Plasma Vitamin B12 Research Articles

Exploring the Impact of Paternal B12 Levels During the Periconceptional Period on IUI Success

Background: The present study is a novel exploration of the effects of vitamin B12 supplementation on seminal fluid parameters and the outcomes of intrauterine insemination (IUI). Specifically, we aimed to evaluate the concentrations of vitamin B12 in blood and seminal plasma before and after two months of supplementation. Objectives: investigate the effects of vitamin B12 supplementation on the characteristics of seminal fluid parameters and IUI outcomes. Material and Methods: A randomized controlled experiment with 100 randomly selected infertile couples. The patients were divided into two equal groups according to their vitamin B12 dosage. Group A consists of 50 couples who are taking B12 supplements. Obtain blood and seminal plasma samples from couples to measure the level of vitamin B12. Group B consists of 50 couples and does not include any supplements. The couples in group B initiated ovulation induction and intrauterine insemination (IUI) during the same month as the medical examination without the use of any additional supplements. Still, after two months of vitamin B12 supplement, group A started ovulation induction. Result: Basal semen parameters for sperm count, sperm motility in grades, and sperm morphology in the study group have a higher sperm count than the control group. Vitamin B12 intake for two months improves sperm morphology and increases sperm motility in grades A and B, according to the current study. This has a favorable effect on sperm count overall. Conclusion: research will determine the positive effect of vitamin B12 supplements on sperm parameters and IUI results.

Vitamin B12 responsive developmental and epileptic encephalopathy due to a novel mutation in the FUT2 gene: a case report

BackgroundVitamin B12 deficiency is a recognised cause of neurological manifestations, including peripheral neuropathy, behavioural changes, and seizures. However, developmental and epileptic encephalopathy due to vitamin B12 deficiency is very rare. Here, we report an infant with vitamin B12-responsive developmental and epileptic encephalopathy due to a novel mutation in the fucosyltransferase 2 (FUT2) gene responsible for vitamin B12 absorption.Case presentationAn 11-month-old girl of non-consanguineous parents presented with recurrent episodes of seizures since four months. Her seizures started as flexor epileptic spasms occurring in clusters resembling infantile epileptic spasms syndrome with hypsarrhythmia in the electroencephalogram. She was treated with multiple drugs, including high-dose prednisolone, vigabatrin, sodium valproate, levetiracetam and clobazam, without any response, and she continued to have seizures at 11 months. She had an early developmental delay with maximally achieving partial head control and responsive smile at four months. Her development regressed with the onset of seizure; at 11 months, her developmental age was below six weeks. On examination, she was pale and had generalised hypotonia with normal muscle power and reflexes.Her full blood count and blood picture revealed macrocytic anaemia with oval and round macrocytes. Bone marrow aspiration showed hypercellular marrow erythropoiesis with normoblastic and megaloblastic maturation. Due to the unusual association of refractory epilepsy and megaloblastic anaemia, a rare genetic disease of the vitamin B12 or folate pathways was suspected. The whole exome sequencing revealed a homozygous missense variant in exon 2 of the FUT2 gene associated with reduced vitamin B12 absorption and low plasma vitamin B12 levels, confirming the diagnosis of vitamin B12 deficiency related developmental and epileptic encephalopathy. She was started on intramuscular hydroxocobalamin, for which she showed a marked response with reduced seizure frequency.ConclusionWe report a novel variant in the FUT2 gene associated with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anaemia. This case report highlights the importance of timely genetic testing in children with refractory developmental and epileptic encephalopathy to identify treatable causes.

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.

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.

Maternal micronutrient biomarkers and risk of non-syndromic cleft lip/palate: A case-control study.

This case-control study investigated the associations between maternal plasma vitamin B12, homocysteine, and red blood cell (RBC) folate levels and the risk of cleft lip with or without cleft palate (CL/P) in offspring. The study compared 94 mothers and children with non-syndromic CL/P from a teaching hospital in Thailand to 94 mother-infant controls from local well-baby clinics, frequency-matched by birth date and mother's education. Data included anthropometric measurements, blood sample analyses, and a questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the associations through multiple logistic regression, adjusting for confounders. Mothers with higher plasma vitamin B12 levels had a lower risk of having a child with CL/P compared to those in the lowest quartile. This association was more pronounced among mothers without a family history of orofacial clefts and those who were not underweight. Conversely, elevated homocysteine levels, a marker of impaired B vitamin metabolism, increased the risk of CL/P. No association was found between RBC folate and CL/P. Higher maternal vitamin B12 levels are associated with a reduced risk of CL/P, while elevated homocysteine levels may increase the risk.

Evaluation of the effects of sodium valproate on plasma homocysteine, folate and vitamin B12 levels in epileptic patients

Evaluation of the effects of sodium valproate on plasma homocysteine, folate and vitamin B12 levels in epileptic patients

Effect of fibromyalgia on demographic, biochemical, metabolic and inflammatory profiles: a single-centre retrospective study.

The objective of this study is to ascertain the disparities in demographic features and biochemical profiles between individuals diagnosed with fibromyalgia (FM) and a control group of healthy individuals. This retrospective, cross-sectional study compared the demographic, biochemical, metabolic, and inflammatory indexes and rates of 174 FM patients diagnosed using the American College of Rheumatology 2016 diagnostic criteria between January 2023 and January 2024, and 186 healthy control groups. There was no difference between the FM and control groups in terms of alcohol consumption, marital status, or diabetes mellitus. The smoking rate is higher, and the educational level was found to be lower for FM versus the control. There was no significant difference between FM and controls regarding waist-height ratio, triglyceride-glucose index, plasma atherogenic index, vitamin B12, and folate levels. Monocyte HDL ratio, cardiometabolic index, magnesium, HbA1c, and ferritin levels were significantly higher in the control than in FM (p<0.001, p=0.039, p=0.007, p<0.001, p<0.001, respectively). C-reactive protein, erythrocyte sedimentation rate, systemic immune-inflammatory index, neutrophil-lymphocyte rate, platelet lymphocyte rate, and vitamin D levels were found to be higher in FM compared to control (p=0.001, p=0.032, p=0.003, p=0.030, p=0.003, p<0.001, respectively). A weak positive correlation was observed between the fibromyalgia impact questionnaire (FIQ) score and disease duration, as well as between pain degree and ESR, and pain degree and CRP. The study revealed a weak inverse relationship between Widespread Pain Index (WPI) and waist circumference. This study highlights fthe association f ibromyalgia with elevated inflammatory markers, altered metabolic parameters, and specific demographic characteristics.

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.

GWAS of Folate Metabolism With Gene-environment Interaction Analysis Revealed the Possible Role of Lifestyles in the Control of Blood Folate Metabolites in Japanese: The J-MICC Study.

The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites, as well as to detect related gene-environment interactions in Japanese. We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B12 (VB12) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene-environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed. For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P < 5 × 10-8). MTHFR also associated with FA, and FUT2 on chr 19 associated with VB12. We investigated gene-environment interactions in both studies and found significant interactions between MTHFR C677T and ever drinking, current drinking, and physical activity >33% on Hcy (β = 0.039, 0.038 and -0.054, P = 0.018, 0.021 and <0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (β = 0.033, P = 0.048). The present GWAS revealed the folate metabolism-associated genetic loci and gene-environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized cardiovascular disease prevention.

Plasma vitamin B12 and folic acid levels in patients with alcoholic cirrhosis in Vietnam

Plasma vitamin B12 and folic acid levels in patients with alcoholic cirrhosis in Vietnam

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.

Vitamin B12 status and hyperhomocysteinemia in patients with Rheumatoid arthritis treated with methotrexate and folic acid

BackgroundRheumatoid arthritis (RA) is an inflammatory arthritis in which the immune system targets synovial joints. Methotrexate serves as the mainstay of treatment for RA due to its efficacy. However, patients treated with methotrexate are uniquely at risk for vitamin B12 deficiency and hyperhomocysteinemia due to coincident disease risk factors and the fact that methotrexate use is associated with malabsorption. The objective of this study was to assess for vitamin B12 deficiency among patients with RA treated with methotrexate and folic acid. MethodsThis cross-sectional study included 50 patients with RA treated with methotrexate and folic acid and 49 patients with RA treated with other therapies. Patients were matched by age, sex, race, renal function, and disease activity. We compared plasma vitamin B12, methylmalonic acid, and homocysteine levels between these two groups utilizing quantitative and categorical analyses. ResultsThirty-seven (74%) RA patients on methotrexate and folic acid had elevated plasma homocysteine levels compared with only 27 (55%) RA patients receiving other therapies (P < 0.05). The proportion of patients with low vitamin B12 and high methylmalonic acid levels did not differ between the two groups. ConclusionsOur data show high plasma homocysteine levels among RA patients treated with methotrexate and folic acid. While plasma vitamin B12 levels were similar between the two groups, high plasma homocysteine is also a sensitive marker of vitamin B12 deficiency. Additional studies should evaluate for the presence of clinical features of vitamin B12 deficiency and hyperhomocysteinemia among RA patients treated with methotrexate and folic acid.

Vitamin B12 is associated negatively with anemia in older Chinese adults with a low dietary diversity level: evidence from the Healthy Ageing and Biomarkers Cohort Study (HABCS)

ObjectiveThe associations between plasma vitamin B12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China.MethodsA total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B12 levels: low (< 277 pg/mL), medium (277–375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia.ResultsSix hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41).ConclusionThe relationship between vitamin B12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B12.

Effect of Smoking on Seminal Plasma Vitamin B6 in Fertile and Subfertile Men.

Despite extensive documentation of the negative consequences of smoking on a wide range of diseases and disorders, the direct effect of smoking on seminal plasma vitamin B6 (vitB6) concentration is not addressed yet. Here, we attempted to examine the influence of smoking on the levels of seminal plasma vitB6 in fertile and subfertile males. One hundred and ninety-five participants were categorized into two groups: fertile men (smokers (n = 32), nonsmokers (n = 43)) and subfertile men (smokers (n = 65), nonsmokers (n = 55)). According to the World Health Organization criteria, conventional semen analysis was performed for all subjects involved in the study. The concentration of vitB6 in semen samples was measured by high-performance liquid chromatography tandem-mass spectrometry. There was no significant difference in the mean seminal plasma concentrations of vitB6 in smokers versus nonsmokers in both fertile (p=0.5096) and subfertile (p=0.5224) groups. Besides, no significant correlations were observed between seminal plasma concentration of vitB6, duration of smoking, and men's age in all tested groups. In conclusion, these findings elucidate that smoking has no significant impact on the levels of seminal plasma vitB6 in both fertile and subfertile men.

Homocysteine, vitamin B12, folic acid levels and its association with Mild Cognitive Impairment in urban and rural dwelling Indians

AbstractBackgroundHomocysteine (Hcy) is a sulfur containing amino acid generated in the metabolism of methionine involving co‐factors such as B vitamins and folic acid. Deficiency of these co‐factors have been associated with increased Hcy levels (Hutto, 1997). Relationship between differing levels of plasma Hcy, vitamin B12, folic acid and cognitive impairment is inconclusive.MethodCross sectional analysis was done using the baseline data from two ongoing longitudinal studies such as Tata Longitudinal Study of Ageing (TLSA, N = 984) and Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG, N = 4404), an urban and rural cohorts (Sundarakumar et al, 2020) respectively. Hcy, vitamin B12, folic acid levels were compared between the subjects of both cohorts. Comparison of these levels between healthy and MCI (Mild Cognitive Impairment) subjects within and across the cohorts were done. CDR (Clinical Dementia Rating) scale was used to classify subjects having normal cognition and MCI, considering score of 0.5 as MCI. Mann‐Whitney U test was used to compare these levels between the groups.ResultHcy, vitamin B12, folic acid levels between the two cohorts showed significant difference, with higher levels of Hcy (median (IQR)) = (17.08 (11) vs 14.63 (10); p &lt;0.001), vitamin B12 (247 (252) vs 220 (143); p &lt;0.001) and folic acid (8.55 (9) vs 5.55(4); p &lt;0.05) in TLSA than SANSCOG. Significant difference seen in Hcy (17.73(11) vs 14.73 (10); p &lt;0.001), vitamin B12 (246 (249) vs 220 (136); p &lt;0.001) and folic acid (8.42 (9) vs 5.53 (4): p &lt;0.001) levels for healthy subjects between cohorts, higher levels were seen in TLSA subjects. Hcy (16.08 (8) vs 14.43 (12); p &lt;0.001) vitamin B12 (305 (341) vs 216 (174); p = 0.03) and folic acid (8.52 (9) vs 5.34 (4): p &lt;0.001) levels were significantly high in TLSA than SANSCOG for MCI subjects. However, these levels were not significantly different between healthy and MCI subjects within cohorts.ConclusionConsistently elevated levels of Hcy was observed in urban cohort. Though elevated level of Hcy was observed with normal vitamin B12 and folic acid, it was not associated with MCI.

Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins

Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds). To compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention. This single-center, population-based randomized clinical trial of 22 pairs of twins (N = 44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data. Twin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks. The primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being. A total of 22 pairs (N = 44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] μIU/mL; 95% CI, -5.3 to -0.4 μIU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg). In this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients. ClinicalTrials.gov Identifier: NCT05297825.

Macro-Vitamin B12 as Cause of Falsely Elevated Cobalamin Levels.

High blood concentrations of vitamin B12 are often caused by over-supplementation. However, there are instances in which augmented vitamin B12 levels are seen in the absence of supplements. Macro-vitamin B12 is an underrated cause of supra-physiological cobalamin plasma levels. A 70-year-old man was referred to an ambulatory internal medicine centre because of high vitamin B12 levels yet he denied taking supplements. An X-ray showed a tumour in the right upper lobe of the lung, which triggered further examinations. An MRI scan of the brain came back normal as well as a CT scan of the abdomen, and colonoscopy. The pulmonologist requested a PET-CT scan, which showed an isolated 18-FDG uptake in the area of the lung mass that was detected earlier. The patient underwent surgery with adjuvant cis-platinum and gemcitabine and is still making good progress. The vitamin B12 levels persisted after successful treatment of lung adenocarcinoma; determination of vitamin B12 after PEG (polyethylene glycol) precipitation showed normal concentrations. A high vitamin B12 plasma concentration in the absence of vitamin supplementation can be a daunting diagnostic problem for the internist, as there are several possible underlying causes. In this case the diagnosis of lung carcinoma was made, the patient was treated appropriately, yet this pathology had no correlation with the cobalamin levels. A high vitamin B12 concentration can be the impetus of thorough medical inquiries. Internists should be careful not to forget macro-vitamin B12 as a possible source of falsely elevated vitamin B12 values. When encountering an otherwise unexplainable B12 hypervitaminosis, the diagnosis of macro-vitamin B12 should be taken into account to avoid unnecessary extensive medical examinations.PEG precipitation can distinguish between a 'real' high vitamin B12 and macro-vitamin B12.A high vitamin B12 concentration is no guarantee for adequate cobalamin storage. In case of suspicion, a vitamin B12 measurement after PEG precipitation should be considered.

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.

Folic acid: The key to a healthy pregnancy - A prospective study on fetomaternal outcome.

The objective of the study is to study the fetomaternal outcome associated with folic acid deficiency in pregnancy. This hospital-based observational study was conducted in the Department of Obstetrics and Gynaecology at Base Hospital, Delhi Cantt, and a total of 351 participants were enrolled who were fulfilling the inclusion criteria. The plasma folic acid level of the selected patients was measured in the booking visit by automated chemiluminescence assay. The cutoff levels of folic acid were taken at 8.6 ng/mL. Based on these values, the study population was divided into two groups, one with folic acid values <8.6 ng/mL and the other with values ≥8.6 ng/mL. Plasma Vitamin B12 levels were measured to check for any concurrent deficiencies. Obstetric outcomes included first- and second-trimester miscarriages, development of anemia, gestational hypertension/preeclampsia, gestational diabetes mellitus, hypothyroidism, placental abruption, and intrauterine fetal growth restriction (FGR). Furthermore, the period of gestation at delivery, fetal weights, APGAR scores at 5 min were documented. The study also considered fetal neural tube defects, intrauterine fetal demise for data collection. Collected data were analyzed statistically to find the association of the above-mentioned outcomes with levels of folic acid. The rate of preterm deliveries was significantly higher in the folic acid group with levels <8.6 ng/mL (16.94%). The incidence of small for gestational age/FGR was higher in the folic acid group with levels <8.6 ng/mL (27.11%) compared to the high folic acid group with levels ≥8.6 ng/mL (13.38%). The differences in the incidence of anemia, gestational hypertension, gestational diabetes, and preeclampsia between the two groups were not statistically significant and no cases of intrauterine fetal demise or placental abruption were observed in either group. Moreover, there was no significant difference in the relative risk of low Apgar scores at 5 min between the two groups. The present study suggests that low folic acid levels during pregnancy are associated with a higher risk of adverse pregnancy outcomes such as anemia, miscarriages, preterm delivery, and FGR. Therefore, adherence to nutritional recommendation of folic acid supplementation during pregnancy is essential to prevent these adverse outcomes.

Maternal-Periconceptional Vitamin B12 Deficiency in Wistar Rats Leads to Sex-Specific Programming for Cardiometabolic Disease Risk in the Next Generation

BackgroundMaternal vitamin B12 deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts. ObjectivesThis study assessed the effects of diet-induced maternal vitamin B12 deficiency on F1 offspring in terms of cardiometabolic health and normalization of these effects by maternal-periconceptional vitamin B12 supplementation. MethodsA diet-induced maternal vitamin B12 deficient Wistar rat model was generated in which female rats were either fed a control AIN-76A diet (with 0.01 g/kg vitamin B12) or the same diet with vitamin B12 removed. Females from the vitamin B12-deficient group were mated with males on the control diet. A subset of vitamin B12-deficient females was repleted with vitamin B12 on day 1 of conception. The offspring in the F1 generation were assessed for changes in body composition, plasma biochemistry, and molecular changes in the liver. A multiomics approach was used to obtain a mechanistic insight into the changes in the offspring liver. ResultsWe showed that a 36% reduction in plasma vitamin B12 levels during pregnancy in F0 females can lead to continued vitamin B12 deficiency (60%–70% compared with control) in the F1 offspring and program them for cardiometabolic adversities. These adversities, such as high triglycerides and low high-density lipoprotein cholesterol, were seen only among F1 males but not females. DNA methylome analysis of the liver of F1 3-mo-old offspring highlights sexual dimorphism in the alteration of methylation status of genes critical to signaling processes. Proteomics and targeted metabolomics analysis confirm that sex-specific alterations occur through modulations in PPAR signaling and steroid hormone biosynthesis pathway. Repletion of deficient mothers with vitamin B12 at conception normalizes most of the molecular and biochemical changes. ConclusionsMaternal vitamin B12 deficiency has a programming effect on the next generation and increases the risk for cardiometabolic syndrome in a sex-specific manner. Normalization of the molecular risk markers on vitamin B12 supplementation indicates a causal role.