microbes in Crohn's disease.

Patients with inflammatory bowel diseases (IBD) are at risk of micronutrient deficiencies, particularly during flares. Vitamin B6 is required for the proper development of brain, nerves, and many other parts of the body. However, limited studies are available to describe the prevalence, relevance and consequences of vitamin B6 deficiencies in IBD. We aim to estimate the prevalence of vitamin B6 deficiencies in Crohn's disease (CD) patients, to identify associated risk factors and to explore the alteration of intestinal microbiota related to vitamin B6 status. A total of 360 CD patients and 55 ulcerative colitis (UC) patients from Shanghai Tenth People's Hospital of Tongji University were included. Serum vitamin B6 concentrations were collected from the computerized laboratory data. The logistic regression was used for statistical analysis. Fecal-associated microbiota was also analyzed using 16S rRNA sequencing in another 20 CD patients (10 of vitamin B6 normal, 10 of vitamin B6 deficiency). The prevalence of vitamin B6 abnormality was significantly higher in CD than in UC patients. Logistic regression analysis showed that small bowel lesion, ileocolonic lesion (L3), extraintestinal manifestations, ileal resection, and usage of immunosuppressor were independently associated with abnormal vitamin B6 in CD. Interestingly, the microbial structure presented significant differences between two CD groups. PICRUSt2 prediction revealed that some enzymes and metabolic pathways between the two groups were significantly different. Collectively, our analysis showed that vitamin B6 reduction occurred frequently in patients with CD and affected the intestinal flora of patients.

Review on Food Insecurity and its Relationship with Iron and Vitamin B12 Status Among Children

Iron and vitamin B12 are essential micronutrients needed for the growth and development of children. Iron is critical for erythropoiesis, notably in haemoglobin synthesis whereby haemoglobin transports oxygen to cells, which is essential for cellular metabolism and energy production. Meanwhile, vitamin B12 is required for deoxyribonucleic acid synthesis, intracellular metabolism, and blood cells formation and maturation. Lack of these essential micronutrients can lead to nutritional deficiency and anaemia, especially among children. Food insecurity is a condition where there is a lack of or uncertain availability of acquiring acceptable food. Food insecurity is associated with lower nutrient intake and micronutrient deficiencies including iron and vitamin B12, which can subsequently lead to poor health outcomes. Various determinants are associated with iron and vitamin B12 deficiency, and food insecurity, such as socio-economic factors, environmental factors, and dietary intake. This review will explore the possible relationship between iron, vitamin B12, and anaemia with food insecurity among children.

Women in Selected Communities of Punjab, India Have a High Prevalence of Iron, Zinc, Vitamin B12, and Folate Deficiencies: Implications for a Multiply-Fortified Salt Intervention.

Dietary intake and biomarkers of micronutrient status of 100 non-pregnant women of reproductive age (NPWRA) were assessed to determine optimal levels of iron, zinc, vitamin B12, and folic acid to include in multiply-fortified salt (MFS) that will be evaluated in an upcoming trial. Weighed food records were obtained from participants to measure intake of micronutrients and discretionary salt, and to assess adequacy using Indian Nutrient Reference Values (NRVs). Statistical modeling was used to determine optimal fortification levels to reduce inadequate micronutrient intake while limiting intake above the upper limit. Fasting blood samples were obtained to assess iron, zinc, vitamin B12, and folate status. In usual diets, inadequate intake of iron (46%), zinc (95%), vitamin B12 (83%), and folate (36%) was high. Mean intake of discretionary salt was 4.7 g/day. Prevalence estimates of anemia (37%), iron deficiency (67%), zinc deficiency (34%), vitamin B12 insufficiency (37%), and folate insufficiency (70%) were also high. Simulating the addition of optimized MFS to usual diets resulted in percentage point (pp) reductions in inadequate intake by 29 pp for iron, 76 pp for zinc, 81 pp for vitamin B12, and 36 pp for folate. MFS holds potential to reduce the burden of micronutrient deficiencies in this setting.

P11-006-23 Vitamin B12 Status in Infancy and the Effect of a Vitamin B12 Injection in Infants With Subclinical Vitamin B12 Deficiency: A Register-Based Randomized Controlled Trial

P11-006-23 Vitamin B12 Status in Infancy and the Effect of a Vitamin B12 Injection in Infants With Subclinical Vitamin B12 Deficiency: A Register-Based Randomized Controlled Trial

P18-045-23 Association of Vitamin B12 Status With Body Composition and Metabolic Risk Factors in Children From Southern India

P18-045-23 Association of Vitamin B12 Status With Body Composition and Metabolic Risk Factors in Children From Southern India

P11-046-23 Optimum Sensitivity and Specificity Cutoffs for Conventional Biomarkers for Inadequate Vitamin B12 Status Based on the New Combined Indicator of Status, cB12

P11-046-23 Optimum Sensitivity and Specificity Cutoffs for Conventional Biomarkers for Inadequate Vitamin B12 Status Based on the New Combined Indicator of Status, cB12

Intake of vitamin B12 in relation to vitamin B12 status in groups susceptible to deficiency: a systematic review.

To systematically review the evidence for whether habitual or different levels of experimental intake of vitamin B12 from diet and supplements is sufficient to ensure adequate B12 status in groups most susceptible to vitamin B12 deficiency. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to 21 May 2021, for intervention studies, prospective cohort studies and case-control studies assessing B12 intake from diet and/or supplements in relation to B12 status (s/p-B12, holotranscobalamin, methylmalonic acid, homocysteine or breastmilk B12). Cross-sectional studies were eligible for studies conducted during pregnancy and lactation. Included populations were children (0-18 years), young adults (18-35 years), pregnant or lactating women, older adults (≥65 years) and vegans or vegetarians. Study selection, data extraction and risk of bias assessment were conducted by two assessors independently. The evidence was synthesized qualitatively and classified according to the World Cancer Research Fund. The searches yielded 4855 articles of which 89 were assessed in full text and 18 included. Three studies were conducted during pregnancy and three during lactation or infancy - all observational. Eight studies were conducted among older adults; most were interventions among B12-deficient participants. Four studies were eligible for vegetarian and vegans, all interventions. The strength of evidence that habitual B12 intake or an intake in line with the current Nordic recommended intake (RI) is sufficient to ensure adequate status was considered Limited - no conclusion for all included populations. Evidence is insufficient to assess if or which level of B12 intake is sufficient to maintain adequate status for all included populations. Population-based cohort studies and low-to-moderate dose interventions that address this question are highly warranted.

Vitamin B12 deficiency in long-term metformin treated type 2 diabetic patients: Prevalence and risk factors in a Tunisian population.

Objectives: To determine the prevalence of vitamin B12 deficiency in a Tunisian population with type 2 diabetes (T2D) on metformin treatment for more than three years and to identify its risk factors. Methods: This is a cross-sectional study conducted on 257 patients with T2D treated with metformin for at least three years. Patients were divided into two groups according to their vitamin B12 status. Low vitamin B12 was defined as ≤ 203 pg/mL. Results: The mean age of the patients was 59.8 ± 7.9 years. The mean duration of metformin use was 10.2 ± 5.2 years. The mean vitamin B12 level was 294.9 ± 156.4 pg/mL. The prevalence of vitamin B12 deficiency was 28.4%. Male gender, HbA1c < 7% and hyperhomocysteinemia were significantly associated with vitamin B12 deficiency (respectively p = 0.02, p < 0.001, p < 0.001). Homocysteine level was negatively correlated with vitamin B12 level (r = -0.2, p = 0.001). Dose and duration of metformin treatment, peripheral neuropathy and anemia were not associated with vitamin B12 deficiency. On multivariate analysis, HbA1c < 7% and hyperhomocysteinemia were independently associated with vitamin B12 deficiency (respectively OR = 3.2, 95%CI = [1.6-6.3] and OR = 2.3, 95%CI = [1.2-4.2]). Discussion: The prevalence of vitamin B12 deficiency in patients with T2D on metformin treatment was high. Hyperhomocysteinemia is associated with vitamin B12 deficiency suggesting that the deficit occurs at the tissue level.

Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation

We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5'-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT). We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings. Furthermore, we included a longitudinal PSC cohort (n= 158) sampled prior to and serially afterLT, and cohorts of people with inflammatory bowel disease (IBD) without PSC (n= 51) or with primary biliary cholangitis (PBC) (n= 100), as disease controls. We used Cox regression to measure the added value of PLP to predict outcomes before and after LT. In different cohorts, 17-38% of people with PSC had PLP levels below the biochemical definition of a vitamin B6 deficiency. The deficiency was more pronounced in PSC than in IBD without PSC and PBC. Reduced PLP was associated with dysregulation of PLP-dependent pathways. The low B6 status largely persisted after LT. Low PLP independently predicted reduced LT-free survival in both non-transplanted people with PSC and in transplant recipients with recurrent disease. Low vitamin B6 status with associated metabolic dysregulation is a persistent feature of PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation. We previously found that people with PSC had reduced gut microbial potential to produce essential nutrients. Across several cohorts, we find that the majority of people with PSC are either vitamin B6 deficient or have a marginal deficiency, which remains prevalent even after liver transplantation. Low vitamin B6 levels strongly associate with reduced liver transplantation-free survival as well as deficits in biochemical pathways dependent on vitamin B6, suggesting that the deficiency has a clinical impact on the disease. The results provide a rationale for measuring vitamin B6 and to investigate whether vitamin B6 supplementation or modification of the gut microbial community can help improve outcomes for people with PSC.

Vitamin B12 Status in Recreational Users of Nitrous Oxide: A Systematic Review Focusing on the Prevalence of Laboratory Abnormalities.

The recreational use of nitrous oxide (N2O) as "laughing gas" is a growing problem. The chronic toxicity of N2O is mainly due to its ability to oxidize vitamin B12, making it dysfunctional as a cofactor in metabolic pathways. This mechanism plays a major role in the development of neurological disorders in N2O users. The assessment of vitamin B12 status in N2O users is important but challenging due to the lack of decrease in total vitamin B12 in most cases despite genuine vitamin B12 functional deficiency. Other biomarkers, such as holotranscobalamin (holoTC), homocysteine (tHcy) and methylmalonic acid (MMA), are interesting candidates to properly assess vitamin B12 status. Here, we conducted a systematic review of case series in order to assess the prevalence of abnormal values of total vitamin B12, holoTC, tHcy and MMA in recreational N2O users, which is an important prerequisite for determining the best screening strategy in future guidelines. We included 23 case series (574 N2O users) from the PubMed database. Total circulating vitamin B12 concentration was low in 42.2% (95% confidence interval 37.8-46.6%, n = 486) of N2O users, while 28.6% (7.5-49.6%, n = 21) of N2O users had low circulating concentrations of holoTC. tHcy levels were elevated in 79.7% (75.9-83.5%, n = 429) of N2O users, while 79.6% (71.5-87.7%, n = 98) of N2O users had increased concentrations of MMA. In summary, the increases in tHcy and MMA were the most prevalent abnormalities, and should be measured alone or in combination in symptomatic N2O users rather than total vitamin B12 or holoTC.

Study of Homocysteine, Vitamin B12 and Folate in children with autism spectrum disorder

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that usually begins at or before the age of 3 years. The etiology of these disorders, includes environmental factors such as vitamins which have important role in central nervous system functioning. Vitamin B12 and folate are involved in the methionine-homocysteine pathway and some studies have shown a relationship between folate, vitamin B12 and homocysteine and various psychiatric diseases including ASDs. Objective: To evaluate the homocysteine, vitamin B12 and folate status in children with ASDs in Bangladesh. Methodology: This case control study included 50 ASD cases and 50 age matched healthy controls, according to inclusion criteria. After taking informed written consent from guardian, a structured questionnaire was filled up for each subject including socio-demographic history, family history, birth history and milestone of development. 5cc venous bloods were collected with all aseptic precautions in clot activator tube and serum homocysteine, vitamin B12 and folate levels were estimated. Collected data was checked, edited and processed with the help of SPSS (23). Results: The mean age of autism children was 5.71±2.06 years and in control group, it was 6.00±1.99 years. Mean S.Vit B12 (pg/ml) and S.Folic acid (ng/mL) were found significantly lower in autism children compared to control children (241.46±60.51 Vs 302.58±76.66 and 7.12±2.16 Vs 9.72±2.96). On the other hand, the mean S. Homocystiene (μmol/L) was found significantly higher in cases than controls (8.08±2.11 Vs 6.12±1.71). Conclusion: This study revealed that serum vitamin B12 and folate levels were significantly decreased, and serum homocysteine were significantly increased in children with autism spectrum disorders (ASDs) compared to normal healthy children. So, screening of serum homocysteine, vitamin B12 and folate in children with autism spectrum disorders is recommended for early management of complications related to the disease process. Bangladesh Medical Res Counc Bull 2022; 48: 127-132

Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance.

The association between markers of vitamin B12 status and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), which precede cognitive impairment, has been investigated by only a few small studies and results have been inconsistent. The aim of this study was to investigate the associations of vitamin B12-related markers with CSF biomarkers of AD and cognitive performance. Data included 462 patients aged 40 to 94 years referred to the Memory Clinic of the Ulm University Hospital, Ulm, Germany. Vitamin B12, holotranscobalamin (HoloTC), homocysteine (tHcy), and methylmalonic acid (MMA) have been measured. CSF values of amyloid β42 (Aβ42 ) and total-tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations. In the multi-adjusted model, higher levels of MMA were associated with raised CSF total-tau values: the odds ratios (ORs) 95% confidence intervals (CIs) were 3.25 (95% CI = 1.35-7.76) for the highest quartile of MMA compared to the lowest. Furthermore, moderately increased MMA were related to lower Aβ42 levels: the ORs and 95% CIs were 3.06 (95% CI = 1.22-7.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning. Markers of vitamin B12 may be independent predictors of CSF biomarkers of AD and cognitive functioning, with MMA showing the most consistent effects. Randomized controlled trials are needed to determine the importance of vitamin B12 supplementation on slowing structural brain changes and cognitive decline. ANN NEUROL 2023;94:223-231.

Should we follow the guidelines on vitamin B12 deficiency and diabetes? A retrospective analysis of data from middle eastern population

ABSTRACT Background Vitamin B12 is a micronutrient required for hematopoietic, neuro-cognitive and cardiovascular function. Biochemical and clinical vitamin B12 deficiency has been recognized in patients with type 2 diabetes mellitus. One of the adverse effects of long-term metformin use is vitamin B12 malabsorption. Aim of the study was to assess the state of vitamin B12 deficiency in people with type 2 diabetes and to ascertain the relationship between vitamin B12 status, metformin use and peripheral neuropathy. It is a retrospective study that was conducted on 8040 subjects included 2126 type 2 diabetic patients, and 5914 nondiabetic individuals. Personal information, medical history, including metformin and multivitamin therapy use as well as the existence of clinical peripheral neuropathy, were all included data. For the purpose of measuring the amount of vitamin B12, blood samples were taken. Serum B12 levels <200 pg/ml was defined as B12 deficiency. Results Vitamin B12 deficiency was detected in 12.9% of diabetic group and 19.9% of control group. The mean value of vitamin B12 level between diabetic (563 ± 470.6 pg/ml) and non-diabetic (429.7 ± 310.9 pg/ml) showed a high significant difference, p value <0.001. The vitamin B12 levels were higher in people with diabetes. Vitamin B12 deficiency was not associated with metformin intake or diabetic neuropathy. Conclusions Vitamin B12 level was significantly higher in diabetic compared to nondiabetic individuals. Neither peripheral neuropathy, anemia nor metformin therapy was associated with vitamin B12 deficiency. Vitamin B12 supplementation is not recommended as a routine practice in people with diabetes. This is contrary to the common practice that is sometimes done. The cost of supplementation can be used to provide more beneficial services and drugs for these people.