Lower Homocysteine Research Articles

New Evidence for Homocysteine Lowering for Management of Treatment-Resistant Hypertension.

New Evidence for Homocysteine Lowering for Management of Treatment-Resistant Hypertension.

Role of Folic Acid in Type 2 Diabetes

The metabolic condition known as diabetes mellitus is marked by hyperglycemia, a host of symptoms affecting the heart, kidneys, nerves, and other organs. Diabetes nephropathy is one of the leading causes of diabetic impermanence and morbid state. Low parameters of pteroylglutamic acid in the blood are associated with Diabetic Nephropathy, whereas endothelial dysfunction increases the risk for T2D.
 Endothelial dysfunction is associated with diabetes, which perhaps is caused by the disjunction of the endothelial nitric oxide (NO) synthase enzyme, which reduces NO availability. Because folic acid can repair the disjunction of NO synthase, we sought to see if pteroylglutamic acid supplementation may affect the function of the endothelial layer and inflammatory indicators in type 2 diabetes patients who did not have vascular disease.
 Recent studies have shown that pteroylglutamic acid also has direct benefits on the function of endo, in addition to its natural function of lowering homocysteine. Folic acid might serve as a "biomarker" for the function of endothelial cells. Many mechanisms have been linked to higher total homocysteine levels and type 2 diabetes risk in diabetic patients. Higher folic acid levels altered endothelial-dependent vasodilation in T2D patients. In patients with coronary heart disease (CAD), folic acid supplementation has been found to reduce homocysteine parameters and improve the function of the endothelial layer. On the other hand, RCTs looking at IR and T2D outcomes have shown mixed results.
 Several mechanisms link higher total homocysteine levels to increased risk of insulin resistance (IR) and type 2 diabetes mellitus (T2D). Treatment with folate has been shown to bring down homocysteine parameters and improve the endothelium functions in people with coronary heart disease (CAD). Randomized controlled trials (RCTs) on IR and T2D outcomes, on the other hand, have produced a wide range of results.

Effectiveness of a fortified drink in improving B vitamin biomarkers in older adults: a controlled intervention trial

BackgroundOlder adults are reported to have sub-optimal B vitamin status; targeted food-based solutions may help to address this. The objectives of the OptiAge food intervention study were to develop and investigate the effectiveness of a B vitamin-fortified drink in improving B vitamin biomarkers in older Irish adults with a primary outcome of change in the B vitamin biomarker status.MethodsA double-blinded randomised controlled trial was performed in parallel at University College Dublin and Ulster University. Participants aged > 50 years were recruited following screening for exclusion criteria (i.e. taking medications known to interfere with B vitamin metabolism, supplements containing B vitamins, consuming > 4 portions of B vitamin-fortified foods per week or diagnosed with gastrointestinal, liver or pulmonary disease). Recruited participants meeting the inclusion criteria were randomised (by sex and study centre) to receive daily for 16 weeks either B vitamin-fortified or placebo drinks as developed by Smartfish, Norway. Each B vitamin-fortified drink (200 ml) contained 200 µg folic acid, 10 µg vitamin B12, 10 mg vitamin B6 and 5 mg riboflavin, while the placebo was an identical, isocaloric formulation without added B vitamins. Fasting blood samples were collected pre- and post-intervention which were used to measure the primary outcome of change in B vitamin biomarker levels.ResultsA total of 95 participants were randomised, of which 81 commenced the trial. Of these, 70 completed (37 in the active and 33 in the placebo groups). Intention to treat (ITT) analysis of the B vitamins demonstrated a significant improvement in all B vitamin biomarkers in the active compared to placebo groups: p < 0.01 for each of serum folate, serum vitamin B12 and plasma pyridoxal 5′-phosphate (vitamin B6) and the functional riboflavin biomarker, erythrocyte glutathione reductase activation coefficient (EGRac). Correspondingly, a significant lowering of serum homocysteine from 11.9 (10.3–15.1) µmol/L to 10.6 (9.4–13.0) µmol/L was observed in response to the active treatment (P < 0.001). Similar results were seen in a per-protocol analysis.ConclusionsThe results demonstrate that a B vitamin-fortified drink was effective in optimising B vitamin status, making this a useful intervention option to improve B vitamin status in older adults.Trial registration ISRCTN, ISRCTN61709781—Retrospectively registered, https://www.isrctn.com/ISRCTN61709781

Relationship between homocysteine levels and post-stroke cognitive impairment in female and male population: from a prospective multicenter study.

ABSTRACTBackground and Objectives:To investigate the relationship between homocysteine levels and post-stroke cognitive impairment (PSCI) in Chinese female and male populations with minor acute ischemic stroke or transient ischemic attack.Materials and methods:A total of 1070 participants with clinically confirmed acute minor ischemic stroke or transient ischemic attack and baseline homocysteine information from a nationwide multicenter prospective registry study in China were included in this study. Of these, 919 patients had cognitive assessments at 3-month follow-ups and 584 participants had cognitive assessments at 12-month follow-ups. The incidence of PSCI was defined as a Montreal Cognitive Assessment score ≤22. The differences in homocysteine levels and the incidence of PSCI were compared between female and male populations. Relationships between homocysteine levels and the incidence of PSCI in female and male populations were analyzed using multiple logistic regression, respectively.Results:Females had lower baseline homocysteine levels than males. Compared to males, females had lower education levels, lower rates of smoking and alcohol intake, and higher rates of diabetes and hypertension. No relationship was observed between elevated homocysteine level and 3-month PSCI incidence in either females or males. After adjusting the confounders, elevated baseline homocysteine significantly increased the 12-month PSCI risk (odds ratio 3.28, 95% confidence interval 1.47–7.34, P = 0.004) in females, but not in males (odds ratio 0.86, 95% confidence interval 0.49–1.49, P = 0.586).Conclusion:Elevated homocysteine levels increased the 12-month PSCI risk in females, but not in males with minor acute ischemic stroke or transient ischemic attack.

Abstract 17117: Hyperhomocysteinemia Associated St Elevation Myocardial Infarction In A Young Male

Case Presentation: A 24-year-old male with a medical history of Crohn’s on mesalamine presented to the emergency room with crushing substernal chest pain at rest. Electrocardiogram revealed ST elevations in Lead V2-V5 (Figure-1a). He was taken emergently to the catheterization laboratory and had 100% thrombotic occlusion of his proximal left anterior descending coronary artery (LAD) (Figure-1b). Intravascular ultrasound (IVUS) confirmed the presence of soft atheromatous lipid-rich plaque in the proximal LAD with heavy thrombus burden (Figure-1c/d). He underwent aspiration thrombectomy and IVUS guided percutaneous coronary intervention with a 4.5 mm x 32 mm drug-eluting stent. Echocardiogram revealed an akinetic anterior wall with an ejection fraction of 35% without a patent foramen ovale. Hypercoagulable workup was initiated and showed a significantly elevated homocysteine level of 84.4 umol/L (normal:3.5-10.4). Family history, drug screen, hemoglobin A1C, and lipid profile were unremarkable. Discussion: The differential diagnosis in a young male presenting with a STEMI includes thromboembolism versus plaque rupture. IVUS showed clear evidence of a lipid-rich plaque demonstrating premature atherosclerotic vascular disease rather than a thromboembolic event. His most striking risk factor was hyperhomocysteinemia with a level of 84.4 umol/L. Elevations in homocysteine plasma concentration has been identified as an independent risk factor for atherosclerosis due to its atherogenic and prothrombotic properties. To date lowering homocysteine levels with folate and additional therapies have not shown to reduce the risk of coronary disease. Our case stresses the importance of intravascular imaging, especially in atypical cases such as a young male presenting with a STEMI to differentiate plaque rupture versus thromboembolism. Further studies are needed to identify risk modifying therapies for hyperhomocysteinemia associated vascular disease.

Maternal One-Carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review.

The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B6, vitamin B12, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (>17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (<7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases.

Association between folic acid, homocysteine, vitamin B12 and erectile dysfunction-A cross-sectional study.

To evaluate the relationship between serum levels of folic acid (FA), homocysteine (HCY), vitamin B12 (B12) and erectile dysfunction (ED) and to explore their internal relationships. The study included 134 ED patients and 50 healthy controls. ED was assessed using IIEF-5 scores. ED group had lower median FA (6.08 versus 10.21; p<.001) and B12 (256.0 versus 337.5; p<.001) levels, and higher median HCY (11.4 versus 7.95; p<.001) levels, and these differences seemed to be more pronounced in the younger participants (age<35yr). FA decreased with the severity of ED (7.52 versus 6.15 versus 5.49 versus 3.97; p<.001), while HCY increased (10.35 versus 11.8 versus 12.9 versus 15; p<.001). Smoking and shift work were associated with lower FA levels. Multivariate analysis showed that serum FA and HCY revealed significant relation with ED. ROC analysis showed that FA≤8.84 and HCY≥10.35 were the best cut-off values for ED diagnosis. Both FA (r=-0.703, p<.001) and B12 (r=-0.576, p<.001) were negatively correlated with HCY. In conclusion, low FA levels and high HCY levels might be independent risk factors for ED. Low serum FA and B12 levels might co-cause high HCY levels and lead to ED.

Exploring the Impact of Flavonoid Interventions on Brain and Cognitive Function

Depression and high total plasma homocysteine (tHcy) are independently associated with cognitive impairment in older adults. We designed this study to determine if high tHcy is a mediator of cognitive performance in older adults with major depression.We recruited 358 community-dwelling older adults experiencing depressive symptoms, 236 (65.9%) of who met DSM-IV-TR criteria for major depression. Assessment included the Montgomery Asberg Depression Rating Scale (MADRS), fasting tHcy and the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery.Individuals with major depression and high tHcy had significantly worse immediate verbal and delayed visual recall. Non-depressed participants with high tHcy had lower MMSE, immediate and delayed recall scores than those with normal tHcy. The odds of cognitive inefficiency for those with high tHcy was nearly doubled for the MMSE (OR 1.9, 95%CI 1.1–3.3), immediate (OR 1.9, 95%CI 1.1–3.5) and delayed (OR 1.9, 95%CI 1.1–3.4) word recall after adjusting for age, gender, IHD and MADRS score.The presence of sub-syndromal depressive symptoms in our non-depressed group and exclusion of participants with established cognitive impairment may limit the generalizability of this study.Elevated tHcy was associated with weaker performance in tests of immediate and delayed memory and global cognitive performance when compared to those with normal tHcy independent of the presence of major depression or the severity of depressive symptoms. Homocysteine lowering B-vitamin supplementation may offer a potential therapeutic target to try and mitigate the often-disabling impact of cognitive deficits found in this population.

Using data mining technology to explore homocysteine at low levels.

A high homocysteine level is known to be an independent risk factor for cardiovascular diseases; however, whether or not low homocysteine level contributes to any damage to the body has not been extensively studied. Furthermore, acquiring healthy subject databases from domestic studies on homocysteine is not trivial. Therefore, we aimed to investigate the causality between serum homocysteine levels and health status and lifestyle factors, particularly with a focus on low serum homocysteine levels. Additionally, we discussed a systematic methodical platform for data collection and statistical analysis, using the descriptive analysis of the chi-square test, t test, multivariate analysis of variance, and logistic regression.This study was a cross-sectional analysis of 5864 subjects (i.e., clients of a health examination clinic) in Taipei, Taiwan during a general health check-up in 2017. The patients’ personal information and associated links were excluded. A sample group was selected as per the health criteria defined for this research whose data were processed using SPSS for descriptive statistical analysis using chi-square test, t test, multivariate analysis of variance, and logistic regression analysis.Those working for >12 hours/day had a higher homocysteine level than those working for <12 hours/day (P < .001). The average serum homocysteine level was 7.9 and 8.6 mol/L for people with poor sleep quality and good sleep quality, respectively (P = .003). The homocysteine value of people known to have cancer was analyzed using the logistic regression analysis, revealing a Δodds value of 0.898. The percentage of subjects with a homocysteine value of ≤6.3 μmol/L, who perceived their health status as “not very good” or “very bad,” was higher than those with a higher homocysteine level. The number of subjects who perceived their health as poor was higher than expected.The results suggest that the homocysteine level could be an effective health management indicator. We conclude that normal homocysteine level should not be ≤6.3 μmol/L. Moreover, homocysteine should not be considered as harmful and its fluctuations from the normal range could be utilized to infer a person's physical status for health management.

Cross-Sectional Examination of Homocysteine Levels with Sarcopenia and Its Components in Memory Clinic Outpatients.

Homocysteine is a common risk factor for cognitive impairment and sarcopenia. However, very few studies have shown an association between sarcopenia and serum homocysteine levels after adjustment for cognitive function. The purpose of this study was to investigate the relationship between homocysteine and sarcopenia in memory clinic patients. This cross-sectional study investigated outpatients in a memory clinic. We enrolled 1,774 participants (≥65 years old) with measured skeletal muscle mass index (SMI), hand grip strength (HGS), and homocysteine. All participants had undergone cognitive assessments and were diagnosed with dementia, mild cognitive impairment, or normal cognition. Patient characteristics were compared according to sarcopenia presence, SMI level, or HGS. Multivariate logistic regression analysis was performed to determine the association of homocysteine with sarcopenia, low SMI, or low HGS. Next, linear regression analysis was performed using HGS as a continuous variable. Logistic regression analysis showed that low HGS was significantly associated with homocysteine levels (p = 0.002), but sarcopenia and low SMI were not. In linear regression analysis, HGS was negatively associated with homocysteine levels after adjustment for Mini-Mental State Examination score (β= -2.790, p < 0.001) or clinical diagnosis of dementia (β= -3.145, p < 0.001). These results were similar for men and women. Our results showed a negative association between homocysteine and HGS after adjustment for cognitive function. Our findings strengthen the assumed association between homocysteine and HGS. Further research is needed to determine whether lower homocysteine levels lead to prevent muscle weakness.

Investigating the causality of metabolites involved in one-carbon metabolism with the risk and age at onset of Parkinson's disease: A two-sample mendelian randomization study

With the aging population and increasing life expectancy, Parkinson's disease (PD), a neurological disorder rapidly increasing in morbidity and mortality, is causing a huge burden on society and the economy. Several studies have suggested that one-carbon metabolites, including homocysteine, vitamin B6, vitamin B12 and folate acid, are associated with PD risk. However, the results remain inconsistent and controversial. Thus, we performed a two-sample Mendelian randomization (MR) study to detect the causality between one-carbon metabolites and PD susceptibility as well as age at PD onset. We collected several genetic variants as instrumental variables from large genome-wide association studies of one-carbon metabolites (homocysteine: N = 14, vitamin B6: N = 1, vitamin B12: N = 10, folate acid: N = 2). We then conducted MR analyses using the inverse variance-weighted (IVW) approach and additional MR-Egger regression, weighted median and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods to further test causality. The results showed no causal association between circulating homocysteine levels and PD risk (p = 0.868) or age at PD onset (p = 0.222) with the IVW method. Meanwhile, similar results were obtained by three complementary analyses. In addition, we did not observe any evidence that the circulating levels of vitamin B6, vitamin B12 and folate acid affected the risk of PD or age at onset of PD. Our findings implied that lowering homocysteine levels through vitamin B6, vitamin B12 or folate acid supplementation may not be clinically helpful in preventing PD or delaying the age at PD onset.

Anemia, hematinic deficiencies, and hyperhomocysteinemia in burning mouth syndrome patients with thyroglobulin antibody/thyroid microsomal antibody positivity but without gastric parietal cell antibody positivity

Background/purposeOur previous study found that 222 of 884 burning mouth syndrome (BMS) patients have thyroglobulin antibody (TGA) positivity and/or thyroid microsomal antibody (TMA) positivity but without gastric parietal cell antibody positivity (GPCAˉTGA+/TMA+BMS patients). This study mainly assessed whether the serum TGA/TMA positivity was significantly associated with anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAˉTGA+/TMA+BMS patients. Materials and methodsThe complete blood count, iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between 222 GPCAˉTGA+/TMA+BMS patients and 553 GPCA-negative, TGA-negative, and TMA-negative BMS patients (GPCAˉTGAˉTMAˉBMS patients) or 442 healthy control subjects. ResultsWe found that 222 GPCAˉTGA+/TMA+BMS patients had significantly lower mean corpuscular volume (MCV) and lower blood Hb and serum iron levels than 442 healthy control subjects and significantly lower MCV and lower serum homocysteine levels than 553 GPCAˉTGAˉTMAˉBMS patients. Moreover, 222 GPCAˉTGA+/TMA+BMS patients had significantly greater frequencies of microcytosis, macrocytosis, blood Hb and serum iron deficiencies, and hyperhomocysteinemia than 442 healthy control subjects and significantly higher frequency of microcytosis but significantly lower frequency of hyperhomocysteinemia than 553 GPCAˉTGAˉTMAˉBMS patients. However, no significant differences in the frequencies of macrocytosis, blood Hb, serum iron, vitamin B12, and folic acid deficiencies were discovered between 222 GPCAˉTGA+/TMA+BMS patients and 553 GPCAˉTGAˉTMAˉBMS patients. ConclusionWe conclude that the disease of BMS itself does play a significant role in causing macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAˉTGA+/TMA+BMS patients. However, the serum TGA/TMA-positivity is not significantly associated with anemia and serum iron, vitamin B12, and folic acid deficiencies in GPCAˉTGA+/TMA+BMS patients.

Homocysteine, vitamin B status and MTHFR polymorphisms in Italian infertile women

ObjectiveThe purpose of this study was to evaluate the vitamin B status related to the homocysteine pathway and the prevalence of polymorphisms of the MTHFR gene in infertile women programming homologous or heterologous ART. Study designWe investigated 393 consecutive Caucasian women, referred to the Internal Medicine Clinic at the Center for Assisted Reproductive Technology, in order to be framed for their vascular risk before starting homologous or heterologous (oocyte donation) procedures. Total homocysteine, Vitamin B12, folate and vitamin B6 were measured. The women were divided into quartiles of serum concentration of folate, vitamin B12 and vitamin B6. The C677T and A1298C polymorphisms of the MTHFR gene were genotyped by an electronic microchip technology. ResultsSixty-one women (15.5%) had hyperhomocysteinemia, 22.9% had reduced levels of vitamin B12, 4.1% had reduced levels of serum folate and 0.1% had a deficiency of vitamin B6. Women in the highest quartile of vitamin B12 and folates had lower homocysteine ​​levels than women in the first and second quartiles (p < 0.0001). The homozygosity for MTHFR C677T polymorphism was detected in 33.3% (131), and heterozygosity for MTHFR C677T polymorphism in 45.3% (178) of women. We observed a significant association between hyperhomocysteinemia and 677T allele, but not 1298C, of the MTHFR polymorphisms (p = 0.04). ConclusionsWe found inadequate vitamin B status related to the homocysteine ​​pathway in women planning Assisted Reproductive Technology. Moreover, interesting association was found regarding hyperhomocysteinemia in women carrying T allele of the C677T MTHFR polymorphism. A specific supplementation with 5-MTHF and adequate vitamin B12 concentrations before Assisted Reproductive Technology warrant serious consideration, in particular in women carrying T allele of the C677T MTHFR polymorphism.

Lipid profile and serum folate, vitamin B12 and homocysteine levels in patients with retinal vein occlusion

BackgroundRetinal vein occlusion (RVO) is mainly related with vascular risk factors (VRF). ObjectivesTo analyze the lipid profile and serum folate, vitamin B12 and homocysteine levels, in patients with RVO and a population-based control group. Patients and methodsCase–control study. Patients with RVO were assessed during an 11-year period. ResultsWe included 368 patients and 325 controls of similar age and sex. HDL cholesterol and folate levels were lower (52 [43–63]mg/dL vs. 55 [46–66]mg/dL; p=0.016 and 7 [5–10]ng/mL vs. 9 [7–13]ng/mL; p<0.0001, respectively) and non-HDL cholesterol and homocysteine levels higher (148.9±37.3mg/dL vs. 142.9±34.5mg/dL; p=0.03 and 13.4 [11.2–18.2]μmol/L vs. 11.1 [9.0–14.4]μmol/L; p<0.001) in patients with RVO than controls. Although total cholesterol, LDL-C, and triglyceride levels were higher and serum vitamin B12 levels were lower in RVO patients, these differences did not reach statistical significance. ConclusionsRVO-patients have lower serum HDL-C and folate levels and higher non-HDL-C and serum homocysteine levels than population-based controls of similar age and sex. In patients with RVO, apart from the lipid profile, determination of serum homocysteine, folate and vitamin B12 levels might be useful, as well as the treatment of their alterations.

The association between homocysteine levels and cardiovascular disease risk among middle-aged and elderly adults in Taiwan

BackgroundOur study aimed to determine the association between homocysteine levels and cardiovascular disease (CVD) risk in middle-aged and elderly adults in a community in northern Taiwan.MethodsParticipants in our study included adults aged 50 to 85 years old during community health examinations in 2019. A total of 396 people were enrolled, the ethnicity of all participants is Chinese. We divided participants according to tertiles of ln[homocysteine] level (low, middle and high groups). The CVD risk was calculated by the Framingham cardiovascular risk score (FRS). An FRS ≥ 20% indicated high CVD risk. Pearson correlation coefficients were calculated between homocysteine level and other cardio-metabolic risk factors while adjusting for age. Multivariate logistic regression analysis was used to determine the association of high and middle ln[homocysteine] groups with high CVD risk after adjusting age, sex, uric acid, creatinine, and body mass index (BMI). The Youden index and receiver operating characteristic (ROC) curves were performed to determine the optimized cut-off value.ResultsThere were 396 people enrolled for analysis; 41.4% of participants were male, and the average age was 64.79 (± 8.76). In our study, we showed a positive correlation of homocysteine with FRS. In the logistic regression models, higher ln[homocysteine] levels was associated with higher CVD risk with a odds ratio (OR) of 2.499 and 95% confidence interval (CI) of 1.214 to 5.142 in the high homocysteine level group compared with the low homocysteine group after adjusting for traditional CVD risk factors. The area under the ROC curve was 0.667, and a ln[homocysteine] cut-off value of 2.495 µmol/L was determined.ConclusionsMiddle-aged and elderly people with increased homocysteine levels were associated with higher FRSs in this Taiwan community. Furthermore, homocysteine was an independent risk factor for high CVD risk in this study.

Impact of H-Type Hypertension on Intraplaque Neovascularization Assessed by Contrast-Enhanced Ultrasound.

Aim: H-type hypertension is connected with carotid atherosclerotic plaques and stroke, whereas neovascularization is a dominant contributor to plaque vulnerability. However, the correlation between H-type hypertension and plaque vulnerability remains unclear. This study aims to explore the influence of H-type hypertension on intraplaque neovascularization (IPN). Methods: We enrolled 235 patients with carotid plaques into the investigation and classified them into four groups: H-type hypertension group, simple hypertension group, isolated hyperhomocysteinemia group, and control group. Contrast-enhanced ultrasound (CEUS) was performed on them and IPN was evaluated using semi-quantitative visual grading: grade 1 (no microbubbles or microbubbles limited to the adventitial side and/or shoulder of plaque) and, grade 2 (diffused microbubbles within plaque or microbubbles enter plaque core). To analyze the correlation between H-type hypertension and the degree of plaque enhancement, logistic regression was used. Results: Compared with those with CEUS grade 1 plaques, those with CEUS grade 2 plaques had higher frequency of ischemic stroke (29.0% vs. 45.1%, P ＜0.05), hypertension (41.0% vs. 56.3%, P ＜0.05), and H-type hypertension (18.0% vs. 29.6%, P ＜0.05). No significant differences existed in plaque morphology, plaque echogenicity, and the severity of carotid artery stenosis between the degree of plaque enhancement (all P ＞0.05). H-type hypertension (multivariate-adjusted OR: 3.036, 95% CI: 1.258–7.329) was independently connected with the degree of plaque enhancement even after adjusting for other covariates. Conclusion: H-type hypertension is expressly connected with the degree of plaque enhancement and may facilitate plaque vulnerability. Our findings may offer a new insight for treating vulnerable plaque, lowering blood pressure, and lowering homocysteine equally crucial.

Choline and Folic Acid in Diets Consumed during Pregnancy Interact to Program Food Intake and Metabolic Regulation of Male Wistar Rat Offspring

North American women consume high folic acid (FA), but most are not meeting the adequate intakes for choline. High-FA gestational diets induce an obesogenic phenotype in rat offspring. It is unclear if imbalances between FA and other methyl-nutrients (i.e., choline) account for these effects. This study investigated the interaction of choline and FA in gestational diets on food intake, body weight, one-carbon metabolism, and hypothalamic gene expression in male Wistar rat offspring. Pregnant Wistar rats were fed an AIN-93G diet with recommended choline and FA [RCRF; 1-fold, control] or high (5-fold) FA with choline at 0.5-fold [low choline and high folic acid (LCHF)], 1-fold [recommended choline and high folic acid (RCHF)], or 2.5-fold [high choline and high folic acid (HCHF)]. Male offspring were weaned to an RCRF diet for 20 wk. Food intake, weight gain, plasma energy-regulatory hormones, brain and plasma one-carbon metabolites, and RNA sequencing (RNA-seq) in pup hypothalamuses were assessed. Adult offspring from LCHF and RCHF, but not HCHF, gestational diets had 10% higher food intake and weight gain than controls (P<0.01). HCHF newborn pups had lower plasma insulin and leptin compared with LCHF and RCHF pups (P<0.05), respectively. Pup brain choline (P<0.05) and betaine (P<0.01) were 22-33% higher in HCHF pups compared with LCHF pups; methionine was ∼23% lower after all high FA diets compared with RCRF (P<0.01). LCHF adult offspring had lower brain choline (P<0.05) than all groups and lower plasma 5-methyltetrahydrofolate (P<0.05) than RCRF and RCHF groups. HCHF adult offspring had lower plasma cystathionine (P<0.05) than LCHF adult offspring and lower homocysteine (P<0.01) than RCHF and RCRF adult offspring. RNA-seq identified 144 differentially expressed genes in the hypothalamus of HCHF newborns compared with controls. Increased choline in gestational diets modified the programming effects of high FA on long-term food intake regulation, plasma energy-regulatory hormones, one-carbon metabolism, and hypothalamic gene expression in male Wistar rat offspring, emphasizing a need for more attention to the choline and FA balance in maternal diets.

The role of dietary supplements that modulate one-carbon metabolism on stroke outcome.

Ischemic stroke results in disability and mortality worldwide. Nutrition is a modifiable risk factor for stroke. For example, deficiencies in one-carbon metabolism have been linked to increased risk of stroke through elevated levels of homocysteine. Some countries world-wide fortify their diets with folates to prevent neural tube defects, but deficiencies in other one-carbon metabolites, such as vitamin B12 and choline are still present in many populations. The aim of this review is to understand the current evidence on how dietary supplementation by nutrients which modulate one-carbon metabolism impact stroke outcome. The results from clinical studies evaluating lowering homocysteine through B-vitamin supplementation on stroke risk remain unclear. Other clinical and preclinical studies have shown increasing dietary intake of one-carbon metabolism has some benefit on stroke outcome. Preclinical studies have shown that increased levels of nutrients which modulate one-carbon metabolism help facilitate recovery in damage models of the central nervous system. One the mechanisms driving these changes is neuroplasticity. The data suggest that increasing dietary nutrients that modulate one-carbon metabolites in patients that are at a higher risk for and suffer from central nervous system diseases, such as stroke, could benefit in addition to other therapies.

The effect of physical activity on total homocysteine concentrations and cardiovascular risk in older Brazilian adults with type 2 diabetes.

A low level of physical activity has a potential association with high levels of homocysteine, which implies an increased chance of older adults with type 2 diabetes mellitus developing cardiovascular disease (CVD). However, the effects of physical activity on homocysteine levels have been poorly explored in the literature. Therefore, this study compared homocysteine levels and cardiovascular risk among physically active and inactive older women with type 2 diabetes mellitus. Fifty-nine women with type 2 diabetes mellitus, between 60 and 91years old, were evaluated. The level of physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) long version to identify active and inactive older women. Blood samples were collected and anthropometric, body composition, and blood pressure measurements were performed to determine homocysteine levels and cardiovascular risk. The results demonstrated that active older women with type 2 diabetes mellitus have lower homocysteine values (F = 17.79, p < 0.001, ηp2 = 0.238), cardiovascular risk scores (F = 15.84, p = p < 0.001, ηp2 = 0.217), and waist circumferences (F = 2.95, p = 0.013, ηp2 = 0.049) when compared with inactive older women. It was concluded that there was a difference in the levels of homocysteine, cardiovascular risk, and waist circumference between active and inactive older women with type 2 diabetes. Active older women are less likely to have cardiovascular risk than inactive older women.

Mechanistic links between vitamin deficiencies and diabetes mellitus: a review

ABSTRACT Vitamin deficiencies are suspected of causing the increasing prevalence of diabetes mellitus. However, this subject has not received adequate attention. This study reviews and communicates the plausible links between vitamin deficiencies and DM. Relevant articles were retrieved from reputable academic databases and the current information revealed that vitamins of primary importance in the pathogenesis of DM are vitamins A, C, D, E, and B-vitamins. Vitamin A enhances beta-cell formation and glucose metabolism. B-vitamins lower homocysteine levels and thus prevent oxidative stress, endothelial dysfunction, β-cell dysfunction, and insulin resistance. Vitamin C reduces free radicals and enhances superoxide dismutase, glutathione, and blood glucose circulation. Vitamin D prevents autoimmunity and promotes cellular and systemic uptake insulin. Vitamin E reduces free radicals and C – reactive proteins, prevents lipid peroxidation, and improves insulin function. These vitamin deficiencies can result in beta-cell abnormalities, insulin resistance, and insulin insufficiency. The major causes of vitamin deficiencies are low dietary supplementation, malabsorption, diseases, and lifestyle. Fortunately, dietary or therapeutic administration of these vitamins can reverse or delay the mentioned pathologies, resulting in improved diabetic conditions. Therefore, people are advised to consider vitamin intervention in the prevention and treatment of diabetic cases having a vitamin deficiency etiology.