B12 Status 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.

Serum Pyridoxal 5'-Phosphate and Pyridoxic Acid Ratio Index with Prognosis of Colorectal Cancer: A Prospective Cohort Study.

Studies on the association between serum vitamin B6 status and colorectal cancer prognosis are limited and have yielded inconsistent results. This study investigated the association of pyridoxal 5'-phosphate (PLP) and pyridoxic acid ratio (PAr) index with colorectal cancer survival. A total of 1286 colorectal cancer patients diagnosed since 2010 were selected from the Guangdong Colorectal Cancer Cohort study. Serum levels of PLP, pyridoxal, and 4-pyridoxic acid were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. The study followed overall mortality and colorectal cancer-specific mortality until December 2023. Multivariable Cox proportional hazards regression models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Restricted cubic spline and stratified analysis were performed. During a median follow-up of 77.36 months, 331 deaths were recorded, with 293 specifically attributed to colorectal cancer. Higher PLP levels were associated with a longer overall survival (HRQ4 vs. Q1, 0.63; 95% CI: 0.46, 0.87; p for trend = 0.008) and colorectal cancer-specific survival (HRQ4 vs. Q1, 0.62; 95% CI: 0.44, 0.87; p for trend = 0.006). Non-linear associations were observed between serum PLP and overall and colorectal cancer-specific survival (p for non-linear < 0.05). However, PAr was not significantly associated with either overall survival (HRQ4 vs. Q1, 1.03; 95% CI: 0.75, 1.41) or colorectal cancer-specific survival (HRQ4 vs. Q1, 1.01; 95% CI: 0.72, 1.42). The association between serum PLP and both overall survival and colorectal cancer-specific survival (p for interaction < 0.05) varied by alcohol drinking status. Higher serum PLP levels, but not PAr, may be associated with improved overall and colorectal cancer-specific survival.

The application and interpretation of laboratory biomarkers for the evaluation of vitamin B12 status.

Vitamin B12 (cobalamin; B12) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B12 deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B12 status include the measurement of serum B12 (also known as total B12 or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B12 status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B12 test, which is readily available and highly automated. In some cases, the sequential use of different B12 status biomarkers or the calculation of a composite B12 status score, derived from a panel of B12 biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarizes the utility of B12-related biomarkers and describes approaches to their application and interpretation.

Assessment of vitamin B12 and folate status and their determinants in children aged 6–59 months with severe acute malnutrition admitted to a tertiary-care centre in North India

ABSTRACT Background Vitamin B12 and folate are essential micronutrients, a deficiency of which causes anaemia, poor growth and an increased risk of infections, along with irreversible neurological damage to the developing brain in children. Methods A hospital-based prospective observational study was conducted in 100 children with severe acute malnutrition (SAM) aged 6–59 months admitted to a tertiary-care facility in northern India from July 2021 to June 2022. A structured proforma was used to record socio-demographic information, a detailed clinical history, results of general and systemic physical examination and a detailed anthropometric assessment. Serum folate and vitamin B12 were estimated by electrochemiluminescence. Results The mean age of the children was 24.18 months, and 64.0% were aged 6–12 months. The male-to-female ratio was 1.08:1. Anaemia was present in 87.0% of the children, and it was severe in 35% of them. There was serum vitamin B12 and folate deficiency in 61.0% and 19.0%, respectively. A deficiency of vitamin B12 was significantly associated with delayed developmental milestones in all domains, a mid-upper-arm circumference of <11.5 cm, severe anaemia, a low platelet count and folate deficiency, and a folate deficiency was significantly associated with older age, delayed developmental milestones in all domains, severe anaemia, a low platelet count and vitamin B12 deficiency. Conclusion Vitamin B12 deficiency is highly prevalent in children aged 6–59 months with SAM, but the prevalence of folate deficiency is much lower. Apart from iron and folic acid supplementation, government programmes should consider vitamin B12 supplementation for children aged 6–59 months.

A systematic review and meta-analysis of functional vitamin B12 status among adult vegans.

The dietary intake of vitamin B12 among unsupplemented vegans is notably lower compared to both vegetarians and omnivores. Prolonged low intakes of vitamin B12, such as seen in those adhering to a vegan diet, lead to physiological deficiency of vitamin B12 and an elevated risk of B12-related morbidity. However, while serum B12 serves as a conventional biomarker for assessing B12 status, its utility is limited given its sensitivity and specificity in ascribing physiological deficiency of B12 and the functional vitamin B12 status of those adhering to vegan diets is unclear. We conducted a systematic review and meta-analysis using data based on the full panel of biomarkers of vitamin B12 status to test whether adherence to a vegan diet is associated with an elevated risk of functional vitamin B12 deficiency compared to vegetarian or omnivorous diets. In addition, subgroup analysis was carried out to look at the effect of vitamin B12 supplement use on B12 status among vegans. Our search identified 4002 records, of which 19 studies met the inclusion criteria for the systematic review and 17 studies were taken forward for the meta-analysis. Meta-analysis results revealed significantly lower serum B12, pmol/ (-0.72 [-1.26, -0.18]; p = 0.01) and elevated total homocysteine, μmol/L (tHcy) (0.57 [0.26, 0.89]; p < 0.001) concentrations, alongside elevated methylmalonic acid, nmol/L (MMA) (0.28 [-0.01, 0.57]; p = 0.06) and lower holotranscobalamin, pmol/ (HoloTC) (-0.42 [-0.91, 0.07]; p = 0.09) levels among vegan adults compared to omnivores, indicating increased functional B12 deficiency in addition to low vitamin B12 status in vegan adults. There were no differences between vegans and vegetarians in HoloTC (0.04 [-0.28, 0.35]; p = 0.814) or MMA (-0.05 [-0.29, 0.20]; p = 0.708), but differences were found in serum B12 (-0.25 [-0.40, -0.10]; p = 0.001) and for tHcy (0.24 [0.09, 0.39]; p = 0.002) concentrations. Subgroup analyses indicated that the use of vitamin B12 supplements among vegans contributes to significant improvements in all biomarker concentrations compared to their unsupplemented counterparts. Our findings underscore the need for improved strategies to redress poor vitamin B12 status with appropriate B12 supplementation use among those adhering to vegetarian and vegan diets.

Assessment of vitamin B12 and homocysteine levels in pregnant women admitted for delivery and cord blood samples of their newborn babies: a multicenter study.

Vitamin B12, an indispensable micronutrient, is pivotal in numerous physiological processes, with particular significance during pregnancy and fetal development. The increasing adoption of vegetarian diets and the economic challenges associated with accessing animal-based food sources contribute to the prevalence of vitamin B12 deficiency. This study aims to examine the levels of vitamin B12 and homocysteine in pregnant women upon admission for delivery and to analyze corresponding cord blood samples from their newborn infants in a substantial sample within the Istanbul metropolitan area. This cross-sectional multicenter study included women aged ≥16 years admitted for delivery and their newborns ≥34 weeks. The demographic data and the results of complete blood counts within the previous 24 hours before birth were recorded. Vitamin B12 and homocysteine levels were measured in maternal and cord blood samples. The study parameters were compared between the groups based on the mothers' and babies' homocysteine and vitamin B12 levels. The study included 832 pregnant women and 832 neonates. Anemia affected 36% of pregnant women, with a higher frequency in mothers with vitamin B12 deficiency. Seventy-eight mothers and 48.9% of neonates showed Vitamin B12 levels below 200 pg/mL, while elevated homocysteine levels were observed in 30% of mothers and 26% of neonates. Maternal vitamin B12 deficiency was significantly correlated with cord blood B12 deficiency and elevated homocysteine. The median cord blood vitamin B12 level was inversely correlated with the number of previous pregnancies. Vitamin B12 deficiency is extremely common in pregnant women before delivery, significantly correlating to cord blood homocysteine and vitamin B12 levels. However, homocysteine alone is not a reliable marker for maternal vitamin B12 status. Implementing strategies to detect vitamin B12 deficiency and supplying adequate vitamin B12 supplementation during pregnancy holds the potential to enhance maternal and neonatal health in Türkiye.

Vitamin B12 deficiency in newborns: impact on individual's health status and healthcare costs.

The identification of vitamin B12 (B12) deficiency in the newborn may prevent neurological damage and a delay in the normal growth. In this study we characterized the incidence of B12 deficiency in newborns, the costs associated to the clinical diagnosis and management, and the relevance to optimize the use of cobalamin biomarkers during treatment follow-up. Starting from a continuous case series of 146,470 screened newborns (November, 1st 2021- December, 3rd 2023), the Regional Reference Laboratory for Neonatal Screening identified 87 newborns having altered levels of biomarkers of cobalamin metabolism measured by Newborn Screening. These subjects were confirmed with a nutritional B12 deficiency of maternal origin by performing the serum B12 measurements and plasma homocysteine (Hcy) both on the newborns and respective mothers. A cost analysis was performed to characterize the costs/year of identifying and managing B12 deficiency cases. At baseline, median (interquartile range) serum B12 levels of 185.0 (142.3-246.0) ng/L and threefold increased plasma Hcy concentrations above the normal level confirmed a severe condition of deficiency in the newborns. After intramuscular B12 supplementation, serum B12 measured at the first follow up visit showed a fivefold increase, and the levels of Hcy returned to normal. From the healthcare perspective, the costs for diagnosing and managing all newborns with B12 deficiency is 188,480 €/year. Preventing B12 depletion in newborns lowers healthcare costs and likely improves their health outcomes. Further studies are however required to address the clinical pathway to identify, treat and monitor pregnant women with marginal and low B12 status, in order to achieve these goals.

Protocol for a community-based, household-randomised, dose-response trial to assess the acceptability, nutritional effects and safety of double-fortified salt containing iodine and folic acid compared with iodised salt among non-pregnant Ethiopian women of reproductive age (DFS-IoFA).

The prevalence of neural tube defects (NTDs) is higher in Ethiopia than most other countries, and ~84% of Ethiopian women of reproductive age (WRA) have folate insufficiency, a major risk factor for NTDs. Salt fortification with folic acid is a potential strategy to improve women's folate status, but data are needed on the acceptability, nutritional impact and safety of folic acid fortification of iodised salt. The study is designed as a community-based, household-randomised, dose-response trial. A total of 360 non-pregnant WRA 18-49 years of age will be randomly assigned to one of three intervention arms: (1) iodised salt fortified with 30 ppm folic acid to provide ~200 µg folic acid/day; (2) iodised salt fortified with 90 ppm folic acid to provide ~600 µg folic acid/day; or (3) iodised salt (comparator). The preweighed salts will be delivered to participants' homes biweekly for 26 weeks; unused salt will be collected and weighed. Fasting, venous blood samples will be collected at baseline, end line and a randomly assigned intermediate time point for assessment of folate, iodine, vitamin B12 and other micronutrient status biomarkers. Women's dietary intakes, including discretionary salt consumption, will be measured using weighed food records; 24-hour urine specimens will be analysed for sodium and iodine excretion. Primary outcomes are women's consumption of study salts, change in biomarkers of folate and iodine status and prevalence of adverse events. Results will be analysed using analysis of covariance models to estimate group mean differences for continuous outcomes, controlling for baseline measurements, and log-binomial or modified Poisson regressions for categorical outcomes. Prespecified effect modifications will be explored. The study has been approved by the Ethiopian Public Health Institute's Institutional Review Board, and the protocol has been registered with ClinicalTrials.gov (registration number NCT06223854). Study results will be published in open access scientific journals and disseminated nationally in Ethiopia. NCT06223854.

Micronutrient intake and status in young vegans, lacto-ovo-vegetarians, pescatarians, flexitarians, and omnivores.

Whether youth who follow plant-based diets in Nordic countries meet their dietary needs for micronutrients remains unclear. This study aims to evaluate micronutrient intake and status in Norwegian youth following vegan, lacto-ovo-vegetarian, pescatarian, flexitarian and omnivore diets. Cross-sectional design, with healthy 16-to-24-year-olds (n = 165). Participants were asked to complete a questionnaire and four 24-hour dietary recalls. Dried blood spots (DBS) and spot-urine samples were collected for analysis of methyl malonic acid (MMA) (n = 65), haemoglobin (Hb) (n = 164) and urinary iodine concentration (UIC) (n = 163). Vegans reported highest habitual supplement usage of multivitamin (58%), B12 (90%) and macroalgae consumption (32%), while flexitarians reported highest habitual usage of omega-3 supplements (56%). For daily supplement usage, vegans reported highest use of multivitamins (42%), B12 (79%), iodine (37%) and iron (63%). Increased risk of inadequate intake (energy-adjusted) were found for vitamin D (60% within lacto-ovo-vegetarians), selenium (70% within lacto-ovo-vegetarians, 65% within omnivores), and iodine (63% within vegans). Median MMA levels suggest low risk of insufficient B12 status across all groups (MMA 0.04‒0.37µmol/l) and 2% had MMA levels indicating possible B12 deficiency and 8% had elevated levels. Median Hb levels indicated low risk of anemia across all groups (≥ 12.0 females, ≥ 13.0g/dl males), though 7% had Hb values indicating risk of mild anemia and 4% risk of moderate anemia. The median UIC indicates mild iodine deficiency in all groups (UIC < 100µg/l), except vegans, who were moderately iodine deficient (UIC < 50µg/l). Our study indicated that the participating youth had low risk of inadequate intake of most micronutrients, partly due to high supplement usage. However, for iodine, vitamin D, and selenium higher risk of inadequate intake was found. UIC corroborated the low iodine intake among vegans. Thus, we suggest iodine status of youth in Norway should be monitored, especially among young fertile women who omits dietary iodine sources, until a mandatory iodine fortification program is implemented. Furthermore, we suggest that food education on how to secure sufficient nutrients from food in general should be provided to the Norwegian youth population, especially how to secure adequate intake of vitamin D, selenium and iodine.

Effect of roasted purple laver (nori) on vitamin B12 nutritional status of vegetarians: a dose-response trial

PurposeTo investigate the bioavailability of vitamin B12 from nori and to evaluate the required dosage for improving vitamin B12 nutritional status in vegetarians not using supplements.MethodsThe study design is an open-label, parallel, dose-response randomized controlled trial. Thirty vegetarians were assigned to control (no nori), low-dose (5 g nori, aiming to provide 2.4 µg vitamin B12 per day), or high-dose (8 g nori, aiming to provide 4 µg vitamin B12 per day) groups. The primary outcome was changes in vitamin B12 status as measured by serum vitamin B12, holotranscobalamin (holoTC), homocysteine (Hcy), and methylmalonic acid (MMA), and a combined score of these four markers (4cB12 score) during the four-week intervention. Dietary vitamin B12 intakes were assessed at baseline and end of the trial with a 17-item food frequency questionnaire designed for vitamin B12 assessment. General linear model was used to compare least square means of changes in each biomarker of vitamin B12 status, among the three groups, while adjusting for respective baseline biomarker.ResultsAfter adjusting for baseline status, nori consumption led to significant improvement in serum vitamin B12 (among-group P-value = 0.0029), holoTC (P = 0.0127), Hcy (P = 0.0225), and 4cB12 (P = 0.0094). Changes in MMA did not differ significantly across groups, but showed within-group pre-post improvement in the low-dose group (median [p25, p75] = -339 [-461, -198] nmol/L). Vitamin B12 status appeared to plateau at low dose (5 g of nori), which compared with control group, improved serum vitamin B12 (lease square mean [95% CI] = + 59 [25, 93] pmol/L, P = 0.0014); holoTC (+ 28.2 [10.1, 46.3] pmol/L, P = 0.0035); Hcy (-3.7 [-6.8, -0.6] µmol/L, p = 0.0226); and 4cB12 score (+ 0.67 [0.24, 1.09], p = 0.0036). High-dose resulted in similar improvements. There was no significant difference between low-dose and high-dose groups in all biomarkers of vitamin B12.ConclusionsConsuming 5 g of nori per day for 4 weeks significantly improved vitamin B12 status in vegetarians. A higher dose (8 g) may not confer additional benefits.Clinical trial registrationClinicalTrials.gov Identifier: NCT05614960. Date of registration: November 14th 2022.

Does Vitamin B6 Act as an Exercise Mimetic in Skeletal Muscle?

Marginal vitamin B6 (B6) deficiency is common in various segments worldwide. In a super-aged society, sarcopenia is a major concern and has gained significant research attention focused on healthy aging. To date, the primary interventions for sarcopenia have been physical exercise therapy. Recent evidence suggests that inadequate B6 status is associated with an increased risk of sarcopenia and mortality among older adults. Our previous study showed that B6 supplementation to a marginal B6-deficient diet up-regulated the expression of various exercise-induced genes in the skeletal muscle of rodents. Notably, a supplemental B6-to-B6-deficient diet stimulates satellite cell-mediated myogenesis in rodents, mirroring the effects of physical exercise. These findings suggest the potential role of B6 as an exercise-mimetic nutrient in skeletal muscle. To test this hypothesis, we reviewed relevant literature and compared the roles of B6 and exercise in muscles. Here, we provide several pieces of evidence supporting this hypothesis and discuss the potential mechanisms behind the similarities between the effects of B6 and exercise on muscle. This research, for the first time, provides insight into the exercise-mimetic roles of B6 in skeletal muscle.

Preoperative Micronutrient Repletion Strategies in Metabolic and Bariatric Surgery: A Systematic Review

BackgroundEvidence is lacking to inform how micronutrient deficiencies should be prevented and treated before metabolic-bariatric surgery to optimize patient outcomes. ObjectiveThis systematic review aimed to examine the effect of preoperative repletion strategies for micronutrient deficiencies on micronutrient biochemistry, quality of life, and complication rates among candidates for metabolic and bariatric surgery compared with usual care, alternate strategies, or no treatment. MethodsPubMed, Embase, CINAHL, and CENTRAL was searched in April 2024. A grey literature search was updated in April 2024 via Google search. Eligible observational and interventional studies were those that provided micronutrient repletion before the surgery and measured micronutrient status pre- and/or postsurgery. Studies with participants who were pregnant, lactating, or elected jejunocolic bypass, jejunoileal bypass, vertical banded gastroplasty, and biliopancreatic diversion were excluded. Risk of bias was assessed using the Academy of Nutrition and Dietetics Quality Criteria Checklist. Findings were narratively synthesized and the Grading of Recommendation, Assessment, Development and Evaluations was adopted when applicable. Twenty studies (n = 27 groups) were included (n = 15 observational; n = 5 interventional). ResultsStrategies targeted vitamins A, D, E, B6, B12, C, thiamin, folate, calcium, iron, selenium, and zinc, including chronic dosing of oral supplements and multivitamins (n = 21), megadoses of oral supplements (n = 1), intramuscular injection (n = 1), intravenous infusion (n = 1), and a mix of injection and oral supplements (n = 3). Preoperative repletion strategies varied in efficacy. Chronic dosing of oral supplements increased vitamin D levels (n = 4 interventional studies; Grading of Recommendation, Assessment, Development and Evaluations rating: moderate). Multivitamins did not improve vitamin B12 status but improved status of vitamin B6, vitamin C, and folate. Iron infusion (n = 1) increased ferritin levels, despite small sample size and low adherence rate, whereas oral iron supplementation resulted in unchanged (n = 4) or decreased (n = 1) ferritin levels. ConclusionsProactive and personalized micronutrient repletion schedules may decrease the risk of preoperative and early postoperative deficiency.

Continuous reference intervals for holotranscobalamin, homocysteine and folate in a healthy paediatric cohort.

The detection of deficiencies in B12 and folate children is important. However, despite the availability of various markers to assess B12 and folate metabolism, there are limited studies describing the reference intervals (RIs) and changes during growth and development for these markers in healthy children. Using samples collected from 378 children aged 30days-< 18years, we derived continuous RIs for holotranscobalamin, homocysteine and red cell folate. The lower RI for holotranscobalamin was lowest at birth, rising during early childhood and then declining following ages 4-6years whereas red cell folate was highest early in life and then declined steadily towards adulthood. Total homocysteine, reflective of both B12 and folate status was elevated early in life, reaching a nadir at age 2 and then increasing towards adulthood. Continuous central 95th percentile RI for holotranscobalamin, homocysteine and red cell folate for children ages 30days to <18years were established. Each marker shows dynamic changes throughout childhood and adolescence which will assist clinicians in more appropriately assessing B12 and folate status in this population.

Prevalence, risk factors, and treatment of anemia in hospitalized older patients across geriatric and nephrological settings in Italy

Anemia is a common but often underdiagnosed and undertreated geriatric syndrome in hospitalized older patients. In this retrospective multicenter study, we aimed at characterizing the prevalence, risk factors, diagnostic and treatment approach to anemia in older patients admitted to acute care hospitals, focusing on differences between nephrology and geriatrics units. Prevalence and risk factors for anemia, diagnostic inertia (lack of iron, vitamin B12, and folate status assessment), replacement inertia (omitted treatment with iron, vitamin B12 or folic acid), and erythropoiesis-stimulating agents (ESA) inertia were explored. 1963 patients aged 82.7 (6.8) years were included in the study; 66.7% of the study population had anemia; among anemic patients, diagnostic inertia and replacement inertia were common with rates of 22–31% and 50–87%, respectively; omitted treatment with ESA affected 67.2% of patients and was more prevalent in geriatric units. In most cases, patients with ESA inertia were not routinely screened for iron tests. COPD, cancer, eGFR 45–60 ml/min were associated with increased tendency to ESA inertia. In conclusion, anemia had a high prevalence in older patients discharged from acute care units, but it is often underdiagnosed and undertreated.

Vitamin B12 Status in Vegan and Vegetarian Seventh-Day Adventists: A Systematic Review and Meta-Analysis of Serum Levels and Dietary Intake.

This systematic review and meta-analysis aimed to evaluate the vitamin B12 status and intake of Seventh-day Adventists following a plant-based diet and compare it with omnivore controls to investigate their susceptibility for vitamin B12 deficiency. Peer-reviewed articles were identified through a comprehensive search in PubMed, Scopus, and Google Scholar databases from inception up to the year 2024 using specific keywords related to vitamin B12 and Seventh-day Adventists. Observational studies published in the English language were included if they reported on vitamin B12 status or intake among plant-based Adventists and compared it with omnivore controls who may or may not have been Adventists. Studies that did not present distinguishable results for vegetarian/vegan from omnivore Adventists or only reported on food item intake without specific vitamin B12 data were excluded. Two independent reviewers extracted data on study characteristics, vitamin B12 intake, and serum levels using a customised data extraction form, resolving discrepancies through consultation with a third reviewer. A meta-analysis was conducted using random-effect models due to anticipated heterogeneity, without any subgroup analysis due to the low number of studies. Sensitivity analysis was performed using the 'leave-on-out' method to assess individual study influence on overall effect size and heterogeneity. Four studies met inclusion criteria, encompassing 1994 participants. Meta-analysis showed no significant differences in serum vitamin B12 levels (MD: -9.85pmol/L; 95% CI: -45.64 to 25.94pmol/L; P = 0.54, I2 = 50%) or daily intake (MD: 3.31mcg/d; 95% CI: -4.70 to 11.32mcg/d; P = 0.42, I2 = 90%) between plant-based Adventists and omnivore controls, although there was high heterogeneity between the studies. Adventists following a vegan or vegetarian diet did not demonstrate increased risk of vitamin B12 deficiency due to the widespread consumption of fortified foods and supplements. The findings underscore the importance of supplementation and the consumption of fortified foods for maintaining adequate B12 status among vegan or vegetarian Adventists but highlight the need for further studies to confirm these observations in diverse geographical areas.

Vitamin B12 status and the risk of developing sepsis in patients with bacterial infection: a prospective observational cohort study

BackgroundData have shown that vitamin B12 has immunomodulatory effects via different pathways, which could influence the pathophysiology of sepsis. The objective of this study was to investigate whether vitamin B12 levels, assessed by the measurement of holotranscobalamin (HTC), total vitamin B12 (B12), and methylmalonic acid (MMA, which accumulates in case of B12 deficiency), are associated with the development of sepsis in patients with onset of bacterial infection.MethodsThis was a single-center, prospective observational pilot study. Adult patients who presented to the emergency department with bacterial infection confirmed by a positive microbiological culture result were included in the study and followed up for 6 days to assess whether they developed sepsis or not. The primary objective was to compare HTC concentration in patients who developed sepsis to those who did not develop sepsis. Secondary objectives were the evaluation of B12 and MMA concentrations in those two groups. Multiple logistic regression models were used, with presence of sepsis as the outcome variable, and HTC, B12, and MMA concentrations as predictor variables, separately, and adjusted for potential confounders.ResultsFrom 2019 to 2022, 2131 patients were assessed for eligibility, of whom 100 met the inclusion criteria. One patient was excluded from the analysis due to missing data. Of the 99 patients, 29 developed sepsis. There was no evidence for an association between HTC or B12 concentration and the development of sepsis (OR 0.65, 95% CI 0.31–1.29, p = 0.232, OR 0.84, 95% CI 0.44–1.54, p = 0.584, respectively). There was an association between MMA concentration and the development of sepsis, with a positive effect, i.e. with increasing MMA, the odds for sepsis increased (OR 2.36, 95% CI 1.21–4.87, p = 0.014). This association remained significant when adjusted for confounders (OR 2.72, 95% CI 1.23–6.60, p = 0.018).ConclusionsOur study found an association between elevated MMA concentration and the development of sepsis. We did not find an association between HTC and B12 concentrations and the development of sepsis. Further, larger studies are warranted, as it could lead to interventional trials investigating whether B12 supplementation provides a clinical benefit to patients with infection or sepsis.Trial registrationThe study was registered on ClinicalTrials.gov under the identifier NCT04008446 on June 17, 2019.

One-carbon metabolism biomarkers and upper gastrointestinal cancer in the Golestan Cohort Study.

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.

Folate and Vitamin B12 Status in Women of Reproductive Age in Rural Haryana, India: Estimating Population-Based Prevalence for Neural Tube Defects.

Folate and vitamin B12 deficiencies in pregnant women are associated with increased risk for adverse maternal and infant health outcomes, including neural tube defects (NTDs). A population-based cross-sectional survey was conducted in two rural areas in Ambala District, Haryana, India in 2017 to assess baseline folate and vitamin B12 status among women of reproductive age (WRA) and predict the prevalence of NTDs. We calculated the prevalence of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 775 non-pregnant, non-lactating WRA (18-49 years). Using red blood cell (RBC) folate distributions and an established Bayesian model, we predicted NTD prevalence. All analyses were conducted using SAS-callable SUDAAN Version 11.0.4 to account for complex survey design. Among WRA, 10.1% (95% CI: 7.9, 12.7) and 9.3% (95% CI: 7.4, 11.6) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The prevalence of RBC folate insufficiency (<748 nmol/L) was 78.3% (95% CI: 75.0, 81.3) and the predicted NTD prevalence was 21.0 (95% uncertainly interval: 16.9, 25.9) per 10,000 live births. Prevalences of vitamin B12 deficiency (<200 pg/mL) and marginal deficiency (≥200 pg/mL and ≤300 pg/mL) were 57.7% (95% CI: 53.9, 61.4) and 23.5% (95% CI: 20.4, 26.9), respectively. The magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline against which results from future post-fortification surveys can be compared.

Vitamin B12 status and skeletal muscle function among elderly: A literature review and pilot study on the effect of oral vitamin B12 supplementation in improving muscle function.

The objective of this study is to understand the role of vitamin B12 supplementation in improving skeletal muscle function among the elderly. A literature review in the Medline database was conducted to understand the association between vitamin B12 and muscle function in Section A. In Section B, 28 healthy elderly participants aged ≥60 years were recruited in a cross-sectional design for estimation of plasma vitamin B12 status and assessment of upper limb muscle strength Maximal voluntary contraction (MVC) and muscle quality (expressed as MVC/total muscle mass). Participants were grouped based on vitamin B12 status into vitamin B12-depleted (<148 pmol/L) and replete (≥148 pmol/L) groups. In a quasi-experimental study design, the vitamin B12-depleted group (n = 14) received daily oral vitamin B12 supplementation of 100 μg for 3 months. All the study measures were repeated post-supplementation. Vitamin B12 deficiency was identified to contribute adversely to muscle strength, quality, and physical performance among older people in the extensive literature review. The pilot intervention study showed significant improvement in MVC and muscle quality (p < 0.050) post-vitamin B12 supplementation, comparable to the vitamin B12-replete group. Vitamin B12 may have a crucial role in the maintenance of muscle function. 3-month oral vitamin B12 supplementation among subclinical vitamin B12 deficient elderly improved muscle strength and quality and reached levels similar to the vitamin B12 replete group.

Vitamin B12 status in hospitalised cancer patients: Prevalence and clinical implications of depletion and hypervitaminosis

Background & AimsThe prevalence and clinical significance of vitamin B12 alterations in patients with cancer are poorly understood. We aimed to assess the prevalence and risk factors of vitamin B12 depletion or hypervitaminosis in patients with cancer. Methods: We retrospectively included hospitalised patients with cancer in 2017-2022. Plasma B12 levels were stratified as very low (VL, <200 pg/ml), low (L, 200-299 pg/ml), normal (N, 300-812 pg/ml), or high (H, ≥813 pg/ml). We collected demographic and several clinical data (e.g., comorbidities, nutritional status, ECOG-PS, cancer site and stage). Univariate and multivariate analyses for factors associated to the vitamin B12 status were fitted. Results: 788 patients (F/M ratio 1.05, median age 72 years, [25th, 75th percentiles 62, 78 years]) were included. Vitamin B12 was VL in 14.1%, L in 19.4%, N in 49.4%, and H in 17.1% cases. Vitamin B12 distribution increased significantly as function of ECOG-PS levels. Patients with breast cancer were characterized by the highest median B12 value, while colorectal cancer patients by the lowest. Vitamin B12 was also significantly higher in advanced compared to early-stage patients as well as in those who had liver failure. Multivariate analysis showed that the probability of H vs. VL B12 levels was significantly increased in patients with hypoproteinemia, hypo-prealbuminemia, and ECOG-PS≥2, and decreased in those with colorectal and gastric cancer. Conclusion: Vitamin B12 impairment is common in cancer patients. Increased vitamin B12 is associated with an impaired clinical status, while vitamin B12 depletion is more common in early-stage cancer and in elderly patients.