B12 Levels Research Articles

Comprehensive Clinicopathologic Features in Autoimmune Atrophic Gastritis: Insights from a European Cohort of 57 Patients

ContextAutoimmune atrophic gastritis (AAG) is a frequently underdiagnosed disease due to its broad-spectrum clinical presentation. The diagnosis is based on histological confirmation of corpus-restricted metaplastic chronic atrophic gastritis. ObjectiveTo thoroughly describe the histological features of a European cohort of AAG patients. DesignClinical and pathological data of 57 out of 676 patients diagnosed with AAG were reviewed. ResultsThirty-nine patients were female and eighteen were male. The mean age was 62 years. Antibodies were identified in 32/42 patients (76%). Vitamin B12 levels were low (< 200pg/ml) in 37/54 patients (69%). Serum gastrin levels was elevated (> 115pg/mL) in all cases tested. Associated autoimmune/inflammatory conditions were identified in 20/57 patients (35%). Histologically, deep chronic inflammation was present in 46/57 (81%) patients. Complete destruction of oxyntic glands was observed in 45/57 (79%) patients. Pyloric metaplasia was present in 54/57 (95%) patients, intestinal metaplasia in 51/57 (89%) patients, and pancreatic metaplasia in 20/57 (35%) patients. Among ECL cell proliferation, linear hyperplasia was present in all 57/57 patients, micronodular hyperplasia in 55/57 patients, and adenomatoid hyperplasia in 10/57 patients. ECL cell dysplasia was identified in 5/57 patients, and neuroendocrine microtumor in 4/57 patients. ConclusionsThe diagnosing of AAG remains challenging due to the greater variability in symptoms than previously recognized. It is important to consider chronic AAG, especially with other concurrent autoimmune conditions. The importance of accurate diagnosis and surveillance is based on the potential development of type 1 gastric neuroendocrine tumor and increased risk of gastric adenocarcinoma.

Seizure solver- pyridoxine dependent seizures

Pyridoxine dependency is a rare cause of seizures. Pyridoxine dependent seizures (PDS) occur despite normal vitamin B6 levels and is due to defective binding of pyridoxine to its apoenzyme, glutamate decarboxylase, which converts glutamic acid to gamma aminobutyric acid (GABA). Pyridoxine-dependent seizure is a rare autosomal recessive disorder that usually presents with neonatal intractable seizures. Parenteral pyridoxine injection test is a highly effective and reproducible test in confirming the diagnosis. Hunt, et al.(l) described the first case of PDS with autosomal recessive inheritance. Since then, several cases have been reported with onset of seizures after neonatal period (2-6). Pyridoxine-dependent epilepsy – ALDH7A1 (PDE-ALDH7A1) is characterized by seizures not well controlled with anti-seizure medication that are responsive clinically and electrographically to large daily supplements of pyridoxine (vitamin B6). This is true across a phenotypic spectrum that ranges from classic to atypical PDE-ALDH7A1. Intellectual disability is common, particularly in classic PDE-ALDH7A1.(7)

Clinical characteristics of megaloblastic anemia with pancytopenia

ABSTRACT Objectives In this study, we aimed to explore the clinical characteristics of patients with megaloblastic anemia and pancytopenia. Methods Data on patient characteristics, laboratory examinations, clinical manifestations, and associated diseases were collected from Changzhou Hospital of Traditional Chinese Medicine. The participants were divided into two groups according to routine blood test results: megaloblastic anemia patients with pancytopenia (Group A) and megaloblastic anemia patients with simple anemia (Group B). Results The number of patients with fever and bleeding in Group A was much higher than that in Group B. Inpatient days and hospitalization costs in Group A were higher than those in Group B. White blood cell count, red blood cell count, haemoglobin level, and platelet count in Group A were lower than those in Group B. There were no significant differences in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and serum levels of lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), albumin (ALB), vitamin B12, folic acid, and ferritin between the two groups. The incidence of associated diseases, particularly pulmonary infections, was significantly higher in Group A than in Group B. There was no significant difference in the degree of bone marrow hyperplasia between the two groups. Conclusion Patients with pancytopenia and megaloblastic anemia often developed infection and bleeding, which caused more severe anemia, higher hospitalization costs, and longer inpatient days. Early diagnosis and active treatment are required to reduce patient complications and costs.

Hypertension and global DNA methylation: a population-based study in rural, Punjab, India

Hypertension is a significant public health concern and a modifiable risk factor for increased mortality worldwide. It is reported to be influenced by gene-environment interactions and micronutrient intake. This study aims to understand the relationship between global DNA methylation levels and hypertension, independently and in the context of micronutrient status, among rural population in Punjab, India. A total of 2300 individuals, aged 30–75 years, (54.9% females) were screened for blood pressure. Of 2300 screened individuals, 900 (age sex matched 450 cases and 450 controls of hypertension) individuals were selected to examine the relationship between hypertension, global DNA methylation (5mC), and biochemicals (Folate, Vitamin B12, and Homocysteine). Folate, vitamin B12, and homocysteine levels were estimated using chemiluminescence technique. The ELISA-based colorimetric technique was used for performing peripheral blood leucocyte (PBL) global DNA methylation (5mC). Statistical analyses were performed using SPSS version 22.0. Hypertensives were found to have significantly lower levels of global DNA methylation than normotensives (0.65 vs. 0.72 respectively; p-value = 0.01*). Individuals in the 1st quartile of 5mC were at significantly (OR: 1.671; 95% CI: 1.206–2.315; p-value = 0.01*) increased risk for hypertension in comparison to those in the 4th quartile (reference). Further hypertensives on medication with controlled blood pressure (BP) were significantly hypermethylated as compared to hypertensives on medication with uncontrolled BP (0.70 vs. 0.62 respectively; p-value = 0.04*). Folate appeared to mediate global DNA methylation among hypertensives on medication-controlled BP. Further hypertension driven hypomethylation hints towards accelerated biological aging among younger hypertensives. Hypertension may be associated with Global DNA hypomethylation in the studied rural population of Punjab, India. Folate sufficiency may prove to be an aid in improving the methylation levels among the cases of hypertension who were on medication and had controlled BP.

Prevalence of Vitamin B12 Deficiency in Libyan Type 2 Diabetic Patients Treated with Metformin

Metformin is the most-used drug in type 2 diabetes mellitus management and its long-term use may consequent to vitamin B12 deficiency. The lack of studies from Libya investigating the risk of association between these two presents a gap in our understanding of this issue. Our study aimed to estimate the prevalence of vitamin B12 deficiency in metformin treated diabetic patients and non-metformin treated patients and its correlation with diabetic duration and gender. Specifically, we tested the hypothesis that T2DM patients treated with metformin exhibit a decrease in vitamin B12 levels and are considered at risk for developing B12 deficiency depending on the diabetic duration and metformin use. A total of 81 samples of metformin treated diabetic patients (N=58) and non-metformin diabetic treated patients (N=23) were collected and underwent assessment of F.B.S, HbA1c and B12 level. The total mean age was 46.4± 8.27 (47.25± 9.22 for males and 45.55± 7.32 for males respectively). Total mean and standard deviation of blood glucose level was 173.93± 29.87 mg/dl (158.25± 27.35 and 184.18± 27.06 for males and females, respectively). Total mean and standard deviation HbA1c level was 6.81± 1.98% (5.94± 1.31 and 7.37± 2.14 for males and females, respectively). Total mean and standard deviation of vitamin B12 level was 435.53± 251.31 (575.62± 250.21 and 342.76± 205.91 for males and females, respectively). Our study indicated that the shortage of vitamin B12 was generally found in our population, insufficient vitamin B12 level was frequently reported in metformin administration to patients with T2DM and could progress into deficiency. Further larger studies are required to assess vitamin B12 level in those patients.

Contribution of haptoglobin phenotypic variation to the presence of hyperhomocysteinemia in type 2 diabetics with and without angiopathy.

The genetic polymorphism of haptoglobin (Hp) has been associated with several cardiovascular risk factors, but a possible relationship between Hp phenotypic variation and increased levels of homocysteine (Hcy) and cysteine (Cy) is still unknown. The objective of this study is to evaluate the relationship between the Hp polymorphism and hyperhomocysteinemia (HHcy) and hypercysteinemia (HCy) in type 2 diabetics (T2D) with and without angiopathy (AGP). A case-control study was carried out on 293 adults: Group I (GI) - 75 subjects with T2D and AGP; Group II (GII) - 75 subjects with T2D without AGP; Group III (GIII) - 143 controls. Plasma levels of Hcy, Cy and vitamin B6 were measured by high performance liquid chromatography (HPLC) and vitamins B9 and B12 determined by electrochemiluminescence (ECL). The Hp polymorphism was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and peroxidase staining. The results were analyzed in SPSS®, version 26.0 with a significance of 95%. Mean Hcy concentrations were significantly lower in carriers of the Hp2-2 phenotype (6.14 µM; p = 0.046) compared to the other genotypes. The presence of Hp2-1 is associated with an approximately 3.3 times greater probability of occurrence of HHcy (p = 0.015) and 3.7 times greater probability occurrence of HCy (p = 0.021) in T2D with AGP. The presence of the Hp2-1 phenotype is associated with the predisposition of HHcy and HCy in individuals with T2D and AGP, possibly through a positive heterosis mechanism. Carriers of the Hp2-2 phenotype appear to have a greater activation of the transsulfuration pathway in the Hcy cycle and consequent protection for its accumulation.

Evaluation of Vitamin B12 deficiency Anemia in Geriatric Patients

Objective: In our study, we aimed to evaluate vitamin B12 deficiency anemia, macrocytosis rate and vitamin B12 values in patients over 65 years of age and compare them with those under 65 years of age.groups. Methods: Retrospectively, A total of 8062 patients, 1213 over the age of 65 and 6849 under the age of 65, admitted between March 2019 and March 2024 were included in the study. The patients' hemoglobin, hematocrit, MCV, White blood cell (WBC), Red cell distribution width (RDW), Platelet (PLT) values and vitamin B12 levels were examined. Patients were divided into two groups as age of 65 and over and age below 65, and each group were divided into two groups in terms of anemia. Groups and subgropus were compared with each other Results: While the ratio of vitamin b12 deficiency anemia in patients over 65 years of age was 20.2%, the ratio of anemia in patients under 65 years of age was 8.3%. It was observed that there was no significant difference in vitamin B12 levels in terms of gender in both age groups. With the roc analyses the cut-off value for vitamin B12 causing anemia in patients over 65 years of age was 327 pg/mL (AUC: 0.602, p≤0.001) with a sensitivity of 94.3% and specificity of 34.2%. Conclusion: The fact that vitamin B12 levels that cause anemia in elderly patients are higher than in young-adult patients made us think that the usual limit values may need to be reconsiderated in geriatric population

Inverted U-shaped relationship between serum vitamin B12 and α-Klotho levels in US adults: a cross-sectional study

BackgroundSerum vitamin B12 and α-Klotho are important markers associated with aging. Limited studies have been conducted on the relationship between vitamin B12 and α-Klotho.ObjectivesThis study investigated the relationship between circulating α-Klotho and vitamin B12.MethodsA total of 4,502 American adults with circulating vitamin B12 levels and α-Klotho levels from the National Health and Nutrition Examination Survey (2011–2014) were included. A weighted multiple linear regression model was used to evaluate the correlation between vitamin B12 and α-Klotho levels. To clarify potential non-linearities, smoothed curve fitting and threshold effects analysis were employed.ResultsA statistically significant non-linear relationship was found between vitamin B12 levels and circulating α-Klotho levels after adjusting for potential confounders. We observed an inverted U-shaped relationship between serum vitamin B12 levels and circulating α-Klotho levels. Notably, serum vitamin B12 levels below the threshold (1,020 pg/mL) exhibited a positive correlation with circulating α-Klotho levels (β = 0.14, 95% confidence interval (CI): 0.09–0.18, p &amp;lt; 0.0001). Conversely, serum vitamin B12 levels above the threshold (1,020 pg/mL) exhibited a negative correlation with circulating α-Klotho levels (β = −0.12,95% CI: −0.17−−0.06, p &amp;lt; 0.0001). Sensitivity analyses were performed and consistent results were obtained.ConclusionThis study demonstrated an inverted U-shaped relationship between circulating vitamin B12 and α-Klotho in American adults. The optimal concentration of serum vitamin B12 in American adults was found.

Prevalence of Vitamin B12 Deficiency in Patients With Type 2 Diabetes Mellitus on Metformin Therapy: A Cross-Sectional Study.

Background Metformin is frequently prescribed as a first-line oral hypoglycemic drug to treat insulin resistance-causing type 2 diabetesmellitus (T2DM). Long-term metformin use results in vitamin B12 deficiency, which is frequently overlooked and undiagnosed. A severe deficit may cause severe anemiaand gastrointestinal, or neurological issues. Studies are scarce onthis issue in Pakistani patients with T2DM. The current study aimed to estimate the prevalence of metformin-induced vitamin B12 deficiency in T2DM patients and to explore how it relates to metformin dosage or duration of therapy. Methodology A descriptive cross-sectional study was conducted on 260 T2DM patients using metformin therapy for more than a year and attending the outpatient diabetes clinic and the medicine department of Sheikh Zayed Hospital, Rahim Yar Khan, Pakistan, from August 2022 to October 2023. All socio-demographic, clinical, and general characteristics were collected. Blood samples were taken to measure the serum vitamin B12 levels, and based on these levels, deficient and normal group characteristics were compared. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York, United States). Results Based on the serum levels of vitamin B12 of the studied T2DM on the metformin regimen, the overall prevalence of vitamin B12 deficiency was found to be 36.54% (95). The B12 deficiency was higher among the age group of 41-50 years (109, 41.9%), female gender (150, 57.7%, p-value=0.0035), urban residents (194, 74.6%), non-smokers (197, 75.8%), and with a history of chronic disease (131, 50.4%). There was a statistically significant difference in vitamin B12 levels based on T2DM duration (p=0.012), with a higher prevalence in patients with a longer diabetes history of more than two years. There was no discernible statistical relationship between patients receiving different dosages of metformin (odds ratio (OR)=0.8627; 95% confidence interval (CI) (0.5195, 1.4326); p-value=0.568), durations of metformin (OR=0.7400; 95% CI (0.442, 1.2325); p-value=0.247), or intake of vitamin B12 (OR=0.8532; 95% CI (0.5073, 1.4351); p-value=0.549). Conclusion The prevalence of vitamin B12 deficiency impacted more than one-third of T2DM patients using metformin (36.54%). The risk of vitamin B12 deficiency may increase in females with higher metformin dosages and longer durations of treatment. Furthermore, a statistically significant correlation exists between vitamin B12 deficiency and the longer duration of T2DM. These findings highlight the relevance of routinely monitoring serum levels of vitamin B12 among those with T2DM, especially when metformin is being given for over a year or at doses greater than 1000 mg per day. These preventive strategies will aid in the early detection of vitamin B12 deficiency, allowing patients to be treated with supplementation before problems such as anemia or neuropathies arise, resulting in improved quality of life and a lower socioeconomic burden.

21 Exploring the clinical presentation and health service utilization in autistic children and adolescents diagnosed with avoidant / restrictive food intake disorder: A descriptive study

Abstract Background Avoidant/restrictive food intake disorder (ARFID) is an eating disorder with much clinical variability, negatively impacting growth, nutrition, psychosocial functioning and overall well-being. ARFID is more frequently reported in neurotypical populations than in neurodivergent populations. Little is known about the clinical presentation and healthcare utilization of autistic individuals with ARFID. Objectives The purpose of this study was to understand the clinical presentation, laboratory abnormalities and health system utilization amongst autistic individuals diagnosed with ARFID within the community. Design/Methods We completed a comprehensive multidisciplinary assessment on autistic individuals less than18 years of age who were diagnosed with ARFID by their community physician. Recruitment period: June 2020-June 2021. Results Nineteen autistic individuals completed a comprehensive multidisciplinary assessment; of these, 42.1% (8/19) met criteria for Autism Spectrum Disorder (ASD) severity level 1. The onset of restrictive eating manifested at M(SD)= 2.5 (0.7) years, and the age of ASD diagnosis was 4.2 (3.8) years. Of these, 78.9% (15/19) had the onset of feeding difficulties either prior to or at the time of their ASD diagnosis (Figure 1). Dependence on enteral feeding or nutritional supplements (74%), psychosocial impairment (68%), and nutritional deficiencies (42%) were the criteria commonly met for ARFID. Sensory-based avoidance (100%) and lack of interest in food (89%) were the two most reported potential drivers for the dysfunctional feeding behaviour based on the Pica , ARFID, and Rumination Disorder Interview-AR-Q. Neurodevelopment disorder comorbidities included ADHD (26.3%), Anxiety (21.1%), and Intellectual Developmental Disability (15.8%). Constipation (68.4%) and nutritional deficits (63.15%) were the most common medical comorbidities recorded. Nutritional profile revealed Vitamin D deficit in 50% (8/16), Anaemia 21% (4/19), Vitamin B1 deficit 20% (2/10). Additionally, three participants (17.7%, 3/17) had deficits in Vitamin B12, Zinc, Vitamin C and low ferritin levels. Four autistic individuals (21.1%, 4/19) were hospitalized because of their restrictive eating. 68.4% (13/19) autistic individuals had involvement of at least one allied health professional (OT or SLP or BT). No participants had a prior multidisciplinary feeding assessment or intervention to address restrictive eating. Conclusion ARFID is an eating disorder observed within autistic individuals. Evidence suggests food related sensory sensitivities and lack of interest in food are potential drivers of ARFID in the context of ASD. A comprehensive multidisciplinary assessment is needed to elucidate factors driving restrictive eating to inform targeted evidence-based interventions.

Association between RBC folate and diabetic nephropathy in Type2 diabetes mellitus patients: a cross-sectional study

Folates play a crucial role as cofactors in metabolic pathways, influencing biological methylation and nucleotide synthesis, which has a significant impact on overall health and disease susceptibility. Diabetic nephropathy (DN) is a prevalent and severe complication of diabetes mellitus (DM). The correlation between RBC folate and DN remains unclear currently. This study aims to assess whether RBC folate is associated with DN. Based on data from the NHANES (2011–2018), we conducted a cross-sectional study involving 3070 adults with type 2 DM (T2DM). Demographic factors, levels of folate and vitamin B12, dietary folate intakes, and relevant laboratory data were obtained from all participants. Logistic regression, fitting smooth curves, interaction effects were utilized to support the research objectives. Regression analyses demonstrated a positive relation between RBC folate and DN. (P < 0.001). A positive association between levels of RBC folate and the risk of DN was observed after full adjustment for all the confounding variables (odds ratio: 1.38, 95% confidence interval: 1.27–1.49, P < 0.001). Similar patterns of association were observed for subgroup analysis (all P values for interaction > 0.05). In addition, curve fitting after adjusting for all the confounding variables demonstrated that there was a linear relationship between RBC folate and DN (P for non-linearity = 0.147). Increased RBC folate levels were linked to a higher risk of DN in type 2 diabetes. RBC folate should be considered as a crucial indicator for folate status in DN.

Folic acid supplementation during fattening period affects growth and nutritional metabolism in Japanese Black beef cattle

The folate requirements for beef cattle have not been established. Therefore, we investigated whether rumen-unprotected folic acid supplementation during the fattening period affects carcass traits and nutritional metabolism in Japanese Black beef cattle. Eighteen Beef cattle aged 16 months were divided into three groups: control, low folic acid supplementation (0.43 g DM/day), and high folic acid supplementation (0.86 g DM/day). Treatment was administered for 12 months. Folic acid supplementation dose-dependently increased serum folate levels, suggesting that supplemental folic acid can be absorbed into the body. Folic acid supplementation dose-dependently decreased serum vitamin B12 levels, while plasma total homocysteine and methylmalonic acid levels—markers for deficiency of folate and/or vitamin B12—were unaffected. Thus, the treatment did not clearly affect the nutritional status of these vitamins. Supplementation increased body weight, with no negative effects on other carcass traits. The levels of insulin-like growth factor 1, retinol, albumin, and some amino acids in serum or plasma were affected by supplementation. These results suggest that rumen-unprotected folic acid supplementation during the fattening period could increase the body weight of Japanese Black beef cattle and the mechanism of action may be related to growth-related hormones and/or the metabolism of some nutrients, including folate.

Vitamin B12 is correlated with insulin resistance and metabolism disorder markers in women with recurrent pregnancy loss

ObjectivesRecurrent pregnancy loss (RPL) seriously affects women's reproductive and mental health, and the incidence has increased in recent years. Insulin resistance (IR) acts as a significant contributing factor to RPL. Studies suggest that vitamin B12, folate intake, and homocysteine are correlated with IR, but the exact nature remains controversial and requires further investigation. In this study, we aimed to assess the levels and correlations between vitamin B12-folate-homocysteine and insulin resistance in RPL patients. Study design73 control subjects and 256 RPL patients (144 RPL patients without IR and 112 RPL patients with IR) were included in this observational retrospective cross-sectional study. The differences in vitamin B12, folate, and homocysteine levels between RPL patients with and without IR were analyzed using a Student's t-test. Pearson correlations were utilized to examine the correlation between vitamin B12-folate-homocysteine and glucose and lipid metabolism parameters. Multivariable linear regressions were used to assess the independent correlation of each factor with HOMA-IR. ResultsCompared to the control subjects, RPL patients exhibited lower vitamin B12 (p < 0.001) and folate (p < 0.001), and higher homocysteine (p = 0.001). RPL patients with IR described decreases in vitamin B12 (p = 0.003) and folate (p = 0.028), and increases in homocysteine (p = 0.033) as RPL patients without IR. Vitamin B12 in RPL patients was significantly negatively correlated with homocysteine (r = −0.348, p < 0.001), HOMA-IR (r = −0.214, p < 0.001), BMI (r = −0.160, p = 0.017), TG (r = −0.148, p = 0.039) and CHO (r = −0.149, p = 0.038) and positively correlated with folate (r = 0.217, p < 0.001). In multivariable linear regressions, after adjusting for age, strong correlations were observed between vitamin B12 (β = −0.197, p = 0.010), BMI (β = 0.466, p < 0.001), and HOMA-IR in RPL patients. ConclusionVitamin B12 is significantly correlated with IR in RPL patients. Circulating vitamin B12-folate-homocysteine metabolism could be a window of the pathological process of IR, obesity, and lipid metabolism disorders in RPL patients.

Delving into diversity: exploring different risk factors of premature greying of hair

Dear Madam, Hair is said to grey prematurely when a minimum of five grey hairs occur before the age of 20 in Caucasians, 25 in Asians and 30 in Africans1. Some authors propose using 25 years as a cut-off for people in the South Asian subcontinent. Also, there's no universal grading system for premature greying of hair (PGH). This letter addresses the various evolving risk factors for PGH in young adults worldwide. PGH may be familial or genetically influenced, traveling in an Autosomal Dominant pattern. A positive family history, in particular the paternal history is the most powerful risk factor2. PGH is also linked to nutritional deficiencies including vitamins (especially B12) and minerals. For example in one study, significantly lower levels of serum calcium, ferritin, vitamin B12, and high HDL were observed in patients3. T3 and T4 act on hair follicles to cause melanogenesis and their deficiency is therefore associated with PGH, alopecia, and changes in hair morphology. Another study found notably reduced levels of copper in cases (PGH) as compared to the control group. This study, however, did not observe lower levels of zinc or iron among the affected population. A separate case-control study concerning the association of epidemiological and biochemical factors with PGH reported that a significantly higher percentage of individuals with premature greying had atopic diathesis, led sedentary lifestyles, had family histories of the condition, smoked, and had reported higher levels of perceived stress compared to controls. Though, interestingly enough, regular application of hair oil seemed to confer a safeguarding effect against premature greying. Upon further review of the literature, it became apparent that both BMI and exposure to sunlight emerged as substantial predictors of PGH. Despite the prescription of various vitamins and minerals like biotin, calcium pantothenate, zinc, copper, and selenium (all of which have been recognized as risk factors), the outcomes have been disappointing. Calcium pantothenate is frequently recommended for premature greying of hair (PGH)4. This highlights an existing knowledge gap concerning the precise causative risk factors, necessitating further investigation for a comprehensive understanding and improved management of individuals experiencing premature greying of hair.

Effect of fasting-induced headache on calcitonin gene related peptide (CGRP) and other clinical biomarkers on the first day of Ramadan: Sub-analysis from a randomized open label clinical trial

BackgroundFasting-induced headaches (FIHs) have been shown to occur on the first day of Ramadan and clearly decline thereafter. Despite the wealth of knowledge about different types of headaches (e.g., migraine-, cluster-, and tension-type headaches), research on the mechanism underlying FIHs, as well as their treatment, remains scarce. Our study aimed to investigate any association between FIHs during the first day of Ramadan and potential headache-related biomarkers, including fasting blood glucose (FBG), C-reactive protein (CRP), magnesium, vitamin B9, vitamin B12, homocysteine, and calcitonin gene related peptide (CGRP), and to assess whether a prophylactic use of paracetamol may influence these biomarkers.MethodsAs part of a randomized, open-label clinical trial that evaluated the effect of paracetamol as a prophylactic therapy for FIH, blood samples from stratified subjects in the prophylaxis and control groups were withdrawn while fasting after the 1st dose of paracetamol (in the prophylaxis group) and prior to reporting headache occurrence.ResultsPlasma and serum were separated for 61 subjects; 31 and 30 subjects from the prophylaxis and control groups, respectively. Overall, no significant differences were found in the levels of FBG, CRP, magnesium, vitamin B9, and vitamin B12 in headache-suffering subjects compared to those without headache despite the use of paracetamol for prophylaxis. Homocysteine, however, was significantly reduced in all subjects who experienced FIH compared to those without headache (median 6.9 [1.6] vs. 7.7 [2.7] umol/L; p = 0.041). On the contrary, when the CGRP was measured using immunoassay, it was found to be significantly elevated in all headache-suffering subjects compared to those without headache (median 126.1 [17.7] vs. 105.8 [19.6] pg/mL; p ≤ 0.0001). This difference was maintained upon comparing the headache to non-headache subjects in both the prophylaxis (median 121.5 [15.4] vs. 105.8 [9.4] pg/mL; p < 0.01) and control groups (median 128.5 [28.3] vs. 105.8 [23.8] pg/mL; p < 0.01). Additionally, an elevated CGRP level was found to increase the odds of having a FIH [OR = 1.32; 95%CI 1.06–1.22].ConclusionsOur findings revealed the role of CGRP in FIHs for the first time and suggest further investigation in signaling pathways downstream CGRP receptors. Furthermore, the modulation CGRP or CGRP receptors could have a clinical application in the prevention of FIHs.Trial registrationThis study was registered with the Saudi Food and Drug Authority in the Saudi Clinical Trials Registry (SCTR; No. 22122102).

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

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

Association between vitamin B6 levels and rheumatoid arthritis: a two-sample Mendelian randomization study.

Micronutrients play a crucial role in rheumatoid arthritis (RA). Changes in micronutrient levels in RA patients can lead to the worsening of their condition. Though significant correlations between RA and micronutrients have been found in earlier observational studies, their underlying causal relationship is still unknown. This study aimed to elucidate the causal genetic relationships between 15 micronutrients (copper, zinc, magnesium, vitamins A, C, E, D, B6, B12, folate, carotene, iron, selenium, calcium, potassium) and RA. The exposure factors and outcome data used in the two-sample Mendelian randomization (MR) were derived from publicly available summary statistics data of European populations. The GWAS data for exposure factors were obtained from the OpenGWAS database. For the outcome data of RA, we utilized data from the FinnGen database. We used the MR principle to remove confounding factors and conducted MR analyses using five methods: inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode, with IVW as the primary method. Then, we identified micronutrients related to RA and performed MR analyses on these elements, including heterogeneity analysis and pleiotropy analysis such as MR-Egger intercept, MR-PRESSO method, and "leave-one-out" analysis. Finally, we conducted multivariable MR analyses and performed sensitivity analyses again. The IVW analysis revealed a relationship between vitamin B6 and RA (p: 0.029, OR: 1.766, and 95% CI: 1.062-2.938). Sensitivity analysis confirmed the validity and reliability of this result. This study revealed a causal relationship between vitamin B6 and RA, with vitamin B6 being identified as a risk factor for RA. This finding could contribute to the diagnosis and supplementary treatment of RA patients, providing a reference for subsequent basic research and developing new drugs.

Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels.

One-carbon metabolism is a critical pathway for epigenetic mechanisms. Circulating biomarkers of one-carbon metabolism have been associated with changes in nuclear DNA methylation levels in individuals affected by age-related diseases. More and more studies are showing that even mitochondrial DNA (mtDNA) could be methylated. In particular, methylation of the mitochondrial displacement (D-loop) region modulates the gene expression and replication of mtDNA and, when altered, can contribute to the development of human illnesses. However, no study until now has demonstrated an association between circulating biomarkers of one-carbon metabolism and D-loop methylation levels. In the study presented herein, we searched for associations between circulating one-carbon metabolism biomarkers, including folate, homocysteine, and vitamin B12, and the methylation levels of the D-loop region in DNA obtained from the peripheral blood of 94 elderly voluntary subjects. We observed a positive correlation between D-loop methylation and vitamin B12 (r = 0.21; p = 0.03), while no significant correlation was observed with folate (r = 0.02; p = 0.80) or homocysteine levels (r = 0.02; p = 0.82). Moreover, D-loop methylation was increased in individuals with high vitamin B12 levels compared to those with normal vitamin B12 levels (p = 0.04). This is the first study suggesting an association between vitamin B12 circulating levels and mtDNA methylation in human subjects. Given the potential implications of altered one-carbon metabolism and mitochondrial epigenetics in human diseases, a deeper understanding of their interaction could inspire novel interventions with beneficial effects for human health.

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

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

6556 Does Autoimmune Hashimoto’s Hypothyroidism Mask the Diagnosis of Ehlers-Danlos-Syndrome?

Abstract Disclosure: S. Azmat: None. U. Rafat: None. J.L. Gilden: None. Does Autoimmune Hashimoto’s Hypothyroidism Mask the Diagnosis of Ehlers-Danlos Syndrome? Background: Hypothyroidism is well-known to be associated with muscle weakness and fatigue. There are other etiologies for decreased muscle tone such as Ehlers-Danlos syndrome (EDS) which is group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility and tissue fragility. Other rheumatological and cardiac conditions associated with this syndrome can pose diagnostic challenges. We present case of 32-year-old female presenting with facial muscle weakness and newly diagnosed Hashimoto’s hypothyroidism. We highlight importance of keeping EDS as another differential in patients with muscle weakness allowing for accurate, prompt diagnosis and treatment to be done in timely manner. Case Description: A 32-year-old female professional musician was referred to Endocrine for mouth muscles weakness and decreasing ability to play her French Horn wind instrument with vocal dystonia and the question of whether these were symptoms of hypothyroidism. She was noted to have mild thyroid enlargement and abnormal thyroid function tests with positive thyroid antibodies. Initial TSH was 7.506 uIU/mL(0.55-4.78), free T4 0.9 ng/dL (0.76-1.46), peroxidase antibody = 96,061U/mL (0-60) and thyroglobulin of 134.9 U/mL (0-60). She also reported low energy, intermittent difficulty swallowing and decreased muscle strength. There was no prior personal and family history of hypo/hyperthyroidism or any other disorders. VS were normal, physical exam showe d no thyromegaly, reflexes revealed objective decrease but normal muscle strength. The skin was noted to be hyperextensible with passive hyperextension of fifth metacarpophalangeal joint beyond 90 degrees, thumb to flexor aspect of forearm and elbows bilaterally with positive Beighton criteria for EDS. She later admitted to intermittent palpitations and easy bruising. Subsequent lab tests were negative ANA, anti-mitochondrial, PCEL and striated muscles antibodies. Additionally she had normal IGA, PTH, AM cortisol- ACTH, vitamin B12 levels with negative 21 hydroxylases antibodies and celiac titers. She was started on levothyroxine 25 mcg and recommended for Cardiology evaluation and genetic testing. Physiotherapy was started. Upon six months follow-up she clinically felt better with improved muscle strength, swallowing and energy level. Repeat lab testing showed improved TSH of 2.67 uIU/mL(0.55-4.78) with free T4 of 1.0 ng/dL (0.76-1.46). Conclusion: This case demonstrates that although muscle weakness can be symptom of hypothyroidism one must evaluate all patients for other possible causes. We highlight importance of keeping EDS as a differential especially in female patients with muscle weakness. Though history and physical exam is crucial allowing for prompt diagnosis and treatment for other conditions. Presentation: 6/1/2024