Increased Homocysteine Levels Research Articles

Elevated serum homocysteine levels associated with poor recurrence-free and overall survival in patients with colorectal cancer

This study aimed to evaluate the significance of homocysteine (HCY) levels in predicting recurrence-free survival (RFS) and overall survival (OS) in colorectal cancer (CRC) patients. This retrospective study involved 1272 CRC patients. The risk of mortality increased with increasing HCY levels in CRC patients. The optimal HCY cutoff value in CRC patients was 15.2 μmol/L. The RFS (45.8% vs. 60.5%, p < 0.001) and OS (48.2% vs. 63.2%, p < 0.001) of patients with high HCY levels were significantly lower than those of patients with low HCY levels. Patients with high HCY levels were older, male, had large tumours, high carcinoembryonic antigen (CEA) levels, and long hospital stays, and incurred high hospitalisation costs. Multivariate analysis showed that when HCY levels exceeded 15.2 μmol/L, the risk of adverse RFS and OS increased by 55.7% and 61.4%, respectively. Subgroup analysis showed that HCY levels could supplement CEA levels and pathological staging. We constructed HCY-based prognostic nomograms, which demonstrated feasible discrimination and calibration values better than the traditional tumour, node, metastasis staging system for predicting RFS and OS. Elevated serum HCY levels were strongly associated with poor RFS and OS in CRC patients. HCY-based prognostic models are effective tools for a comprehensive evaluation of prognosis.

Elevated homocysteine is negatively correlated with plasma cystathionine β‐synthase activity in givosiran‐treated patients

AbstractGivosiran is a subcutaneously administered, liver‐targeted RNA interference (RNAi) therapeutic that has been approved for treating acute hepatic porphyria (AHP). Elevation in plasma homocysteine (hyperhomocysteinemia) has been reported in AHP patients, and treatment with givosiran has been reported to further increase homocysteine levels in some patients. The mechanism of homocysteine elevation during givosiran treatment is unknown, but has been hypothesized to be mediated by a reduction in activity of cystathionine β‐synthase (CBS), which uses homocysteine as a substrate. A liquid chromatography‐tandem mass spectrometry‐based assay was adapted to measure circulating CBS activity. Using plasma collected from the Phase III ENVISION study, CBS activity was measured to directly evaluate whether it is associated with elevated homocysteine levels in givosiran‐treated patients. CBS activity was reduced following givosiran treatment and both homocysteine and methionine levels were inversely correlated with CBS activity. Following administration of a supplement containing vitamin B6, a cofactor for CBS, in four patients during the trial, plasma CBS activity was found to increase, mirroring a corresponding decrease in homocysteine levels. These results support the hypothesis that elevated homocysteine levels following givosiran treatment result from a reduction of CBS activity and that vitamin B6 supplementation lowers homocysteine levels by increasing CBS activity.

Association between Homocysteine and Vitamin D Levels in Asymptomatic Korean Adults.

An increased homocysteine level is a risk factor for cardiovascular disease, venous thromboembolism, cerebrovascular disease, and chronic kidney disease. In addition, vitamin D deficiency is associated with coronary artery disease and metabolic disorders. The present study included data from 1375 adults (895 men and 480 women) with a mean age of 52.62 ± 9.94 years who visited the Health Promotion Center of the University Hospital in Gyeonggi-do, Republic of Korea from January 2018 to December 2022 for routine checkups that included assessments of their homocysteine and vitamin D levels. Homocysteine levels were positively associated with age, a history of hypertension, a history of diabetes, current smoking habits, and levels of low-density lipoprotein cholesterol, creatinine, uric acid, and high-sensitivity C-reactive protein. By contrast, vitamin D levels were negatively associated with serum levels of homocysteine after adjusting for covariates (β = -0.033, p < 0.001). Additional long-term prospective studies are needed to elucidate the presence of a causal relationship between vitamin D status and serum levels of homocysteine in asymptomatic Korean adults. An intervention trial is warranted to determine whether the administration of vitamin D is helpful for the primary prevention of cardiovascular disease by lowering the homocysteine level in this population.

The influence of chronic hyperhomocysteinemia on the structure and immune processes of the spleen in young rats

Homocysteine is a sulfur-containing amino acid that is an intermediate product of methionine metabolism. Entering the body with products of animal origin, methionine undergoes a number of biochemical transformations. Hyperhomocysteinemia has a negative effect on the body, causing damage to all organs and systems and leading to disruption of homeostasis. The study aims to study the characteristics of changes in the structure and immune processes of the spleen of young rats with chronic hyperhomocysteinemia. Experiments were performed on 22 white male rats. The animals were divided into control and experimental groups (11 individuals in each group) during the experiment. Chronic hyperhomocysteinemia was achieved by administering D, L-thiolactone homocysteine hydrochloride to experimental group animals at a dose of 200 mg/kg of body weight intragastrically in a 1 % starch gel solution once a day for eight weeks. After the end of the experimental simulation of chronic hyperhomocysteinemia, the animals were removed from the experiment by anaesthetising by decapitation and using thiopental anaesthesia. Histological preparations were studied using an SEO SСAN light microscope. Experimental modelling of chronic hyperhomocysteinemia in young rats was not accompanied by significant morphological changes in the stroma and red pulp of the spleen. T-cell periarterial sheaths and B-cell nodules in animals from the experimental group underwent changes. B-cell proliferation leads to growth within the white pulp, expansion of the marginal zones, which become more blurred and infiltration of these cells into the red pulp. Evaluation of the red pulp in the spleen of young rats from the experimental group showed a particular expansion in the venous sinuses, which may be a sign of reaction to the influence of homocysteine and slight swelling of these vessels. The number of T-cells in young animals in the periarterial cuffs is slightly reduced, which can be explained by the increasing activity of macrophages. However, T-cells also infiltrated the red pulp. Such penetration of white blood cells into the red pulp is accompanied by the expansion and “washing out” of the marginal zones of lymph nodes. Thus, the increased homocysteine level significantly potentiated proliferation and partially inhibited apoptosis in T-lymphocytes but did not directly affect dormant T-cells.

High paternal homocysteine causes ventricular septal defects in mouse offspring

Maternal hyperhomocysteinemia is widely considered as an independent risk of congenital heart disease (CHD). However, whether high paternal homocysteine causes CHD remains unknown. Here, we showed that increased homocysteine levels of male mice caused decreased sperm count, sperm motility defect and ventricular septal defect of the offspring. Moreover, high levels of paternal homocysteine decrease sperm DNMT3A/3B, accompanied with changes in DNA methylation levels in the promoter regions of CHD-related genes. Folic acid supplement could decrease the occurrence of VSD in high homocysteine male mice. This study reveals that increased paternal homocysteine level increases VSD risk in the offspring, indicating that decreasing paternal homocysteine may be an intervening target of CHD.

CURRENT DATA ON THE ROLE OF HOMOCYSTEINE IN THE FORMATION OF CARDIOVASCULAR DISEASES

Recent research has made it possible to expand and complement the modern understanding of the regulation of many physiological processes of the body. At the same time, there are many controversial questions about the role of increasing homocysteine levels in the development of certain diseases, mainly cardiovascular pathology. Purpose. To analyze the current literature on the contribution of hyperhomocysteinemia to the formation of cardiovascular diseases (CVD). Material and methods. The data of foreign and domestic articles on the research topic found in Pubmed and eLibrary and published over the past 7 years are analyzed. Conclusions. Hyperhomocysteinemia leads to amplification of the adverse effects of classical CVD risk factors such as hypertension, smoking, lipid metabolism by participating in the formation of endothelial dysfunction.

Importance of Raised Serum Homocysteine Levels in Ischemic Stroke Patients

Background: Around 5.5 million people die from stroke each year, making it the second leading cause of mortality worldwide. Increased homocysteine levels lead to early neurological deteriorations in ischemic stroke and may have an association with other risk factors of stroke. Objective: To determine how closely homocysteine levels are associated with other risk factors for ischemic stroke. Methods: This is a cross-sectional study, which was performed in the Department of Neurology, Liaquat National Hospital, Karachi from January to December 2021. All ischemic stroke patients of either gender above the age of 16 were included. Ischemic stroke was identified by neuroimaging MRI in patients presenting with focal neurological deficits lasting more than 24 hours. For statistical analysis, data was entered into SPSS version 21. Results: A total of 100 patients were included in the study with a mean age of 56.8 ± 15.6 years. Most of the patients were males (65%). Hypertension and diabetes were present in 76% and 42% of patients respectively. 45% of patients had homocysteine levels &lt;15 μmol/l while 55 % had raised homocysteine levels. Amongst them, 42% had levels of homocysteine in the range of 15-30 μmol/l (mild) whereas 13% had &gt;30 μmol/l homocysteine levels (intermediate). None of them had a level &gt;100 μmol (severe). On univariate analysis, the odds of increasing homocysteine levels were higher in males than females. Increasing B12 levels were associated with decreased odds of intermediate homocysteine levels. On the multivariable model after adjusting the model with other covariates, increasing B12 levels remained associated with homocysteine levels with a lower likelihood of intermediate homocysteine levels. Conclusion: According to the results of our study, there is a strong correlation between high homocysteine levels and low B12 levels, making homocysteine a substantial risk factor for ischemic stroke. Vitamin B12 has a major role in homocysteine pathomechanisms and its deficiency predisposes to hyperhomocysteinemia and hence stroke. Larger multicenter studies may be done to evaluate the role of B12 as a homocysteine-lowering agent both for the treatment and prevention of ischemic stroke.

Analysis of risk factors and pregnancy outcomes in pregnant women with subchorionic hematoma.

Subchorionic hemorrhage (SCH) or hematoma is one of the abnormal ultrasonic manifestations. At present, there are few studies on the pathogenesis of SCH, and its underlying mechanism is still unclear. It may be related to abnormal placenta formation and implantation, autoimmune dysfunction, and coagulation dysfunction. As a unique complication of pregnancy, SCH has a controversial effect on pregnancy outcome. The aim of the present study was to explore the possible etiology of SCH, especially its association with autoimmune dysfunctions, as well as the pregnancy outcomes of SCH patients. This retrospective cohort study was conducted at the Third Affiliated Hospital of Zhengzhou University. Patients with a singleton pregnancy of ≤14 weeks gestation from June 2021 to June 2022 were included. Patients with SCH detected by ultrasound were selected as the study group, while patients without SCH during the same period were chosen as the control group. Immunological indicators and pregnancy outcomes were primarily compared between the 2 groups. The decrease in protein S activity and antithrombin-III levels, the increase in homocysteine levels, and the presence of autoantibodies (such as lupus anticoagulant, anticardiolipin antibody, and antinuclear antibody spectrum) were found to be risk factors for SCH. SCH in the first trimester was associated with higher rates of premature rupture of membranes (13.5% vs 3.8%) and miscarriage (14.4% vs 6.4%). However, there were no significant differences in the rates of placental abruption, fetal distress, cesarean section, neonatal birth weight, and gestational age. The incidence of miscarriage was also significantly higher in patients with subchorionic hematoma (SCH) who tested positive for autoantibodies (28.2% vs 7.6%). There were no significant differences in other clinical characteristics and pregnancy outcomes between patients with SCH who had positive autoantibodies and those who did not. The occurrence of SCH may be related to maternal immune abnormalities. SCH may increase the risk of premature rupture of membranes and abortion. However, there is no correlation between the presence or absence of SCH and neonatal outcomes.

Association between maternal plasma one-carbon biomarkers during pregnancy and fetal growth in twin pregnancies

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (β=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (β=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.

The Epidemiology of Deficiency of Vitamin B12 in Preschool Children in Turkey.

Background: Vitamin B12 is a water-soluble vitamin with important cellular functions; it is an essential vitamin. The aim of this study is to determine the B12 levels of children in the period from the 6th month when they start taking additional foods to the age of seven (preschool children) and the risk factors affecting them. Methods: One hundred pediatric patients aged 6-72 months who were diagnosed with vitamin B12 deficiency and their parents who agreed to attend Istanbul Atlas University, Medical Faculty, "Medicine Hospital" Pediatric Clinic between September 2022 and June 2023 were prospectively included in this study. Results: B12 deficiency was significantly higher in the 6-11 (25%)-month group than in the 12-23 (5.8%)- and 24-47 (2.8%)-month groups. Homocysteine levels were highest in those with insufficient B12 levels compared to the other groups. There was no statistically significant difference in weekly dairy and meat consumption levels between age groups. B12 levels were lower in the 6-11-month group than in the other groups. Homocysteine levels were highest in those with insufficient B12 levels (<200 pg/mL (148 pmol/L)). Folic acid levels were lower in the 24-47-month and 48-72-month groups than in the 6-11-month and 12-23-month groups. Conclusions: The results obtained in this study showed that low vitamin B12 and increased homocysteine levels seem to be important risk factors in preschool children, especially from the 6th month when they start consuming additional foods. The diagnosis of B12 deficiency can be confirmed by elevated serum total homocysteine levels, which are evidence of functional cobalamin deficiency.

The role of homocystein in the progression of cardiovascular diseases

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): grant research A number of studies have shown a relationship between the progression of atherosclerosis and atherocalcinosis and an increase in homocysteine levels. The purpose of the study: to evaluate the role of homocysteine (HC) in the progression of cardiovascular diseases (CVD). Material and methods 150 persons aged 40-70 were examined. When assessing cardiovascular risk (CVR), an updated SCORE algorithm was used - SCORE2 - the risk of death and fatal cases of CVD. The patients were divided into groups: group 1 consisted of persons with low and moderate cardiovascular risk (56 patients), group 2 - with high cardiovascular risk (47), and group 3 - persons with very high cardiovascular risk, but without coronary diseases (8 patients), group 4 - 49 patients with diagnosed coronary diseases. The control group consisted of 20 healthy individuals. The examination included: assessment of hemodynamic parameters (BP), indicators of lipid metabolism (total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL) and low density (LDL), determination of homocysteine levels by a biochemical method. Results According to the results of our study, there was a tendency to increase the level of total cholesterol, LDL in people with low and moderate risk, with a significant increase in people with high CVR by 12.5% (p&amp;lt;0.05), 26% (p&amp;lt;0.001); in persons with very high CVR without coronary CVD by 15.1% (p&amp;lt;0.05), 32% (p&amp;lt;0.001); in persons with very high cardiovascular risk with coronary CVD by 13.4% (p&amp;lt;0.05), 20.8% (p&amp;lt;0.05), respectively, compared with the control group. The level of homocysteine in the blood fluctuates around 10–11 µmol/l. According to a number of authors, the level of homocysteine in the blood plasma is 5–15 µmol / L. Hyperhomocysteinemia is diagnosed when the level of homocysteine in the blood exceeds 15 µmol/L. The results of our study showed an increase in serum homocysteine levels with significant values in patients with very high CVR in groups 3 and 4 with an increase of 35.8% (p&amp;lt;0.05) and 39.7% (p&amp;lt;0.05) respectively, compared with the indicators of the control group and in patients with CVD in group 4 was 15.5±7.2 µmol/l. The results of our study confirm the role of hyperhomocysteinemia as a marker of CVD - in patients with pathology of the cardiovascular system, there is a tendency to hyperhomocysteinemia. Also, the revealed dependence of the level of hyperhomocysteinemia with the level of CVR draws attention. A direct correlation was found between the level of homocysteine and low density lipoproteins (r = 0.76). Сonclusion. Thus, according to the results of our study, it was noted that in the group of very high cardiovascular risk in groups 3 and 4, an increase in the level of homocysteine was detected in group 4 with hyperhomocysteinemia with a level of 15.5±7.2 µmol/l. The dependence of the level of hyperhomocysteinemia with the level of CVR and LDL was revealed.

Significance Of Nutrition In Preventing Miscarriage, An Ignored But Modifiable Risk Factor.

Madam, Miscarriage or spontaneous abortion is defined as the pregnancy loss occurring before the 24th week of gestation. This term is used when an ultrasound has confirmed an intrauterine pregnancy1. It is the commonest adverse fate of pregnancy, with vaginal bleeding and abdominal pain as alarming symptoms. It is found that around 12-15% of confirmed pregnancies end up in a miscarriage. Although genetic factors (chromosomal abnormalities) top the list, maternal factors, especially nutritional status, can affect the developing embryo and result in early pregnancy foetal demise2. During pregnancy, maternal requirements for energy, macronutrients (carbohydrates, proteins and fats) and micronutrients increase to cope with the physiological changes occurring in the mother’s body and to support adequate foetal development. Two Case control studies have been conducted and have found a preventive effect of milk consumption and dairy products on spontaneous abortion3. There is also an association between decreased animal fat and carotene intake and increased risk of hydatidiform mole, which can ultimately lead to a miscarriage2. Studies proved that not only macronutrients but deficiency of micronutrients also contribute to poor pregnancy outcomes. Some essential micronutrients include iron, magnesium, zinc, vitamin b12 and folic acid., Due to its antioxidant effects, Vitamin C is also required during this stage and contributes to a healthy pregnancy1. Besides deficiencies, even excess of some micronutrients, like caffeine, especially during the pre-pregnancy state contributed to the risk of early pregnancy loss4. Studies have been done to determine the mechanism behind the nutrition’s effect on the outcome of pregnancy. In the pre pregnancy state, nutritional imbalances result in the alteration of germ cell morphology, which hinders the chances of fertilisation of the altered germ cell. In addition to this, nutritional status during the peri-implantation and placental developmental stage (embryonic stage) play a vital role in the establishment of pregnancy and fetal development so any deficiency during this stage increases the risk of miscarriage. Folic acid deficiency during this stage is harmful. Although it mainly results in the development of congenital anomalies in infants, it is seen that by increasing homocysteine levels it can also lead to miscarriage, although the association is still unknown1. Not only undernutrition but overweight and obesity in mothers also lead to poor pregnancy outcomes. ---Continue

Large Vessel Occlusion Related Ischemic Stroke From Vitamin B12-Deficiency Related Homocysteine (P8-5.029)

<h3>Objective:</h3> <h3>Introduction:</h3> Vitamin-B12 deficiency-related homocysteinemia is an infrequent cause of stroke. Homocysteinemia is associated with hypercoagulability, increased cholesterol-synthesis, increased oxidative-stress, reduced apolipoprotein-A1 synthesis needed to make protective high-density lipoprotein (HDL), along with cumulative mechanisms that impair endothelial function¹. We present a case of acute ischemic large vessel stroke in a young patient who was incidentally found to have low Vitamin-B12 related homocysteinemia. <h3>Background:</h3> N/A <h3>Design/Methods:</h3> <h3>Case report:</h3> 33-year-old male presented with acute onset motor-aphasia 30 minutes prior to arrival. Exam was significant for complete motor aphasia, facio-bucco-lingual apraxia and a right nasolabial-fold flattening. CT-head was negative for hemorrhage or acute ischemia and CT angiogram revealed an abrupt cut off of the left M1 segment. Patient received thrombolysis with Tenecteplase (TNK) and was emergently taken for mechanical-thrombectomy. On conventional angiogram, the M1 segment showed restored patency after TNK. Work up for secondary causes of stroke including telemetry, transesophageal echocardiogram, hypercoagulability labs, antinuclear antibody (ANA), and syphilis serology were unremarkable. Vitamin-B12 levels were significantly low at &lt; 148 (normal 213–816pg/ml), folate levels were borderline low at 5.0 (5.4–20ng/ml) and homocysteine was significantly elevated at 35 (5.1–15.4mcmol/l). Patient was treated with dual antiplatelet therapy with aspirin 81mg , clopidogrel 75mg and initiated on B12 and folate supplements. Patient was discharged home with near-complete symptom resolution and occasional word-finding difficulty. <h3>Results:</h3> N/A <h3>Conclusions:</h3> <h3>Discussion:</h3> Vitamin-B12 deficiency increases homocysteine levels which is associated with premature atherosclerosis² and is a risk factor for thrombotic events. While vitamin-supplementation can lower homocysteine levels, the benefits as primary-prophylaxis remain uncertain³. It is worthwhile to consider vitamin-supplementation with folic-acid (2.5 mg) and B-complex vitamin (50 mg B6 and 1 mg B12) ¹ supplements in patients with cryptogenic-strokes who have vitamin-B12 deficiency and homocysteinemia as a plausible cause for stroke. Further studies are needed to understand the pathophysiology of these two entities as risk factors for stroke. <b>Disclosure:</b> Dr. Harish has nothing to disclose. Dr. Rau has nothing to disclose. Dr. Diaz Rojas has nothing to disclose.

Hyperhomocysteinemia due to Vitamin B12 Deficiency with MTHFR Gene Mutation, an Atypical Metabolic Cause of Young Ischemic Stroke: A Case Report

Background: Vitamin B12 deficiency can impair the metabolism of homocysteine, leading to hyperhomocysteinemia that can cause thrombosis in the intracranial blood vessels resulting in a stroke. Case Presentation: A 15-year-old Muslim young boy initially presented with pallor, slurred speech, right facial weakness, and right-sided hemiplegia. On examination, he was found moderately anemic, nonicteric, and with right-sided stroke evidenced by hypertonia, reduced muscle power jerk exaggerated with extensor plantar response. There was no lymphadenopathy, bony tenderness, intellectual impairment, or organomegaly, and normal vital parameters with the unremarkable cardiovascular examination. Laboratory investigations revealed pancytopenia, with reduced Vit B12, folic acid, and moderately increased homocysteine level. Bone marrow study suggestive of megaloblastic anemia. Immunological, infectious screens; and prothrombotic markers were found negative. CT scan of the head revealed a hypodense lesion in the left parieto-occipital region, DWI sequence on MRI Brain revealed diffusion restriction in the same area while an MR angiogram of the Brain revealed occlusion of the left middle cerebral artery due to thrombus sparing a small segment after its origin. In addition, he had MTHFR c677 C&gt;T (Methyl tetrahydrofolate reductase) gene mutation and responded both clinically and biochemically after vitamin B12, folic supplementation along with aspirin in 5 months. Conclusion: Vitamin B12 deficiency along with MTHFR c677 C&gt;T gene mutation has increased the chance of thrombotic stroke. Vitamin B12 supplementation might be beneficial for patients with an MTHFR gene mutation positive. J MEDICINE 2023; 24: 51-55

A Rare Case of Deep Vein Thrombosis Secondary to Protein S Deficiency and Antithrombin III Deficiency with MTHFR (C677T) Heterozygous Mutation, and Crohn’s Disease

Deep vein thrombosis is a condition wherein a thrombus develops in the deep veins of the body, most commonly in the legs, due to increasing tendency of the blood to coagulate. One such reason is the MTHFR gene mutation, wherein an increase in homocysteine levels causes irritation of the blood vessel endothelium, causing a disturbance in Virchow’s triad, hence triggering clot formation. [1]

High Homocysteine Levels Are Associated with Cognitive Impairment in Patients Who Recovered from COVID-19 in the Long Term.

In this study, we measured the levels of depression and cognition in people recovering from COVID-19. Moreover, we aimed to investigate the relationship between depression and cognition levels by measuring homocysteine concentrations. It included 62 people recovering from COVID-19 (at least 3 months after positive RT-PCR) and 64 people without COVID-19 (control group). At first, the homocysteine levels of participants were measured. Beck Depression Inventory (BDI) and Montreal Cognitive Assessment (MoCA) were performed to collect data. Homocysteine levels of the group recovering from COVID-19 (x- = 19.065 µmol/L) were higher than the control group (x- = 11.313 µmol/L). There was no significant difference between the groups for BDI scores. The MoCA scores of the group recovering from COVID-19 (x- = 20.774) were lower than the control group (x- = 24.297). There was a negative high (r = -0.705, p < 0.001) correlation between homocysteine levels and MoCA scores. Linear regression analysis is shown to be significant, and the MoCA explanatory value of the variables in the model is 58.6% (p < 0.0001). A 1 µmol/L observed increase in homocysteine level constituted a risk for a 0.765-point decrease in MOCA scores. In patients recovering from COVID-19, early interventions to high homocysteine levels may prevent cognitive impairments that may persist in the long term.

STUDY OF PREVALENCE OF HYPERHOMOCYSTEINEMIA IN CHRONIC KIDNEY DISEASEPATIENTS AT TERTIARY CARE HOSPITAL IN NORTHWEST MAHARASHTRA

Introduction-Chronic Kidney Disease is growing problem across all over world and India as well. Chronic kidney disease encompasses a spectrum of different pathophysiological processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate(GFR).The risk for cardiovascular disease (CVD) morbidity and mortality remains high in all stages of CKD, including in patients with hemodialysis. More patients with CKD die of CVD than of the progression of kidney failure.The increase of homocysteine level, referred as hyperhomocysteinemia, is highly prevalent in CKD patients and associated with an increased risk of CVD complications. Proposed mechanisms for hyperhomocysteinemia in kidney failure is due to reduced clearance of total plasma homocysteine (tHcy) secondary to defective kidney and/or extra kidney metabolism of tHcy and deficiencies of folate, vitamin B12, and pyridoxal 5-phosphate (PLP). Aim-To study Serum Homocysteine levels in patients with Chronickidney disease and to estimate Serum Homocysteine levels in different stages of Chronic kidney disease. Materials And Methods- All the patients presenting with clinical, biochemical and ultrasound kidney evidence of chronic kidney disease in department of medicine at tertiary care centre in northern Maharashtra. Normal plasma homocysteine level was considered to bebelow 15 umol/litre. Results- A study of 54 patients with Chronic Kidney disease of both sex were taken as sample. Of the 54 patients 38 were males and 16 were females .36 patients were in age range of 41-60 . 32 patients were in stage 5 CKD , 14 were in stage 4 CKD , 8 were in stage 3 CKD. Hyperhomocysteinemia was observed in 78 % of CKD patients. Serum Homocysteinemia levels were maximum in patients with higher grade of CKD. The associationbetween decreased GFR and increase in serum homocysteine levels was found to be statistically significant. (p&lt;0.05). Conclusion-Study concludes that hyperhomocysteinemia is highly prevalent in CKD patients. Homocysteine is commonly considered as toxicthrombogenic amino acid which causes atherosclerosis and cardiovascular diseases. Mortality due to cardiovascular diseases is high in CKD. Hence early screening and treatment for Hyperhomocysteinemia should be done in CKD to prevent cardiovascular diseases.

The interplay between prolactin and cardiovascular disease.

Hyperprolactinemia can be caused by several conditions and its effects on the hypothalamic-pituitary-gonadal axis are understood in more detail. Nevertheless, in recent decades, other metabolic effects have been studied and data pointed to a potential increased cardiovascular disease (CVD) risk. A recent study showed a decrease in total and LDL- cholesterol only in men with prolactinoma treated with dopamine agonists (DA) supporting the previous results of a population study with increased CVD risk in men harboring prolactinoma. However, other population studies did not find a correlation between prolactin (PRL) levels and CVD risk or mortality. There is also data pointing to an increase in high-density lipoprotein levels, and decreases in triglycerides, carotid-intima-media thickness, C-reactive protein, and homocysteine levels in patients with prolactinoma on DA treatment. PRL was also implicated in endothelial dysfunction in pre and postmenopausal women. Withdrawal of DA resulted in negative changes in vascular parameters and an increase in plasma fibrinogen. It has been shown that PRL levels were positively correlated with blood pressure and inversely correlated with dilatation of the brachial artery and insulin sensitivity, increased homocysteine levels, and elevated D-dimer levels. Regarding possible mechanisms for the association between hyperprolactinemia and CVD risk, they include a possible direct effect of PRL, hypogonadism, and even effects of DA treatment, independently of changes in PRL levels. In conclusion, hyperprolactinemia seems to be associated with impaired endothelial function and DA treatment could improve CVD risk. More studies evaluating CVD risk in hyperprolactinemic patients are important to define a potential indication of treatment beyond hypogonadism.

Increased Plasma Homocysteine Levels Are Associated with Left Ventricular Hypertrophy in Hypertensive Patients with Normal Renal Function

Introduction: Renal function has an important bearing on plasma homocysteine levels. Plasma homocysteine is related to left ventricular hypertrophy (LVH). However, it remains unclear whether the association between plasma homocysteine levels and LVH is influenced by renal function. This study aimed to investigate relationships among left ventricular mass index (LVMI), plasma homocysteine levels, and renal function in a population from southern China. Methods: A cross-sectional study was performed in 2,464 patients from June 2016 to July 2021. Patients were divided into three groups based on gender-specific tertiles of homocysteine levels. LVMI ≥115 g/m2 for man or ≥95 g/m2 for woman was defined as LVH. Results: LVMI and the percentage of LVH were increased, while estimated glomerular filtration rate (eGFR) was decreased with the increase in homocysteine levels, both significantly. Multivariate stepwise regression analysis showed that eGFR and homocysteine were independently associated with LVMI in patients with hypertension. No correlation was observed between homocysteine and LVMI in patients without hypertension. Stratified by eGFR, further analysis confirmed homocysteine was independently associated with LVMI (β = 0.126, t = 4.333, p < 0.001) only in hypertensive patients with eGFR ≥90 mL/(min·1.73 m2), not with 60≤ eGFR <90 mL/(min·1.73 m2). Multivariate logistic regression indicated that in hypertensive patients with eGFR ≥90 mL/(min·1.73 m2), the patients in high tertile of homocysteine levels had a nearly twofold increased risk of occurring LVH compared with those in low tertile (high tertile: OR = 2.780, 95% CI: 1.945–3.975, p < 0.001). Conclusion: Plasma homocysteine levels were independently associated with LVMI in hypertensive patients with normal eGFR.

Effects of coffee supplementation on homocysteine and leptin levels: a systematic review and meta-analysis of clinical trials.

It has been reported that the consumption of antioxidant foods and beverages may benefit the development of cardiovascular risk factors. However, the impact of coffee consumption on some of these factors, such as homocysteine and leptin is controversial. Some clinical trials have suggested that coffee administration increases plasma total homocysteine levels, while others have found no significant changes in leptin concentrations. This study aimed to assess the effects of coffee supplementation on homocysteine and leptin concentrations in a meta-analysis of clinical trials. PubMed, Web of Science, Scopus, ClinicalTrials.gov, and Google Scholar databases were searched from inception to September 29, 2021. A fixed-effects model and the generic inverse variance weighting method were used for meta-analysis. The meta-analysis demonstrated that coffee administration significantly increases homocysteine levels (WMD: 0.55 µmol/L, 95% CI: 0.17, 0.93, p = 0.005, I2 = 0%) but has no significant changes in leptin concentrations (WMD: 1.34 ng/mL, 95% CI: -0.78, 3.45, p = 0.21, I2 = 0%). Additionally, the sensitivity analysis was robust for both homocysteine and leptin levels. The results of the present meta-analysis revealed that coffee supplementation raises serum homocysteine concentrations but has no effect on circulating leptin levels.