Serum Homocysteine Concentrations Research Articles

272 Effects of increasing folic acid on nursery pig growth performance and serum homocysteine

Abstract Barrows (n = 350; DNA 200×400; [n = 2,172; initial body weight (BW) = 6.0 ± 0.06 kg] were used in a 38-d growth trial to determine the effects of increasing folic acid on nursery pig growth performance and serum homocysteine. Pigs were weaned at 21 d of age and randomly allotted to 1 of 5 dietary treatments in a completely randomized design. A total of 70 pens were used with 5 pigs per pen and 14 replications per treatment. Dietary treatments were corn-soybean meal-based and consisted of increasing added folic acid: 0, 5, 10, 20, or 40 mg/kg. Treatment diets were fed in three phases from d 0 to 10 (phase 1), d 10 to 23 (phase 2), and d 23 to 38 (phase 3) after weaning. For phase 1, there were no differences (P > 0.10) in BW, average daily gain (ADG) and average daily feed intake (ADFI) across treatments (Table). However, increasing folic acid resulted in decreased gain to feed ratio (G:F; linear, P = 0.032). For phase 2, there was a marginally significant response in BW, ADG, and ADFI where performance was decreased as folic acid increased with the poorest performance observed when pigs were fed 20 mg/kg (quadratic, P ≤ 0.079). No treatment differences (P > 0.10) were observed for G:F. For phase 3 and overall (d 0 to 38), final BW, ADG, ADFI, and G:F were reduced with increasing folic acid with the poorest performance observed when pigs were fed 20 mg/kg (quadratic, P ≤ 0.049). No differences (P > 0.10) were observed for mortality or removals across treatments with a very low amount of overall mortality. On d 10 and 23, blood samples were collected from 70 pigs to determine serum homocysteine concentrations. A marginally significant treatment × d interaction was observed (linear folic acid × d, P = 0.069). An increase (linear, P = 0.037) in homocysteine concentrations was observed as folic acid increased from 0 to 40 mg/kg in the diet on d 10; however, no differences were observed across increasing folic acid treatments on d 23 (P = 0.450). Pigs had increased (P < 0.001) homocysteine concentrations on d 10 compared with d 23. In summary, the addition of folic acid resulted in reduced growth performance with the greatest impact observed when pigs were fed 20 mg/kg.

Health Patterns across Adulthood: An Age-Based Investigation of the Nutritional Status, Homocysteine, and CoQ10 of Bank Staff.

This study aimed to evaluate age-specific variations in the blood levels of micronutrients, homocysteine, and CoQ10, along with physical activity (PA) patterns, among 123 Austrian adult bankers in operational and frontline roles (mean age: 43 years; 50% female). Blood analysis was conducted to assess micronutrients and the serum concentrations of homocysteine and CoQ10. The micronutrient values in whole blood were compared to sex-specific reference ranges and categorized as below, within, or above them. The Global Physical Activity Questionnaire was utilized to assess PA patterns. Participants were classified as young adults (18-34 years), middle-aged adults (35-49 years), and older adults (50-64 years). Significant age-based differences were found in participants' mean homocysteine levels (p = 0.039) and homocysteine categories (p = 0.034), indicating an increasing prevalence of hyperhomocysteinemia with age. No significant difference between age categories was observed for sex, BMI, diet types, PA levels, sedentary behavior, and CoQ10 (p > 0.05). There was no significant age-based difference in the blood concentrations of most minerals and vitamins (p > 0.05), except for magnesium among females (p = 0.008) and copper among males (p = 0.042). The findings offer initial evidence of the age-related differences in the health status of adult bankers, providing insights for customized approaches to occupational health that support the importance of metabolic health and overall well-being across adulthood.

Elevated Serum Homocysteine Concentrations in Severe Preeclampsia and Eclampsia

Background & objective: Preeclampsia, a pregnancy-specific syndrome, is a major cause of maternal and perinatalmorbidity and mortality all over the world. Several studies have indicated that homocysteine concentrations areincreased in women with preeclampsia. However, there is still conflicting evidence on the extent to which elevatedmaternal homocysteine contributes to this deadly complication of pregnancy. The present study was, therefore,intended to see the association between serum homocysteine and preeclampsia. Methods: This cross-sectional study was carried out in the Department of Obstetrics and Gynaecology, Dhaka MedicalCollege Hospital, Dhaka over a period of 2 (two) years from July 2007 to June 2009. Pregnant women with gestationalage ranging between 24 – 40 weeks having preeclampsia or eclampsia were considered as cases, while gestationalage-matched pregnant women without preeclampsia and eclampsia were considered as controls. However, pregnancywith diabetes mellitus, known renal or hepatic disease, urinary tract infection, cardiovascular disease, and takinganti-epileptics were excluded from the study. A total of 100 pregnant women – 50 cases and 50 controls were selectedfor the study. Among the cases, 16 had mild preeclampsia, 17 had severe preeclampsia, and 17 had eclampsia. Result: Two-thirds of the cases and 60% of the controls were in their 3rd decade of life with no significant differencebetween the study groups (p = 0.651). There was no significant difference between the groups in terms of gravidityand gestational age. However, the past history of PE demonstrated its more significant presence in the case group thanthat in the control group (p = 0.030). Out of 50 cases, 30(60%) had severe proteinura (+++), 15(30%) had moderateproteinuria (++) and 5(10%) had mild proteinuria. The mean serum homocysteine level was significantly higher inmild PE (7.2±1.2 μmol/L) than that in normal pregnant women (5.3±1.0 μmol/L). The concentration of homocysteineincreases with the increase in severity of preeclampsia (p = 0.004) and turning preeclampsia into eclampsia (p =0.027). The data show as the grade of proteinuria increases progressively (from mild to severe) the concentrations ofhomocysteine level also increase progressively from 6.3 ± 1.6 μmol/L in mild proteinuria to 11.4 ± 3.7 μmol/L insevere proteinuria. Conclusion: The serum homocysteine level is significantly elevated in mild PE than that in normal pregnant women.The concentration of homocysteine increases further with the increase in the severity of preeclampsia and ineclampsia. Ibrahim Card Med J 2022; 12 (2): 10-14

Relationship between Serum Homocysteine Concentration and Dietary Factors in Young Japanese Women.

Homocysteine is a methionine metabolism intermediate and its increased blood levels are associated with a higher risk of noncommunicable diseases. Reportedly, blood homocysteine levels increase with inadequate folate, vitamin B6, and vitamin B12 intake; however, its relationship with dietary factors other than these three vitamins remains unknown. Thus, we investigated the relationship of homocysteine with other nutrient intake. We performed a dietary survey on 227 young women using a food record with approximate amounts for 7 consecutive days in conjunction with digital imaging. We collected early morning fasting blood samples the day after the dietary survey was completed and analyzed the serum homocysteine levels. We observed that the serum homocysteine concentrations were significantly negatively associated with soluble, insoluble, and total fiber intake. In addition, participants with high fruit and mushroom intake displayed lower serum homocysteine concentrations, suggesting dietary fiber involvement from these foods. However, we observed no serum homocysteine concentration-related association with cereals and vegetables (well-documented dietary fiber sources) or with fruits and mushrooms. In conclusion, fiber quality-related differences could thus be caused by different sources, including antioxidant components such as fruit polyphenols and mushroom antioxidant and anti-inflammatory factors.

The role of the transsulfuration pathway in spermatogenesis of vitamin D deficient mice

Vitamin D deficiency is a global health problem and has been linked to defective spermatogenesis and male infertility. In this study, we aimed to investigate the main enzymes involved in the transsulfuration pathway of 1-carbon metabolism, and spermatogenesis function. Therefore, sixteen male C57 mice were addressed to a control (standard diet) or vitamin D deficient (VDD) diet for 14 weeks. The results show that compared to the standard diet, VDD increased final body weight and reduced sperm quality, caused damage to the testicular structure, and decreased the serum levels of testosterone. In addition, serum concentrations of homocysteine, vitamin B12, and sperm oxidative stress markers increased. In testicular tissues, the CBS and CSE protein levels were down-regulated whereas HO-1 was up-regulated at both mRNA and protein expression levels. Within a mice deprivation model, VDD deeply suppressed testosterone and impaired spermatogenesis with oxidative stress-mediated mechanisms. The effects of the deprivation appeared to be at least in part independent of genomic and receptor-mediated vitamin D actions and suggest a specific impairment of the alternative transsulfuration pathway.

Reference intervals for total serum homocysteine concentration in shenzhen adults investigated with the aid of nanomaterials

Hyperhomocysteinemia is a risk factor for cardiovascular disease. Therefore, assessing the reference intervals of total serum homocysteine concentration is a critical step in the process of preventing cardiovascular disease. The primary goals of this study were to evaluate gender- and age-related differences in homocysteine concentration in the general population of Shenzhen and possible influencing factors. This retrospective study enrolled 2665 healthy subjects aged 18 to 89 years (mean age, 46.68 years). Blood samples were collected and serum indexes were detected with the aid of magnetic nanoparticles, and serum homocysteine concentration was evaluated by the circulating enzymatic method. The reference intervals (5th and 95th percentiles) of total serum homocysteine concentrations were analyzed by the Hoffmann approach. This approach has been widely used to evaluate reference intervals for various analytical parameters. There were significant differences between males and females in some anthropometric and laboratory indexes in the Shenzhen general population. Men had higher levels of creatinine, uric acid, blood urea nitrogen, and homocysteine, whereas women had higher levels of estimated glomerular filtration rate and thyroid-stimulating hormone. Further studies showed that the reference intervals of total serum homocysteine showed significant differences between males and females and among subjects of different ages. These concentrations were higher in males (mean, 12.74 μmol/L) than in females, and the reference intervals increased with age. Men aged 18 to 40 years had a higher risk of hyperhomocysteinemia than women of the same age. Age- and gender-specific reference ranges of serum homocysteine were defined.

Association of plasma folic acid, vitamin-B12 and homocysteine with recurrent pregnancy loss. "A case control study".

To investigate the relationship of serum homocysteine, folic acid, and vitamin-B12 levels with recurrent pregnancy loss (RPL). A case-control study was conducted in the Department of Gynecology and Obstetrics, Dr. Ruth Pfau Civil Hospital, Karachi from July 2021 to June 2022. Total 124 participants were recruited from gynecology outpatient department after taking informed consent. The participants included 62 non-pregnant females with two or more consecutive unexplained RPLs and 62 healthy women having at least two successful deliveries without any pregnancy loss. Serum folic acid and vitamin-B12 levels were measured by chemiluminescent method and serum homocysteine was measured by enzyme-linked immunosorbent assay (ELISA). Comparison of quantitative variables with RPL cases and control was done by Mann-Whitney U-test (for non-normally distributed data) and independent sample t-test (for normally distributed data), while Pearson's chi-square test was used for the association of qualitative variables with RPL cases and control. Correlation of homocysteine with vitamin-B12 and folic acid was assessed in RPL cases. The median age of the study population was 27 (IQR 25-32) years. The median body mass index (BMI) was 26.25 (IQR 22-29) kg/m2. Cases had significantly lower serum folic acid (p-value=0.022), while vitamin-B12 was decreased in cases as compared to controls (p-value=0.295). Mean concentration of serum homocysteine was higher in RPL cases as compared to controls (p-value=0.094). There was significant association of serum vitamin B12 (p-value=0.001) and folic acid levels (p-value=0.004) with RPL. The homocysteine was not significantly correlated with vitamin-B12 (r=0.124, p=0.338) and folic acid (r=0.067, p=0.606) in the RPL group. Reduced level of serum folic acid and vitamin B12 was significantly associated with RPL cases, while homocysteine was marginally raised however the difference was not significant. Folic acid and vitamin B12 supplementation before next pregnancy in RPL patients is likely to be beneficial in improving pregnancy outcomes.

Associations of serum 25-hydroxyvitamin D with serum folate, cobalanin, and homocysteine concentrations and methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in healthy adults.

The aim of this study was to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with various demographic, anthropometric, and genetic characteristics and biochemical parameters in healthy Greek adults. Demographic (age and sex), anthropometric (body mass index/BMI), and genetic (MTHFR gene polymorphisms) characteristics and biochemical parameters (serum folate, cobalamin/Cbl, and total homocysteine/tHcy concentrations), which had been recorded and measured, among others, in the framework of periodic medical examination (military personnel) or check-up (non-military personnel) of 383 healthy Greek adults (199 men and 184 women) were analyzed. Serum 25(OH)D, tHcy, folate, and Cbl levels were determined using immunoassay methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Serum 25(OH)D concentrations were correlated with Cbl levels and MTHFR C677T gene polymorphism, while they had a reverse correlation with serum tHcy levels, age, and BMI. There was no significant correlation between serum 25(OH)D concentrations and sex, serum folate levels, and smoking status. Individuals with the 677TT genotype had statistically significantly lower serum 25(OH)D levels than those with the 677CC or 677CT genotype, while individuals with the 1298CC genotype had statistically significantly higher serum 25(OH)D levels than those with 1298AA or 1298AC genotype. Moreover, the reverse correlation between the serum 25(OH)D and tHcy levels was statistically significant in all six MTHFR genotypes. Serum 25(OH)D levels are associated with age, BMI, serum tHcy, and Cbl levels and MTHFR C677T gene polymorphism. The most significant finding of our study is the observed reverse correlation of serum 25(OH)D levels with serum tHcy levels. Considering that vitamin D deficiency and hyperhomocysteinemia (HHcy) are associated with an increased risk for cardiovascular diseases (CVDs), we suggest that individuals with high serum tHcy levels should be further investigated for, inter alia, their serum 25(OH)D levels.

INFLUENCE OF THE METHYLENE TETRAHYDROFOLATE REDUCTASE (MTHFR) GENE POLYMORPHISMS ON SERUM FOLATE, COBALANIN AND HOMOCYSTEINE LEVELS IN HEALTHY GREEK ADULTS

Objective: Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. It is well known that hyperhomocysteinemia is associated with an increased risk for cardiovascular disease. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. Design and method: The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men; mean age±SD: 37.3±8.2 years) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Results: Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. On the contrary, the A1298C gene polymorphism had no significantly influence on serum folate and tHcy levels. Conclusions: Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

Serum homocysteine concentration as a marker for advanced diabetic nephropathy in a cohort of elderly patients

BackgroundHyperhomocysteinemia has been linked with chronic kidney disease (CKD). The present study investigated whether homocysteine (Hcy) serum levels might serve as a marker for the advancement of diabetic nephropathy (DN).MethodsClinical and laboratory indicators including Hcy, vitamin D (VD), urine protein, estimated glomerular filtration rate (eGFR) and the urinary protein/creatinine ratio in subjects > 65 years with DN (n = 1,845), prediabetes (n = 1,180) and in a non-diabetes (control) group (n = 28,720) were analyzed.ResultsDN patients had elevated Hcy concentrations, decreased VD and higher urinary protein levels, a reduced eGFR and a higher urinary protein/creatinine ratio compared with prediabetic and control subjects. After correcting for urinary protein quantitation, multivariate analysis revealed that both the Hcy concentration (P < 0.010) and urinary protein/creatinine ratio (P < 0.001) were risk factors, while the VD2 + VD3 serum concentration (P < 0.001) was a protective factor for DN. Moreover, Hcy > 12 µmol/L was a cut-off value for predicting advanced DN.ConclusionHcy serum concentration is a potential marker for the advancement of CKD in DN but not prediabetes patients.

Association Between Serum Homocysteine Concentration, Aneurysm Wall Inflammation, and Aneurysm Symptoms in Intracranial Fusiform Aneurysm

The pathophysiology of fusiform intracranial aneurysm (FIA) involves inflammatory processes, and homocysteine plays a role in the inflammatory processes in the vessel wall. Moreover, aneurysm wall enhancement (AWE) has emerged as a new imaging biomarker of aneurysm wall inflammatory pathologies. To investigate the pathophysiological mechanisms of aneurysm wall inflammation and FIA instability, we aimed to determine the associations between the homocysteine concentration, AWE, and FIAs' related symptoms. We retrospectively reviewed the data of 53 patients with FIA who underwent both high-resolution magnetic resonance imaging and serum homocysteine concentration measurement. FIAs' related symptoms were defined as ischemic stroke or transient ischemic attack, cranial nerve compression, brainstem compression, and acute headache. The contrast ratio of the signal intensity of the aneurysm wall to the pituitary stalk (CRstalk) was used to indicate AWE. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine how well the independent factors could predict FIAs' related symptoms. Predictors of CRstalk were also investigated. Spearman's correlation coefficient was used to identify the potential associations between these predictors. Fifty-three patients were included, of whom 23 (43.4%) presented with FIAs' related symptoms. After adjusting for baseline differences in the multivariate logistic regression analysis, the CRstalk (odds ratio [OR]=3.207, P=.023) and homocysteine concentration (OR=1.344, P=.015) independently predicted FIAs' related symptoms. The CRstalk was able to differentiate between FIAs with and without symptoms (area under the ROC curve [AUC]=0.805), with an optimal cutoff value of 0.76. The homocysteine concentration could also differentiate between FIAs with and without symptoms (AUC=0.788), with an optimal cutoff value of 13.13. The combination of the CRstalk and homocysteine concentration had a better ability to identify symptomatic FIAs (AUC=0.857). Male sex (OR=0.536, P=.018), FIAs' related symptoms (OR=1.292, P=.038), and homocysteine concentration (OR=1.254, P=.045) independently predicted the CRstalk. A higher serum homocysteine concentration and greater AWE indicate FIA instability. Serum homocysteine concentration may be a useful biomarker of FIA instability; however, this needs to be verified in future studies.

Potential mechanism for hyperhomocysteinemia in Greyhound dogs.

Greyhounds have been reported to have hyperhomocysteinemia (HHC), but the underlying mechanisms and clinical implications are unclear. Our primary aim was to assess serum concentrations of homocysteine (HCy) and related analytes in Greyhounds and to identify a likely metabolic pathway for HHC. A secondary aim was to determine whether HHC is associated with evidence of oxidative stress. Healthy pet Greyhounds (n = 31) and non-sighthound control dogs (n = 15). Analysis of serum HCy, cobalamin, folate, and methionine, and plasma cysteine, glutathione, and total 8-isoprostane concentrations. Homocysteine concentrations were higher in Greyhounds (median, 25.0 μmol/L) compared to controls (13.9 μmol/L; P < .0001). Cobalamin concentrations were lower in Greyhounds (median, 416 ng/L) compared to controls (644 ng/L; P = .004) and were inversely correlated with HCy (r = -0.40, P = .004). Serum concentrations of folate, which is regenerated when HCy is converted to methionine, also were inversely correlated with HCy (r = -0.47, P = .002). Serum methionine concentrations were more than 4-fold lower in Greyhounds (median, 3.2 μmol/L) compared to controls (median, 15.0 μmol/L), but this difference was not significant (P = .3). Plasma cysteine, glutathione, and 8-isoprostane concentrations did not differ significantly between groups. Our findings suggest a primary defect in conversion of HCy to methionine in Greyhounds, with related impaired folate generation. Ineffective cycling by methionine synthase could lead to secondary cobalamin depletion. Notably, low serum folate and cobalamin concentrations can be observed in Greyhounds without signs of intestinal disease.

Impact of correction of homocisteinemia on clinical outcomes of lung damage associated with COVID-19 coronavirus infection

Aim. To assess the effect of serum homocysteine levels on treatment outcomes in patients with COVID19-associated lung damage, depending on the use of folic acid in complex treatment.Materials and methods. An open, prospective comparative study included 71 hospitalized adult patients with COVID-19-associated lung disease who did not require mechanical ventilation. The main group included 51 patients who received folic acid 15 mg per day in a complex treatment in a fixed combination with pyridoxine hydrochloride and cyanocobalamin. The comparison group included 20 patients in whose therapy folic acid was not used.Results. The use of folic acid was accompanied by a decrease in serum homocysteine concentration by 2.120 (-0.230; 3.680) µmol/L (p=0.004). When constructing a logistic regression model, the effect of a decrease in serum homocysteine (OR 1.289; 95% CI 1.026‒1.620; p=0.029), methylenetetrahydrofolate reductase MTHFR C677T genotype (OR 10.897; 95% CI 1.240‒95.772; p=0.031) on the achievement of 7th day of hospitalization, the cessation of isolation of SARS-CoV-2 virus RNA from the respiratory tract. Multiple linear regression analysis showed an association between the duration of hypoxemic respiratory failure, determined with SaO2≤93%, with the degree of change in serum homocysteine concentration after treatment, single nucleotide polymorphisms of methylenetetrahydrofolate reductase MTHFR C677T, methionine synthase MTR A2756G and methionine synthase reductase MTRR A66G, initial volume of lung damage ≥50% according to CT data, indicators of D-dimers, C-reactive protein, hemoglobin, platelets, concomitant hypertension, diabetes mellitus (R=0.699; R2=0.489; p=0.005).Conclusion. The dynamics of the decrease in serum homocysteine after treatment is an important predictor of the cessation of isolation from the respiratory tract of the SARS-CoV-2 virus RNA on the 7th day of treatment, reducing the duration of hypoxemic respiratory failure in patients with lung damage associated with COVID-19 infection.

Long-term dietary folic acid supplementation attenuated aging-induced hippocampus atrophy and promoted glucose uptake in 25-month-old rats with cognitive decline

The brain has high energy demand making it sensitive to changes in energy fuel supply. Aging shrinks brain volume, decreases glucose uptake availability of the brain, and finally, causes cognitive dysfunction. Folic acid supplementation delayed cognitive decline and neurodegeneration. However, whether folic acid affects brain energy metabolism and structural changes is unclear. The study aimed to determine if long-term dietary folic acid supplementation could alleviate age-related cognitive decline by attenuating hippocampus atrophy and promoting brain glucose uptake in Sprague-Dawley (SD) rats. According to folic acid levels in diet, 3-months old male SD rats were randomly divided into four intervention groups for 22 months in equal numbers: folic acid-deficient diet (FA-D) group, folic acid-normal diet (FA-N) group, low folic acid-supplemented diet (FA-L) group, and high folic acid-supplemented diet (FA-H) group. The results showed that serum folate concentrations decreased and serum homocysteine (Hcy) concentrations increased with age, and dietary folic acid supplementation increased serum folate concentrations and decreased Hcy concentrations at 11, 18, and 22 months of intervention. Dietary folic acid supplementation attenuated aging-induced hippocampus atrophy, which was showed by higher fractional anisotropy and lower mean diffusivity in the hippocampus, increased brain 18F-Fluorodeoxyglucose (18F-FDG) uptake, then stimulated neuronal survival, and alleviated age-related cognitive decline in SD rats. In conclusion, long-term dietary folic acid supplementation alleviated age-related cognitive decline by attenuating hippocampus atrophy and promoting brain glucose uptake in SD rats.

The Importance of Serum Homocysteine as a Biomarker in Diabetic and Obese COVID-19 Patients.

Homocysteine is a possible risk marker in hematological complications of COVID-19 infection. This study aimed to elucidate the significance of homocysteine as a biomarker for COVID-19 infection, and the relation of homocysteine with COVID-19 severity in obese people and diabetic patients. The study groups were 1- COVID-19 patients + Diabetic + Obese (CDO), 2- COVID-19 patients + Diabetic (CD), 3- COVID-19 patients + Obese (CO), 4- Healthy Group (HG). Serum levels of homocysteine, IL-6, D-dimer, vitamin B12, and folate were measured by a fully automated biochemistry device Cobas 6000 analyzer series.The mean serum concentration of homocysteine in the COD, CD, CO and H groups were 32.0114, 23.604, 19.4154, and 9.3206 umol/l respectively. The mean concentration of homocysteine levels between every two groups was statistically significant differences (P<0.05) except for the CD and the CO group (P=0.957). In the CDO group, the males have higher mean concentrations than females (P<0.05). The means of homocysteine concentrations in the CDO group among different age groups were different (P <0.001). The serum homocysteine level in the CDO group has a strong positive correlation (R=0.748) with D-dimer and a strong negative correlation (R= - 0.788) with serum folate, while its correlation with serum vitamin B12 is moderate negative (-0.499) and its correlation with serum IL-6 is weakly positive (R=0.376). The AUC value for homocysteine in predicting COVID-19 in the CDO group was 0.843, while 0.714 for the CD group, and 0.728 for the CO group. The serum homocysteine concentration test for all study groups was compared to the serum IL-6 test and the sensitivity was equal to 95% and its specificity was 67.5%. Serum homocysteine has potential predictive power in COVID-19 patients, and the severity of COVID-19 infection and the type of comorbidity is associated with higher sensitivity and specificity of homocysteine serological tests.

Dietary Methionine does not Reduce Penetrance in Curly Tail Mice but Causes a Phenotype-Specific Decrease in Embryonic Growth

The mouse mutation, curly tail, has incomplete penetrance and variable expression. Approximately 60% of the mice have a curly tail (CT), from which up to 20% may have lumbosacral spina bifida. Approximately 40% are normal, with a straight tail (ST). We tested whether L-methionine, which reduces the penetrance of neural tube defects in the Axd mouse mutant, has beneficial effects in the curly tail mutant. A single injection of L-methionine (200–1600 mg/kg body wt) on d 9 of pregnancy had no effect on the embryos, whereas there was a minor increase in penetrance at the highest dose. Chronic supplementation of L-methionine via the drinking water (1554 mg·kg body wt-1·d-1) did not shift penetrance. However, it decreased the weight of d 13 embryos from ST dams but not of those from CT dams. This phenotype-specific difference in response was evident and most unexpected. Mice from curly tail and other inbred strains were subjected to an L-methionine loading test and serum homocysteine assay. The different strains varied in their basal serum homocysteine concentrations, and they had proportionate significant increases after L-methionine loading. In CT and ST mice, basal serum homocysteine concentrations as well as the levels after loading were similar to each other and intermediate in the range of the mice tested. We conclude that L-methionine does not reduce penetrance in the curly tail mouse and that this strain reflects no derangement in L-methionine handling.

Associations of Serum Folate and Homocysteine Concentrations with All-Cause, Cardiovascular Disease, and Cancer Mortality in Men and Women in Korea: the Cardiovascular Disease Association Study

BackgroundEvidence on the association of serum folate and homocysteine concentrations with risk of mortality in the general population is unclear. ObjectivesThis study aimed to examine the associations of serum folate and homocysteine concentrations with all-cause, CVD, and cancer mortality risk in Korean men and women aged ≥40 y. MethodsIn this population-based prospective cohort study, serum folate and homocysteine concentrations were measured in a subset of participants enrolled between 2005 and 2012. A total of 21,260 participants were linked to mortality data from the survey date to 31 December 2019. Cox proportional hazards models and restricted cubic splines were used to identify the associations of serum folate and homocysteine concentrations with mortality. ResultsDuring a median follow-up of 12.3 y, 2501, 549, and 842 deaths were attributed to all-cause, CVD, and cancer, respectively. The prevalence of folate deficiency and hyperhomocysteinemia were higher in men than in women. In men, a nonlinear inverse association was observed between serum folate concentrations and all-cause mortality. Men in the third quartile of serum folate concentrations exhibited a lower risk of all-cause mortality (HR: 0.85; 95% CI: 0.73, 0.99) than those in the lowest quartile. Serum homocysteine concentration was positively associated with all-cause and CVD mortality. Men and women in the highest compared with those in the lowest serum homocysteine quartile showed a higher risk of CVD mortality (HR: 1.60; 95% CI: 1.07, 2.39; and HR: 1.79; 95% CI: 1.11, 2.89, respectively). Hyperhomocysteinemia combined with folate deficiency was associated with increased all-cause, CVD, and cancer-related mortality rates. ConclusionsHigher serum homocysteine and lower serum folate concentrations were associated with an increased risk of all-cause, CVD, and cancer-related mortality in Korean adults. The finding of a nonlinear inverse relationship between serum folate concentration and mortality in men warrants further investigation.

Association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with serum folate, cobalanin and homocysteine concentrations in Greek adults

Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men and 184 women) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The MTHFR C677T and not the A1298C gene polymorphism had a significantly influence on serum folate and tHcy levels. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

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&lt;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 (&gt;15 μmol/L), p&lt;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.

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.