Serum Homocysteine Research Articles

Association of high blood pressure with raised homocysteine level among urban population- A case control study

Abstract Introduction: Hypertension is a major risk factor for cardiovascular diseases. Raised homocysteine level is also an important independent risk factor for CVD. This study sought to determine whether there is any relationship between plasma homocysteine and blood pressure levels. Method: A case control study was conducted among 200 hypertensive cases and 200 normal healthy control groups. Cases were from the Department of medicine and hypertensive clinics at GMC, Baramati and similar controls were selected from patients’ neighborhood. Detailed clinical assessment as well as plasma homocysteine level were assessed and compared in both. Results: Hypertensive cases had higher mean homocysteine level (21.3 ± 4.6 μmol/L) from controls (13.0 ± 6.0 μmol/L), p<0.001. Homocysteine is positively correlated with both systolic and diastolic blood pressure among both hypertensive patients and healthy controls. In both hypertensive subjects and healthy control, homocysteine level has weak positive correlation with DBP and moderate to strong positive correlation with SBP. The hypertensive cases had very high chance (OR=52.4) of developing hyperhomocysteinemia (>15 μmol/L), p<0.001. Conclusion: This study showed higher mean plasma homocysteine levels in hypertensive subjects than controls. Serum homocysteine concentrations were positively associated with both systolic and diastolic blood pressure levels in a general adult population.

Relationship of vitamin B12, folic acid and homocysteine level with time domain measures of heart rate variability in female Metabolic Syndrome

Background: Metabolic syndrome (MetS) is a major risk factor for cardiac mortality and morbidity. Hyperhomocysteinemia and folic acid are related with MetS. Both MetS and hyperhomocysteinemia adversely affect heart rate variability (HRV). Objectives: To assess the relationship of vitamin B12, folic acid and homocysteine levels with HRV in female MetS patients. Methods: This cross sectional study was carried out on 40 female MetS patients of 25-45 years of age. Forty apparently healthy female with similar age were control. Chemiluminescent immunoassay measured serum vitamin B12, folic acid, homocysteine level and time domain parameters of HRV were recorded by Powerlab 8/35, AD instruments, Australia. Independent sample ‘t’ test and pearson correlation coefficient test was used for statistical analysis Results: In this study, all the time domain HRV variables ( Standard deviation of all RR intervals-SDRR, Coefficient variation of RR interval-CVRR, The square root of mean squared difference of RR intervals-RMSSD and Number of R-R interval differing >50ms from adjacent intervals divided by the total number of all R-R intervals-pRR50%) were significantly lower (p<0.05) in MetS patients compared to control. But correlation analysis showed only the folic acid level was significantly negatively correlated (p<0.05) with SDRR, CVRR, RMSSD and pRR50%. Conclusion: The result of this study showed inverse relation of low HRV with low serum folic acid levels in female MetS patients. J Bangladesh Soc Physiol. 2022, June; 17(1): 41-48

Poly(N-2-hydroxypropylmethacrylamide)-capped gold nanoparticles as nanozymes with peroxidase-mimicking performance for the colorimetric monitoring of serum homocysteine

Recently, nanozymes based on polymer-stabilized gold nanoparticles (AuNPs) have attracted more and more attention on account of their polymer-ligands' multiple functionalization sites. However, the contribution of polymer hydrogen bonding to the catalytic activity of AuNPs has received little attention. This study designed and fabricated poly(N-2-hydroxypropylmethacrylamide)-capped AuNPs (PHPAM@AuNPs) using a hydroxyl-rich polymer as the ligand. The PHPAM@AuNPs exhibited good peroxidase-mimicking activity capable of efficiently oxidizing 3,3'5,5'-tetramethylbenzidine (TMB) with H2O2. The effect of PHPAM hydrogen bonding on the catalytic activity of PHPAM@AuNPs was investigated. Under peroxidase-mimicking catalysis, homocysteine introduced a notable reduction in oxidation, allowing the creation of a colorimetric method for homocysteine detection with high selectivity and sensitivity. The ultraviolet-visible absorption intensity of oxidized TMB showed a strong linear relationship with homocysteine concentration in the range of 3.0-20.0μM (R2 = 0.998), with a limit of detection of 0.4μM. The proposed colorimetric protocol was used to monitor homocysteine in rat serum following intraperitoneal injection. This work provides a new way to refine AuNP-based nanozymes by relying on polymer-ligand hydrogen bonding. It has strong application potential in the analysis of endogenous molecules in real samples.

Nitrous oxide abuse leading to extreme homocysteine levels and thrombosis in young adults: a case series

BackgroundNeurologic complications from recreational use of nitrous oxide (N2O), which are attributed to vitamin B12 deficiency, have been well documented. With increasing dosages and frequency of N2O use, an additional association with thromboembolisms is becoming apparent. ObjectivesTo assess thrombotic complications of recreational N2O use. MethodsAll medical charts at the largest hospital in Amsterdam were searched for N2O use and subsequent neurologic and/or thrombotic events. For patients with thrombotic events, we extracted data on the risk factors for arterial and venous thrombosis as well as serum vitamin B12 and homocysteine concentrations. ResultsBetween January 2015 and May 2021, 326 patients who reported recreational use of N2O were identified; of these, 17 (5%) patients presented with severe thrombotic events associated with N2O (71% men; median age, 26 years [range, 18-53 years]), 5 patients presented with arterial thrombosis (3 with acute coronary syndrome, 1 with femoral artery thrombosis, and 1 with middle cerebral artery thrombus), and 12 patients presented with venous thromboembolisms (10 with pulmonary embolisms, 1 with portal vein thrombosis and 1 with cerebral vein thrombosis). Additionally, homocysteine were concentrations severely increased (median, 125 μmol/L [range, 22-253 μmol/L]; reference, <15 μmol/L). Patients reported use of 400 to 6000 g (ie, 50-750 balloons) of N2O in 1 day. Fifty percent of these patients had experienced neurologic symptoms before the thrombotic event. ConclusionWe describe an alarming incidence of serious thrombotic events among young adults after excessive recreational use of N2O, accompanied by extremely high homocysteine concentrations. The upward trend in the recreational use of N2O warrants more awareness of its dangers among both users and medical professionals. Furthermore, these findings could reopen the discussion on possible associations between hyperhomocysteinemia and thrombosis mediated through N2O.

The acute postprandial response of homocysteine to multivitamin and mineral supplementation with a standard meal is not impaired in older compared to younger adults.

B vitamins are required for the complex regulation of homocysteine and one-carbon (1C) metabolism. Nutritional supplements are frequently used by older adults to counter nutritional inadequacies. However, the postprandial use of B vitamins from supplements in 1C metabolism may be altered with age owing to impaired nutrient absorption and metabolic regulation. Despite implications for health and nutritional status, postprandial 1C metabolite responses have not been characterised in older adults. Healthy older (n = 20, 65-76years) and younger (n = 20, 19-30years) participants were recruited through online and printed advertisements in Auckland, New Zealand. Participants consumed a multivitamin and mineral supplement with a standard breakfast meal. Blood samples were collected at baseline and hourly for 4h following ingestion. Plasma 1C metabolites (betaine, choline, cysteine, dimethylglycine, glycine, methionine, serine) were quantified using liquid chromatography coupled with mass spectrometry. Serum homocysteine, folate and vitamin B12 were quantified on a Cobas e411 autoanalyzer. Older adults had higher fasting homocysteine concentrations (older: 14.0 ± 2.9µmol/L; younger: 12.2 ± 2.5µmol/L; p = 0.036) despite higher folate (older: 36.7 ± 17.4nmol/L; younger: 21.6 ± 7.6nmol/L; p < 0.001) and similar vitamin B12 concentrations (p = 0.143) to younger adults. However, a similar postprandial decline in homocysteine was found in older and younger subjects in response to the combined meal and supplement. Except for a faster decline of cystathionine in older adults (p = 0.003), the postprandial response of other 1C metabolites was similar between young and older adults. Healthy older adults appear to maintain postprandial responsiveness of 1C metabolism to younger adults, supported by a similar postprandial decline in homocysteine concentrations.

The role of the deficiency of vitamin B12 and folic acid on homocysteinemia in children with Turner syndrome

Premature atherosclerosis and ischemic heart disease represent a major cause of comorbidities among children with Turner syndrome. The identification of non-traditional risk aspects is crucial for the early identification and management of such comorbidities through establishing effective preventive measures. The aim of the study is to explore the role of the deficiency of vitamin B12, folic acid and homocysteine in children withTurner syndrome. The study included 78 children with Turner syndrome and 67 healthy age and sex matched children. Karyotype was implemented for all patients. The serum levels of vitamin B12, folic acid and serum homocysteine were assessed. The prevalence of the deficiency of vitamin B12 and folic acid was estimated to study its correlation to hyperhomocysteinemia in Turner syndrome children. The karyotype analysis showed 45,X (monosomy X) in the 78 patients. Vitamin B12 and folic acid were significantly decreased in children with Turner syndrome in 65-73% of the patients, respectively, while the serum level of homocysteine significantly increased to 48.7% compared to healthy controls. Homocysteine level negatively correlated with vitamin B12 and folic acid. The deficiency of vitamin B12 and folic acid increased the risk of hyperhomocysteinemia in children with Turner syndrome (OR 2.49 and 2.36, respectively). This report highlights that hyperhomocyste-inemia in children with Turner syndrome may be related to the deficiency vitamin B12 and folic acid.

Serum homocysteine is a valuable marker for predicting aggravation of infection in intestinal obstruction patients.

The aim of this study was to investigate the expression of serum homocysteine (HCY), procalcitonin (PCT), and C-reactive protein (CRP) in abdominal infectious disease and analyze their relationship with the degree of abdominal infection. We conducted a retrospective study involving 157 patients with abdominal infections at Xuzhou Central Hospital between January 2016 and October 2019. The patients were composed of intestinal obstruction (73 cases), appendicitis (45 cases), perforation of the digestive tract (25 cases), and cholecystitis (14 cases). The HCY, PCT, and CRP levels of patients with abdominal infections were detected using enzyme-linked immunosorbent assay (ELISA), and correlation analysis between the HCY, PCT, and CRP levels and abdominal infection was performed using Pearson's correlation analysis. Compared with before treatment, the HCY, PCT, and CRP levels in the four groups decreased significantly after treatment. The levels in the patients in the intestinal obstruction group decreased more markedly than in those in the other groups. There were positive correlations among the HCY level, PCT, and CRP before treatment only in patients with intestinal obstruction (P < 0.001). The difference was statistically significant in the HCY level between the non-operation and the operation groups in patients with intestinal obstruction (P < 0.001). Serum HCY may be a valuable marker for predicting aggravation of infection in patients with intestinal obstruction.

ВЗАИМОСВЯЗИ ГИПЕРГОМОЦИСТЕИНЕМИИ И ФУНКЦИОНАЛЬНОГО СОСТОЯНИЯ ПОЧЕК У ДЕТЕЙ С НАРУШЕНИЕМ ПУРИНОВОГО ОБМЕНА

Among the modified risk factors for chronic kidney disease hyperhomocysteinemia (HHC) and hyperuricemia (HU) play an important role in the development of the cardiorenal continuum. The purpose of the research was to study the relationship between HHC and the functional state of the kidneys in children with impaired purine metabolism. Materials and methods used: a single-center one-stage (cross-sectional) study was conducted in 54 pediatric patients aged 9 to 15 y/o with purine metabolism disorders (in the form of isolated HU or in combination with hyperuricosuria) in Feb. 2017 - March 2021. The level of homocysteine in the blood serum was determined by enzyme immunoassay. Evaluated clearance, excreted fraction, filtered volume and reabsorption of uric acid; the glomerular filtration rate (GFR) was calculated. The two groups were distinguished: the [main] Group 1 of 26 children with HHC; and the [comparison] Group 2 of 28 children with normal homocysteine levels. Results: the frequency of diagnosis of HHC among the examined was 47.8%, which is almost 5 times higher than in the population. In the main group, the analysis of Spearman's rank correlation revealed a positive statistically significant correlation between the level of homocysteine and uric acid: Rs=0.32, p=0.048. In this group, the clearance of uric acid, its excreted fraction and filtered volume were statistically significantly lower, while reabsorption and GFR were higher relative to the comparison group. The daily excretion of uric acid directly correlated statistically significantly with its clearance (Rs=0.71, p&lt;0.001) and excreted fraction (Rs=0.66, p=0.004) and inversely significantly correlated with the level of its reabsorption (Rs=- 0.66, p=0.004). Statistically significant direct correlation of blood homocysteine and creatinine levels (Rs=0.38, p=0.020) and inverse correlation with uric acid excretion (Rs=-0.38, p=0.020) were obtained. Conclusion: in children with impaired purine metabolism, HHC is associated with the early formation of tubular dysfunction, which is evidenced by a statistically significant decrease in the clearance of uric acid, its excreted fraction and filtered volume. The increase in GFR in this case probably reflects the formation of hyperfiltration as the initial stage of metabolic renal damage.

The predictive value of four serum biomarkers for major adverse events in patients with small abdominal aortic aneurysm

BackgroundThe primary aim of this study was to test which of a group of four inflammation and thrombosis biomarkers were independently predictive of major adverse cardiovascular events (MACE) in patients with small abdominal aortic aneurysm (AAA). MethodsA total of 471 participants with a 30- to 54-mm AAA had serum C-reactive protein (CRP), fibrinogen, neutrophil-lymphocyte ratio (NLR), and homocysteine measured. The primary outcome was MACE, which was defined as the first occurrence of myocardial infarction, stroke, or cardiovascular death. The association of biomarkers with events was assessed using Kaplan-Meier and Cox proportional hazard analyses. The net improvement in risk of event categorization with addition of a biomarker to clinical risk factors alone was assessed using net reclassification index. ResultsParticipants were followed for a median of 2.4 years (interquartile range, 0.8-5.4 years), and 102 (21.7%) had a MACE. The incidence of MACE was 13.2% in participants with CRP >3.0 mg/L, compared with 10.1% in those with CRP ≤3.0 mg/L at 2.5 years (P = .047). After adjusting for other risk factors, higher CRP was associated with a significantly higher risk of MACE (hazard ratio, 1.19; 95% confidence interval, 1.05-1.35). None of the other biomarkers were associated with the risk of MACE. According to the net reclassification index, CRP significantly improved the risk classification of MACE compared with clinical risk factors alone. ConclusionsCRP can assist in classification of risk of MACE for patients with small AAA.

Homocysteine causes neuronal leptin resistance and endoplasmic reticulum stress.

Abnormally high serum homocysteine levels have been associated with several disorders, including obesity, cardiovascular diseases or neurological diseases. Leptin is an anti-obesity protein and its action is mainly mediated by the activation of its Ob-R receptor in neuronal cells. The inability of leptin to induce activation of its specific signaling pathways, especially under endoplasmic reticulum stress, leads to the leptin resistance observed in obesity. The present study examined the effect of homocysteine on leptin signaling in SH-SY5Y neuroblastoma cells expressing the leptin receptor Ob-Rb. Phosphorylation of the signal transducer and activator of transcription (STAT3) and leptin-induced STAT3 transcriptional activity were significantly inhibited by homocysteine treatment. These effects may be specific to homocysteine and to the leptin pathway, as other homocysteine-related compounds, namely methionine and cysteine, have weak effect on leptin-induced inhibition of STAT3 phosphorylation, and homocysteine has no impact on IL-6-induced activation of STAT3. The direct effect of homocysteine on leptin-induced Ob-R activation, analyzed by Ob-R BRET biosensor to monitor Ob-R oligomerization and conformational change, suggested that homocysteine treatment does not affect early events of leptin-induced Ob-R activation. Instead, we found that, unlike methionine or cysteine, homocysteine increases the expression of the endoplasmic reticulum (ER) stress response gene, a homocysteine-sensitive ER resident protein. These results suggest that homocysteine may induce neuronal resistance to leptin by suppressing STAT3 phosphorylation downstream of the leptin receptor via ER stress.

Homocysteine as a Predictor of Preeclampsia

Homocysteine is an amino acid that is a product of methionine metabolism, is related to preeclampsia in 20-30%, the increase of this or hyperhomocysteinemia may result from the genetic defect of the enzyme methylenetetrahydrofolate reductase involved in the synthesis of homocysteine. Maternal mortality due to preeclampsia is up to 44% and perinatal mortality is reported at up to 27.8%. The objective of this research was to determine homocysteine levels as a predictor of preeclampsia in pregnant women 12 to 20 weeks pregnant. This was an observational, longitudinal and prospective investigation. The study population were patients attending the first antenatal care consultation between 12 to 20ava. weeks, the sample was random that included 360 patients who determined serum homocysteine Sand excluded 48 patients whodid not meet the inclusion and exclusion criteria; they found homogeneity among the patients, 270 patients (86.5%) had a normal evolutionary pregnancy, 27 patients (8.65%) had gestational hypertension, 9 (2.88%) mild preeclampsia and 6 patients (1.9%) severe preeclampsia, none developed HELLP syndrome. Increased homocysteine levels were found in 9 patients who were not related to hypertensive pregnancy disorders. In the present research, homocysteine was not shown to be a predictor of hypertensive disease in pregnancy.

Development of an improved standard reference material for folate vitamers in human serum.

The US National Institute of Standards and Technology (NIST) developed a Standard Reference Material® (SRM®) 3949 Folate Vitamers in Frozen Human Serum to replace SRM 1955 Homocysteine and Folate in Human Serum. The presence of increased endogenous levels of folic acid and 5-methyltetrahydrofolate (5mTHF) in SRM 3949, enhanced folate stability via addition of ascorbic acid, and inclusion of values for additional minor folates are improvements over SRM 1955 that should better serve the clinical folate measurement community. The new SRM contains folates at three levels. To produce SRM 3949, pilot sera were collected from 15 individual donors, 5 of whom were given a 400-µg folic acid supplement 1h prior to blood draw to increase serum levels of 5mTHF and folic acid for the high-level material. To stabilize the folates, 0.5% (mass concentration) ascorbic acid was added as soon as possible after preparation of serum. These pilot sera were screened for five folates plus the pyrazino-s-triazine derivative of 4-α-hydroxy-5-methyltetrahydrofolate (MeFox) at the US Centers for Disease Control and Prevention (CDC) by isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS). Based on these results, a blending protocol was specified to obtain the three desired folate concentrations for SRM 3949. ID-LC-MS/MS analysis at the CDC and NIST was utilized to assign values for folic acid and 5mTHF, as well as several minor folates.

Effects of a diet low in excitotoxins on PTSD symptoms and related biomarkers

ABSTRACT Post-traumatic stress disorder (PTSD) develops after trauma exposure and involves symptoms of avoidance, intrusive re-experiencing, mood and cognitive dysfunction, and hypervigilance. PTSD is often comorbid with Gulf War Illness (GWI), a neurological condition involving widespread pain, cognitive dysfunction, digestive problems, and other symptoms, in Gulf War veterans. PTSD tends to be more severe when comorbid with GWI. Low cortisol and elevated homocysteine levels have been found in PTSD, making them potential PTSD biomarkers. The low-glutamate diet, which aims to reduce excitotoxicity by eliminating the consumption of free glutamate and aspartate, has been shown to significantly reduce GWI and PTSD symptoms. This study examined whether changes in serum cortisol and homocysteine are associated with reduced PTSD severity in veterans with GWI after one month on the low-glutamate diet, and whether reducing the consumption of dietary excitotoxins was associated changes in PTSD and serum biomarkers. Data were analyzed for 33 veterans. No serum biomarkers significantly changed post-diet; however, cortisol increased as dietary excitotoxin consumption decreased, which held in a multivariable linear regression after adjustment for sex. Reduced dietary excitotoxin consumption was also associated with reduced hyperarousal symptoms, which held in a multivariable linear regression after adjustment for sex. Cortisol increase was associated with reduced avoidance symptoms after adjustment for change in BMI, and was marginally associated with overall PTSD reduction. Change in homocysteine was not significantly related to dietary adherence nor change in PTSD. Results suggest that reducing the consumption of dietary excitotoxins may normalize cortisol levels, which has been associated with alleviating PTSD.

The clinical prediction factors for non-culprit lesion progression in patients with acute ST elevation myocardial infarction after primary percutaneous coronary intervention

BackgroundTo investigate the relationship between the clinical features and progression of non-culprit lesions in patients with ST-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI).MethodsA total of 480 patients (57.1 ± 9.2 y) with STEMI who underwent PPCI between January 2016 and December 2017 in Beijing Anzhen Hospital were enrolled in this study. All patients underwent PPCI as a treatment for culprit lesions. Clinical and angiographic follow-up were performed for 12 months. All patients were divided into a non-culprit lesions (NCL) progression group (205 cases) and a control group (275 cases) based on angiographic follow-up outcomes at 12 months. The clinical and angiographic features were analyzed.ResultsBody mass index (BMI), serum creatinine (Scr), fasting blood glucose (FBG), glycated serum albumin, glycated hemoglobin and homocysteine levels in the NCL progression group were significantly higher than those in the control group (P < 0.05). A logistic regression analysis showed that FBG (odds ratio 1.274, 95% confidence interval 1.077–1.505, P = 0.005) and Scr (odds ratio 1.020, 95% confidence interval 1.002–1.038, P = 0.027) were independent predictors of NCL progression. A partial correlation analysis showed that FBG was positively correlated with NCL progression (r = 0.231, P = 0.001). A receiver operating characteristic curve showed that the boundary point of FBG to predict NCL progression was 5.715 mmol/L, and the sensitivity was 74.4% and the specificity was 46.4%.ConclusionFBG is a valuable predictor for NCL progression in patients with STEMI after PPCI.

Increased serum homocysteine in first episode and drug-naïve individuals with schizophrenia: sex differences and correlations with clinical symptoms

BackgroundAccumulating evidence shows that homocysteine (Hcy) is implicated in the pathophysiology of schizophrenia, and plays an important role in clinical characteristics. This study evaluated the relationships between Hcy levels and clinical features in first-episode, Chinese Han, drug-naïve (FEDN) patients with schizophrenia.MethodsFEDN individuals (119 with schizophrenia and 81 healthy controls matched for age, sex, education, and body mass index (BMI)) were enrolled. The serum Hcy levels were determined by enzyme cycle assay experiments. Severities of clinical symptoms were rated on the Positive and Negative Syndrome Scale (PANSS).ResultsFEDN individuals with schizophrenia had higher Hcy levels compared with healthy controls (F = 46.865, P < 0.001). Correlation analysis and multiple stepwise regression analyses showed that serum Hcy levels in FEDN schizophrenia individuals were positively correlated with PANSS general psychopathology subscale (r = 0.294, P = 0.001) and PANSS total score (r = 0.273, P = 0.003). No significant association was found between Hcy and age, BMI, PANSS positive subscale, and the PANSS negative subscale (all, P > 0.05). Male individuals had significantly higher serum Hcy levels than female individuals (F = 7.717, P = 0.006) after controlling for confounding factors (F = 0.759, P = 0.011).ConclusionsSerum Hcy levels were increased in FEDN individuals with schizophrenia, and Hcy levels may be involved in pathophysiological mechanisms. Sex differences in Hcy levels were observed, with higher levels in male FEDN individuals compared to females.

Homocysteine, folate, and nonalcoholic fatty liver disease: a systematic review with meta-analysis and Mendelian randomization investigation

Circulating concentrations of homocysteine and folate are inconsistently associated with the risk of nonalcoholic fatty liver disease (NAFLD) in observational studies. We conducted a meta-analysis and Mendelian randomization (MR) analyses to examine these associations. We performed a meta-analysis of observational studies identified from 3 databases to evaluate the associations of serum homocysteine and folate concentrations with NAFLD from inception to 7 April 2022. We conducted MR analyses to strengthen the causal inference in these associations. Independent single-nucleotide polymorphisms without linkage disequilibrium (r2<0.01) that were strongly associated (P < 5×10-8) with serum homocysteine (n=13) and folate (n=2) concentrations were selected as instrumental variables from 2 meta-analyses of genome-wide association studies (GWASs) of 44,147 and 37,645 individuals of European ancestry, respectively. Data on NAFLD were obtained from a GWAS of 8434 NAFLD cases and 770,180 controls of European ancestry. We further included 4 liver enzymes as secondary outcomes from a GWAS of 361,194 individuals with European descent. Twenty-two observational studies comprising 30,368 participants were included in the meta-analysis. There was a positive association between serum homocysteine and NAFLD risk (n=20; OR: 1.96; 95% CI: 1.57, 2.45) and an inverse association between serum folate and NAFLD risk (n=12; OR: 0.75; 95% CI: 0.58, 0.99). In MR analysis, the ORs of NAFLD were 1.17 (95% CI: 1.01, 1.36) and 0.75 (95% CI: 0.55, 1.02) per 1-SD increment of genetically predicted circulating concentrations of homocysteine and folate, respectively. Each 1-SD increase of genetically predicted circulating homocysteine and folate conferred a change in ALT concentrations of 0.62 U/L (95% CI: 0.20, 1.04) and -0.84 U/L (95% CI: -0.14, -1.54). This study suggests a potential role of circulating homocysteine and possibly folate in NAFLD, which calls for future clinical exploration of the possibility of lowering homocysteine concentrations to prevent NAFLD. This systematic review was registered at PROSPERO as CRD42021296434.

Proton pump inhibitor use and its effect on vitamin B12 and homocysteine levels among men and women: A large cross-sectional study.

Previous studies have demonstrated an association between proton pump inhibitors (PPI) use and vitamin B12 deficiency. However, data regarding PPI use and elevated serum homocysteine level, an important marker of vitamin B12 deficiency, are scant. Data were collected from medical records of subjects examined at a screening center in Israel. Cross sectional analysis was conducted on 25,953 subjects. Levels of vitamin B12 and homocysteine were compared between subjects who consumed PPI medications and those who did not. The mean age of the study population was 45 years and 33% were females. Subjects who received PPI medications had a minor higher vitamin B12 levels (320 pmol/L vs 300 pmol/L, p=0.024). Levels of vitamin B12 remained higher in females receiving PPI medications after performing a stratified analysis according to subjects' gender. Homocysteine levels were higher in subjects receiving PPI medications as compared to those who did not (12.0 μmol/L vs 11.6 0 μmol/L, p<0.001). Levels remained higher in female subjects after performing a stratified analysis according to subjects' sex. There was no statistically significant difference in the prevalence of vitamin B12 deficiency (according to two cutoffs: vitamin B12≤200 or ≤140 pmol/L) as well as the prevalence of hyperhomocysteinemia (defined as homocysteine >15.0 μmol/L) between the two groups. According to our study, no association was found between PPI medication use and vitamin B12 deficiency or hyperhomocysteinemia. Patients receiving PPI medications had slightly higher levels of vitamin B12 and homocysteine, however these differences were too small to have any clinical relevance.

Effect of combination of metformin with B12 and folic acid on lipid profile and levels of homocysteine in adult male rabbits

The present study aims to evaluate the effects of metformin in combination with vitamin B12 and folic acid on lipid profiles and serum homocysteine levels in male rabbits. The study included twenty-four male rabbits that weighed (1.5-2 kg), and were divided randomly into four groups (six rabbits/group). The control first group was administrated (5 ml) of distilled water; The second group was given metformin (125g/kg B.W) plus vitamin B12 (500 μg/kg B.W) daily, the third group was given metformin (125g/kg B.W) plus folic acid (5g/kg B.W) daily and the fourth group was given metformin (125g/kg B.W), folic acid (5g/kg B.W) and vitamin B12 (500 μg/kg B.W) daily, the rabbits were followed up for one month. The results revealed a decrease in the final body weight and body weight gain in all treated groups as compared to the control group. The homocysteine parameter decreases significantly in the second group which was given metformin and B12 and the third group was given metformin in combination with folic acid as compared with the control group and group four. It showed a significant decrease in the fourth group (metformin + folic acid + vitamin B12) compared with the second and third groups also the glucose level increased significantly in group three compared to group second, fourth, and control group. The results showed that serum cholesterol and TG have decreased in G2 and G3 while an increase in G4 as compared with the control group, and the HDL was decreased in G2 and G4 compared with control and G3 groups. While the results of LDL and VLDL were increased in G3 and G4 compared with G2 and the control group

ROLE OF HOMOCYSTEINE IN DEVELOPMENT OF ABDOMINAL PAIN IN PATIENTS WITH IRRITABLE BOWEL SYNDROME AND CONSTIPATION

Introduction. Irritable bowel syndrome with constipation poses a serious medical and social problem. Studying the pathogenetic mechanisms of irritable bowel syndrome with constipation may improve therapeutic approaches and patient’s quality of life.&#x0D; The aim of this study is to investigate the homocysteine role in the development of abdominal pain syndrome in patients with irritable bowel syndrome and constipation, taking into account body mass index.&#x0D; Subjects and methods. The study involved 55 patients with functional bowel disorders, who were divided into 2 groups: group I (n=27) included patients with functional constipation; II group (n=28) involved patients with irritable bowel syndrome and constipation. The average age of patients in group I was 35.7±8.63 years, in group II – 34.50±9.06 years, the ratio of men and women was 7(25.9%) / 20(74.1%) and 10 (35.7%) / 18(64.28%), respectively. A modified faces pain scale was used to assess pain intensity. Height, weight, and waist circumference were measured, body mass index was calculated according to formula: body mass index = weight (kg)/height (m2). The homocysteine level in the blood serum was measured.&#x0D; Results. Abdominal obesity with the waist circumference greater than 88 cm for women and greater than 102 cm for men was recorded in 6 (21.42%) patients with irritable bowel syndrome and constipation and in 4 (14.81%) patients with functional constipation. The severity of pain and meteorism according to the modified faces scale in patients with irritable bowel syndrome with constipation were respectively 2.4 and 1.7-fold (р˂0.0001) higher than the respective parameters in the patients with functional constipation.&#x0D; The content of homocysteine in the blood serum in the patients with irritable bowel syndrome and constipation was 1.9-fold (р˂0.0001) higher than in the patients with functional constipation. Increased homocysteine level led to the increase in the risk of developing irritable bowel syndrome and constipation (RR=3.61; 95%CI 1.37–9.52; p&lt;0.01). It is important to stress that the serum homocysteine level in the patients with irritable bowel syndrome with constipation was directly correlated with the pain severity assessed by the modified faces pain scale (r=+0.9; p=0.0001).&#x0D; Conclusion. The severity of abdominal pain and meteorism in patients with irritable bowel syndrome and constipation is associated with the homocysteine level in the blood serum.

Association between serum homocysteine and sarcopenia among hospitalized older Chinese adults: a cross-sectional study

ObjectiveHyperhomocysteinemia (HHcy) is considered to increase the risk of sarcopenia (S) and remains controversial. In this study, we aimed to investigate the prevalence of S among older Chinese adults and explore whether homocysteine (Hcy) was independently associated with S.MethodsThis cross-sectional study was performed among older adults hospitalized in the Geriatric Hospital of Nanjing Medical University between June 2017 and December 2021. We measured all participants’ serum Hcy levels, hand grip strength, gait speed and appendicular skeletal muscle index(ASMI) using bioelectrical impedance analysis (BIA). S was defined based on the criteria of the Asian Working Group for Sarcopenia 2 (AWGS2), which included muscle mass (ASMI< 7.0 kg/m2 for men and ASMI< 5.7 kg/m2 for women by BIA) and low muscle strength (handgrip strength < 28 kg for men and < 18 kg for women), and/or gait speed < 1.0 m/s. HHcy defined as Hcy ≥10 μmol/L. The strength of the association between Hcy and the risk of S was analyzed by multivariate logistic regression using three models that adjusted for possible confounding variables to calculate the odds ratios (ORs) and 95% confidence intervals (CIs).ResultsAmong the 441 subjects, 161 (36.5%) were diagnosed with S, and 343 (77.8%) were diagnosed with HHcy. A significant association was detected between S and serum Hcy per 1-μmol/L increase after adjustment for age, gender, education, smoking, body mass index (BMI), Mini Nutritional Assessment Short Form (MNA-SF), alanine aminotransferase (ALT), C-reactive protein (CRP), hemoglobin (Hb), albumin (ALB), diabetes, kidney disease, and statin use (OR = 1.07, 95% CI = 1.03–1.12, P = 0.002). The OR for S in the HHcy group (≥10 μmol/L) was nearly 5-fold that in the normal Hcy group (OR 4.96, 95% CI 2.67–9.24, P < 0.001). In a gender-based subgroup analysis that adjusted for age, education, smoking, BMI, MNA-SF, ALT, CRP, Hb, and ALB, female subjects with HHcy had an increased risk of S (OR 10.35, 95% CI 2.84–37.68, P < 0.001).ConclusionsOur results demonstrated that elevated Hcy levels have an independent association with S in older adults. This suggests that the downward adjustment of HHcy (cutoff value < 10 μmol/l) might decrease the risk of S.