Vitamin B12 Deficiency in Patients Taking Metformin: Pathogenesis and Recommendations.

Metformin is a cornerstone therapy for type 2 diabetes mellitus due to its glucose-lowering efficacy and additional benefits such as reducing cardiovascular mortality. However, accumulating evidence suggests an association between long-term metformin use and vitamin B12 deficiency, which can lead to serious clinical consequences. This review aims to synthesize current knowledge on the pathogenesis, prevalence, clinical implications, and management of metformin-induced vitamin B12 deficiency. Given the significant clinical implications, it is crucial to monitor and manage vitamin B12 levels in patients using metformin. This review emphasizes the importance of early detection and supplementation to prevent adverse outcomes. By analyzing the current evidence, the review aims to inform healthcare professionals about best practices for managing vitamin B12 deficiency in patients on metformin, offering insights to guide future clinical practices and research directions.

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.

Objectives: The objective of this study is to understand the role of vitamin B12 supplementation in improving skeletal muscle function among the elderly. Methods: 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. Results: 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. Conclusions: 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.

Food-sourced guanidinoacetic acid and methylation cycle biomarkers in individuals aged one year and older: a population-based cross-sectional study.

PURPOSE: Several preliminary studies suggest dietary guanidinoacetic acid (GAA) might impact methyl group availability and/or methylation biomarkers, fueling ongoing debates. This study aimed to explore the relationship between dietary GAA intake and plasma indicators of the methylation cycle in individuals aged one year and older, using data from the 2001-2002 National Health and Nutrition Examination Survey (NHANES). METHODS: Dietary information was obtained from individuals who completed a 24-hour Dietary Recall, with total daily intake of GAA calculated by aggregating all relevant food items. Relevant variables related to the methylation cycle, such as red blood cell (RBC) folate and serum folate, vitamin B12, total homocysteine (tHCy), and methylmalonic acid (MMA), were identified from the NHANES 2001-2002 laboratory assessments. RESULTS: A total of 9,115 individuals (51.3% females) were included in the final analysis. Linear regression unveiled a significant association between higher GAA intake and diminished RBC folate (p < 0.001), serum folate (p < 0.001), and MMA levels (p = 0.007). It also revealed an elevation in tHCy levels with increased GAA intake (p < 0.001). These associations remained significant even after adjusting for demographic variables and dietary factors pertinent to the methylation cycle (p < 0.05). CONCLUSION: Our findings suggest that dietary exposure to GAA (resulting in conversion to creatine) could be considered a nutritional factor associated with the consumption of methyl groups in the general population.

Nanoparticles of nucleotide-free analogue of vitamin B12 formed in protein nanocarriers and their neuroprotective activity in vivo.

Recently, we have described the first supermolecular nanoentities of vitamin B12 derivative, viz. monocyano form of heptabutyl cobyrinate, unique nanoparticles with strong noncovalent intermolecular interactions, emerging optical and catalytic properties. Their nearest analogue, heptamethyl cobyrinate (ACCby), exhibits bioactivity. Here, we demonstrate the first example of the formation of nanoparticles of this nucleotide-free analogue of vitamin B12 in protein nanocarriers and neuroprotective activity in vivo of the own nanoform of the drug. The preparation and characterization of nanocarriers based on bovine serum albumin (BSA) loaded with vitamin B12 (viz. cyano- and aquacobalamins) and ACCby were performed. Nucleotide-free analogue of vitamin B12 is tightly retained by the protein structure and exists in an incorporated state in the form of nanoparticles. The effect of encapsulated drugs on the character and severity of primary generalized seizures in rats induced by the pharmacotoxicant thiosemicarbazide was studied. Cyanocobalamin and ACCby exhibited a neuroprotective effect. The best influence of the encapsulation on the effectiveness of the drugs was achieved in the case of AСCby, whose bioavailability as a neuroprotector did not change upon introduction in BSA particles, i.e., 33 % of surviving animals were observed upon ACCby administration in free form and in encapsulated state. No surviving rats were observed without the administration of drugs. Thus, BSA nanocarriers loaded by nanoparticles of nucleotide-free analogues of vitamin B12, including hydrophobic ones, can be recommended for neuroprotection and targeted delivery.

Progressive Decrease in Function and Ambulation Potential: A Case of Subacute Combined Degeneration.

Subacute combined degeneration (SCD) is a reversible cause of posterior and lateral spinal cord degeneration. Prolonged vitamin B12 deficiency is a common cause of SCD as it leads to inhibition of proper myelin synthesis and reduces myelin integrity. When left untreated, SCD causes progressive debility that can lead to irreversible damage. We describe the case of a 49-year-old male patient who presented with one year of worsening weakness, back pain, paresthesias, and gait abnormalities. Laboratory values revealed vitamin B12 deficiency, elevated homocysteine and methylmalonic acid, and megaloblastic anemia. Following a diagnosis of SCD, the patient began treatment with intramuscular vitamin B12, and his pain and ambulation improved considerably in the following weeks. Prompt identification of vitamin B12 deficiency can lead to considerable improvements in function and quality of life.

Long-Term Use of Nitrous Oxide Resulting in Vitamin B12 Deficiency Causing Cervical Myelopathy.

Nitrous oxide, commonly known as laughing gas, gained popularity in the medical field as an anesthetic. It also causes euphoria and acts as an anxiolytic in the human body. However, there is limited information available on its toxicity, particularly its neurotoxicity, which has been emerging in younger populations using it for recreational purposes. Here, we present a case of a young patient with subacute combined degeneration secondary to vitamin B12 deficiency from chronic use of nitrous oxide.

Association between gastrectomy and the risk of type 2 diabetes in gastric cancer survivors: a nationwide cohort study.

AIM: Postprandial glycemic fluctuations after gastrectomy are seen in patients with gastric cancer but, no studies have investigated the association between gastrectomy and type 2 diabetes mellitus (T2DM) in gastric cancer survivors. This study aimed to elucidate the relationship between gastrectomy (total or subtotal) and incident T2DM. In addition, we explored whether vitamin B12 supplementation modulates this risk among patients who have undergone total gastrectomy. METHODS: In this large nationwide population-based retrospective cohort study using the National Health Insurance Service database of South Korea, we identified patients aged >20 years who underwent gastrectomy from 2008 to 2015 (n=150,074) and age- and sex-matched controls without gastrectomy (n=301,508). A Cox proportional hazards model was used. RESULTS: During the median follow-up duration of 4.4 years after the 2-year time lag after gastrectomy, of the 78,006 subjects, 4,597 (5.9%) developed T2DM. Compared with matched controls, the adjusted hazard ratio (AHR[95% confidence interval]) for T2DM of patients with total gastrectomy was 1.34[1.23;1.47]. The corresponding AHR after subtotal gastrectomy was 0.81[0.76;0.86]. Among the patients with total gastrectomy, the risk of T2DM was significantly increased in those who did not receive any vitamin B12 supplementation (AHR=1.60[1.33;1.92]), whereas the risk of T2DM was lower (close to being statistically significant) in those who received continuous vitamin B12 supplementation after gastrectomy (AHR=0.70[0.49;1.01]). CONCLUSION: These results show a significantly reduced risk of T2DM in gastric cancer patients undergoing subtotal gastrectomy and a significantly increased risk of T2DM in gastric cancer patients undergoing total gastrectomy, which is mitigated by continuous vitamin B12 supplementation.

Association of maternal and cord vitamin B12 levels with anthropometry in term neonates born to malnourished mothers in coastal South India.

Background: Malnourished pregnant women are at increased risk of micronutrient deficiency. We assessed the vitamin B12 status in both malnourished and normally nourished pregnant women and their neonates. Additionally, we studied the association between maternal B12 levels, cord B12 levels and neonatal anthropometry. Methods: This cross-sectional study enrolled 63 malnourished and 63 normally nourished mothers and neonates. Maternal and cord blood samples were collected at the time of delivery for estimation of vitamin B12 levels. Maternal and cord vitamin B12 levels were compared using the Mann-Whitney U test. Neonatal anthropometry was correlated with maternal and cord B12 levels using Spearman's correlation. Data were analyzed using SPSS version 25. Results: Mean maternal age was 26.58 yrs. The median cord B12 levels were lower than the maternal B12 levels. Maternal B12 levels showed a strong positive correlation with cord B12 levels (rho = 0.879; p < 0.001). Maternal (p < 0.001) and cord (p < 0.001) vitamin B12 levels were significantly lower in the malnourished group than in the normally nourished group. In malnourished group, 66.8% mothers and 95.2% neonates were Vitamin B12 deficient, whereas 1.5% mothers and 4.7% neonates were vitamin B12 deficient in normally nourished group. In the malnourished group, maternal B12 levels were positively correlated with birth weight (rho 0.363, p = 0.003) and length (rho 0.330, p =0.008), whereas cord B12 levels were positively correlated with birth weight in the normally nourished group. (rho 0.277 p= 0.028). Conclusion: High rates of vitamin B12 deficiency were observed in malnourished mothers and neonates. There was a positive correlation between birth weight, length, and maternal vitamin B12 levels in malnourished mothers. These findings emphasize the need to address maternal malnutrition and vitamin B12 deficiency to improve neonatal health.

Vitamin B12 Deficiency Manifesting As Pancytopenia, Lymphadenopathy, and Fever: A Clinical Mimic of Hematologic Malignancies.

Pancytopenia is a complex medical condition characterized by decreased levels of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). It can arise from impaired production, peripheral destruction, or a combination of both. The causes of pancytopenia range from reversible factors like infections and medication reactions to irreversible conditions. Vitamin B12 deficiency is a notable reversible cause that can take years to manifest in adults due to stored reserves. However, deficiencies caused by impaired absorption, especially due to the lack of intrinsic factors (IFs), can lead to rapid deterioration within two to five years. A healthy 39-year-old male with an athletic lifestyle presented with symptoms such as dizziness, nausea, vomiting, palpitations, and fainting over a few days. These symptoms were preceded by weeks of persistent body aches, headaches, weakness, daily fevers, chills, and night sweats. Vital signs were stable. The physical examination revealed conjunctival pallor and lymphadenopathy in the submandibular and superficial cervical regions. Initial blood tests showed normocytic anemia (Hgb 4.9, MCV 80), leukopenia (2.99), thrombocytopenia (142), and elevated liver enzymes (AST 199, ALT 96, and total bilirubin of 2.04). The peripheral smear showed tear-drop cells and hypochromic cells. The initial impression was hematologic malignancy, including but not limited to leukemia, lymphoma, or myelofibrosis given clinical findings such as B-symptoms like night sweats, neck lymphadenopathy, and subjective daily fever, along with pancytopenia. The patient received a bolus of normal saline and a transfusion of two units of packed RBCs. CT scans of the chest, abdomen, and pelvis showed no adenopathy or splenomegaly. Although initial clinical assessment pointed toward a potential hematologic malignancy, comprehensive testing, including SPEP, reticulocyte count/fraction, serum folate, and serum vitamin B12, revealed only severe vitamin B12 deficiency, with a level of less than 150, with the presence of IF antibodies. Treatment involved intensive in-patient vitamin B12 injections followed by a detailed outpatient regimen. The patient completed a daily dose of vitamin B12 injections for seven consecutive days, followed by weekly injections for the next four weeks. Subsequent laboratory results demonstrated an increase in WBC count to 8.39, Hgb level to 13.2, and PLT count of 249, indicating a continued positive response to the vitamin B12 replacement therapy. In summary, pancytopenia poses a diagnostic challenge that demands careful evaluation of patient data and comprehensive testing. Vitamin B12 deficiency, which encompasses pernicious anemia (PA), is among the reversible factors to consider. This aspect holds significance before opting for more invasive measures like a bone marrow biopsy. Nutritional deficiencies need to be considered first as differentials in pancytopenia, even in the absence of typical signs of vitamin B12 deficiency (like macrocytosis and hypersegmented neutrophils) and in the presence of compelling clinical indications pointing to a hematologic malignancy.

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

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

Emission-based sensing of cobalt (II) and vitamin B12 via a bis-indole derivative.

In this study, a bis-indole compound was synthesized, characterized by 1H NMR, Fourier transform infrared, and mass spectroscopic measurements and used as a selective and efficient probe for the spectrofluorimetric analysis of Co (II). The cobalt-induced quenching in the emission maximum at 567 nm was considered as the analytical signal in calibration studies. When encapsulated in a polymethyl methacrylate (PMMA) matrix, the bis-indole compound exhibited a limit of detection (LOD) of 3.60 × 10-11 M for Co (II). Vitamin B12, which contains a cobalt ion in the center of a corrin ring in its structure, was also successfully quantified using the same probe. The bis-indole compound showed a linear response based on quenching for increasing concentrations of vitamin B12, partially mimicking the contracted tetrapyrrole ring found naturally in the center of vitamin B12. The LOD for vitamin B12 was found to be 76 nm. Promising photophysical properties of the proposed probe, including high molar extinction coefficient, considerable quantum yield (0.46 and 0.64 in tetrahydrofuran and PMMA, respectively), high Stoke's shift and satisfactory photostability, make it a good choice for fluorescence-based Co (II) determination. The ML3-type stoichiometry of the complex between the dye and cobalt was elucidated both by Job's method and by high-resolution mass spectrometry (HR-MS).

W/O/W Pickering emulsions stabilized by complex modified phycocyanin.

BACKGROUND: A water-in-oil-in-water (W/O/W) double emulsion can simultaneously load hydrophilic and hydrophobic substances due to its unique two-membrane, three-phase structure. However, thermodynamic instability greatly limits the application of double emulsions in food processing. Further development of Pickering emulsions based on proteins, etc., can improve the stability and loading capacity. It is of great significance to promote their practical application. RESULTS: Herein, we prepared ultrasound pretreatment complex glycation-modified phycocyanin (UMPC) to stabilize a W/O/W Pickering emulsion for the codelivery of vitamin B12 (VB12) and vitamin E (VE). First, an inner water phase and oil phase containing polyglycerin polyricinoleate were homogenized to prepare a W/O emulsion. Subsequently, the W/O emulsion was homogenized with an outer water phase containing UMPC to obtain a W/O/W Pickering emulsion. A gel-like inner phase emulsion with excellent storage and thermal stabilities was obtained under the condition that the W/O emulsion volume ratio was 80% and the UMPC was stabilized by 10 g kg-1. The double emulsion after loading VB12 and VE showed good encapsulation effect during the storage period, the encapsulation rate could reach more than 90%, it also showed excellent protection effect under long-time storage and UV irradiation and the retention rate increased by more than 65%. In addition, the bioavailability of VB12 and VE significantly increased during simulated gastrointestinal digestion and reached 46.02% and 52.43%, respectively. CONCLUSION: These results indicate that the UMPC-stabilized W/O/W Pickering emulsion is an effective carrier for the codelivery of hydrophilic and hydrophobic bioactive molecules and also provides a means for useful exploration of an efficient and stable emulsion system stabilized by biological macromolecules. © 2024 Society of Chemical Industry.

A Case Series of Low-Level Laser Therapy Treatment in Patients with Peripheral Facial Palsy.

BACKGROUND: Peripheral Facial Palsy (PFP) is a facial paralysis with various etiologies, including idiopathic causes (Bell's palsy), infections, trauma, and genetic factors. Traditional treatments involve antiviral medications, corticosteroids, and physiotherapy. However, new therapies, such as Low-Level Laser Therapy (LLLT), are emerging with promising results. METHODS: This case series reports on two patients with PFP treated with LLLT combined with Vitamin B1, B6, and B12 supplementation. The first case involved a 52-year-old female with PFP due to a viral infection. The second case was a 33-year-old male who developed PFP following a traumatic brain injury. Both patients received LLLT sessions every two weeks, targeting 10 points along the facial nerve pathway from the facial notch across the face. The laser device used was the Theraphy EC (DMC, Sao Carlos, SP, Brazil), with each point receiving 4 Joules of energy applied perpendicular to the skin after cleaning the face with water and soap to remove lipids that could interfere. The administration of Vitamin B was done using NEUROBIONTA tablets (Vitamin B1 + Vitamin B6 + Vitamin B12; Procter & Gamble, Santiago, Chile) with one tablet taken daily for 30 days. RESULTS: After six to seven sessions, both patients showed significant improvement in facial muscle function and overall facial symmetry. In the first case, improvements were noted in muscle tonicity and facial movements, with the patient reporting reduced facial disfigurement. In the second case, notable recovery in facial mobility and symmetry was observed, with the patient experiencing decreased paresthesia and restored muscle functionality. CONCLUSION: These findings suggest that LLLT, combined with Vitamin B1, B6, and B12 supplementation, may effectively improve facial muscle function and symmetry in PFP patients. The non-invasive nature and ease of application make LLLT a viable option for PFP treatment. Further studies with larger sample sizes and standardized protocols are necessary to confirm these results and establish LLLT as a standard treatment for PFP.

Vitamin B12 Metabolism: A Network of Multi-Protein Mediated Processes.

The water-soluble vitamin, vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B12 deficiency. A prolonged lack of vitamin B12 may have severe consequences including increased morbidity to neurological and cardiovascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabolism. Despite nearly 70 years of knowledge since the isolation and characterization of this vitamin, there are still gaps in understanding its metabolic pathways. Thus, this review aims to compile current knowledge about the crucial proteins necessary to efficiently accumulate and process vitamin B12 in humans, presenting these systems as a multi-protein network. The epidemiological consequences, diagnosis, and treatment of vitamin B12 deficiency are also highlighted. We also discuss clinical warnings of vitamin B12 deficiency based on the ongoing test of specific moonlighting proteins engaged in vitamin B12 metabolic pathways.

Vitamin B12 deficiency misdiagnosed as TTP: What can we learn from it?

The case report by Dwyre et al. shows that vitamin B12 deficiency may be misdiagnosed as acute thrombotic thrombocytopenic purpura. Together with similar observations, this underlines that acquired vitamin B12 deficiency-besides the inherited disorder of intracellular cobalamin metabolism, cbl C disease-should be listed as a separate entity of the thrombotic microangiopathies. Commentary on: Dwyre et al. Microangiopathic thrombocytopenia caused by vitamin B12 deficiency responding to plasma exchange. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19625.

Vitamin D, Folate, Vitamin B12, and Iron Status in Pregnant/Postpartum Old Order Anabaptist Women in Southwestern Ontario.

Purpose: To assess vitamin D, folate, vitamin B12, 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 B12, 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 B12 (<148 pmol/L); serum vitamin B12 was high (>652 pmol/L) for 24%. None had vitamin B12 intakes

Study of Correlation between Serum Vitamin B12 Level and Aberrant DNA Methylation in Infertile Males.

Introduction: Altered DNA methylation pattern in sperms has been associated with infertility in males demonstrating defective spermatogenesis or low semen quality. Vitamin B-12, by affecting 1-carbon metabolism pathways, might alter the DNA methylation pattern. We aimed to study the correlation of serum vitamin B12 levels with aberrant DNA methylation in infertile male patients. Methods: A cross-sectional study was conducted on 17 oligozoospermic infertile males (WHO criteria, 2010) and 10 healthy fertile males. Serum vitamin B12 levels were estimated using the chemiluminescence method. Global methylation was determined using the ELISA system (Imprint Methylated DNA Quantification Kit, Sigma-Aldrich). The levels of global DNA methylation were calculated and compared relative to the methylated (100%) control DNA provided with the kit. Results: Mean serum vitamin B12 concentration in the control group was higher than that of the case group. This difference in serum vitamin B12 concentration in both groups was found statistically significant. Although the results of this study show that oligozoospermic men have relatively lower global DNA methylation as compared to normozoospermic control, the values could not reach a statistically significant level. A small positive correlation was found between serum vitamin B12 levels and percent methylation defect (r = 0.14) but was statistically insignificant. Conclusion: Our study concludes that oligozoospermic infertile males have a significant deficiency of vitamin B12 as compared to normozoospermic fertile males. This study did not find any significant difference in global DNA methylation between the two groups. The present study does not suggest any correlation between serum vitamin B12 level and percent DNA methylation.

The Impact of the Dietary Intake of Vitamin B12, Folic Acid, and Vitamin D3 on Homocysteine Levels and the Health-Related Quality of Life of Levodopa-Treated Patients with Parkinson's Disease-A Pilot Study in Romania.

BACKGROUND AND OBJECTIVES: Previous studies have shown that the levodopa treatment of Parkinson's disease (PD) elevates circulating homocysteine levels, which are associated with an increased risk of cardiovascular and neurological disorders, or thrombosis. The present trial aimed to examine whether the intake of vitamin B12, folic acid, and vitamin D3 supplements improved homocysteine level and quality of life (QoL). MATERIALS AND METHODS: An interventional prospective trial was conducted in multiple centers across Romania. Participants with clinically established PD taking at least 300 mg/day of levodopa for more than 1 year received a daily tablet of a supplement containing 800 UI of vitamin D3, 1000 µg of folic acid, and 15 µg of vitamin B12. They were followed for 6 months and their serum homocysteine, vitamin B12, vitamin D, and QoL scores were measured at baseline and at 6 months of treatment. QoL was measured using a 15D questionnaire, which assesses mobility, vision, hearing, breathing, sleeping, eating, speech, excretion, usual activities, mental function, discomfort and symptoms, depression, distress, vitality, and sexual activity. RESULTS: Twenty-four PD patients with a mean age of 71 ± 5.04 years (54.2% male and 45.8% female) finished the study. After the intervention, the mean score of speech, mental function, discomfort and symptoms, depression, and QoL significantly increased (p < 0.05 for all). Also, the serum homocysteine and vitamin D were significantly enhanced (p < 0.0001 and p = 0.025, respectively). Changes in vitamin B12 were not statistically significant at 6 months of treatment (p = 0.996). No gender differences were found among the changes that we have demonstrated for homocysteine, vitamin B12, vitamin D, and QoL levels (p < 0.05 for all). CONCLUSIONS: The findings of this study showed that the dietary intake of vitamin B12, folic acid, and vitamin D3 remarkably decreased the dimensions of homocysteine and finally increased the total score of QoL in PD patients. We have successfully captured the potential benefits of the supplementation regimen over time and provided insights into the broader implications for managing PD with a focus on nutritional support.

Acute psychotic and vitamin B12 deficiency in patient with nitrous oxide misuse: A case report.

Nitrous oxide, also called nitrous monoxide, or nitrous oxide, is a colorless and odorless gas, without toxicological effect, but it can be asphyxiating at high concentration, its misuse is increasing especially among young people. Chronic use of N2O may cause psychiatric complications, including depression, hypomania, and paranoid psychosis with visual and auditory hallucinations. We present a case of nitrous oxide abuse "laughing gas" in 25 years old woman with bizarre behavior delusions and hallucinations with a normal neurological examination. The patient had low levels of vitamin B12 (135 pmol/L). Treatment with antipsychotics and vitamin B12 (cobalamin) resolved her psychosis. In addition to the hematological and neurological effects, rare cases of acute psychosis, especially in young people with or without psychiatric history, use varies from 1 month to years. Clinicians are increasingly in need of knowledge regarding the misuse of nitrous oxide.

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

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