High Homocysteine Research Articles

Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura

Hyperhomocysteinemia (hHCY) is a metabolic disorder characterized by elevated levels of homocysteine in plasma. hHCY correlates with a high risk of migraine headaches, especially migraine with aura. Cortical spreading depression (CSD) is a wave of depolarization passing through neurons and glial cells of the cortex and is considered an electrophysiological correlate of migraine aura. The aim of the present study was to analyze neuronal activity and CSD in the somatosensory cortex of rats in vivo with prenatal hHCY and to assess cortex viability after 2 h of CSD generation. Female rats were fed a diet high in methionine, and their offspring with high homocysteine levels in plasma were further used in experiments. Recurrent CSD was evoked by local KCl application on the dura surface. Neuronal viability was assessed by measuring the activity of lactate dehydrogenase (LDH) in the brain and 2,3,5-triphenyltetrazolium chloride staining of the somatosensory cortex after two hours of CSD generation. Animals with hHCY exhibited higher neuronal activity, and more CSDs were generated in response to KCl, indicating higher cortical excitability. Propagation of recurrent CSD was impaired in supragranular cortical layers, and the recovery of multiple unit activity and evoked sensory potentials after CSD was delayed in the hHCY group. Finally, in animals with prenatal hHCY, an ischemic focus was identified as a consequence of multiple CSDs, along with elevated levels of LDH activity in brain tissues, suggestive of diminished neuronal viability. These findings imply that prolonged elevated levels of homocysteine may not only predispose to migraine with aura but also potentially elevate the risk of migrainous infarction.

Serum homocysteine levels and mortality: a cohort study

Abstract Background Homocysteine, an intermediate metabolite derived from dietary methionine, plays a pivotal role in deoxyribonucleic acid expression and contribute to its antioxidant capabilities. Elevated homocysteine levels can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorder; however, low levels of homocysteine are generally not considered harmful. This study evaluates the association between all levels of homocysteine-both low and high-and the risk of all-cause and cause-specific mortality in Korean adult men. Methods A study involving 221,356 Korean adult men categorized them into quintiles based on their homocysteine levels. The main outcomes examined were mortality from all causes, cardiovascular disease (CVD), cancer, and dementia. Hazard ratios (HRs) were determined using Cox proportional hazards models, and the dose-response relationship between homocysteine levels and mortality risk was further analyzed using a restricted cubic splines model. Results Compared to the reference category (Q2, 8.8-9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high homocysteine levels after adjusting for multiple variables (Pinteraction=0.002). Furthermore, spline regression revealed a U-shaped relationship between homocysteine levels and both all-cause and CVD mortality, with an inflection point at 9.1 µmol/L. This U-shaped association was not observed in the subgroup that received vitamin supplements. Conclusions Among young and middle-aged Korean adult men, both low and high homocysteine levels were found to increase the risk of all-cause and CVD mortality, demonstrating a U-shaped relationship. However, this association lost statistical significance with vitamin supplementation. These findings underscore the importance of monitoring both low and high homocysteine levels as potential mortality risk factors in men and suggest a possible protective role of vitamins. Key messages • Both low and high levels of homocysteine in young and middle-aged Korean men are associated with increased risks of all-cause and cardiovascular mortality, demonstrating a U-shaped relationship. • Vitamin supplementation appears to nullify this association, suggesting a potential protective effect against mortality.

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.

Association Between Homocysteine Levels and Ovarian Reserve in Subfertile Women.

To evaluate the relationship between homocysteine levels and anti-mullerian hormone (AMH) levels, a biomarker of ovarian reserve, and the effect of high homocysteine levels on ovarian reserve in subfertile women. Observational case-control study. Place and Duration of the Study: Samsun Training and Research Hospital, Samsun, Turkiye, from October to December 2023. Seventy-nine subfertile women and 35 healthy fertile women were included in this study. AMH, homocysteine, thyroid stimulating hormone (TSH), free T3 (fT3), free T4 (fT4), iron, and ferritin levels of subfertile and fertile women were compared. Logistic regression, receiver operating characteristic, and Kaplan-Meier analyses were performed for homocysteine levels. AMH, fT4, iron, and ferritin levels were lower in subfertile women than in fertile women (p <0.001). Homocysteine and TSH levels were higher in subfertile women than in fertile women (p <0.001). The sensitivity for homocysteine levels was 94.90% and the specificity was 94.30%. In the Kaplan-Meier analysis, homocysteine levels of 12.90 μmol/L and above were found to be risky in terms of fertility. Homocysteine levels, AMH, and ferritin levels were negatively correlated and TSH levels were positively correlated in subfertile women (p <0.001). However, these correlations were not observed in fertile women (p >0.05). High homocysteine levels can be considered as a risk factor affecting ovarian reserve in subfertile women. Anti-mullerian hormone, Female subfertility, Homocysteine, Hyperhomocysteinaemia, Ovarian reserve.

Hyperhomocysteinemia and its effect on ageing and language functions – HEAL study

Hyperhomocysteinemia or high levels (> 15 µmol/L) of homocysteine (Hcy)in the blood has been suggested to affect the brain through vascular and neurodegenerative pathways and potentially impact cognition. The current study aims to explore the association of high homocysteine with cognition and brain volume changes in a cohort of middle and old agedr adults. The study recruited 1296 participants aged ≥ 45 years from Tata Longitudinal Study of Ageing (TLSA), an ongoing cohort study. The participants underwent detailed cognitive assessments using Addenbrooke’s Cognitive Examination-III (ACE-III) and Computerized Assessment of Adult Information Processing (COGNITO) neuropsychological battery and MR imaging using a 3T scanner. The participants were classified based on the median homocysteine level (16.89 µmol/L) into low Hcy (≤ median) and high Hcy (> median) groups. When adjusted for age, gender, years of education, vitamin B12, folate and dyslipidaemia, Generalised Linear Model (GLM) found a significant association of high Hcy with vocabulary task [β (95% CI) − 1.354 (− 2.655, − 0.052); p = 0.041]. Significant associations was also obtained between cerebral white matter volume and high Hcy [β (95% CI) − 5617.182 (− 11062.762, − 173.602); p = 0.043]. The results suggest that people with high Hcy levels performed poorer in cognitive tasks related to language domain and had lesser cerebral white matter volume. This indicates that homocysteine might have a profound impact on brain structure as well as function.

Serum Homocysteine Levels and All-Cause and Cause-Specific Mortality in Korean Adult Men: A Cohort Study.

Hyperhomocysteinemia can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorders; however, hypohomocysteinemia is generally not considered harmful. This study aimed to evaluate the relationship between all levels of homocysteine, both low and high homocysteine levels, and the risk of all-cause and cause-specific mortality in adult Korean men. Adult Korean men (n = 221,356) were categorized into quintiles based on their homocysteine levels. The primary endpoints were all-cause, CVD, cancer, and dementia mortality. Hazard ratios were calculated using Cox proportional hazards models, and the dose-response relationship between homocysteine levels and mortality risk was further explored using restricted cubic spline models. Compared with the reference category (Q2, 8.8-9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high levels after multivariable adjustment (Pinteraction = 0.002). Additionally, in spline regression, a U-shaped association between homocysteine levels and all-cause and CVD mortality was observed (inflection point = 9.1 µmol/L). This association was not observed in the vitamin supplementation subgroup. Among Korean adult men, both low and high homocysteine levels increased the risk of all-cause and CVD mortality, indicating a U-shaped relationship. However, this relationship was not statistically significant with vitamin supplementation, suggesting a potential protective role for vitamins.

Cerebral venous sinus thrombosis and SCN1A, a novel association?

Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke. Acquired and inherited prothrombotic conditions are the most common risk factors for CVST. Sometimes, an etiology is not found. Wide utilization of next generation sequencing technologies in clinical practice may lead to identification of risk factors other than those classically associated with CVST. This retrospective clinical-laboratory observational study has a reference patient who presented with CVST as an adolescent. Work up for prothrombotic conditions showed high homocysteine level secondary to homozygosity for a common polymorphism, c.677C > T in the methylenetetrahydrofolate reductase (MTHFR) gene. His older unaffected brother has a similar MTHFR genotype and high homocysteine. The whole exome sequencing revealed a likely pathogenic variant in the sodium voltage gated channel, alpha subunit 1(SCN1A) gene. CVST is a multifactorial disease. Prothrombotic conditions are the most common risk factors for CVST. High homocysteine due to the common MTHFR polymorphisms was previously attributed to various thrombotic conditions including CVST. Although high homocysteine due to MTHFR polymorphism may be a contributing factor, additional risk factors such as blood flow abnormalities during SCN1A related seizures may be needed for thrombosis.

Assessment of Plasma Homocysteine in Patients with Hypothyroidism in a Nigerian Tertiary Hospital

Introduction: Hypothyroidism, a risk factor for atherosclerotic cardiovascular disease has been seen to be associated with hyperhomocysteinemia. The plasma levels of homocysteine and its relationship with hypothyroidism was assessed. Material and Methods: A total of 120 patients aged 20 – 60 years comprising of 60 hypothyroid and 60 euthyroid controls were assessed for the study. Evaluation of plasma homocystein was done using human homocysteine ELISA my BioSource. FT3, FT4 and TSH were also evaluated by enzyme linked immunosorbent assay (ELISA) technique using stat fax-2100. Result: In our study, we have found the values of FT3 in the subjects as 1.21+ 0.89pg/ml lower than controls values of 1.92+0.66pg/ml, values of FT4 in subjects as 0.60+0.53ng/dl as compared to control group value of 1.40+0.30ng/dl, values of TSH as 2.07+1.19µiU/ml higher than the control group of 0.48+1.67µiU/ml. The mean values of plasma homocysteine (Hcy) for subjects was 34.50+10.01µmol/L higher than the control group with 9.30+2.11µmol/L. Conclusion: Our study findings suggest that patients with hypothyroidism also have a high plasma homocysteine known to pose cardiovascular complications.

Analysis of MTHFR C677T genotype and related factors in H-type hypertension in Tibet, China

Background and aimsH-type hypertension is essential hypertension combined with high homocysteine, and both synergistically increase the risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the risk factors of H-type hypertension in Tibetan plateau population and correlation with MTHFR C677T gene.Methods and resultsA multi-stage cluster random sampling method was used to select the research subjects in Tibet Autonomous Region from June 2020 to November 2021. Among Tibetans, the incidence of H-type hypertension accounted for 84.31% of hypertensive patients. The logistic regression analysis demonstrated that age, uric acid (UA), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were risk factors for the prevalence of H-type hypertension, the OR (95% CI) was 1.083(1.073–1.094), 1.002(1.001–1.004), 1.240(1.050–1.464) and 2.274(1.432–3.611), respectively. MTHFR C677T TT genotype patients with H-type hypertension OR (95% CI) was 1.629(1.004–2.643). Based on this, a nomogram model was established, and the reliability of the model was proved by area under ROC curve, Brier score and average absolute error. The model’s results indicate that for every five years of age, the score increases by 6 points; for a 2mmol/L increase in TG, the score increases by 5.5 points; for a 1mmol/L increase in LDL-C, the score increases by 10 points; and individuals with the TT genotype receive 8 points. The higher the score, the greater the risk of disease.ConclusionThe MTHFR C677T TT genotype is a risk locus for Tibetan patients with H-type hypertension, with age, TG, and LDL-C were identified as risk factors for the disease.

Case presentation: a severe case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia

BackgroundThe etiology of nephrotic syndrome can vary, with underlying metabolic diseases being a potential factor. Cobalamin C (cblC) defect is an autosomal recessive inborn error of metabolism caused by mutations in the MMACHC gene, resulting in impaired vitamin B12 processing. While cblC defect typically manifests with hematological and neurological symptoms, renal involvement is increasingly recognized but remains rare.Case PresentationWe describe a 7-month-old male patient presenting with fatigue and edema. His initial laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia and proteinuria. Further examinations reveals hemolysis in peripheral blood smear. During his follow up respiratory distress due to pleural effusion in the right hemithorax was noticed. And fluid leakage to the third spaces supported a diagnosis of nephrotic syndrome. The patient’s condition deteriorated, leading to intensive care admission due to, hypertensive crisis, and respiratory distress. High total plasma homocysteine and low methionine levels raised suspicion of cobalamin metabolism disorders. Genetic testing confirmed biallelic MMACHC gene mutations, establishing the diagnosis of cblC defect. Treatment with hydroxycobalamin, folic acid, and betaine led to remarkable clinical improvement.Discussion/ConclusionThis case underscores the significance of recognizing metabolic disorders like cblC defect in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive management are vital to prevent irreversible renal damage. While cblC defects are more commonly associated with atypical hemolytic uremic syndrome, this case highlights the importance of considering cobalamin defects in the differential diagnosis of nephrotic syndrome, especially when associated with accompanying findings such as hemolysis. Our case, which has one of the highest homocysteine levels reported in the literature, emphasizes this situation again.

The association between frailty biomarkers and 20-year all-cause and cardiovascular mortality among community-dwelling older adults

ABSTRACT Objectives While several biomarkers were previously associated with frailty and mortality, data are still contradicting. We aimed to evaluate the association between novel biomarkers and frailty among community-dwelling older adults to enhance understanding of the pathophysiology of frailty. Methods Nine hundred and sixty-three older adults were screened during the third phase (1999–2008) of the Israel study on Glucose Intolerance, Obesity, and Hypertension (GOH). Frailty was defined as sedentary individuals, past 10 years hospitalizations, or at least one of the following: body mass index (BMI) <21 kg/m2; albumin <3.2 g/dl; ≥2 major baseline diseases. Biomarkers were evaluated for their association with frailty, all-cause, and cardiovascular mortality. Results Mean baseline age was 72 ± 7 years, 471 (49%) were women, and 195 (20%) were classified as frail. Median follow-up for cardiovascular and all-cause mortality was 11 and 13 years, with 179 (18.6%) and 466 (48.4%) deaths recorded, respectively. Multivariable logistic regression showed greater odds for frailty with lower quartile of alanine aminotransferase (ALT) (OR = 1.8, 95%CI: 1.2–2.8, p = 0.01), and for each 5 µmol/L increment in homocysteine levels (OR = 1.3, 95%CI: 1.1–1.5, p = 0.001). Multivariate Cox regression showed greater all-cause and cardiovascular mortality risk for individuals with low ALT (HR = 1.6, 95%CI: 1.3–2.0, p < 0.001 and HR = 1.5, 95% CI: 1.0–2.2, p = 0.03, respectively), and high homocysteine (HR = 1.1, 95%CI: 1.1–1.3, p = 0.003 and HR = 1.2, 95%CI: 1.0–1.3, p = 0.04, respectively). Homocysteine association with mortality was more pronounced in those with baseline ischemic heart disease (IHD) compared with subjects free of IHD (P for interaction = 0.01). Conclusions Lower ALT and higher homocysteine were associated with frailty, all-cause and cardiovascular mortality. These available and low-cost biomarkers underscore the nutritional and metabolic aspects of frailty when screening high-risk older adults, especially those with IHD, and may be considered as preferable screening biomarkers to be tested among these individuals for frailty and mortality risk.

Folate and Vitamin B12 Levels in Chilean Women with PCOS and Their Association with Metabolic Outcomes.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet and deficiencies in essential nutrients. This study aimed to assess the levels of folate and vitamin B12 (B12) and their relationship with metabolic factors in women with PCOS. Anthropometric, clinical, and genetic analyses were conducted to evaluate markers related to one-carbon metabolism in women with PCOS and in a control group. The PCOS group had a higher BMI and HOMA-IR (1.7 vs. 3.1; p < 0.0001). HDL cholesterol levels were 23% lower and triglyceride levels were 74% higher in women with PCOS. Although there were no significant differences in folate and B12 levels between the PCOS and control groups, over 60% of women with PCOS had low B12 levels (<300 pg/mL) and high homocysteine levels. In addition, the MTHFR A1298C and C677T polymorphisms were not associated with PCOS. Moreover, erythrocyte folate levels were positively correlated with fasting glucose, triglycerides, and free androgen index, and negatively correlated with SHBG and LH levels. These results suggest that B vitamins may be associated with the metabolic phenotype in PCOS. This study emphasizes the potential link between folate, vitamin B12, and metabolic and hormonal outcomes in women with PCOS.

Role of Folate in Liver Diseases.

Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines and is one of the essential vitamins for human growth and reproduction. Folate deficiency due to low dietary intake, poor absorption of folate, and alterations in folate metabolism due to genetic defects or drug interactions significantly increases the risk of diseases such as neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Recent studies have shown that folate deficiency can cause hyperhomocysteinemia, which increases the risk of hypertension and cardiovascular disease, and that high homocysteine levels are an independent risk factor for liver fibrosis and cirrhosis. In addition, folate deficiency results in increased secretion of pro-inflammatory factors and impaired lipid metabolism in the liver, leading to lipid accumulation in hepatocytes and fibrosis. There is substantial evidence that folate deficiency contributes to the development and progression of a variety of liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis, and liver cancer. Here we review key studies on the role of folate in the pathophysiology of liver diseases, summarize the current status of studies on folate in the treatment of liver diseases, and speculate that folate may be a potential therapeutic target for liver diseases.

Low magnesium in conjunction with high homocysteine increases DNA damage in healthy middle aged Australians

PurposeMagnesium is one of the most common elements in the human body and plays an important role as a cofactor of enzymes required for DNA replication and repair and many other biochemical mechanisms including sensing and regulating one-carbon metabolism deficiencies. Low intake of magnesium can increase the risk of many diseases, in particular, chronic degenerative disorders. However, its role in prevention of DNA damage has not been studied fully in humans so far. Therefore, we tested the hypothesis that magnesium deficiency either on its own or in conjunction with high homocysteine (Hcy) induces DNA damage in vivo in humans.MethodsThe present study was carried out in 172 healthy middle aged subjects from South Australia. Blood levels of magnesium, Hcy, folate and vitamin B12 were measured. Cytokinesis-Block Micronucleus cytome assay was performed to measure three DNA damage biomarkers: micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) in peripheral blood lymphocytes.ResultsData showed that magnesium and Hcy are significantly inversely correlated with each other (r = − 0.299, p < 0.0001). Furthermore, magnesium is positively correlated both with folate (p = 0.002) and vitamin B12 (p = 0.007). Magnesium is also significantly inversely correlated with MN (p < 0.0001) and NPB (p < 0.0001). Individuals with low magnesium and high Hcy exhibited significantly higher frequency of MN and NPBs compared to those with high magnesium and low Hcy (p < 0.0001). Furthermore, there was an interactive effect between these two factors as well in inducing MN (p = 0.01) and NPB (p = 0.048).ConclusionsThe results obtained in the present study indicate for the first time that low in vivo levels of magnesium either on its own or in the presence of high Hcy increases DNA damage as evident by higher frequencies of MN and NPBs.

Association between Cerebral Small Vessel Disease and Plasma Levels of LDL Cholesterol and Homocysteine: Implications for Cognitive Function

Background: Investigate the correlation between low-density lipoprotein (LDL) cholesterol, homocysteine and cognitive function in patients with cerebral small vessel disease (CSVD). Methods: 240 patients with CSVD confirmed by head MRI in the Department of Neurology from January 2020 to December 2023 were retrospectively included in the study. All the patients had complete blood biochemical examination, and their cognitive function was evaluated by Montreal Cognitive Assessment Scale (MoCA), and after correcting for the factor of years of education, the patients were divided into a group of normal cognition (MoCA ≥26, 70 patients) and a group of cognitive function (MoCA ≥26, 70 patients) according to the scores. After correcting for the factor of years of education, the patients were divided into the normal cognitive function group (70 cases with MoCA ≥26) and the cognitive dysfunction group (170 cases with MoCA &lt;26) according to their scores. The general information of the two groups and the patients' cognitive function characteristics, including visuospatial and executive ability, naming, attention and calculation, language, abstraction, delayed memory, and orientation, were compared, and the independent influences on the occurrence of cognitive dysfunction in patients with CSVD were analyzed by two-category multifactorial logistic regression. Results: Compared with the group with normal cognitive function, the cognitive dysfunction group had lower years of education and higher homocysteine, and the differences were statistically significant (P &lt; 0.05). Compared with the group with normal cognitive functioning, the cognitive dysfunction group had lower MoCA total scores, lower visuospatial and executive ability, naming, attention and calculation, language, abstraction, delayed memory, and orientation scores, and the differences were statistically significant (P &lt; 0.05). Two-category multifactorial logistic regression analysis showed that low-density lipoprotein cholesterol (OR=2.756, 95% CI:0.673-0.938, P=0.012) and homocysteine (OR=1.859, 95% CI: 1.024-1.324, P=0.016) were the independent factors influencing cognitive dysfunction in CSVD patients. The lower the risk of cognitive impairment in CSVD patients, the higher the plasma LDL cholesterol and homocysteine levels, the higher the risk of cognitive impairment in CSVD patients. Conclusion: Plasma LDL cholesterol and homocysteine levels are associated with and may be predictors of cognitive dysfunction in patients with CSVD.

Evaluation of serum folic acid level in patients with type 2 diabetes mellitus

Background and objectives: Type-2 diabetes mellitus is a metabolic disorder. Diabetic patients with low folic acid, high homocysteine levels, have a higher chance of developing coronary heart disease based on previous studies. Therefore, this study aimed to investigate the serum levels of folic acid and homocysteine in type-2 diabetes mellitus patients and their association with insulin resistance. Methods: This cross-sectional study has been conducted on 138 participants from February 2nd 2022 to August 3rd 2022, at Azadi teaching hospital/clinical biochemistry department- Duhok, Kurdistan region, Iraq. The participants were composed of two groups, 70 patients with type-2 diabetes mellitus, and 68 apparently healthy control. Both groups have been investigated for serum folic acid level, serum glucose, serum insulin, serum homocysteine, glycosylated hemoglobin, and Homeostatic Model Assessment for Insulin Resistance. Results: The mean age for type 2 diabetic patients was (51.24 years) with males predominant (64.29%). Type 2 diabetic patients showed a low level of mean serum folic acid concentrations (2.73 ng/ml) in comparison with healthy subjects (5.91 ng/ml) (p&lt;0.001), and the mean serum homocysteine concentration was (13.493 ?mol/L) among type 2 diabetic patients compared to healthy subjects (10.041 ?mol/L) (p&lt;0.001). Significant correlation was found between serum folic acid and serum homocysteine levels, and glycosylated hemoglobin (p&lt;0.05 and p&lt;0.001, respectively). Conclusion: Patients with type-2 diabetes mellitus were associated with low mean serum folic acid levels and high mean serum homocysteine levels.

Docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, and neural tube defects in Tunisian population.

To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR (C677T and A1298C) and MTRR A66G polymorphisms, on maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) levels and the risk of neural tube defects (NTDs). ARA, EPA, and DHA composition was assessed using capillary gas chromatography. ARA and DHA levels were higher in controls than in case mothers for low plasma folate status. For low red blood cell folate status, DHA levels were higher in controls than in case mothers. For high homocysteine levels, ARA and DHA levels were higher in controls than in case mothers. NTD mothers had lower EPA and DHA levels for low vitamin B12 levels. NTD mothers had lower DHA levels for low vitamin D levels. For low plasma folate status, DHA levels in the MTHFR C677T gene and ARA and EPA levels in MTHFR A1298C gene were different among the three genotypes in case mothers. DHA levels in the MTHFR C677T gene were different among the three genotypes in case mothers for both low and high homocysteine levels. For low vitamin B12 levels, ARA and DHA levels were different among the three genotypes of the MTHFR C677T gene in case mothers. In the MTHFR C677T gene, ARA and DHA levels were different among the three genotypes in case mothers for low vitamin D levels. More advanced research is required to verify a suitable biochemical parameter status in relation to the genotypes in pregnant women.

Homocysteine concentration in coronary artery disease and severity of coronary lesions.

Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.

Homocysteine levels in first-episode patients with psychiatric disorders

A high homocysteine (Hcy) level is a risk factor for schizophrenia, depression, and bipolar disorder. However, the role of hyperhomocysteinemia as either an independent factor or an auxiliary contributor to specific psychiatric symptoms or disorders remains unclear. This study aimed to examine Hcy levels in first-episode inpatients with psychotic symptoms and various psychiatric diseases to elucidate the association between Hcy levels and psychiatric disorders. This study enrolled 191 patients (aged 18–40 years) with psychiatric disorders. Seventy-five patients were diagnosed with schizophrenia, 48 with acute and transient psychotic disorders, 36 with manic episodes with psychosis, 32 with major depressive episodes with psychosis, and 56 healthy controls. Serum Hcy levels were measured using the enzyme cycle method. A Hcy concentration level of &amp;gt; 15 μmol/L was defined as hyperhomocysteinemia. Hcy levels were significantly higher in first-episode patients with psychiatric disorders compared to healthy controls (5.99 ± 3.60 vs. 19.78 ± 16.61 vs. 15.50 ± 9.08 vs. 20.00 ± 11.33 vs. 16.22 ± 12.06, F = 12.778, P &amp;lt; 0.001). Hcy levels were significantly higher in males with schizophrenia, acute and transient psychotic disorder, and major depressive disorder but not in mania [schizophrenia, (t = -4.727, P &amp;lt; 0.001); acute and transient psychotic disorders, (t = -3.389, P = 0.001); major depressive episode with psychosis, (t = -3.796, P &amp;lt; 0.001); manic episodes with psychosis, (t = -1.684, P = 0.101)]. However, serum Hcy levels were not significantly different among the psychiatric disorder groups (F = 0.139, P = 0.968). Multivariate linear regression showed that males had an increased risk for homocysteinemia. (95% CI = 8.192–15.370, P &amp;lt; 0.001). These results suggest that first-episode patients with psychiatric disorders have higher Hcy levels than in the general population, and men are at greater risk for psychiatric disorders. In conclusion, elevated Hcy levels may contribute to the pathogenesis of first-episode patients with psychotic symptoms.

Is serum homocysteine level a biomarker of suicide attempts: A preliminary study

Suicide is a global public health concern, and understanding its multifaceted determinants is crucial for effective prevention. This study was designed to find an answer to the question of whether serum homocysteine level can be a biomarker of suicide attempts. This preliminary study involving 90 participants (45 suicide attempt cases and 45 controls) was conducted at Elazig Fethi Sekin City Hospital. Biochemical analyses were performed to assess serum homocysteine, vitamin B12, and folic acid levels. Statistical analyses, including t-tests, Mann-Whitney U tests, and ROC analysis, were employed to explore differences between groups and assess the diagnostic potential of homocysteine. Elevated homocysteine levels were found in individuals who attempted suicide compared to the control group (p= <0.001). Additionally, lower levels of vitamin B12 (p=<0.001) and folic acid (p=<0.001) were observed in the suicide attempt group. ROC analysis indicated a significant diagnostic potential for homocysteine in predicting suicide attempts (AUC = 0.845, sensitivity = 91%, specificity = 71%). This study establishes a significant association between high homocysteine levels and suicide attempts, accompanied by lower vitamin B12 and folic acid levels. The findings suggest a potential link between disturbances in homocysteine metabolism and suicidal tendencies, urging further research to establish causation and explore therapeutic implications. Consideration of the study's limitations and directions for future research are warranted.