Plasma Vitamin B12 Concentrations Research Articles

Maternal Nutritional Factors Enhance Birthweight Prediction: A Super Learner Ensemble Approach

Birthweight (BW) is a widely used indicator of neonatal health, with low birthweight (LBW) being linked to higher risks of morbidity and mortality. Timely and precise prediction of LBW is crucial for ensuring newborn health and well-being. Despite recent machine learning advancements in BW classification based on physiological traits in the mother and ultrasound outcomes, maternal status in essential micronutrients for fetal development is yet to be fully exploited for BW prediction. This study aims to evaluate the impact of maternal nutritional factors, specifically mid-pregnancy plasma concentrations of vitamin B12, folate, and anemia on BW prediction. This study analyzed data from 729 pregnant women in Tarragona, Spain, for early BW prediction and analyzed each factor’s impact and contribution using a partial dependency plot and feature importance. Using a super learner ensemble method with tenfold cross-validation, the model achieved a prediction accuracy of 96.19% and an AUC-ROC of 0.96, outperforming single-model approaches. Vitamin B12 and folate status were identified as significant predictors, underscoring their importance in reducing LBW risk. The findings highlight the critical role of maternal nutritional factors in BW prediction and suggest that monitoring vitamin B12 and folate levels during pregnancy could enhance prenatal care and mitigate neonatal complications associated with LBW.

Oral vitamin B12 supplementation in pernicious anemia: a prospective cohort study

BackgroundThe absorption of vitamin B12 is hindered in pernicious anemia (PA) owing to intrinsic factor deficiency. Traditionally, intramuscular vitamin B12 injections were the standard treatment, bypassing the impaired absorption. Although there is potential for oral vitamin B12 supplementation through passive enteral absorption, it is not commonly prescribed in PA owing to limited studies assessing its efficacy. ObjectivesWe aimed to assess the efficacy of oral vitamin B12 supplementation in PA. MethodsWe enrolled participants diagnosed with incident vitamin B12 deficiency related to PA. The diagnosis of PA was based on the presence of classical immune gastritis and of anti-intrinsic factor and/or antiparietal cell antibodies. To evaluate the vitamin B12 status, we measured total plasma vitamin B12, plasma homocysteine, and plasma methylmalonic acid (pMMA) concentration and urinary methylmalonic acid–to–creatinine ratio. Participants were treated with oral cyanocobalamin at a dosage of 1000 μg/d throughout the study duration. Clinical and biological vitamin B12 deficiency related features were prospectively and systematically assessed over the 1-y study duration. ResultsWe included 26 patients with vitamin B12 deficiency revealing PA. Following 1 mo of oral vitamin B12 supplementation, 88.5% of patients were no longer deficient in vitamin B12, with significant improvement of plasma vitamin B12 [407 (297–485) compared with 148 (116–213) pmol/L; P < 0.0001], plasma homocysteine [13.5 (10.9–29.8) compared with 18.6 (13.7–46.8) μmol/L; P < 0.0001], and pMMA [0.24 (0.16–0.38) compared with 0.56 (0.28–1.09) pmol/L; P < 0.0001] concentrations than those at baseline. The enhancement of these biological parameters persisted throughout the 12-month follow-up, with no patients showing vitamin B12 deficiency by the end of the follow-up period. The median time to reverse initial vitamin B12 deficiency abnormalities ranged from 1 mo for hemolysis to 4 mo for mucosal symptoms. ConclusionsOral supplementation with 1000 μg/d of cyanocobalamin has been shown to improve vitamin B12 deficiency in PA.

Evaluation of plasma biotin, folate, and vitamin B12 concentrations of Holstein dairy cows fed adequate or high concentrations of dietary vitamin D3, vitamin E, calcium, and selenium under heat stress

The aim of this study was to determine plasma biotin (B8), folate (B9), and vitamin B12 (B12) concentrations of multiparous dairy cows under heat stress (HS) fed with adequate or high concentrations of vitamin D3 (VITD) and E (VITE), Ca, and Se. Twelve multiparous Holstein cows were used in a split-plot design. The main plot was: (1) Adequate VITE and Se; (2) High VITE and Se. Within each main plot, cows were assigned to treatments: (1) HS with adequate concentrations of VITD and Ca; (2) HS with high concentrations of VITD and Ca; (3) pair-feeding (PF) with HS in thermoneutrality with adequate concentrations of VITD and Ca in a duplicated 3 × 3 Latin square. There were no treatment effects on plasma B8 and B12. Plasma B9 was lower by 21% for HS with adequate VITD and Ca than PF cows. Results suggested that HS might modify folate status in dairy cows, regardless of treatments.

Associations between homocysteine, vitamin B12, and folate and the risk of all-cause mortality in American adults with stroke.

Associations between plasma homocysteine (Hcy), vitamin B12, and folate and the risk of all-cause mortality are unclear. This study aimed to examine whether plasma Hcy, vitamin B12, and folate levels independently predict the risk of all-cause mortality in American adults with stroke. Data from the United States National Health and Examination Survey (NHANES; 1999-2006) were used and linked with the latest (2019) National Death Index (NDI). Cox proportional hazards models and restricted cubic splines were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of all-cause mortality for Hcy, folate, and B12 levels in adults with stroke. Sample weights were calculated to ensure the generalizability of the results. A total of 431 participants were included (average age: 64.8 years). During a median follow-up of 10.4 years, 316 deaths occurred. Hcy was positively associated with all-cause mortality in adults with stroke (HR, 1.053; 95% CI: 1.026-1.080). Stroke patients with plasma Hcy levels in the fourth quartile had a 1.631-fold higher risk of all-cause mortality (HR, 1.631; 95% CI: 1.160-2.291) than those in the first quartile. The association between plasma Hcy and all-cause mortality was strong significant in older patients (p for interaction = 0.020). Plasma folate and vitamin B12 concentrations were inversely correlated with Hcy concentrations [B-value (95% CI): -0.032 (-0.056- -0.008), -0.004 (-0.007- -0.002), respectively]. No significant associations were observed between folate, vitamin B12 levels, and all-cause mortality in adults with stroke. Plasma Hcy levels were positively associated with all-cause mortality in older adults with stroke. Folate and vitamin B12 levels were inversely correlated with Hcy. Plasma Hcy may serve as a useful predictor in mortality risk assessment and targeted intervention in adults with stroke.

High Plasma Vitamin B12 and Cancer in Human Studies: A Scoping Review to Judge Causality and Alternative Explanations.

Patients with cancer have been reported to show elevated plasma concentrations of vitamin B12, thus causing uncertainties regarding safety of vitamin B12. We conducted a systematic literature search and a scoping review of human studies published in PubMed between January 2005 and March 2022, to investigate the association between vitamin B12 (concentrations of B12 biomarkers, intake, and genetic determinants) and cancer. Except for liver cancer, the association between plasma vitamin B12 concentrations and cancer was not consistent across the studies. Vitamin B12 intake from food, or food and supplements, showed even less consistent associations with cancer. There was no evidence for temporality, coherence, or a biologically meaningful dose-response relationship between plasma vitamin B12 concentrations and cancer. Genetically determined high plasma vitamin B12 was likely to be associated with cancer. Available randomized controlled trials have used a high dose of multivitamin supplements and cancer was the unplanned outcome, thus the causality of B12 in cancer cannot be judged based on these trials. Additionally, low plasma vitamin B12 concentrations were common in patients with cancer. Therefore, there is not sufficient evidence to assume that high plasma vitamin B12, high B12 intake, or treatment with pharmacological doses of vitamin B12, is causally related to cancer. Low vitamin B12 status in patients with cancer needs to be diagnosed and treated in order to prevent the hematological and neurological sequela of the deficiency.

The effects of oral drenching with Co or vitamin B12, drenching frequency and Co via rumen bolus on plasma vitamin B12 concentration in weaned lambs

Weaned lambs (n = 88) were stratified by sex and body weight (BW) and allocated at random to 1 of 10 treatments for 12 weeks (consecutive 6-week periods), to evaluate the effects of supplementation with Co or vitamin B12 (B12) on the concentrations of B12 in blood plasma. The treatments were: no supplementation (Control); rumen bolus containing Co only (Bolus); and oral administration of a liquid solution (Drench) containing Co or B12 at intervals of 1, 2, 3 or 6 weeks. One bolus (expected Co release [by leaching] of 0.8 mg/day for 4 months) was administered to the bolus group at the initiation of the study (day 0). The lambs on the drench treatments received totals of 63 mg Co (as CoSO4·7H2O) or 34.5 mg B12 over each 6-week period; drench concentrations were 2.1 mg/ml and 2.3 mg/ml for Co and B12, respectively. The lambs were managed in a rotational-grazing system on predominately perennial ryegrass swards. Blood samples were collected weekly (immediately prior to treatment administration), starting on day 0, and plasma was analysed for B12 and Co. Lambs on the Co-drench treatments had higher B12 concentrations (P < 0.001) than the Control in both 6-week periods but the difference exhibited a quadratic decline in both periods as the drenching interval increased (P < 0.001). Drenching with B12 increased plasma B12 concentration in both periods but the difference only reached significance (P < 0.05) in the second period and the effect of drenching frequency was not significant in either period. Lambs on the Co-drench had higher (P < 0.01) plasma B12 concentrations than lambs on the B12-drench treatments, and the control. Bolus lambs had a higher plasma B12 concentration (P < 0.01) than lambs drenched with Co at 2-, 3- or 6-week intervals in the first 6-week period but did not differ (P > 0.05) from these treatments in the second period. Lambs on the Bolus treatment had a higher plasma B12 concentration than Control lambs over the first (P < 0.001) and second (P < 0.05) periods. It is concluded that drenching with Co is more effective than drenching with B12, in terms of the effect on plasma B12 concentration. Drenching with Co at intervals of 1 or 2 weeks was more effective than drenching at intervals of 3 or 6 weeks. While the bolus treatment was effective in increasing plasma B12 concentration compared to Control over weeks 1 to 12, the difference between these treatments declined significantly over time.

Evaluating Deficiency of Vitamin B12 and Risk Factors in Healthy Infants

Background: The deficiency of vitamin b12 is highly extensive within the developed countries and is often found to remain undiagnosed within these populations. the main feature within infants suffering from vitamin b12 deficiency is altered neurological development and generalized growth. Effects of vitamin b12 deficiency on the brain can be prevented. To avoid these morbidities and mortality associated with vitamin b12 deficiency it is pivotal for clinicians to understand what other risk factors are associated with a deficiency within the infant population of developing countries. Materials and methods: This cross-sectional study was conducted on 82 healthy infants for the assessment of Vitamin B12 at Pediatric Department of LGH, Lahore from March 2021 to August 2021. Participants were selected who were healthy. After recruitment, participants underwent hematological and biochemical indices analysis. Hemoglobin, serum vitamin b12, homocysteine and methylmalonic acid were different parameters measured. Maternal vitamin b12 deficiency was investigated along with risk factor vitamin b12 deficiency in healthy infants. Results: A total of 82 recruited participants were selected after screening and meeting the recruitment criteria. After assessment of hematological data, anemia was diagnosed in 67.82% of infants (n=56). The breakdown of the anemic population showed that the male population was predominant with 58.2% affected males and 41.8% affected females. Decreased levels of plasma vitamin b12 concentration were documented in 22% of the population with a total number of 18 participants (male: 11, female: 7). Increased levels of homocysteinemia were documented in 49.1% of infants with n=40. Increased levels of methylmalonic acid were appreciated in all infants. As defined by previous criteria, the diagnosis of vitamin b12 deficiency was appreciated in 30 infants with a percentage of 38%. Furthermore, an assessment of folate deficiency showed that 8 out of 82 participants had concurrent folate deficiency in red cells with a percentile prevalence of 9.7%. maternal vitamin b12 deficiency was considered as risk factor for infant vitamin b12 deficiency Conclusion: The prevalence of vitamin b12 deficiency in healthy infants is significantly high in developing and underdeveloped countries. Vitamin b12 deficiency cooccurs with anemia and other variation of biological markers. The study concluded that among the various risk factors that may predispose an infant to vitamin b12 deficiency, maternal b12 deficiency remains the highest appreciated risk factor. Keywords: Vitamin B12, Risk Factors, Vitamin B12 deficiency, Maternal B12

Association between urinary arsenic levels and anemia among older adults in nine longevity areas of China

Objective: To investigate the association between urinary arsenic levels and anemia among older adults in nine longevity areas of China. Methods: A total of 1 896 subjects aged 65 years and above who participated in the Healthy Aging and Biomarkers Cohort Study (HABCS) in 2017-2018 were included. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information from the subjects. Through physical examination, data including height, weight and blood pressure were determined and body mass index (BMI) was calculated. Blood and urine samples were collected for the detection of hemoglobin (Hb), blood glucose, blood lipids, plasma vitamin B12 and urinary arsenic concentrations. The urinary arsenic levels were divided into four groups according to the quartiles of urinary arsenic concentrations (μg/g creatinine): Q1 (<18.7), Q2 (18.7-34.5), Q3 (34.6-69.5) and Q4(≥69.6). Multivariate logistic regression model and restricted cubic spline fitting logistic regression model were used to analyze the association between urinary arsenic levels and anemia. Results: The age of the 1 896 subjects (M (Q1, Q3)) was 83 (74, 92) years, including 952 females (50.21%), and the concentration of Hb (M (Q1, Q3)) was 135 (124, 147)g/L. The prevalence of anemia was 24.89% (472 cases). The geometric mean and M (Q1, Q3) of urinary arsenic concentrations were 37.5 and 34.6 (18.7, 69.6)μg/g creatinine, respectively. Multivariate logistic regression model analysis showed that after adjusting for age, gender, BMI, education level, smoking and drinking status, residence, economic level, ethnicity, the status of vitamin B12 deficiency, consumption frequency of aquatic products and meat, the prevalence of hypertension, diabetes and dyslipidemia, urinary arsenic levels were positively associated with anemia (Taking group Q1 as a reference, OR (95%CI) values in Q2, Q3 and Q4 groups were 1.73 (1.20-2.50), 2.08 (1.43-3.02) and 1.52 (1.02-2.28), respectively). The results of restricted cubic spline fitting logistic regression analysis showed a non-linear association between urinary arsenic concentrations and anemia (P<0.001). Subgroup analysis showed there was a negative multiplicative interaction between the prevalence of chronic diseases and urinary arsenic levels with OR (95%CI) was 0.55 (0.30-0.99), while no multiplicative interaction was found between age, gender, residence, smoking status, drinking status and urinary arsenic levels (P>0.05). There was a positive association between urinary arsenic levels and anemia in participants who were absence of chronic diseases,male, living in rural, smoking and drinking with OR (95%CI) values of 3.62 (1.30-10.06),2.46 (1.34-4.52), 1.70 (1.03-2.80), 2.21 (1.01-4.82) and 2.79 (1.23-6.33), respectively. Conclusion: There is a positive association between urinary arsenic levels and anemia among older adults in nine longevity areas of China.

The effects of supplementation with cobalt, and method of administration, on ewe reproduction and offspring performance to weaning

The concentration of Co in the herbage of a large proportion of grassland farms in Ireland is lower than that required by sheep. The effects of supplementing ewes with Co, and method of supplementation, on ewe and offspring performance, were evaluated over 2 years. The ewes (359 in year 1, 241 in year 2), representing 3 genotypes, were allocated to one of 3 treatments. The treatments were: Control - no supplementation; Drench – Co supplementation via oral drench (31.5 mg Co as CoSO4•7H2O) administered every 14 days; Bolus – Co supplementation via rumen bolus (effective life of ∼6 months) that only contained Co as CoSO4•7H2O with an expected Co release rate of 0.6 mg/day in year 1 and 1 mg/day in year 2. Drench treatment was administered from 7 weeks pre joining, until 6 weeks prior to expected lambing date (early – to mid - March). One bolus was administered to ewes on the bolus treatment at the start of the study (day 0) each year. The ewes were managed as one flock in a rotational-grazing system until housing in early December each year; they were shorn at housing and offered grass silage ad libitum plus a concentrate supplement during late pregnancy. Ewes and lambs were put to pasture within 3 days of lambing. Supplementation with Co, via drench or bolus, increased the concentration of Co (p< 0.001) and vitamin B12 in ewe plasma at ∼day 50 and ∼day 100 of pregnancy and these effects were generally greater for Drench than Bolus treatments. Supplementary Co had no effect (p > 0.05) on ewe BW or body condition score at joining (day 49), mid-pregnancy, lambing, 5 weeks post lambing or weaning. Likewise, supplementation had no effect (p > 0.05) on litter size, lamb mortality or number of lambs reared per ewe joined, or on lamb BW at birth or weaning. The only significant animal-performance difference detected between the Bolus and Drench treatments concerned the incidence of lambs classified as ‘born dead or died within 24 h of birth’ (3.1% for Drench, 6.5% for Bolus; p < 0.05). It is concluded that, whilst supplementing ewes (high proportion whom (30 to 60%) had marginal plasma B12 status) with Co from 7 weeks pre-joining until late pregnancy increased plasma Co and vitamin B12 concentrations and reduced the proportion classified as having marginal or low Co status. There was no effect on ewe or progeny performance.

Effect of dietary supplementation of 2 forms of a B vitamin and choline blend on the performance of Holstein calves during the transition and postweaning phase

The transition from a liquid- to a solid-based diet involves several adaptations in calves. Development of ruminal function is likely to alter B vitamin and choline supply, although little is known about the extent of these changes relative to the calf's requirements and consequences for the calf around weaning. Moreover, literature data are equivocal concerning the need to supplement B vitamins and choline through weaning and transition phase of the dairy calf. To evaluate the effect of increasing B vitamin and choline supply on performance, 61 Holstein calves were individually housed and raised from birth to 13 wk of age. Calves were fed milk replacer (28% crude protein, 15% fat) up to 1.6 kg of dry matter (DM)/d at 15% solids (3 times/d) from birth to 4 wk of age. At that time, calves were randomly assigned to one of 3 treatments: a rumen-protected blend of B vitamins and choline (RPBV); a 30:70 mix of a nonprotected blend of B vitamins and choline and fat (UPBV); or fat only, used as control (CTRL). Calves were maintained on milk replacer and offered ad libitum quantities of a starter grain (25.5% crude protein) specifically formulated to supply all essential amino acids with no added B vitamins or choline. The supplements were provided in gel capsules and administered once a day to each calf in quantities corresponding to 0.39 and 0.28% of the previous day's starter DM intake for the vitamin blends and control, respectively. Calves were weaned gradually from d 49 to 63. Body weight and stature were measured, and blood was collected and analyzed for hematocrit, plasma urea nitrogen, β-hydroxybutyrate, folates, and vitamin B12. Body weight and stature were similar among treatments. Overall gain (0.99 kg/d), DM intake (1.90 kg of DM/d), and feed efficiency (0.52) were not affected by vitamin supplementation. Plasma vitamin B12 concentrations were not different between RPBV and UPBV but tended to be higher at the end of weaning and were greater postweaning in RPBV and UPBV treatments compared with CTRL. Both forms of the vitamin blend effectively improved vitamin B12 status postweaning with no effect on folate status. No differences were observed in other blood measurements. Under conditions of this study, additional B vitamins and choline did not improve calf performance before, during, or after weaning.

Investigating the effects of a novel rumen-protected folic acid supplement on feedlot performance and carcass characteristics of beef steers.

Angus-crossbred steers (n = 180; 292 ± 18 kg) from a single ranch were used to investigate the effects of a novel rumen-protected folic acid (RPFA) supplement on feedlot performance and carcass characteristics. On d 0, steers were blocked by body weight to pens (5 steers/pen), and pens within a block were randomly assigned to dietary treatments (n = 6 pens/treatment): target intake of 0 (CON), 30 (RPFA-30), 60 (RPFA-60), 90 (RPFA-90), 120 (RPFA-120), or 150 (RPFA-150) mg RPFA·steer−1·d−1. Steers were weighed before feeding on d −1, 0, 55, 56, 86, 87, 181, and 182. Pen average daily gain (ADG), dry matter intake (DMI), and gain:feed (G:F) were calculated for growing (d 0 to 56), dietary transition (d 56 to 87), finishing (d 87 to 182), and overall (d 0 to 182). Liver and blood samples were collected from two steers/pen before trial initiation and at the end of growing and finishing. Steers were slaughtered on d 183, and carcass data were collected after a 48-h chill. Data were analyzed as a randomized complete block design using ProcMixed of SAS 9.4 (fixed effects of treatment and block; experimental unit of pen). Liver abscess scores were analyzed using the Genmod Procedure of SAS 9.4. Contrast statements assessed the polynomial effects of RPFA. Supplemental RPFA linearly increased plasma folate at the end of growing and finishing (P < 0.01), and linearly decreased plasma glucose at the end of growing (P = 0.01). There was a cubic effect of RPFA on liver folate at the end of growing (P = 0.01), driven by lesser concentrations for RPFA-30, RPFA-60, and RPFA-150. Growing period ADG and G:F were greatest for CON and RPFA-120 (cubic P ≤ 0.03). Transition period DMI was linearly increased due to RPFA (P = 0.05). There was a tendency for a cubic effect of RPFA on the percentage of livers with no abscesses (P = 0.06), driven by a greater percentage of non-abscessed livers in RPFA-30 and RPFA-60. Despite supplementing 1 mg Co/kg DM, and regardless of treatment, plasma vitamin B12 concentrations were low (<200 pg/mL), which may have influenced the response to RPFA as vitamin B12 is essential for recycling of folate.

HIGH PREVALENCE OF ELEVATED VITAMIN B12 LEVELS AT A TEACHING HOSPITAL

<h3>Introduction</h3> Measurement of serum vitamin B12 and folate levels is an integral part of the laboratory evaluation at our geriatric psychiatry clinic. While B12 testing is typically done to detect abnormally low B12 levels, in our clinic and elsewhere the tests often detect vitamin B12 abnormalities consisting of high rather than low levels of B12. The apparent high frequency of excessively high levels of vitamin B12 at our clinic led us to explore this issue in a more systematic manner. <h3>Methods</h3> This presentation examined all the B12 results completed at Hackensack Meridian Health- Jersey Shore University Medical Center [JSUMC] in 2018 and 2019. The initial query elicited 15833 test results. All cases whose folate was low (n=58) or unavailable (n=3987) were excluded from further analysis resulting in a sample of 11787 tests. Furthermore, duplicate tests for the same individual were excluded, holding on to the earliest performed test, resulting in a sample of 8901 B12 tests across all ages. This presentation examines the interplay between three variables: Vitamin B12 level, Age, and MCV. All three parameters were examined as continuous as well as categorical variables. The three variables were converted from continuous to categorical variables as follows: B12 level (low 0-179 Pg/Ml = 132 pmol/L; normal 180-914 Pg/Ml (that is 133-677 pmol/l); high 915 Pg/Ml (677 pmo/l) and up), Age (young 0– 17 yrs; adult 18-64; senior 65 and up), MCV (low 0-79.9; normal 80-100; high 100.1 and up). The conversion ratio for vitamin B12 is is 1.35 pg/ml = 1 pmol/l. <h3>Results</h3> 1. 22% of the whole sample had above normal Vitamin B12 levels 2. 27% of Seniors (65 and older) had above normal Vitamin B12 levels 3. B12 levels correlated positively with age; Seniors (65 and older) had significantly higher (by about 20%) B12 levels compared to adults (18-64 of age) 4. 8% of Seniors had high MCV despite normal or above normal plasma B12, suggesting possible functional B12 deficiency 5. 3.3% of Seniors had normal MCV despite B12 deficiency. <h3>Discussion</h3> During a two year period over a quarter of all vitamin B12 tested patients at JSUMC in general, and seniors in particular had above normal B12 levels. Oral B12 supplements may contribute to above normal B12 plasma levels, but the literature is equivocal on this issue. Unfortunately because in this sample specific clinical data was not available regarding the B12 intake in this population, the nature of the relation between oral intake of vitamin B12 supplements and abnormal high plasma B12 levels could not be explored. Several studies have reported on the prevalence of abnormal high vitamin B12 levels: Jammal et al., 2013 found it in 12% of cases, Carmel et al.,2001 in 14% and Chiche et al., 2013 in 18% of patients. Using 914 Pg/Ml as a cutoff point resulted in 27.5 % of JSUMC seniors falling in the above normal range category well above the published results. Above normal vitamin b12 levels are known to be associated with a long list of serious conditions including: 1. Hematological malignancies / blood dyscrasias, 2. Liver diseases, 3. solid organ tumors, 4. Autoimmune disorders 5. Renal disease / kidney failure, 6. Infectious diseases 7. Possibly with excessive b12 supplements intake. 8. Increased all-cause mortality Two recent studies have reported on the relationship between serum B12 concentrations. Wolffenbuttel et al., 2020 found, that there was a small but significant increase in cardiovascular mortality in the groups with low or high serum B12. The 2020 Flores-Guerrero et al., study found "that higher levels of plasma concentrations of vitamin B12 were associated with increased risk of all-cause mortality...". <h3>Conclusions</h3> 1. Over a quarter of the seniors tested at JSUMC had abnormally high vitamin B12 levels. The reason for this higher than expected prevalence requires further exploration. 2. In addition, since elevated B12 levels are known to be associated with a long list of serious medical conditions and a higher mortality rate, this project emphasizes the importance of conducting a careful clinical review for possible serious hidden causes for such findings. 3. High vitamin B12 may be the result of oral intake of large amounts of vitamin B12 supplements, but this information is typically not systematically collected. This project also highlights the importance of collecting accurate quantitative information regarding vitamin supplement intake when completing the medication reconciliation process in routine clinical practice. 1. Andrès E, et al., 2013 PMID: 23447660. 2. Arendt JF, et al., 2013 PMID: 23241600. 3. Carmel R, et al., 2001 PMID: 11843883. 4. Jammal M, et al 2013 PMID: 2314212. 5. Chiche L, et al., 2013 PMID: 23708236. 6. Wolffenbuttel BHR, 2020 PMID: 33032595. 7. Flores-Guerrero JL, 2019 PMID: 31940038.

Effect of zinc supplementation on hemogram parameters and circulating concentrations of homocysteine, vitamin B12, and folate in zinc-deficient children and adolescents

BackgroundZinc deficiency may exacerbate some pathologies and may also explain alterations in circulating concentrations of various molecules. Zinc has previously been reported to affect plasma concentrations of vitamin B12, homocysteine, and folate; however, the current evidence is inconclusive. We aimed to evaluate plasma zinc, hemoglobin, red blood cell count, mean corpuscular volume, ferritin, vitamin B12, folate, and homocysteine concentrations during and after zinc supplementation for treatment of zinc deficiency. MethodsThis prospective, open-label, single-arm study included children who presented to outpatient clinics with symptoms of growth retardation, anorexia or frequent infections, and who were considered deficient based on plasma zinc concentrations (<70 mcg/dl). Zinc supplementation of 15 mg per day was administered to all participants, and fasting blood samples collected 3 months later were analyzed for plasma zinc, vitamin B12, homocysteine, and folate concentrations. ResultsEighty-three children (27 males and 26 females) admitted to the outpatient clinics with anorexia, growth retardation, and complaints of frequent infections. The mean age of the children was 9.64 ± 5.05 (min-max, 1–15) years, and the mean plasma zinc concentration before zinc supplementation was 61.7 ± 6.3 mcg/dl. Zinc concentrations were significantly elevated after zinc sulfate supplementation for 3 months, at 107.1 ± 18.8 mcg/dl (p < 0.01). Hemoglobin (p < 0.01), mean corpuscular volume (p < 0.01), and ferritin (p = 0.049) levels were significantly increased after zinc supplementation, but no significant difference was found in red blood cell count (p = 0.83). Vitamin B12 and homocysteine concentrations were significantly decreased after zinc treatment (743.5 ± 498.8 vs 373.3 ± 128 mcg/dl p < 0.01; and 11.2 ± 5.3 vs 6.7 ± 3.4 mcg/dl p < 0.01, respectively). However, the change in folate concentrations was not significant (p = 0.05). ConclusionsAnemia was not detected in patients with zinc deficiency, but ferritin level significantly increased after zinc treatment. Therefore, it can be said that zinc therapy has a positive effect on iron absorption. Elevations in vitamin B12 and homocysteine may be associated with zinc deficiency, and these elevations may in turn influence the prognoses of liver, kidney, cardiorespiratory, and neoplastic conditions. This can be corrected through appropriate zinc supplementation.

Relationship between intake and plasma concentrations of vitamin B12 and folate in 873 adults with a physically active lifestyle: a cross-sectional study.

BackgroundVitamin B12 and folate function as co‐factors in pathways used during physical activity. Physical activity may therefore increase vitamin requirements, leading to a risk of deficient plasma concentrations. We aimed to investigate the relationship between intake and plasma concentrations of vitamin B12 and folate in physically active adults, as well as identify other determinants of vitamin B12 and folate plasma concentrations.MethodsThe study population consisted of 873 adults (528 men and 345 women), aged 19–78 years, who participated in a 4‐day walking event. The relationship between intake and plasma concentrations of vitamin B12 and folate was assessed using correlation and linear regression analyses. In addition, potential other determinants (sex, age, body mass index, energy intake and physical activity) of vitamin plasma concentrations were investigated.ResultsSignificant positive correlations were observed between intake and plasma concentrations of vitamin B12 [Pearson’s correlation coefficient = 0.15; 95% confidence interval (CI) = 0.08–0.21] and folate (Pearson’s correlation coefficient = 0.18; 95% CI = 0.12–0.25). In addition to vitamin intake, sex, age and energy intake were also determinants of both vitamin B12 and folate plasma concentrations in multivariable regression models.ConclusionsThe results suggest a positive association between intake and plasma concentrations for both vitamin B12 and folate in physically active people. By contrast to our hypothesis, physical activity was not a determinant of vitamin B12 and folate plasma concentrations. However, sex, age and energy intake were found to be determinants. Thus, when studying the relationship between intake and plasma concentrations of vitamin B12 or folate, these factors should be taken into account.

Elevated Plasma Vitamin B12 in Patients with Hepatic Glycogen Storage Diseases.

Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B12 status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B12 status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B12 intake were studied. Results: GSD patients had significantly higher plasma vitamin B12 concentrations than healthy controls (p = 0.0002). Plasma vitamin B12 concentration remained elevated in GSD patients irrespective of vitamin B12 intake. Plasma vitamin B12 concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B12 status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B12 (irrespective of B12 intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B12 with triglyceride levels suggests an influence of metabolic control on the vitamin B12 status of GSD patients. Elevated vitamin B12 was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B12 in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B12 on GSD.

Association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status: evidence from a cluster randomized controlled trial.

Evidence about the effect of maternal vitamin B12 supplementation on offspring's vitamin B12 status is limited. The present interventional study sought to evaluate the association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status. In an ongoing cluster randomized controlled trial conducted in three rural counties in northwest China, pregnant women < 20weeks of gestation were randomized to three treatment groups: blank control, iron supplements, or vitamin B complex supplements. All women were administered folic acid supplements during the periconceptional period. In a sub-study, we collected cord blood samples of 331 participants from the control or vitamin B complex groups in the Xunyi county from January 2017 to December 2017. Plasma concentrations of folate, vitamin B12, and homocysteine were measured. Linear mixed models with a random intercept for cluster were used to compare biochemical indexes between groups after controlling for covariates. Compared with newborns whose mothers were in the control group, newborns of the vitamin B complex-supplemented women had significantly higher cord plasma vitamin B12 (P = 0.001) and lower homocysteine concentrations (P = 0.043). The association of antenatal vitamin B complex supplementation with cord blood vitamin B12 concentrations appeared to be more pronounced among newborns with high folate status than those with low folate status (Pinteraction = 0.060). Maternal vitamin B complex supplementation during pregnancy was associated with better neonatal vitamin B12 status in rural northwest China.

Combined effect of polymorphisms of MTHFR and MTR and arsenic methylation capacity on developmental delay in preschool children in Taiwan.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B12 levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and vitamin B12 levels and if these influences cause developmental delay in preschool children. A total of 178 children with developmental delay and 88 without developmental delay were recruited from August 2010 to March 2014. A high-performance liquid chromatography-hydride generator and atomic absorption spectrometer were used to determine urinary arsenic species. Plasma folate and vitamin B12 concentrations were measured by SimulTRAC-SNB radioassay. Polymorphisms of MTHFR C677T, MTHFR A1298C, and MTR A2756G were examined by polymerase chain reaction and restriction fragment length variation. The results show that MTHFR C677T C/T and T/T genotypes had a lower risk of developmental delay than the C/C genotype (odds ratio [OR] = 0.47; 95% confidence interval, 0.26-0.85). Subjects with the MTHFR C677T C/C genotype had significantly lower plasma folate and vitamin B12 levels than those with the MTHFR C677T C/T and T/T genotype. The MTHFR C677T C/C genotype combined with high total urinary arsenic and poor arsenic methylation capacity indices significantly increased the OR of developmental delay in a dose-response manner. This is the first study to show the combined effect of MTHFR C677T genotype and poor arsenic methylation capacity on developmental delay.

Nitrous oxide and vitamin B12 in sickle cell disease: Not a laughing situation

Nitrous oxide (N2O) is widely used as an anesthetic or an analgesic. N2O prolonged and recurrent administration is known to affect vitamin B12 metabolism with subsequent clinical consequences. We report herein the case of a 13-year-old girl with sickle cell disease exhibiting severe neurological and biochemical signs of functional vitamin B12 deficiency due to prolonged and repeated exposure to N2O. This was an incentive to prospectively investigate functional vitamin B12 deficiency in patients affected by sickle cell disease regularly exposed to N2O. We measured plasma concentrations of vitamin B12, total homocysteine, methionine and methylmalonic acid in 39 patients with sickle cell disease between 2015 and 2016. No patients developed neurological symptoms related to N2O administration but 19 patients (49%) had biochemical abnormalities suggesting mildly disturbed vitamin B12 metabolism e.g. decreased B12 vitamin, hypomethioninemia, or slightly increased methylmalonic acid or homocysteine. The clinical case highlight the potential severe deleterious effects of N2O over exposure on B12 vitamin metabolism in particular in patients affected with sickle cell disease. Conversely, when used without excess even repeatedly, there seem to be no overt clinically relevant abnormalities in vitamin B12 metabolism as observed on the cohort of 39 sickle cell disease affected patients.

Cross-sectional study of the effect of diet composition on plasma folate and vitamin B12 concentrations in Holstein cows in the United States and Canada

The objective of this cross-sectional study was to assess the variability of plasma folate and vitamin B12 concentrations in lactating Holstein cows across the United States and Canada. We also evaluated the effect of diet composition and cow characteristics on folate and vitamin B12 plasma vitamin concentrations. A total of 22 and 24 US and Canadian dairy herds were enrolled, totaling 427 and 476 cows at 10 to 197 days in milk across all US and Canadian herds, respectively. Blood samples were taken to analyze plasma folate and vitamin B12 concentrations, and ingredients of the diet were collected to determine nutrient composition. To reduce the number of interdependent variables in the analysis of the association of diet composition with plasma vitamin concentrations, we conducted a principal component analysis. Plasma folate concentrations were lower for US cows [13.4 ng/mL, 95% confidence interval (CI): 12.7-14.2] than for Canadian cows (14.5 ng/mL, 95% CI: 13.7-15.2), and the opposite was observed for plasma vitamin B12 concentrations (US 206 pg/mL, 95% CI: 192-221; Canada 170 pg/mL, 95% CI: 159-181). The highest plasma concentrations of both vitamins were observed in the Northwest region of the United States (Oregon and Washington). Cows in California had the lowest plasma folate concentrations, and cows in Québec and New York State had the lowest plasma vitamin B12 concentrations. Plasma folate concentrations were higher for multiparous than for primiparous cows and plasma vitamin B12 concentrations progressively increased from parity 1 to 3 and higher. For both studied vitamins, plasma concentrations were lower at 0 to 55 than at 56 to 200 days in milk. Of 3 principal components, the one associated with dietary carbohydrates was significantly correlated with plasma folate and vitamin B12 concentrations. Indeed, plasma folate concentrations decreased with dietary fiber concentrations (i.e., neutral and acid detergent fibers and lignin) and increased with dietary nonfiber carbohydrate concentrations. We obtained the opposite results for plasma vitamin B12 concentrations. Both multivariable models explained 41% (pseudo-R2) of the variation in plasma folate and vitamin B12 concentrations. Information gathered in this study is the first step toward determining sources of variation in plasma folate and vitamin B12 concentrations, as well as the vitamin status of cows.

Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands

Higher plasma concentrations of vitamin B12 have been associated with mortality in elderly and hospitalized populations, including patients with chronic kidney disease, but the association of plasma concentrations of vitamin B12 with mortality in the general population remains unclear. To investigate the association of plasma concentrations of vitamin B12 with all-cause mortality. This longitudinal cohort study used post hoc analysis to examine data from participants of the Prevention of Renal and Vascular End-stage Disease Study in Groningen, the Netherlands. Participants included individuals who completed the second screening visit beginning January 1, 2001, excluding those who were missing values of vitamin B12 plasma concentrations or used vitamin B12 supplementation. Follow-up time was defined between the beginning of the second screening round to end of follow-up on January 1, 2011. Data analysis was conducted from October 2, 2018, to February 22, 2019. Plasma vitamin B12 concentration level. Death as recorded by the Central Bureau of Statistics of Groningen, the Netherlands. A total of 5571 participants (mean [SD] age, 53.5 [12.0] years; 2830 [50.8%] men) were included in analyses. Median (interquartile range) plasma concentration of vitamin B12 was 394.42 (310.38-497.42) pg/mL. During the median (interquartile range) of 8.2 (7.7-8.9) years of follow-up, 226 participants (4.1%) died. According to quartiles of the distribution of plasma vitamin B12 concentration levels, mortality rates were 33.8 deaths per 10 000 person-years for the quartile with the lowest plasma concentration of vitamin B12 and 65.7 deaths per 10 000 person-years for the quartile with the highest plasma concentration of vitamin B12. After adjustment for multiple clinical and laboratory variables, Cox regression analyses found a significant association between higher vitamin B12 plasma concentration level and increased risk of all-cause mortality (hazard ratio per 1-SD increase, 1.25 [95% CI, 1.06-1.47]; P = .006). These findings suggest that higher levels of plasma concentrations of vitamin B12 were associated with increased risk of all-cause mortality after adjusting for age, sex, renal function, and other clinical and laboratory variables. The mechanisms underlying this association remain to be established.