Search

Background: Residual low back and leg pain can occur after percutaneous endoscopic interlaminar discectomy (PEID) and compromise early surgical outcomes. This study aimed to determine the efficacy of combining dexamethasone with vitamin B12 (VB12) via epidural injection in improving the symptoms of low back and leg pain after PEID, and the underlying mechanism of action., Methods: Patients who underwent PEID for lumbar disc herniation (LDH) were enrolled and randomly assigned to the single surgery (SS) group, where disc removal was performed via PEID alone, or the combined treatment (CT) group, which received epidural injections of dexamethasone and VB12 alongside surgery. The outcome measures were the Visual Analog Scale (VAS), Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index (ODI), serum inflammatory factor expression, adverse surgical events, duration of postoperative hospitalization, and modified MacNab criteria., Results: Compared with the SS group, the CT group exhibited lower VAS scores for low back and leg pain at 1, 3, and 7 days post-surgery (P < 0.05). JOA and ODI scores were significantly improved in the CT group than in the SS group 7 days post-surgery (P < 0.05); however, no significant differences were observed at other time points. Serum inflammatory factors were lower in the CT group than in the SS group 3 days post-surgery (P < 0.05). The duration of postoperative hospitalization was shorter in the CT group (P < 0.05). Both groups had similar good outcomes (89.3% vs. 92.2%, P = 0.945)., Conclusions: Epidural injection of dexamethasone and VB12 effectively reduces early postoperative low back and leg pain, lowers postoperative inflammatory factor expression, and improves early PEID outcomes. Its clinical adoption merits consideration., Trial Registration: This trial was registered with the China Clinical Trial Registration Center (Identifier: ChiCTR2400088854)., (© 2024. The Author(s).)

Traumatic brain injury is a highly irreversible process that consists of primary as well as secondary injury which develops and progresses over months to years, leading to cognitive dysfunctions. Vitamin B 12 received considerable interest due to its potential therapeutic properties. The pathways of vitamin B 12 are closely related to neuronal survival but its effects on the pathophysiology of injury with respect to cognition is a relatively unexplored area of research. In this study, we investigated, the effect of vitamin B 12 and its involvement in neuroprotection on TBI-induced pathophysiology in male Swiss albino mice. Our findings suggested that vitamin B 12 supplementation improves TBI-mediated neurological impairments, spatial and recognition memory, and anxiety-like behavior. Furthermore, the oxidative stress was reduced by declined homocysteine level with vitamin B 12 supplementation validating declined expression of astrocytes and TBI biomarkers. The studies on neuronal morphology revealed that vitamin B 12 supplementation increases the dendritic arborization and density of mushroom and filopodia-shaped spines and further increases the expression of synaptic plasticity-related genes and proteins. Taken together, our findings reveal that, supplementation of vitamin B 12 restored the TBI-induced downregulation of dendritic arborization, and spine density which ultimately increases synaptic plasticity, cell survival, and recovery of cognitive dysfunctions., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Inflammatory diseases of the skin have a considerable high prevalence worldwide and negatively impact the patients' quality of life. First-line standard therapies for these conditions inherently entail important side effects when used long-term, particularly complicating the management of chronic cases. Therefore, there is a need to develop novel therapeutic strategies to offer reliable alternative treatments. Abnormally high reactive oxygen species (ROS) levels are characteristic of this kind of illnesses, and therefore a reasonable therapeutic goal. Cyanocobalamin, also known as Vitamin B 12 , possesses notable antioxidant and ROS-scavenging properties which could make it a possible therapeutic alternative. However, its considerable molecular weight restricts passive diffusion through the skin and forces the use of an advanced transdermal delivery system. Here, we present several prototypes of Cyanocobalamin-loaded Dissolving Microarray Patches (B 12 @DMAPs) with adequate mechanical properties to effectively penetrate the stratum corneum barrier, allowing drug deposition into the skin structure. Ex vivo penetration and permeability studies noted an effective drug presence within the dermal skin layers; in vitro compatibility studies in representative cell skin cell lines such as L929 fibroblasts and HaCaT keratinocytes ensured their safe use. The in vivo efficacy of the selected prototype was tested in a delayed-type hypersensitivity murine model that mimics an inflammatory skin process. Several findings such as a reduction of MPO-related photon emission in a bioluminescence study, protection against histological damage, and decrease of inflammatory cytokines levels point out the effectivity of B 12 @DMAPs to downregulate the skin inflammatory environment. Overall, B 12 @DMAPs offer a cost-effective translational alternative for improving patients' skin healthcare., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: The associations between 1-carbon metabolism (OCM) nutrients (methionine, folate, vitamin B-6, and vitamin B-12) and Alzheimer disease (AD) remains inconclusive., Objectives: This study aimed to investigate the association of dietary OCM nutrients with subsequent risk of AD and further assess whether participants with high genetic risk for AD might benefit from dietary OCM nutrients., Methods: We analyzed data from 192,214 participants who completed at least one 24-h dietary questionnaire and had no previous history of AD based on the UK Biobank. Nutrients intake was calculated using McCance and Widdowson's The Composition of Food and USDA's Food and Nutrient Database for Dietary Studies. Cox proportional models with restricted cubic splines were applied to explore the associations., Results: Over a median follow-up of 13.35 y, 959 cases of AD (41 early-onset cases and 918 late-onset cases) were identified. Compared with those in the low-intake OCM group (quartile 1), participants in the high-intake OCM group (quartile 4) had reduced risk of developing AD. The corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for methionine, folate, vitamin B-6, and vitamin B-12 intake were 0.66 (0.54, 0.80), 0.71 (0.58, 0.87), 0.71 (0.59, 0.87), and 0.77 (0.64, 0.93), respectively. Similar associations were observed in late-onset AD. In early-onset AD, high methionine and vitamin B-12 intake were associated with 70% (HR: 0.30; 95% CI: 0.10, 0.86) and 71% (HR: 0.29; 95% CI: 0.09, 0.96) reduction in risk, respectively. Participants with low genetic risk and high OCM nutrients intake had >75% reduced AD risk compared with high-risk, low-intake participants., Conclusions: In this prospective cohort study, we found that higher intake of OCM nutrients is associated with reduced risk of AD. Participants with high genetic risk of AD are more likely to benefit from dietary OCM nutrients intake., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Chronic inflammatory demyelinating polyneuropathy (CIDP) during pregnancy presents diagnostic and management challenges. We report a case of a primigravida in her 30s, exhibiting progressive quadriparesis starting in the second trimester. Initially, her symptoms of weakness, numbness and progressive quadriparesis were attributed to vitamin B12 deficiency, leading to the administration of intramuscular methylcobalamin injection. After referral to our tertiary care centre at 37 weeks of pregnancy and after further evaluation, neurological examination revealed findings characteristic of CIDP, which were confirmed by nerve conduction studies showing typical features of the condition. Treatment included intravenous methylprednisolone followed by intravenous immunoglobulin. An elective caesarean section was carried out because the patient was unable to effectively participate in labour due to her condition. The patient exhibited improved limb power postoperatively after immunoglobulin therapy. Challenges include delayed diagnosis, treatment initiation and management decisions. Multidisciplinary collaboration is crucial for optimal outcomes in CIDP during pregnancy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The present study aimed to assess the potential effect of vitamin B 12 (Vit B 12 ) on cognition impairment caused by nicotine (Nic) cessation in adolescent male rats. Adolescent male rats were categorized into two main groups as vehicle (normal saline, intraperitoneally), and Nic group in which received Nic (2 mg/kg) from 21 to 42 days of ages and then the Nic group were divided into three groups as withdrawal (the animals returned to regular diet without treatment), second and third groups received bupropion (20 mg/kg), and Vit B 12 at three different doses including 0.5,1, and 1.5 mg/kg by oral gavage as treatments to attenuate Nic withdrawal symptoms. The last group including normal animals received the highest doses of Vit B 12 just in the Nic abstinence period to compare the effect of that with vehicle. In MWM, Vit B 12 and bupropion increased the time spent in the target quadrant that is strongly associated with spatial memory as well as the more time spent with the NORT. Vit B 12 and bupropion modulated both oxidant/antioxidant and inflammatory/anti-inflammatory balance, alongside inhibitory effect on AChE, and GFAP. However, BDNF and amyloid-B showed insignificant difference as compared to Vit B 12 and bupropion. Considering the present results and similar related studies, Vit B 12 can be introduced as a strong anti-oxidant, and anti-inflammatory agent by which probably improved memory impairment caused by Nic addiction accompanied by withdrawal. Further, other mechanisms including activity reduction of AChE, and GFAP should be considered; however, it needs further investigation and larger-scale evidences., Competing Interests: Declaration of Competing Interest There was no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: Nutrition plays a crucial role in the development and health of the human brain, from early stages to adulthood. The complex process of neurodevelopment necessitates interaction among various factors, with balance in the concentration of vital macronutrients and micronutrients being essential. Regarding micronutrients, vitamin B12 stands out, playing a vital role in the development and functioning of the motor nervous system. The objective was to investigate the influence of reduced levels of vitamin B12 on infant motor development and analyze the effects of supplementation on this aspect of development., Methods: For this purpose, the criteria of the PRISMA method and registration in the PROSPERO database were used. The search was conducted in the following databases: PubMed (Medline), Scopus, PsycINFO, Web of Science, and ScienceDirect. A total of 684 records were initially identified., Results: Of the eight included articles, there was diversity regarding geographical contexts and study designs. The final sample comprised a total of 1,559 participants of both sexes. Studies aimed at correcting low levels of vitamin B12 opted for supplementation, following various protocols that varied in dose, administration method, and duration. At the end of the studies, the serum level of this vitamin ranged from 131 pmol/L to 1141 pmol/L., Conclusion: There is a complex array of factors contributing to reduced levels of vitamin B12, especially in the early stages of life, which significantly impacts infant motor development. Despite methodological variations among studies, evidence suggests that low levels of vitamin B12 may affect motor development and that supplementation could be an effective means of enhancing motor aspects in healthy children. However, due to the diversity of outcomes, it is important to promote comprehensive public policies to encourage appropriate interventions in this area., Competing Interests: Declaration of competing interest The authors declare that they have no financial or personal conflicts of interest that could influence the results or interpretation presented in this work., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: Recent development in understanding the pathophysiology of amyotrophic lateral sclerosis (ALS) has led to increasing number of promising test drugs in the pipeline along with the existing ones. We will review these agents focusing on ultra-high dose methylcobalamin, which is pending approval in Japan. Clinical trial design best suited for ALS will also be discussed., Recent Findings: The most recent phase 3 trial (JETALS) of ultra-high dose methylcobalamin demonstrated significant slowing of ALSFRSR changes (0.5/month), with marked reduction of serum homocysteine levels in the initial double-blind period. The post hoc analysis of the previous phase 2/3 study (E761 trial; Eisai) showed that it prolonged survival of ALS patients, if started within 1 year of onset, but the previous studies suggested its efficacy even in later stages, depending upon the rate of progression. Phase 3 trial of AMX0035 or Relyvrio on the other hand showed negative results despite the promising phase 2 data. The latter did not adjust the disease progression rate before entry., Summary: Ultra-high dose methylcobalamin is not a vitamin supplement but a novel disease-modifying therapy for ALS, and it emphasizes homocysteine as a key factor in the disease process. Clinical trial design must include entering patients early and with similar rates of progression using pretrial observation periods for meaningful results, since ALS is a chronologically heterogenous condition with similar phenotypes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Context: Previous research evaluating the effects in B-vitamins on the prevention and treatment of cardiovascular disease (CVD) has substantial limitations and lacks recently published large prospective studies; hence, conducting an updated meta-analysis is needed., Objective: We investigated the association between vitamin B status and human CVD development in order to provide more specific advice about vitamin B intake for those at risk of CVD., Data Sources: Relevant articles were identified by JSTOR, PubMed, and ProQuest databases., Data Extraction: Key words used to identify the studies included the different combinations of B-vitamins, folate, folic acid, vitamin B6, vitamin B12, homocysteine, cardiovascular disease, stroke, coronary disease, myocardial infarction, and cerebrovascular and transient ischemic attack. The database search was supplemented by hand-searching of reference lists of selected articles., Data Analysis: Pooled estimates were calculated from the mean differences using a random-effects model., Results: Supplementation with folic acid was reported to have a clinical benefit of significantly reducing carotid intima-media thickness. Higher intakes of folic acid, vitamin B6, and vitamin B12 were generally associated with a lower risk of CVD in the general population, except in those without normal renal function and those with unstable angina or past non-ST-elevation myocardial infarction., Conclusion: Vitamin B supplementation resulted in the greatest cardiovascular benefit in those with normal renal function and without unstable angina or non-ST-elevation myocardial infarction recently. Factors such as age, gender, and genetic polymorphisms contribute to varying effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study aimed to compare the anthropometry and body composition of vegetarian and omnivorous adults living in Portugal, while exploring nutritional and health parameters underlying observed differences., Methods: 425 omnivorous (OMNI), lacto-ovo-vegetarian (LOV), or vegan (VEG) healthy adults were recruited. Anthropometry was measured, and bioelectrical impedance analysis was performed. Participants answered food frequency, sociodemographic, and lifestyle questionnaires. Serum iron, ferritin, and CRP were quantified by spectrophotometry, and serum B12 vitamin and homocysteine were quantified by chemiluminescent microparticle immunoassay., Results: Total protein intake significantly decreased with increasing strictness of vegetarian habits (median (P25; P75) in g/day: 98.6 (79.5; 123.1), 90.4 (65.9; 121.0), and 87.6 (59.8; 118.5) for OMNI, LOV and VEG, respectively; p = 0.020), and carbohydrate intake was the highest in LOV (median (P25; P75) in g/day: 231.5 (178.4; 287.9), 283.9 (227.3; 342.6), and 263.0 (222.0; 348.3) for OMNI, LOV and VEG, respectively; p = 0.001). VEG were the main users of B12 vitamin (93% in VEG vs. 17% in OMNI and 59% in LOV, p = 0.001), and LOV were the main users of iron supplements (29% in LOV vs. 14% in OMNI and 13% in VEG, p = 0.042), respectively. Blood levels of B12 vitamin correlated negatively with blood homocysteine ( r s = -0.386, p < 0.001) and positively with % muscle mass ( r s = 0.136, p = 0.005). Participants using iron supplements presented higher C-reactive protein (CRP) ( p = 0.014) and they had lower % MM ( p = 0.003). Finally, when compared to being OMNI, being LOV independently associated with: (a) having +4.8% ( p = 0.002) of fat mass, which could be due to higher carbohydrate intake, and (b) having -2.2% ( p = 0.043) of muscle mass. Our data suggest that the association between diet and muscle mass could be attenuated in VEG due to B12 supplementation and/or aggravated in LOV due to iron supplementation-associated inflammation.

Background: With the increasing prevalence of pregnant women adhering to a vegan diet, gaining insight into their nutritional intake and its association with maternal and fetal outcomes is essential to providing recommendations and developing guidelines for general practice. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of the available scientific literature in Medline, Embase, and Cochrane was conducted in January 2024. Results : The titles and abstracts of 2211 unique articles were screened. Only six studies were eligible for inclusion and assessed for methodological quality using the (National Institutes of Health Study Quality (NIHSQ) Assessment Tool. The intake of protein and various micronutrients was significantly lower among vegan pregnant women compared to omnivorous women. Vitamin B12 supplements seemed sufficient in optimizing maternal and umbilical cord vitamin B12 levels amongst vegan mothers. Further, women on a vegan diet less often showed excessive pregnancy weight gain. However, children from women on a vegan diet had a significantly lower birth weight than those from women on an omnivorous diet. Conclusion: So far, only a few studies, with a large diversity of (assessment of) outcomes and insufficient power, have been published on this topic, limiting our ability to make firm conclusions about the effects of a vegan diet during pregnancy on maternal and fetal outcomes.

Background: Celiac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten, affecting approximately 1% of the global population and two million Americans. An increasing number of studies have identified a link between celiac disease and adverse maternal and fetal outcomes during pregnancy and after birth. Additionally, both celiac disease and pregnancy are associated with an increased risk for nutrient deficiencies, specifically vitamin B12 and folate. Methods: This review examines the current literature related to the folate trap and vitamin B12 deficiency in patients with celiac disease and pregnant women independently and provides rationale for future research to explore the relationship between the folate-to-12 ratio in pregnant women with celiac disease. Results: Deficiencies in vitamin B12 are linked with several negative maternal and fetal health outcomes including pre-eclampsia, gestational diabetes, spontaneous abortion/miscarriage, preterm birth, neural tube defects, intrauterine growth restriction, and low gestational age and birthweight. Conclusions: Folic acid supplementation is widely recommended during pregnancy, but complementary vitamin B12 supplementation is not standard. Physicians should consider celiac disease screening during pregnancy as well as vitamin B12 supplementation.

Aim: To investigate the efficacy of Palmitoylethanolamide (PEA, 300 mg), Superoxide Dismutase (SOD, 70 UI), Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) in one tablet in people with Diabetic Neuropathy (DN)., Patients-Methods: In the present pilot study, 73 people (age 63.0 ± 9.9 years, 37 women) with type 2 Diabetes Mellitus (DMT2) (duration 17.5 ± 7.3 years) and DN were randomly assigned to receive either the combination of ten elements (2 tablets/24 h) in the active group ( n = 36) or the placebo ( n = 37) for 6 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold (VPT) with biothesiometer, and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was assessed with SUDOSCAN, which measures electrochemical skin conductance in hands and feet (ESCH and ESCF). Pain score (PS) was assessed with Pain DETECT questionnaire. Quality of life was assessed by questionnaire., Results: In the active group, there was a large improvement of pain (PS from 20.9 to 13.9, p < 0.001). There was also a significant improvement of vitamin B12 (B12) levels, MNSIQ, SNCV, VPT, and ESCF (222.1 vs. 576.3 pg/ mL, p < 0.001; 6.1 vs. 5.9, p = 0.017; 28.8 vs. 30.4, p = 0.001; 32.1 vs. 26.7, p = 0.001; and 72.2 vs. 74.8, p < 0.001 respectively). In the placebo group, neither pain (21.6 vs. 21.7, p = 0.870) or any other aforementioned parameters changed significantly, and MNSIE worsened (2.9 vs. 3.4, p < 0.001). As a result, changes from baseline to follow-up in pain, B12 levels, VPT, and MNSIQ differed significantly between the two groups ( p < 0.001, 0.025, 0.009, and <0.001, respectively). CARTs, SNAP, ESCH did not significantly change in either of the two groups., Conclusions: The combination of the ten elements in one tablet for 6 months at a daily dose of two tablets in people with DN significantly improves pain, vibration perception threshold, and B12 levels.

Deficiency in vitamins B9 and B12 are common in general practice, due to their high prevalence in the population, especially among elderly patients. This article will present the clinical manifestations of vitamin B9 and B12 deficiencies, which can sometimes be insidious. We will discuss screening strategies, which are based on the presence of compatible symptoms as well as risk factors for deficiency. The choice of administration route for substitution depends both on severity and etiology; but the oral route has demonstrated similar effectiveness compared to intramuscular administration., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: No prospective study has evaluated the efficacy of oral supplementation with cobalamin in hypocobalaminemic cats., Objectives: To investigate the efficacy of oral or SC supplementation with cyanocobalamin in normalizing serum cobalamin and methylmalonic acid (MMA) concentrations in hypocobalaminemic cats with chronic gastrointestinal disease (CGID) or exocrine pancreatic insufficiency (EPI)., Animals: Forty-eight client-owned hypocobalaminemic (<290 ng/L) cats with normal or abnormally high serum MMA concentrations., Methods: This study was conducted based on the prospective randomized clinical trial method. Cats with CGID or EPI were randomly assigned to 2 groups that received either oral or SC supplementation with cobalamin (250 μg/cat) for 12 and 10 weeks, respectively, in addition to other medical and dietary interventions. Each cat was evaluated 3 times (baseline, 6-week postsupplementation, and 1-week postcompletion) by measuring serum cobalamin and MMA concentrations., Results: In cats with CGID or EPI, cobalamin concentrations were normalized in all cats that received either oral or SC supplementation (mean 100% [95% CI: 80.6%-100%] in both groups in cats with CGID and 100% [67.6%-100%] in both groups in cats with EPI). Among 37 cats with elevated MMA concentrations at baseline (21 cats with CGID and 16 cats with EPI), MMA concentrations were normalized in most cats with CGID (70% in oral and 82% in SC group) or EPI (88% in both groups)., Conclusions and Clinical Importance: In hypocobalaminemic cats with CGID or EPI, in conjunction with other medical and dietary interventions, both oral and SC supplementation are effective at normalizing serum cobalamin and MMA concentrations., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Methylcobalamin (MBL) is a vitamin B12 coenzyme and is effective for treating peripheral neuropathies. Little is known about pharmacokinetics (PK) of MBL in animals, we have developed a simple assay for MBL by using only 0.01 mL of plasma for PK of MBL in rats. Under minimal light exposure (<5 lx), MBL was extracted by a simple protein precipitation using methanol and detected by liquid chromatography with tandem mass spectrometry. MBL in rat plasma at 20-10,000 ng/mL was quantified using only 0.01 mL of plasma. Relative error and relative standard deviation met the acceptance criteria in reproducibility assessments, indicating the robustness of the assay. PK of MBL was evaluated after intravenous, intramuscular, and subcutaneous administration. PK of MBL was dose proportional at 5-20 mg/kg in both intramuscular and subcutaneous administrations. Bioavailability after the two dosing routes was complete (ca. 100 %). The incurred sample reanalysis also supported that the assay is robust. The established assay was successfully applied to PK studies in rats to find that MBL showed high bioavailability after intramuscular and subcutaneous administrations., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To assess vitamin D, folate, vitamin B 12 , and iron status in Old Order Anabaptist (OOA) pregnant/postpartum women. Methods: Blood was analyzed for plasma 25 hydroxy vitamin D (25(OH)D), red blood cell (RBC) folate, serum vitamin B 12 , and iron status indicators. Dietary intakes (food and supplements) from 3-day estimated records were compared to Dietary Reference Intakes and Canada's Food Guide (2007). Results: Fifty women participated in this descriptive cross-sectional study. Concentrations of 25(OH)D were low (<50 nmol/L for 20% and < 75 nmol/L for 63%); 42% had total vitamin D intakes < estimated average requirement (EAR). All women had RBC folate above the 1360 mmol/L cut-off. Nineteen percent had folate intakes upper limit. One woman had low serum vitamin B 12 (<148 pmol/L); serum vitamin B 12 was high (>652 pmol/L) for 24%. None had vitamin B 12 intakes 12 . These findings provide guidance to ensure appropriate dietary and supplement intakes in this potentially vulnerable and rarely studied population.

Background: Healthy plant-based diets, such as the lacto-ovo-vegetarian and the vegan diet, offer numerous benefits to human health. Poorly designed plant-based diets, however, bear the risk for vitamin- and micronutrient deficiencies. Vitamin B12 (B12, cobalamin) is a nutrient of particular concern in both diets, and should be readily supplemented on a continuous basis to ensure adequate B12 levels and to prevent deficiencies., Case Report: This case reports describes the history of a healthy man in his mid-30s who adopted a vegan diet approximately 10 y ago. Well informed about the risks of vitamin B12 deficiency on a plant-based diet, he regularly supplemented methylcobalamin for years (single oral dose: 500 µg, 3-4 times a week) in order to maintain an adequate vitamin B12 status. In late 2023, however, he decided to cease B12 supplementation for undisclosed reasons. Subsequent to this decision, we closely monitored his B12 status and longitudinally measured serum B12, homocysteine, and holotranscobalamin (holo-TC). Total serum folate was also determined as it is a modifier of homocysteine concentration. A gradual decrease in holo-TC and vitamin B12 levels was observed after 4 weeks and supplements had to be re-introduced after 16 weeks. Homocysteine increased concomitantly up to 18.2 μmol/L after 20 weeks., Conclusions: While a short-term B12 supplement intake cessation might be well tolerated by vegans with an adequate B12 status, an interruption of more than 8 weeks could signify B12 loss approaching suboptimal status. This case report reiterates the need for continuous B12 supplementation in persons following an unfortified plant-based diet., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Context: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Chinese patent medicines (CPMs) are widely used in clinical practice to treat DPN., Objective: This study aims to summarize the latest evidence on the harms and benefits of CPMs as adjunctive therapy for DPN., Materials and Methods: We conducted searches for randomized controlled trials (RCTs) evaluating CPMs in conjunction with mecobalamin (Mec) or alpha-lipoic acid (αLA) across eight databases up to July 2024. The surface under the cumulative ranking area (SUCRA) was utilized to assess the clinical efficacy rate (CER), the peroneal motor nerve conduction velocity (pMNCV), the peroneal sensory nerve conduction velocity (pSNCV), the median motor nerve conduction velocity (mMNCV), and the median sensory nerve conduction velocity (mSNCV)., Results: The search yielded 128 eligible studies with 31 CPMs with Mec and 39 eligible studies with 17 CPMs with αLA. SUCRA rankings indicated that, when combined with Mec, Mailuoning liquid (lMLN) was the most effective regimen for CER, Honghua injection (iHH) for pMNCV, Maixuekang capsule (cMXK) for pSNCV, Dengzhanxixin injection (iDZXX) for mMNCV, and Tongxinluo capsule (cTXL) for mSNCV. Combined with αLA, Danhong injection (iDH) showed the highest efficacy for CER, pSNCV, and mSNCV, while Xueshuantong injection (iXShT) was the most effective for pMNCV and mMNCV., Conclusion: This network meta-analysis confirms the efficacy and safety of 37 CPMs combined with Mec or αLA for treating DPN. However, given the potential risk of bias and the very low certainty of the evidence, these recommendations should be adopted with caution.

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., (© 2024 The Author(s). Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

Purpose: To investigate the bioavailability of vitamin B 12 from nori and to evaluate the required dosage for improving vitamin B 12 nutritional status in vegetarians not using supplements., Methods: The 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 B 12 per day), or high-dose (8 g nori, aiming to provide 4 µg vitamin B 12 per day) groups. The primary outcome was changes in vitamin B 12 status as measured by serum vitamin B 12 , 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 B 12 intakes were assessed at baseline and end of the trial with a 17-item food frequency questionnaire designed for vitamin B 12 assessment. General linear model was used to compare least square means of changes in each biomarker of vitamin B 12 status, among the three groups, while adjusting for respective baseline biomarker., Results: After adjusting for baseline status, nori consumption led to significant improvement in serum vitamin B 12 (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 B 12 status appeared to plateau at low dose (5 g of nori), which compared with control group, improved serum vitamin B 12 (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 B 12 ., Conclusions: Consuming 5 g of nori per day for 4 weeks significantly improved vitamin B 12 status in vegetarians. A higher dose (8 g) may not confer additional benefits., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT05614960. Date of registration: November 14th 2022., (© 2024. The Author(s).)

Background: A persistent difficult-to-treat cough can be exhausting. Iron is an essential element that plays an important role in regulating the production of pro-inflammatory cytokines, and its deficiency may potentiate airway inflammation and dysfunction. There is a paucity of data regarding a link between iron deficiency (ID) and idiopathic cough., Objectives: In this study, a case of persistent non-productive cough, which was unresponsive to targeted treatment approaches but responsive to iron therapy, is reported., Methods: A 53-year-old woman came to a medical clinic with complaints of a chronic and progressive non-productive cough. She underwent a complete clinical and paraclinical evaluation., Results: Her vital signs were stable and no abnormalities were found on the physical examination. The results of the spirometry and chest radiography were unremarkable. The laboratory test indicated hypochromic microcytic anemia, with a hemoglobin value of 9.6 g/dL. Her cough was resolved after treatment of iron-deficiency anemia with an oral nutraceutical capsule containing 28 mg of elemental iron (as ferrous bis-glycinate) plus folic acid, vitamin B12, and vitamin C, once daily for six months., Conclusion: In the case of unexplained chronic cough, resistant to targeted therapies, investigation and treatment of ID may contribute to the resolution of cough., Competing Interests: Declarations Conflicts of Interest The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)

Background: Cyanocobalamin or B 12 deficiency is common in the Indian population, and responsible for anemia. Various clinical manifestations include central nervous system and cardiovascular manifestations, secondary to a rise in serum homocysteine levels., Method and Patients: In a routine outpatient department at Bawaskar Hospital and Clinical Research Centre, Mahad, patients with suspected clinical signs and symptoms suggestive of cyanocobalamin deficiency were studied in detail regarding their dietary habits, serum hemoglobin, B 12 , and homocysteine levels., Findings: A total of 1,992 (female 1,009, 50.75%) were clinically examined in detail. Of these, 945 (49.94%), 999 (50.17%), and 48 (2.40%) were strict vegetarians, both vegetarian and nonvegetarian, and strict nonvegetarians, respectively. Common occupations associated with B 12 deficiency include 666 (33.4%) housewives, 396 (19.9%) service workers, 316 (15.9%) businesspeople, 180 (9%), and 198 (9.9%) retired and industrial populations, respectively. Clinical manifestations include recurrent scalp hair loss in 268 (13.5%), poor memory in 240 (12%), tingling and numbness in 200 (10%), and generalized weakness in 387 (19.4%) patients. Additionally, 541 (27.15%) patients had pigmentation of the nail bed, knuckles, oral mucosa, and tongue, while 237 (10.81%) suffered from hypertension and ischemic heart disease. During the process of preparation of vegetarian and nonvegetarian food, there is a 30-48% reduction in vitamin content. Supplementation of vitamin by adding table salt to food on a plate at the time of eating improves the vitamin level in the blood., Conclusion: In the absence of laboratory investigations in rural settings, clinical signs and symptoms are helpful in detecting B12 deficiency. Directly adding vitamin powder, similar to table salt, to cooked food on the plate improved blood vitamin levels., (© Journal of the Association of Physicians of India 2024.)

Aim: Vitamin B 12 deficiency is common in the elderly population. Standard treatment via intramuscular injections, however, has several disadvantages. Safer and more convenient dosage forms such as intranasal are therefore being explored. This study compares the effects of two intranasal vitamin B 12 dosage regimens in elderly vitamin B 12 -deficient patients., Methods: Sixty patients ≥65 years were randomly assigned to either a loading dose (daily administration for 14 days followed by weekly administration) or a no loading dose (administration every 3 days) regimen for 90 days. Each dose contained 1000 μg cobalamin. Total vitamin B 12 , holotranscoblamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy) levels in serum were measured on days 0, 7, 14, 30, 60 and 90., Results: Both dosage regimens resulted in a rapid increase of vitamin B 12 and holoTC concentrations and normalization of initial high, MMA and tHcy concentrations. The loading dose regimen resulted in the fastest and greatest increase to a median vitamin B 12 of 1090 pmol/L (reference 350-650 pmol/L) concentration after 14 days. Following weekly administration, B 12 rapidly decreased to a median concentration of 530 pmol/L after 90 days. The no loading dose regimen resulted in a steady increase to a median vitamin B 12 of 717 pmol/L after 90 days., Conclusions: Intranasal vitamin B 12 administration is an effective and suitable way to replenish and sustain vitamin B 12 levels in elderly patients., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Nitrous oxide, an inhalational anaesthetic, is popular with adolescents worldwide as an accessible recreational drug which induces a euphoric effect. However, chronic abuse leads to serious complications such as myeloneuropathy and bone marrow suppression by inactivation of vitamin B 12 . A 17-year-old girl presented with nitrous oxide-induced myeloneuropathy. She reported chronic nitrous oxide inhalation for 10 months and was admitted to the emergency department on account of repeated falls for 2 weeks. She also had ascending paraesthesia in both legs and urinary incontinence. Neurological examination demonstrated bilateral lower extremity weakness [motor power: proximal muscles 4/5, plantar flexion and extensor hallucis longus (EHL) 3/5], decreased sensation, proprioception and vibration of the lower extremities. Deep tendon reflexes were absent in the ankles and knees. Laboratory results demonstrated mild anaemia [Hb 11.2 g/dL (12.0-16.0), haematocrit 35.4% (36-50), MCV 89.4 fl (78-102)] with significant hypersegmented neutrophils in a peripheral blood smear. Serum vitamin B 12 was 340 pg/mL (197-771), but serum homocysteine was increased at 65.8 µmol/L (5-15). A nerve conduction study was prolonged, and F-waves were absent from the bilateral perineal and tibial nerves, indicating diffuse demyelinating motor polyneuropathy. Magnetic resonance imaging of the whole spine demonstrated faint T2 hypersignal intensity and an inverted V-shape appearance at the posterior column of the upper thoracic cord (around T2-T6), a pathognomonic sign of vitamin B 12 deficiency or subacute combined degeneration of the nitrous oxide-induced myeloneuropathy. A 7-day course of 1000 µg cyanocobalamin was given intramuscularly, followed by weekly doses for 4 weeks. Supplements of daily oral vitamin B 1 , B 6 and B 12 (65 µg vitamin B 12 ) were administered, along with rehabilitation. At the 6-months outpatient follow-up, there were a few residual neurological abnormalities: weakness of the left EHL (grade 4/5) and an absent deep tendon reflex in the left ankle. This case emphasises the significant health consequences of chronic abuse of nitrous oxide, myeloneuropathy and megaloblastic anaemia, by inactivation of vitamin B 12 . The myelopathy is noticeably improved by cyanocobalamin. Abbreviations: EHL: extensor hallucis longus; MRI: magnetic resonance imaging; NCS: nerve conduction study.

Purpose: Musculoskeletal pain may occur after becoming infected with SARS-Cov2. This study was designed to evaluate the efficacy of mesotherapy in treating chronic pain following COVID-19 infection., Methods: A retrospective review was conducted of the records of 96 patients with post-COVID pain syndrome. Those who were eligible for oral therapy or mesotherapy, included in the study. Patients receiving oral treatment with diclofenac potassium, thiocolchicoside and cyanocobalamin were included in one group (n = 46), and patients receiving intradermal mesotherapy with 2% lidocaine + cyanocobalamin were included in another group (n = 50). The results of the Visual Analogue Scale (VAS) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were individually assessed before and one week after the treatment., Findings: The participants were 40.2 ± 11.1 years old on average. Of the participants, 35.4% (n = 34) were male and 64.6% (n = 62) were female. Before treatment, there was no statistically significant difference between the patients in terms of VAS and LANSS scores. Following the treatment, a notable positive response was observed in both groups. Nevertheless, when compared to the oral treatment group, the mesotherapy group exhibited a more pronounced enhancement in VAS and LANSS scores (P < 0.001, P < 0.001, respectively)., Implications: While both mesotherapy and oral therapy offer benefits in reducing pain and alleviating neuropathic symptoms in post-COVID pain syndrome, mesotherapy stands out as an especially effective and well-tolerated treatment method, surpassing the efficacy of the oral alternative., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Vitamin B 12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B 12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality., Objectives: The study aims to determine the effect of vitamin B 12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B 12 deficiency., Methods: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 μg (2-3 recommended daily allowances) vitamin B 12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B 12 status, hemoglobin, sex, and growth indices., Results: LTL at end-study did not differ between the vitamin B 12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B 12 on LTL in any of the subgroups., Conclusions: Providing daily vitamin B 12 for 1 y during infancy in a population at risk of vitamin B 12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Aims: To describe the clinical features and outcomes of patients with myelopathy and neuropathy due to recreationally inhaled nitrous oxide., Methods: We identified patients presenting with nitrous oxide-associated myelopathy from an electronic database of all discharges in a large tertiary hospital between 2016 and 2023. Demographics, clinical features and the results of investigations were recorded. The primary outcome was modified Rankin Scale score (mRS) at least 3 months after hospital discharge where available., Results: There were 12 patients identified, six women, mean (SD) age 27.5 (5.1) years, range 19-47 years. The most common symptoms were numbness, weakness and mental state changes. Four patients used large amounts of inhaled nitrous oxide and also took over-the-counter vitamin B12 supplements. The median (range) hospital length of stay was 8.5 (2-56) days. Functional independence at last assessment (median [range] of 3 [1-34] months after discharge) was achieved in nine of the patients, with three requiring ongoing support for activities of daily living (mRS ≥3)., Conclusion: Nitrous oxide abuse and its neurological complications are an important public health issue. Clinicians should be aware that some patients who use large amounts of nitrous oxide may self-supplement vitamin B12., Competing Interests: The authors have no conflicts of interest to declare., (© PMA.)

Vitamin B12 and folate deficiency are reversible causes of megaloblastic anemia . Strict vegetarians are at risk of megaloblastic anemia due to low cobalamin in their diet . Knuckle hyperpigmentation in patients with megaloblastic anemia is due to excess melanin synthesis in skin. Here we present a case of a young vegetarian male with megaloblastic anemia with knuckle hyperpigmentation managed successfully with intravenous followed by oral vitamin b12 and folate supplementation., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The etiology of cerebral venous sinus thrombosis (CVST) is multifactorial. Although many acquired and genetic factors have been recognized as risk factors, hyperhomocysteinemia (hHcy) is independently associated with CVST. We describe three cases of CVST in this case series. All of them presented with headache. Two patients had papilledema and visual disturbances. On evaluation, there was CVST, and prothrombotic workup showed hHcy. In addition, two of them reported very low Vitamin B12 levels. All of them were treated with low-molecular-weight heparin followed by oral anticoagulation and Vitamin B6, B9, and B12 supplements. All of them responded to treatment, and follow-up imaging studies in two of them showed resolution of thrombosis. hHcy should be considered in the evaluation of CVST, especially in the setting of a pure vegetarian diet. Fortification of the diet with Vitamin B12 may be considered the majority of Indians consume predominantly vegetarian food., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Background: The 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., Objectives: We aimed to assess the efficacy of oral vitamin B12 supplementation in PA., Methods: We 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., Results: We 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., Conclusions: Oral supplementation with 1000 μg/d of cyanocobalamin has been shown to improve vitamin B12 deficiency in PA., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: Neurologic problems are frequently described in infants with nutritional vitamin B12 (cobalamin) deficiency.Major neurologic consequences of infantile cobalamin deficiency include delays or regression in neurodevelopment and the occurrence of involuntary movements METHODS: We reviewed the medical records of infants with cobalamin deficiency and divided infants with involuntary movements into two groups as those, who developed involuntary movements during vitamin B12 supplementation (Group I) and those, who developed involuntary movements prior to supplementation therapy (Group II)., Results: We evaluated a total of 32 infants with the diagnosis of cobalamin deficiency. Involuntary movements were observed in 12 out of 32 infants. Group I and Group II consisted of 6 infants each. Of the infants with involuntary movements, five were exclusively breastfed until the time of diagnosis. The majority of infants in Group II had choreoathetoid movements; twitching and myoclonus in the face, tongue, and lips, and tremor in the upper extremities. These involuntary movements disappeared in one to three weeks after clonazepam therapy. In Group I; shaking movements, myoclonus, tremor, and twitching or protrusion were observed in patients' hands, feet, tongue, and lips on the 3rd-5th day of cobalamin supplementation. These involuntary movements disappeared within 5-12 days of clonazepam therapy., Conclusion: Recognition of nutritional cobalamin deficiency is important to perform a differential diagnosis of the condition from seizures or other causes of involuntary movements and avoid aggressive therapy and over treatment., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among the elderly, presenting a significant public health concern. However, there is currently a deficiency in pharmacological interventions that can effectively cure or significantly reverse the progression of cognitive impairment. Methyl donor nutrients (MDNs), including folic acid, choline, and vitamin B12, have been identified as potential enhancers of cognitive function. Nevertheless, there remains a dearth of comprehensive research investigating the connection between the dietary intake of MDNs and CI. In our study, we comprehensively assessed the relationship between MDNs' dietary intake and CI in older adults, utilizing 16S rRNA gene sequencing to investigate the potential underlying mechanisms. The results showed an obvious difference in the methyl-donor nutritional quality index (MNQI) between the dementia (D) group and the dementia-free (DF) group. Specifically, there was a lower MNQI in the D group than that in the DF group. For the gut microbiome, the beta diversity of gut flora exhibited higher levels in the high methyl-donor nutritional quality (HQ) group as opposed to the low methyl-donor nutritional quality (LQ) group, and lower levels in the D group in comparison to the DF group. Subsequently, we performed a correlation analysis to examine the relationship between the relative abundance of microbiota, the intake of MDNs, and Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with potential regulatory functions. Additionally, KEGG pathway analyses suggested that the one-carbon metabolism, chronic inflammation, and DNA synthesis potentially serve as pathways through which MDNs may be promising for influencing cognitive function. These results implied that MDNs might have the potential to enhance cognitive function through the regulation of microbiota homeostasis. This study offers dietary recommendations for the prevention and management of CI in the elderly.

Background: One-carbon metabolism coenzymes may influence brain aging in cognitively unimpaired adults., Methods: Baseline data were used from the UK Biobank cohort. Estimated intake of vitamin B6, B12, and folate was regressed onto neural network functional connectivity in five resting-state neural networks. Linear mixed models tested coenzyme main effects and interactions with Alzheimer's disease (AD) risk factors., Results: Increased B6 and B12 estimated intake were linked with less functional connectivity in most networks, including the posterior portion of the Default Mode Network. Conversely, higher folate was related to more connectivity in similar networks. AD family history modulated these associations: Increased estimated intake was positively associated with stronger connectivity in the Primary Visual Network and Posterior Default Mode Network in participants with an AD family history. In contrast, increased vitamin B12 estimated intake was associated with less connectivity in the Primary Visual Network and the Cerebello-Thalamo-Cortical Network in those without an AD family history., Conclusions: The differential patterns of association between B vitamins and resting-state brain activity may be important in understanding AD-related changes in the brain. Notably, AD family history appears to play a key role in modulating these relationships., Competing Interests: The authors declare no conflicts of interest.

The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Methyl donor micronutrients might affect muscle strength via DNA methylation. We aimed to evaluate the combined relationship of dietary methyl donor micronutrients containing betaine, choline, methionine, vitamin B 12 , vitamin B 6 and folate on muscle strength. This cross-sectional study was conducted on 267 subjects including 113 men and 154 women. Dietary intake of micronutrients was assessed utilising a validated 168-item semi-quantitative FFQ, and methyl donor micronutrient score (MDMS) was calculated. The muscle strength of the participants was measured using a digital handgrip dynamometer. The association was determined using linear regression analysis. The mean age of participants was 36·8 ± 13·2 years. After taking into account potential confounding variables, there was no significant association between dietary methyl donor micronutrient score (MDMS) and the mean left-hand muscle strength ( β : 0·07, se: 0·05, P = 0·07); however, the changes were significant in the mean right-hand muscle strength ( β : 0·09, se: 0·04, P = 0·03). There was also a significant positive relationship between mean muscle strength and methyl donors' intake after fully adjusting for potential confounders ( β : 0·08, se: 0·04, P = 0·04). In conclusion, our findings revealed that higher dietary methyl donor micronutrient consumption is associated with enhanced muscle strength. As a result, advice on a higher intake of methyl donor-rich foods including grains, nuts, dairy products and seafood might be recommended by dietitians as a general guideline to adhere to. Additional prospective studies are needed to confirm the findings.

Background: Vitamin B12 deficiency is commonly diagnosed using thresholds developed for adults, yet emerging evidence indicates these levels may not be appropriate for children and adolescents. This misalignment can lead to underdiagnosis in younger populations, with potential long-term health implications., Case Summary: Chief Complaint: The 17-year-old female patient experienced severe fatigue, menstrual irregularities, psychological distress, and neurological symptoms over several years. The 13-year-old male patient had behavioral changes, gastrointestinal complaints, and sensory disturbances from an early age.Diagnosis: Both adolescents displayed B12 levels that were considered low-normal based on adult thresholds, complicating their diagnostic processes. Their diverse and atypical symptomatology required a comprehensive review of their medical and family histories, clinical symptoms, and risk factors.Intervention: Treatment included administration of hydroxocobalamin injections, complemented by dietary adjustments.Outcome: Both patients responded well to the treatment, showing significant improvements in their symptoms and overall quality of life., Conclusion: The main takeaway from these cases is the importance of tailoring diagnostic adequate thresholds and treatment plans to the pediatric population to address and manage B12 deficiency effectively. This approach can significantly enhance patient outcomes and prevent the progression of potentially severe complications in later life., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: It is difficult to recognize vitamin B12 deficiency and to evaluate the effect of B12 treatment due to a broad range of variable clinical symptoms overlapping with other diseases and diagnostic biomarkers that quickly normalize during treatment. This poses a risk of delay in diagnosis and a challenge to uniformly monitor the effect of B12 treatment. There is a need for a new clinical outcome measure suitable for clinical practice and clinical evaluation studies., Objective: To develop a Patient-Reported Outcome Measure (PROM) which measures the severity of vitamin B12 deficiency symptoms., Methods: The B12 PROM was developed by (1) gathering input from experts and literature review to define a construct and develop a conceptual model, (2) processing input from health care providers, scientists, and patients to develop items and response options, and (3) improving items based on the feedback from laypersons, test interviews, semi-structured cognitive interviews with patients, and forward and backward translation (ENG-NL)., Results: The B12 PROM includes 62 items grouped into 8 categories of symptoms related to vitamin B12 deficiency (General, Senses, Thinking, In limbs and/or face, Movement, Emotions, Mouth & Abdomen, Urinary tract & Reproductive organs). Cognitive interviews demonstrated good comprehensibility and comprehensiveness., Conclusions: This study is the first step in the development of a disease-specific PROM for vitamin B12 deficiency to measure the burden of symptoms. Further validation and reliability testing are necessary before the PROM can be applied in clinical practice and research., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pernicious anemia (PA) is a type of macrocytic anemia caused by autoimmune gastritis. To facilitate timely diagnosis and treatment of PA there is a pressing need for improved understanding among Healthcare providers of the condition's symptoms and diagnostic criteria., Objective: This systematic review aims to extend existing clinical knowledge on the presentation of PA by determining which symptoms and clinical complications are reported in published adult case studies., Methods: Relevant studies were identified through electronic searches of PsycINFO, Embase, and MEDLINE, via OvidSP. During data extraction symptoms were categorized according to the International Classification of Diseases and were grouped based on frequency., Results: Symptoms were documented for 103 adults with a diagnosis of PA; the most frequent symptoms were fatigue (55%), loss of sensation in limbs (32%), excessive weight loss (27%), and a sore tongue (23%)., Conclusions: This review highlights the diverse symptomology of adults who are diagnosed with PA. Most symptoms documented in case studies are consistent with the core signs of B 12 and folate deficiencies. Research is needed to identify if there are common clusters of PA symptoms that can be used as prompts for diagnostic testing in patients with suspected B 12 deficiency., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Vitamin B12 deficiency is a critical medical condition that, if left untreated, can lead to severe symptoms and potentially serious and life-threatening complications. Clinical guidelines are designed to provide a standardized approach to diagnosis and treatment, aiming for consistency and effectiveness. However, it is well-established that not all patients fit into general guidelines., Objective: To investigate the clinical relevance of the submitted research to support these protocols for diagnosing and treating a B12 deficiency., Approach: Conducting a literature review of the references focused and used on diagnosing and treating vitamin B12 deficiency in adults and children., Results: No robust clinical trial nor RCT has been found to back up the current protocols. The research used is primarily based on assumptions rather than solid clinical evidence., Conclusion: Existing guidelines for vitamin B12 deficiency need to be significantly revised and improved through clinical research, clinical experience by experts in the field with input from patient groups worldwide., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This systematic review and network meta-analysis aimed to evaluate the three different administration routes of vitamin B12: oral, intramuscular (IM), and sublingual (SL) routes., Methods: We searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane CENTRAL Register of Controlled Trials). We included only comparative studies. We performed a frequentist network meta-analysis to measure network estimates for the relative outcomes. Moreover, we conducted a pairwise meta-analysis using a random effect model to obtain direct estimates for outcomes. All outcomes were continuous, and the relative treatment effects were pooled as mean difference (MD) with 95% confidence intervals., Results: Thirteen studies were included in the meta-analysis, with a total of 4275 patients. Regarding increasing vitamin B12 levels, the IM route ranked first, followed by the SL route (MD = 94.09 and 43.31 pg/mL, respectively) compared to the oral route. However, these differences did not reach statistical significance owing to the limited number of studies. Regarding the hemoglobin level, the pooled effect sizes showed no difference between all routes of administration that could reach statistical significance. However, the top two ranked administration routes were the oral route (78.3) and the IM route (49.6)., Conclusion: All IM, oral, and SL routes of administration of vitamin B12 can effectively increase the level of vitamin B12 without significant differences between them, as thought previously. However, the IM route was the top-ranked statistically but without clinical significance. We found no significant difference among studied administrated routes in all other CBC parameters and homocysteine levels., (© 2024. The Author(s).)

This article is a commentary on the role of vitamin B 12 in age-related cognitive decline, with a meta-commentary on the misuse of the term "Alzheimer's Disease." The article describes the historical origins of the term "Alzheimer's Disease" and argues that the term should be restricted to a narrower segment of the age-related dementia spectrum. The article also outlines the role of vitamin B 12 in age-related cognitive decline and outlines the rationale for the treatment of B 12 deficiency to address a potentially reversible factor in cognitive decline., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Plant-based diets are increasingly popular worldwide. A well-planned plant-based diet lowers the risk of cardiovascular disease, type 2 diabetes and certain cancers. In contrast, a poorly planned plant-based diet increases the risk of certain micronutrient deficiencies, chiefly, vitamin B 12 (B 12 ). Because B 12 is not present in plants or in unfortified plant-based foodstuffs, the safest way to prevent its deficiency in plant-based diets is to take an oral B 12 supplement. Studies determining the dose and frequency of B 12 to be taken by healthy individuals on a plant-based diet to support an adequate B 12 status are scarce. Here, we summarize the natural sources, metabolic requirements, biomarker findings with and without supplementation with B 12 , and current recommendations to help prevent vitamin B 12 deficiency in healthy individuals adhering or transitioning to plant-based diets. This review focuses on the prevention of vitamin B 12 deficiency in healthy individuals adhering to plant-based diets. The information covered in this review does not apply to individuals suffering from autoimmune-based malabsorption of vitamin B 12 resulting from pernicious anemia due to atrophic gastritis, other acquired causes of B 12 malabsorption or to those with genetic disorders that impair vitamin B 12 absorption, transport and utilization., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There is concern that during a low-risk pregnancy, women are consuming more than recommended (400 µg/day) supplemental folic acid and may not meet recommendations for other nutrients. The objective of this study was to determine folic acid supplement use and dietary folate intakes in the second trimester (week 18) of pregnancy in women ( n  = 2996) in the Canadian CHILD cohort study. Vitamin B12 and choline intakes were also assessed because they are metabolically related to folate. The majority of participants (71.6%) were consuming a daily prenatal supplement. Twenty-eight percent of women ( n  = 847) reported consuming a folic acid supplement and of these women, 45.3% had daily supplemental folic acid intakes above the upper intake level (UL; 1000 µg/day). Daily dietary folate intakes were (mean (SD)) 575 (235) DFE µg/day. In contrast, only 24.8% of women met the dietary choline adequate intake (AI) recommendation (AI ≥ 450 mg/day) with a mean (SD) intake of 375 (151) mg/day. Further understanding of the impact of supplemental folic acid intake above the UL and low choline intake during pregnancy requires further investigation., Competing Interests: Authors have no conflicts of interest to disclose.

Background: An increasing number of adult individuals are at risk of vitamin B12 deficiency, either from reduced nutritional intake or impaired gastrointestinal B12 absorption., Objective: This study aims to review the current best practices for the diagnosis and treatment of individuals with vitamin B12 deficiency., Methods: A narrative literature review of the diagnosis and treatment of vitamin B12 deficiency., Results: Prevention and early treatment of B12 deficiency is essential to avoid irreversible neurological consequences. Diagnosis is often difficult due to diverse symptoms, marked differences in diagnostic assays' performance and the unreliability of second-line biomarkers, including holo-transcobalamin, methylmalonic acid and total homocysteine. Reduced dietary intake of B12 requires oral supplementation. In B12 malabsorption, oral supplementation is likely insufficient, and parenteral (i.e. intramuscular) supplementation is preferred. There is no consensus on the optimal long-term management of B12 deficiency with intramuscular therapy. According to the British National Formulary guidelines, many individuals with B12 deficiency due to malabsorption can be managed with 1000 µg intramuscular hydroxocobalamin once every two months after the initial loading. Long-term B12 supplementation is effective and safe, but responses to treatment may vary considerably. Clinical and patient experience strongly suggests that up to 50% of individuals require individualized injection regimens with more frequent administration, ranging from daily or twice weekly to every 2-4 weeks, to remain symptom-free and maintain a normal quality of life. 'Titration' of injection frequency based on measuring biomarkers such as serum B12 or MMA should not be practiced. There is currently no evidence to support that oral/sublingual supplementation can safely and effectively replace injections., Conclusions: This study highlights the interindividual differences in symptomatology and treatment of people with B12 deficiency. Treatment follows an individualized approach, based on the cause of the deficiency, and tailored to help someone to become and remain symptom-free., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background & Aims: Both maternal metabolic dysregulation, e.g., gestational diabetes mellitus (GDM), and maternal supply of nutrients that participate in one-carbon (1C) metabolism, e.g., folate, choline, betaine, and vitamin B 12 , have been demonstrated to influence epigenetic modification such as DNA methylation, thereby exerting long-lasting impacts on growth and development of offspring. This study aimed to determine how maternal 1C nutrient intake was associated with DNA methylation and further, development of children, as well as whether maternal GDM status modified the association in a prospective cohort., Methods: In this study, women with (n = 18) and without (n = 20) GDM were recruited at 25-33 weeks gestation. Detailed dietary intake data was collected by 3-day 24-h dietary recall and nutrient levels in maternal blood were also assessed at enrollment. The maternal-child dyads were invited to participate in a 2-year follow-up during which anthropometric measurement and the Bayley Scales of Infant and Toddler Development™ Screening Test (Third Edition) were conducted on children. The association between maternal 1C nutrients and children's developmental outcomes was analyzed with a generalized linear model controlling for maternal GDM status., Results: We found that children born to mothers with GDM had lower scores in the language domain of the Bayley test (p = 0.049). Higher maternal food folate and choline intakes were associated with better language scores in children (p = 0.01 and 0.025, respectively). Higher maternal food folate intakes were also associated with better cognitive scores in children (p = 0.002). Higher 1C nutrient intakes during pregnancy were associated with lower body weight of children at 2 years of age (p < 0.05). However, global DNA methylation of children's buccal cells was not associated with any maternal 1C nutrients., Conclusions: In conclusion, higher 1C nutrient intake during pregnancy was associated with lower body weight and better neurodevelopmental outcomes of children. This may help overcome the lower language scores seen in GDM-affected children in this cohort. Studies in larger cohorts and with a longer follow-up duration are needed to further delineate the relationship between prenatal 1C nutrient exposure, especially in GDM-affected pregnancies, and offspring health outcomes., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Bouillon is a promising candidate for fortification to complement existing large-scale food fortification (LSFF) programs. We used household dietary data from Burkina Faso to model potential contributions of bouillon fortified with vitamin A (40-250 μg/g bouillon), folic acid (20-120 μg/g), vitamin B12 (0.2-2 μg/g), iron (0.6-5 mg/g), and zinc (0.6-5 mg/g) for meeting micronutrient requirements of women of reproductive age (15-49 years; WRA) and children (6-59 months). Most households (82%) reported bouillon consumption, with higher proportions of resource-constrained (84-88%) and rural households (88%) consuming bouillon. Accounting for the contributions of existing LSFF, household diets were inadequate to meet the micronutrient requirements of many WRA and children, exceeding 90% and 60% inadequacy for vitamins A and B12, respectively. Modeling results showed bouillon fortification could reduce inadequacy by up to ∼30 percentage points (pp) for vitamin A, ∼26 pp for folate among WRA (∼11 pp among children), ∼38 pp for vitamin B12, and 11-13 pp for zinc, with comparable reductions across socioeconomic strata and urban and rural residence. Predicted reductions in iron inadequacy were <3 pp. These results suggest dietary micronutrient inadequacies are a concern in Burkina Faso, and fortified bouillon can make substantial contributions to reducing micronutrient inadequacies, including among resource-constrained and rural populations., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

Background: An optimal cobalamin status is necessary for normal neurodevelopment., Objective: To give a description of the epidemiology, pathophysiology and diagnostic challenges related to cobalamin insufficiency in neonates and infants in order to prevent its occurence., Results: Inadequate cobalamin status is prevalent among neonates and young infants, due to a high prevalence of maternal cobalamin deficiency, exclusive breastfeeding for extended periods and late introduction of animal food. Cobalamin insufficiency is associated with delayed neurodevelopment and subtle clinical symptoms like feeding difficulties, regurgitations and constipation in young infants. Early diagnosis and treatment of impaired cobalamin status is important to prevent neurologic damage., Conclusion: Clinical suspicion of cobalamin insufficiency in infants should infer immediate biochemical testing and a plasma total homocysteine > 5.0 µmol/L indicate cobalamin insufficiency in need of intramuscular treatment with hydroxycobalamin, followed by introduction of animal food after 4 months of age., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.