Gender Disparities in Health Biomarkers, Lifestyle Patterns, and Nutritional Status among Bank Staff: A Cross-Sectional Study.

Background and Objectives: Despite the importance of nutritional status and a healthy lifestyle in shaping overall well-being, little is known about examining gender-specific differences and trends in health, lifestyle, and nutritional status. The present study aimed to evaluate blood levels of micronutrients, homocysteine, and CoQ10, as well as physical activity (PA) levels and sedentary behavior, among a cohort of Austrian bank staff, with a particular focus on identifying gender differences as well as gender-specific nutritional deficiencies compared to the reference ranges. Materials and Methods: Following a cross-sectional study design, 123 Austrian bank staff (mean age: 43 years; 51% females) participated in this study. Blood samples were collected to evaluate participants' micronutrient status and serum levels of homocysteine and CoQ10. Whole-blood values of macronutrients were compared to gender-specific reference ranges and categorized into three groups: below, within, or over the range. The WHO's Global Physical Activity Questionnaire was used to assess PA levels and sedentary behaviors. Results: No significant difference between males and females was found for diet types, PA levels, sedentary time, homocysteine levels, or CoQ10 values (p > 0.05). A high PA level was reported by 64% of males and 58% of females. 71% of females and 56% of males were found to have a vitamin D deficiency. 63-98% of females and 72-97% of males showed normal blood levels for the remaining micronutrients, including potassium, calcium, magnesium, copper, iron, zinc, selenium, manganese, molybdenum, B6, B9, and B12. Conclusions: The findings highlight the necessity of implementing tailored strategies to foster healthy lifestyle behaviors, thereby enhancing the overall state of health, particularly in the context of occupational health.

Assessment of vitamin B12 levels and cardiovascular risk factors in metformin- and non-metformin-treated type 2 diabetic patients.

Oxidative stress enhances cardiovascular risk. Metformin decreases intestinal absorption of vitamin B12. Our objective was the evaluation of type 2 diabetics focusing on differences due to their treatment. A prospective study on 224 type 2 diabetics was realized between 2015-2018 in Targu Mures, Romania, divided into 2 subgroups (metformin vs. other therapy - 2nd/3rd generation sulfonylureas, insulin, dietary regimen -, followed for at least one year) and non-diabetic controls (n=25) for oxidative stress level comparison. Serum homocysteine (HC), vitamin B12 were determined by chemiluminescence (Immulite One). Lipid peroxidation was assessed by serum malondialdehyde (MDA) measurement (HPLC). Biochemical tests, minerals, cystatin C, high-sensitivity C reactive protein (hs-CRP) were measured on Konelab20Xti, glycated hemoglobin on Nycocard Reader. GraphPad InStat-3 was used for statistics. Negative correlation occured between serum vitamin B12 and HC, this vitamin's level was significantly lower and serum zinc was significantly higher in patients on metformin. Hyperhomocysteinemia was present in 87% of the subjects, 46% had zinc deficiency and 41% elevated hs-CRP. Serum cystatin C showed positive correlation with creatinine. Serum MDA was significantly higher in diabetics compared to control patients. Elevated hs-CRP and homocysteine represent raised cardiovascular risk. Intense oxidative stress, vitamin, mineral deficiencies are frequent in diabetic subjects.

[Modern approaches to developing a system of valid methods for monitoring individual health and maintaining active longevity]. / Sovremennye podkhody k razrabotke sistemy validnykh metodov monitoringa individual'nogo zdorov'ya i podderzhaniya aktivnogo dolgoletiya.

Life expectancy In Russia in 2023, according to preliminary data, exceeded 73 years, returning to the pre-pandemic level. The increase in life expectancy is associated both with an improvement in the quality of medical care In Russia and with a more responsible attitude towards the health of citizens, which is confirmed by an improvement in the quality of nutrition, a decrease in alcohol consumption and an increase in the number of people involved in sports. At the same time, there are many signs of aging, both cellular and molecular, some of the main ones are genome stability, telomere shortening, epigenetic alterations, impaired proteostasis and nutrient recognition, mitochondrial dysfunction, depletion of the stem cell pool and changes in intercellular interactions, extracellular matrix rigidity, as well as retrotransposon activation and chronic inflammation. For these reasons, in modern healthcare, the tasks of preventing premature aging and treating age-related diseases are becoming priorities. MATERIAL AND METHODS: In total, at the first stage of work (in 2023), we examined 80 people, whose average age was 59.6±0.7 years. When analyzing and assessing data, the study adopted a division into age groups (WHO). The following indicators were studied: HbA1, fructosamine, HDL cholesterol, LDL cholesterol, insulin, homocysteine, C-peptide, TSH, free T4, prolactin, total testosterone, cortisol, arginine, asymmetric dimethylarginine, leptin, TNF-a, ferritin, interleukin 1 and 6, telomere length, creatinine, uric acid and urea. RESULTS: As a result of the study, it was revealed that the aging process of the body affects many indicators, while the main markers that changed in men aged 18 to 44 years were total testosterone, leptin and telomere length; aged 44 to 60 years - HbA1, fructosamine, HDL cholesterol, homocysteine, C-peptide, total testosterone, leptin and telomere length; from 60 to 75 years - fructosamine, HDL cholesterol and telomere length and for 75-90 years - HbA1, HDL cholesterol, insulin, total testosterone, leptin and telomere length, interleukin 6 and uric acid. In women aged 18 to 44 years, only an increase in leptin was observed against the background of shortening telomere length; at the age of 44 to 60 years, the main markers that changed were total testosterone, leptin and telomere length; for the age group 60-75 years - indicators of HbA1, homocysteine, C-peptide, prolactin, total testosterone and leptin, interleukin 6 and uric acid, telomere length was shorter by only 2%; in the age group of 75-90 years, the main markers that changed were insulin, total testosterone, leptin, interleukin 6, while the indicators of uric acid, urea and telomere length differed from the reference values by 2-4%. Shortening of telomere length in all age groups, both men and women, indicates the presence of signs of premature aging. In an individual analysis, data were obtained on a more dramatic shortening of telomeres in 16 subjects in the presence of impaired glucose tolerance and insulin secretion, especially in comparison with healthy subjects, which was confirmed by the data of glycated hemoglobin (HbA1c), while, with shortening of telomere length, the HbA1 indicator was significantly higher (6.8±0.5) than in individuals with long telomeres and no chronic pathology (5.1±0.4). CONCLUSION: A system of highly valid methods and panels of markers has been developed that indicate the presence of aging processes, taking into account gender and age characteristics, which can be used to identify premature aging processes, monitor individual health and maintain active longevity, as well as for the prevention of age-associated diseases.

Assessment of MTR Rs1805087 SNP as Possible Modifier of Sickle Cell Disease Severity in a Nigerian Population.

BACKGROUND: Sickle cell disease is the commonest genetic disorder in Nigeria, affecting 2-3% of an estimated population of 160 million people. The role of genetic mutations in folate cycle genes, and the variable phenotypic expressions constituting disease severity, needs to be critically examined. OBJECTIVE: This study was carried out to establish the pattern of methionine synthase gene mutations (rs1805087 SNP), and its possible association with disease severity in adults with sickle cell anaemia in Lagos, Nigeria. METHODOLOGY: This is a cross-sectional study of seventy (70) subjects with sickle cell disease (HbSS) matched for age and gender with known apparently healthy haemoglobin genotype AA (HbAA) subjects, as cases and controls respectively. Structured questionnaires were used to obtain demographic, clinical and other phenotypic data needed to compute disease severity. Pattern of MTR A2756G gene mutation and homocysteine assay (Hcy) were assessed by Polymerase Chain Reaction and Enzyme- linked Immunosorbent Assay respectively. Full blood count analysis of participants was done using the KX-21 Automated Analyzer (Sysmex Corporation, Japan). RESULTS: The mutant genotypes MTR 2756 AG/GG were recorded in 46.4% (n =55) of subjects with disease severity score >7. Elevated plasma homocysteine (HHcy) was significantly associated with disease severity among HbSS subjects (OR=17.2, CI: 3.490-86.079; p=0.0001). Conversely, no significant association was observed with the mutant genotypes MTR 2756 AG/GG and disease severity (p>0.05). CONCLUSION: While HHcy is significantly associated with phenotypic expression of HbSS, the MTR 2756 SNPs did not appear to independently influence homocysteine level or disease severity in HbSS subjects.

CONTEXTE: La drépanocytose est la maladie génétique la plus répandue au Nigeria, affectant 2 à 3 % d'une population estimée à 160 millions de personnes. Le rôle des mutations génétiques dans les gènes du cycle du folate, et les expressions phénotypiques variables constituant la gravité de la maladie, doivent être examinés de façon critique. OBJECTIF: Cette étude a été menée pour établir le schéma des mutations du gène de la méthionine synthase (rs1805087 SNP), et son association possible avec la gravité de la maladie chez les adultes atteints de drépanocytose à Lagos, au Nigeria. MÉTHODOLOGIE: Il s'agit d'une étude transversale de soixantedix (70) sujets atteints de drépanocytose (HbSS) appariés pour l'âge et le sexe avec des sujets connus apparemment sains de génotype d'hémoglobine AA (HbAA), comme cas et contrôles respectivement. Des questionnaires structurés ont été utilisés pour obtenir des données démographiques, cliniques et autres données phénotypiques nécessaires au calcul de la gravité de la maladie. Le profil de la mutation du gène MTR A2756G et le dosage de l'homocystéine (Hcy) ont été évalués respectivement par réaction en chaîne par polymérase et par test immunologique enzymatique. L'analyse de la formule sanguine complète des participants a été effectuée à l'aide de l'analyseur automatisé KX-21 (Sysmex Corporation, Japon). RÉSULTATS: Les génotypes mutants MTR 2756 AG/GG ont été enregistrés chez 46,4 % (n =55) des sujets présentant un score de gravité de la maladie > 7. L'homocystéine plasmatique élevée (HHcy) était significativement associée à la gravité de la maladie chez les sujets HbSS (OR=17,2, CI : 3,490­86,079 ; p=0,0001). À l'inverse, aucune association significative n'a été observée entre les génotypes mutants MTR 2756 AG/GG et la gravité de la maladie (p>0,05). CONCLUSION: Alors que l'HHcy est significativement associée à l'expression phénotypique de l'HbSS, les SNP MTR 2756 ne semblent pas influencer indépendamment le niveau d'homocystéine ou la gravité de la maladie chez les sujets HbSS.

An assessment of serum vitamin B12 and folate in patients with Crohn's disease.

Crohn's disease is a chronic inflammatory condition that can involve any area in the gastrointestinal tract often involving the distal ileum where vitamin B12 is specifically absorbed. The aim of this study was to ascertain serum vitamin B12 and folate levels in order to investigate the correlation among these vitamin levels and disease activation, localization, duration and age at the onset of the disease. Study population included 103 patients with Crohn's disease and a healthy control group of 114 individuals. C-reactive protein, vitamin B12, folate levels were studied along with hemogram analyses. The results were evaluated in statistical comparisons. While serum vitamin B12 levels and serum folate levels were 161.9 ±â€…63.2(73-496) pg/mL and 4.9 ±â€…1.4(1.2-9.4) ng/mL in the Crohn's patient group respectively, they were 321.7 ±â€…126.3(85-680) pg/mL and 7.6 ±â€…3.8(3-25.1) ng/mL in the control group respectively. Vitamin B12 and folate levels were distinctly lower in patients with Chron's disease than those of the control group (P < .001). The intragroup analysis of the patient group revealed that low vitamin B12 levels were significantly lower in the moderate group classified according to the Crohn's Disease Activity Index (P < .001), along with those in the L1 group with terminal/distal ileal involvement (P < .001). Vitamin B12 and folate deficiencies are quite prevalent in patients with Crohn's disease while this condition can lead to various complications and they prove to be important risk factors associated especially with thrombosis and its complications. Patients must be regularly followed-up for vitamin B12 and folate levels to supplement them where needed.

A Retrospective Study on Clinical Assessment of Cognitive Impairment in a Swedish Cohort: Is There Inequality Between Natives and Foreign-Born?

BACKGROUND: People with a migration background are underrepresented in dementia research and disfavored in assessment and treatment, and many foreign-born individuals with dementia remain undiagnosed. OBJECTIVE: The aim of this study was to examine whether there is inequality in the clinical assessment of dementia between native and foreign-born individuals in Sweden. METHODS: Information was gathered retrospectively from a cohort of 91 native and 36 foreign-born patients attending four memory clinics in Skåne, Sweden. Data included information on cognitive test results, cerebrospinal fluid biomarkers, scores at structural imaging scales of global cortical atrophy (GCA), medial temporal lobe atrophy (MTA) and the Fazekas scale, laboratory measures of thyroid-stimulating hormone, calcium, albumin, homocysteine, hemoglobin, cobalamin (vitamin B12), and folate (vitamin B9), contact with health care, and treatment. RESULTS: Foreign-born patients had lower educational level and scored lower on Mini-Mental State Examination and Clock Drawing Test (p < 0.001-0.011). Relatives initiated contact with health care to a higher extent in the foreign-born group (p = 0.031). Foreign-born patients had less white matter lesions (p = 0.018). Additionally, Alzheimer's disease (AD) biomarkers were significantly less used in foreign-born patients to support an AD diagnosis (p = 0.001). No significant differences were found for scores on GCA and MTA, laboratory measures, or initiated treatment. CONCLUSION: Although native and foreign-born patients were predominantly homogenous regarding examined variables, differences in the diagnostic process and underlying biological correlates of dementia exist and need to be further investigated in a larger sample.

Commutability assessment of reference materials for homocysteine.

OBJECTIVES: Commutability of reference materials is essential for ensuring the traceability of patient measurement results and the technical basis for the use of reference materials. Commutability is only relevant for matrixed reference material; it is a prerequisite for the accuracy and authenticity of calibration methods. In this study, we evaluated the commutability of reference materials for homocysteine. METHODS: Five conventional measurement methods were applied to simultaneously measure 30 serum samples and seven homocysteine reference materials from the National Institute of Standards and Technology and the National Institute of Metrology. Liquid chromatography tandem-mass spectrometry was used as a reference method. Two methods were used to evaluate the commutability of the seven reference materials according to the Clinical and Laboratory Standards Institute EP30-A and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) commutability assessment document. RESULTS: Among 35 combinations of the five conventional methods and seven reference materials, after evaluation in accordance with the EP30-A, the seven reference materials passed the commutability assessment, and 34 combinations were commutable. According to the IFCC, the commutability evaluation of 28 combinations was conclusive (commutable or non-commutable), while results for the remaining seven combinations could not be determined. CONCLUSIONS: The homocysteine reference materials showed good commutability. The sensitivity of the measurement procedure, measurement deviation and uncertainty, and differences in the "measurand" selected by different methods may affect the evaluation results. Additionally, different judgment standards for different methods may explain the observed variations in evaluation results.

Assessment of asymmetric dimethylarginine and homocysteine in epileptic children receiving antiepileptic drugs.

BACKGROUND: Epilepsy is a neurological disease that requires long-term antiepileptic drugs (AEDs). The old generation of AEDs may affect serum homocysteine and asymmetric dimethylarginine (ADMA) and disturb lipid levels. The aim of the study was to evaluate serum ADMA, homocysteine, lipid profile, and carotid intima-media thickness (CIMT) in epileptic children. METHODS: This study was implemented on 159 epileptic children who were subdivided into 3 subgroups, with 53 receiving sodium valproate, 53 receiving levetiracetam, and 53 receiving polytherapy, for over 6 months and 53 healthy children. RESULTS: Low-density lipoprotein, triglycerides, and cholesterol levels were increased in epileptic children (p < 0.001), which were higher in those receiving multidrug followed by a valproate receiver. While high-density lipoprotein was lower in those receiving multidrug more than those receiving valproate. ADMA and homocysteine levels increased in epileptic patients than in controls (p < 0.001). Higher ADMA was also observed in the multidrug receiver (5.78 ± 0.62), followed by the levetiracetam group (5.56 ± 0.61). Homocysteine levels were significantly higher in multidrug and valproate-treated children than those treated with levetiracetam. CIMT was significantly higher in multidrug and valproate-treated patients (p < 0.001). CONCLUSIONS: Long-term use of AEDs, especially old-generation polytherapy, can elevate lipid profiles, homocysteine, ADMA levels, and carotid intima-media thickness compared to the minimal effect of new AEDs. IMPACT: The long-term use of antiepileptic drugs, especially old-generation polytherapy, can increase lipid profiles, homocysteine levels, ADMA, and carotid intima thickness compared to the minimal effect of new antiepileptic generation. A routine follow-up of these markers and a lifestyle modification are recommended to avoid cerebrovascular events as much as possible.

Dietary Intake of Folate and Assessment of the Folate Deficiency Prevalence in Slovenia Using Serum Biomarkers.

Folate deficiency is associated with various health issues, including anemia, cardiovascular disease, and birth defects. Low folate intake and suboptimal folate status were found in several countries; however, this topic has not yet been investigated in Slovenia. Dietary folate intake and serum folate status were investigated through the nationally representative food consumption study SI.Menu/Nutrihealth. Folate intake was estimated using a sample of N = 1248 subjects aged 10-74 years, stratified in three age groups (adolescents, adults, elderly population), through two 24 h-dietary recalls and food propensity questionnaire. Data on serum folate and homocysteine was available for 280 participants. Very low folate intake (<300 µg/day) was observed in 59% of adolescents, 58% of adults and 68% of elderlies, and only about 12% achieved the WHO recommended level of 400 µg/day. Major dietary contributors were vegetables and fruit, and cereal products. Living environment, education, employment status and BMI were linked with low folate intake in adults; BMI, and sex in adolescents; and sex in elderlies. Considering low serum folate (<7 nmol/L) and high serum homocysteine (>15 nmol/L), folate deficiency was found in 7.6 and 10.5% in adults and elderlies, respectively. Additional public health strategies should be employed to promote the consumption of folate-rich foods. With current folate intakes, supplementation with folic acid is relevant especially in specific vulnerable populations, particularly in women planning and during pregnancy.

A quantitative method for the assessment of homocysteine thiolactonase enzyme activity.

This assay elucidates an accurate, simple, and precise protocol to quantify the activity of homocysteine thiolactonase (HTase). To establish HTase activity, the enzyme samples were incubated with a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer, which contained suitable concentrations of the homocysteine thiolactone as a substrate. To stop the enzyme's reaction, the CUPRAC reagent (Cu(Nc)22+) was added after a suitable incubation time. The reduction of Cu(II)-neocuproine complex (Cu(Nc)22+) to highly coloured Cu(I)-neocuproine complex (Cu(Nc)2+) by the produced homocysteine was quantified spectrophotometrically at 450 nm (CUPRAC method). The increase in the absorbance of the coloured Cu(I)-neocuproine complex (Cu(Nc)2+) was correlated directly to the activity of HTase. ANOVA analysis was utilised to validate the new method against homocysteine thiolactonase activity using the H+ ions liberating method in matched samples. In conclusion, according to the obtained correlation coefficient (0.9995) from the comparison of the current method with the reference method, the current method is effective in assay HTase activity with high reliability.

Assessment of Vitamin B12 Deficiency and Risk Factors in Healthy Infants.

OBJECTIVE: To study vitamin B12 deficiency in apparently healthy infants and their mothers and assess the risk factors. METHODS: A hospital-based, cross-sectional, observational study was conducted from July 2016 through December 2017. Consecutive healthy and normally developing infants were enrolled. Red blood cell folate, plasma vitamin B12, homocysteine and methylmalonic acid levels of mothers and infants were assessed. RESULTS: Seventy-four healthy infants were enrolled. Male-to-female ratio was 1.5:1. Anemia in 66.2% (n = 49), low plasma B12 in 17.6% (n = 13), hyperhomocysteinemia in 48.6% (n = 36), plasma methylmalonic acid in 100% (n = 74) and 'confirmed' B12 deficiency in 38% (n = 28) infants were noted. The proportion of hyperhomocysteinemia increased to 75.7% (n = 56) infants using a lower cut-off of >10 µmol/L. In mothers, low B12 in 19%, hyperhomocysteinemia in 57% and elevated plasma methylmalonic acid in 100% were noted. Median plasma B12 level was 314 pg/ml (IQR 221-421), median plasma homocysteine 15.4 µmol/L (IQR 11.3-21.7) and median plasma methylmalonic acid was 8.28 µmol/L (IQR 4.4-13.1) in mothers. Folate deficiency was noted in 9.4% infants and 12% of mothers. Overall, 63.5% mothers were vegetarian and, 64% of the mothers of infants with confirmed vitamin B12 deficiency were pure vegetarians. Odds of developing vitamin B12 deficiency increased by more than 5 times in those whose mothers' serum vitamin B12 levels were low as compared to normal maternal vitamin B12 levels (OR 5.42; 95% CI: 1.96-16.6; p 0.002). CONCLUSIONS: There is a high prevalence of vitamin B12 deficiency in infants and their mothers. There is urgent need to supplement our population with vitamin B12.

CO2 Capture in Ionic Liquids Based on Amino Acid Anions With Protic Side Chains: a Computational Assessment of Kinetically Efficient Reaction Mechanisms.

Absorption and capture of CO2 directly from sources represents one of the major tools to reduce its emission in the troposphere. One of the possibilities is to incorporate CO2 inside a liquid exploiting its propensity to react with amino groups to yield carbamic acid or carbamates. A particular class of ionic liquids, based on amino acids, appear to represent a possible efficient medium for CO2 capture because, at difference with current industrial setups, they have the appeal of a biocompatible and environmentally benign solution. We have investigated, by means of highly accurate computations, the feasibility of the reaction that incorporates CO2 in an amino acid anion with a protic side chain and ultimately transforms it into a carbamate derivative. Through an extensive exploration of the possible reaction mechanisms, we have found that different prototypes of amino acid anions present barrierless reaction mechanisms toward CO2 absorption.

Assessment of Reference Range of Serum Homocysteine from the Post-therapy Values of Cobalamin and Folate Deficiency Patients.

OBJECTIVES: Ideally, the upper reference limit of plasma or serum homocysteine (Hcy) is to be defined from the studies done on individuals with normal cobalamin and folate status. It is difficult to separate the truly healthy (Cobalamin/Folate Replete) individuals from the randomly selected, apparently healthy individuals who are sub-clinically deficient of cobalamin/folate. The present study was aimed at defining the reference values for the serum homocysteine from individuals with normalized cobalamin and folate status. METHODS: In our study, 215 patients with cobalamin, folic acid deficiency were treated accordingly till complete restoration of clinical and laboratory abnormalities. The post-therapy serum Hcy values were used as reference values. RESULTS: Post-therapy serum Hcy values 12.56 µmol/L (95th percentile), 11.4 µmol/L (85th percentile), 9.8 µmol/L (67th percentile) were seen. The hyperhomocysteinemia was more visible (17.3% gain in prevalence) in the same patient group if interpreted using the post-therapy Hcy value (11.4 µmol/L) as the cut-off. There was no difference between the genders and age groups in the pre or post-therapy Hcy values. CONCLUSIONS: The benefit of the gain in prevalence of disease or the increase in the sensitivity of the test, though small, gets magnified in common diseases and in populous countries. Selection of the individuals is as important as the method or the reagent used in the method when a particular parameter is studied. Repleting the vitamin stores in the confirmed vitamin-deficient patients is more appropriate and easily feasible, since anyway they require treatment, than doing the same on the apparently healthy people. The data thus obtained can be better used as the reference value, for a more meaningful interpretation. The reference range can in turn be used to identify the sub-clinically deficient but asymptomatic people and managed accordingly.

PON1 status and homocysteine levels as potential biomarkers for cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death. The mainly risks factors for CVD are diabetes, hypertension and high levels of homocysteine (Hcys), among others. Paraoxonase 1 (PON1) has been proposed as an antiatherogenic target for its ability to hydrolyzing oxi-Low-Density-Lipoproteins (LDL) and Hcys-thiolactone. Thus, the aim of the present study was to evaluate the association of Hcys levels, and the activities and concentration of PON1, as well as vitamin B from the diet with a risk for CVD. METHODS: A case-control study was carry out in patients with cardiovascular diseases (CVD), Arterial hypertension, but not CVD (AH), and in healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, intake of vitamin B, Hcys, serum amyloid A (SAA), PON1 concentration, and PON1 activities (Arylesterase activity (ARE), Lactonase activity (LAC), and CMPA activity (CMPA)) were evaluated. RESULTS: The CVD group had the highest concentration of Hcys and SAA than in the AH and control groups (p < 0.01). ARE, LAC, and CMPA activities and PON1 concentration were lowest in the CVD group. A positive-independent association between Hcys levels and CVD was found (OR = 2.09; 95% CI: 1.69-2.56) and this increase when it was adjusted by age, BMI, ApoA1, vitamin B intake, SAA, and PON1 (OR = 14.41; 95% CI: 1.75-118.71). LAC and CMPA, as well as PON1 concentration, were inversely associated with CVD. CONCLUSION: LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD and their association could be modified by the intake of vitamin B.

Prevalence, characteristics, and costs of diagnosed homocystinuria, elevated homocysteine, and phenylketonuria in the United States: a retrospective claims-based comparison.

BACKGROUND: Classical homocystinuria (HCU), an inborn error of homocysteine metabolism, has previously been estimated to affect approximately 1 in 100,000-200,000 people in the United States (US). HCU is poorly detected by newborn screening, resulting in underestimates of its prevalence. This study compared characteristics, healthcare use and costs, and projected prevalence between patients with diagnosed HCU, elevated total homocysteine (tHcy), and diagnosed phenylketonuria (PKU). METHODS: Patients in the MarketScan® Research Databases were identified with strictly-defined HCU (> 2 diagnoses, including 1 ICD-10), broadly-defined HCU (> 1 ICD-10), elevated tHcy (> 20 µmol/L) without an HCU diagnosis, or > 1 ICD-9/ICD-10 PKU diagnosis during 1/1/2010-12/31/2016 (first qualifying claim = index). Demographics and healthcare utilization and costs per patient per month (PPPM) were compared between all cohorts, frequencies of comorbidities and medications were compared between HCU and elevated tHcy patients, and healthcare provider types were assessed among HCU patients. The prevalence of patients meeting each cohort definition was projected to the United States (US) population. RESULTS: Patients with strictly-defined (N = 2450) and broadly-defined (N = 6613) HCU, and with elevated tHcy (N = 2017), were significantly older than PKU patients (N = 5120) (57 vs. 56 vs. 53 vs. 18 years; p < 0.05). Vitamin D deficiency, hyperlipidemia, folic acid/B vitamins, and lipid-lowering medications, among others, were more common among diagnosed HCU patients vs. those with elevated tHcy (all p < 0.05). Rates of healthcare utilization were generally higher among HCU and elevated tHcy patients, compared to PKU, though total healthcare costs were similar between groups. Most HCU patients (~ 38%) received their index diagnosis from a primary care physician; very few (~ 1%) had any claim from a geneticist during their enrollment. The age-adjusted national prevalence of HCU was projected at 31,162 (95% CI: 30,411 - 31,913; ~ 1 in 10,000 of the US population) using the broad definition. CONCLUSIONS: The actual prevalence of HCU may be > 10 times prior estimates, at 1 in 10,000 in the US, and this study suggests that HCU is not being diagnosed until later in life. Improvements to newborn screening, detection in young children, and physician education regarding HCU among patients may be necessary to alleviate the burden of this genetic disease.

Assessment of folate and cobalamin concentrations in relation to their dependent intracellular metabolites in serum of pigs between 6 and 26 weeks of age.

Folate (vitamin B9) and cobalamin (vitamin B12) play an important role in amino acid metabolism, nucleic acid synthesis, and methyl group transfer. Two intracellular enzymes, methionine synthase and methylmalonyl-CoA mutase, are folate and/or cobalamin-dependent, respectively. At the cellular level, a lack of folate and cobalamin leads to accumulation of serum homocysteine (HCY) and a lack of cobalamin leads to increased methylmalonic acid (MMA) concentrations. Altered serum HCY and MMA concentrations can influence amino acid metabolism and nucleic acid synthesis in pigs. Therefore, we aimed to evaluate serum folate, cobalamin, HCY, and MMA concentrations in postweaning pigs between 6 and 26 weeks of age. Serum samples from 12 pigs collected at week 6, 7, 8, 9, 10, 14, 18, 22, and 26 as part of an unrelated study were analyzed. Serum folate (p < .0001), cobalamin (p = .0001), HCY (p < .0001), and MMA (p < .0001) concentrations differed significantly during the postweaning period between 6 and 26 weeks of age; with significantly higher serum HCY (at weeks 6 and 7 compared to weeks 9, 14, 18, 22, and 26) and MMA concentrations (at weeks 6, 7, and 8 compared to weeks 14, 18, 22, and 26) and an overall decrease of serum MMA concentrations from week 6 to week 14 in the pigs studied. This study suggests age-dependent changes in intracellular folate- and cobalamin-dependent metabolites (i.e., HCY and MMA) in pigs between 6 and 26 weeks of age, possibly reflecting decreased availability of intracellular folate and/or cobalamin for amino acid metabolism, nucleic acid synthesis, and methyl group transfer.

Assessment of cellular cobalamin metabolism in Gaucher disease.

BACKGROUND: Gaucher disease (GD) is a lysosomal disorder caused by biallelic pathogenic mutations in the GBA1 gene that encodes beta-glucosidase (GCase), and more rarely, by a deficiency in the GCase activator, saposin C. Clinically, GD manifests with heterogeneous multiorgan involvement mainly affecting hematological, hepatic and neurological axes. This disorder is divided into three types, based on the absence (type I) or presence and severity (types II and III) of involvement of the central nervous system. At the cellular level, deficiency of GBA1 disturbs lysosomal storage with buildup of glucocerebroside. The consequences of disturbed lysosomal metabolism on biochemical pathways that require lysosomal processing are unknown. Abnormal systemic markers of cobalamin (Cbl, B12) metabolism have been reported in patients with GD, suggesting impairments in lysosomal handling of Cbl or in its downstream utilization events. METHODS: Cultured skin fibroblasts from control humans (n = 3), from patients with GD types I (n = 1), II (n = 1) and III (n = 1) and an asymptomatic carrier of GD were examined for their GCase enzymatic activity and lysosomal compartment intactness. Control human and GD fibroblasts were cultured in growth medium with and without 500 nM hydroxocobalamin supplementation. Cellular cobalamin status was examined via determination of metabolomic markers in cell lysate (intracellular) and conditioned culture medium (extracellular). The presence of transcobalamin (TC) in whole cell lysates was examined by Western blot. RESULTS: Cultured skin fibroblasts from GD patients exhibited reduced GCase activity compared to healthy individuals and an asymptomatic carrier of GD, demonstrating a preserved disease phenotype in this cell type. The concentrations of total homocysteine (tHcy), methylmalonic acid (MMA), cysteine (Cys) and methionine (Met) in GD cells were comparable to control levels, except in one patient with GD III. The response of these metabolomic markers to supplementation with hydroxocobalamin (HOCbl) yielded variable results. The content of transcobalamin in whole cell lysates was comparable in control human and GD patients. CONCLUSIONS: Our results indicate that cobalamin transport and cellular processing pathways are overall protected from lysosomal storage damage in GD fibroblasts. Extending these studies to hepatocytes, macrophages and plasma will shed light on cell- and compartment-specific vitamin B12 metabolism in Gaucher disease.

Plasma homocysteine concentration in privately owned healthy adult cats: assessment of biological determinants and establishment of a reference interval.

OBJECTIVES: The assessment of homocysteine status in diseased cats has indicated high plasma concentrations in chronic kidney disease and yielded conflicting results with respect to cardiovascular disorders. Previous investigations in small populations of normal cats revealed greater-than-expected variability in plasma homocysteine concentration. The purpose of this study was to determine biological determinants and the reference interval (RI) of plasma homocysteine concentration in the feline species, under strict pre-analytical conditions. METHODS: In this prospective observational study, privately owned healthy adult cats underwent a complete physical examination, urinalysis and blood testing, in order to rule out any signs of disease. Plasma homocysteine concentration was measured using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Of 151 cats recruited, 30 cats were not included owing to abnormal physical examination or fractious behaviour, and 30 cats were excluded based on abnormalities on blood work or urinalysis. Plasma homocysteine concentrations >28 µmol/l were associated with a dietary protein content >9.3 g/100 kcal metabolisable energy. The RI for plasma homocysteine concentration was determined to be 6.2-52.3 µmol/l. CONCLUSIONS AND RELEVANCE: Normal values for plasma homocysteine concentration in cats have a wide RI, suggesting high inter-individual variability. Whether some healthy cats exhibit impaired homocysteine metabolism remains to be elucidated.

Prudent dietary pattern influences homocysteine level more than folate, vitamin B12, and docosahexaenoic acid: a structural equation model approach.

PURPOSE: A structural equation model (SEM) was used to test multiple and simultaneous relationships between socio-demographic factors, dietary patterns, biochemical levels of folate, vitamin B12, docosahexaenoic acid (DHA), and its effects on homocysteine (Hcy) level. METHODS: Socio-demographic and lifestyle characteristics, blood sample, anthropometric measurements, and a food-frequency questionnaire (FFQ) were obtained from 281 individuals of ISA-Capital study (Sao Paulo, Brazil). The dietary patterns (DP) were estimated using factor analysis with principal component's estimation based on the frequency of daily intake derived from the 38-item FFQ. The SEM considered a theoretical model where the DP were expected to be directly associated with Hcy level, and indirectly via biochemical levels of folate, vitamin B12, and DHA. The variables sex, age, ethnicity, and MTHFR C677T polymorphism were included in the model. RESULTS: The Prudent DP (- 0.12, p = 0.04) had a negative effect, while MTHFR C677T polymorphism (0.16, p = 0.01), age (0.22, p < 0.01), and being man (0.16, p = 0.01) had a positive effect on Hcy level. There were no indirect effects of any dietary patterns on Hcy level, neither via folate, vitamin B12, nor DHA. DHA was negatively associated with the Modern DP (- 0.12, p = 0.04) and positively associated with the Prudent DP (0.19, p < 0.01). CONCLUSIONS: The DP mainly composed of fruits and vegetables, natural juices, potato/cassava/cooked cornmeal, fish, and chicken, which was negatively associated with the Hcy level in this population. These findings support the role of a healthy dietary pattern in health outcomes, rather than promoting specific foods or nutrients, for policy-based health promotion strategies.