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Effects of individualized administration of folic acid on prothrombotic state and vascular endothelial function with H-type hypertension: A double-blinded, randomized clinical cohort study.
Zhang, S, Wang, T, Wang, H, Tang, J, Hou, A, Yan, X, Yu, B, Ran, S, Luo, M, Tang, Y, et al
Medicine. 2022;(3):e28628
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Abstract
BACKGROUND Hypertension and hyperhomocysteinemia (HHcy) have long been associated with adverse cardiovascular and cerebrovascular health outcomes. This study evaluated the effect of individualized administration of folic acid (FA) on homocysteine (Hcy) levels, prothrombotic state, and blood pressure (BP) in patients with H-type hypertension (combination of HHcy and hypertension). METHODS In this double-blinded, randomized clinical cohort study, 126 patients with H-type hypertension who were treated at our hospital were randomly divided into treatment and control groups (n = 55 each). The control group was treated with oral levamlodipine besylate tablets 2.5 mg and placebo, once a day (in the morning). The treatment group was first treated with oral levamlodipine besylate 2.5 mg and FA tablets 0.8 mg, once a day (in the morning), for 12 weeks. Then, in a second 12-week phase, the FA dose was adjusted using the methylene tetrahydrofolate reductase C677 polymorphism genotype. The levels of Hcy and coagulation factors, prothrombotic state parameters, BP, and adverse drug reactions were compared between the 2 groups. RESULTS Pretreatment general patient characteristics, including Hcy levels, were similar between the 2 groups (P > .05). BP and prothrombotic status did not differ before and after the first phase of treatment (P > .05). However, Hcy and endothelin-1 (ET-1) levels decreased, while nitric oxide levels increased significantly in the intervention group (P < .05). In the second phase, after 3 months' treatment with an FA dose adjusted according to methylene tetrahydrofolate reductase C677T genotype, the Hcy and ET-1/NO levels were significantly decreased in the intervention group and were lower than those after the first treatment phase and lower than in the control group (P < .01). BP, D-dimer levels, and fibrinogen scores were significantly lower after the second treatment phase (P < .01). There was no significant difference in the incidence of adverse drug reactions between the 2 groups (P > .05). CONCLUSIONS Individualized administration of FA tablets can effectively reduce BP, and Hcy and coagulation factor levels, and significantly improve prothrombotic status in patients with H-type hypertension.
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[Thromboembolic event and metabolic hyperhomocysteinemia: A case report and review of literature].
Biron, F, Rousseau, JF, Baulin, JM, Guérin-Boyer, M, Lanéelle, D
Annales de cardiologie et d'angeiologie. 2021;(3):177-182
Abstract
INTRODUCTION Venous thromboembolic diseases have an incidence of 1.57/1000. Among patients under 50 years old, thrombophilia is assessed, the indications for which are increasingly stringent. Today, the need of plasma homocysteine assay is uncertain. OBSERVATION Our case is a 42 year-old man, in whom a pulmonary embolism associated with macrocytosis made us discover a B12 deficiency secondary to Biermer's disease. In the literature, patients are men with an average age limit to the realisation of the assessment of thrombophilia. Not all of these patients had any causal other than hyperhomocysteinemia secondary to Biermer's disease. The support is not detailed. CONCLUSION Hyperhomocysteinemia is probably not the only thromboembolic factor. The patient received anticoagulation and vitamin B12 supplementation. A good reading of the complete blood count is essential.
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The recent effects of small dose of folic acid on lipoprotein-associated phospholipase A2 and systolic blood pressure variability in coronary heart disease patients with hyperhomocysteinemia: A single-center prospective cohort study.
Liu, X, Tang, L, Fan, W, Li, A, Pang, J, Feng, Y
Medicine. 2020;(51):e23573
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Abstract
To Investigate the recent effects of small dose of folic acid on lipoprotein-associated phospholipase A2 (LP-PLA2) and systolic blood pressure variability in coronary heart disease (CHD) patients with hyperhomocysteinemia.In this prospective cohort study, a total of 167 CHD patients with hyperhomocysteinemia were consecutively enrolled, and they were divided into Group A (without folic acid intervention, n = 99), Group B (with 0.4 mg of folic acid intervention, n = 34), Group C (0.8 mg of folic acid intervention, n = 34). General information, fasting blood glucose, and blood lipid, folic acid, homocysteine, Lp-PLA2, and blood pressure variability were compared among 3 groups. The above indicators were reviewed after 3 months of treatment.There were no statistically significant differences of age, gender, blood pressure, incidence of type 2 diabetes mellitus, fasting blood glucose, folic acid, homocysteine, Lp-PLA2, total cholesterol, 3 acyl glycerin, apolipoprotein B, lipoprotein (a), high density lipoprotein cholesterol, and low density lipoprotein cholesterol were found among 3 groups (P > .05); however, after being treated for 3 months, there was statistically significant difference in folic acid among 3 groups (P < .05), there was statistically significant difference in apolipoprotein A between Group A and Group B (t = 0.505, P = .039), and also between Group A and Group C (t = 0.052, P = .017). There were statistically significant differences in Lp-PLA2 (t = 24.320, P = .016) and systolic blood pressure variability (t = 0.154, P = .018) between Group A and Group C.For CHD patients with hyperhomocysteinemia, the higher dose (0.8 mg) of folic acid supplement was beneficial for increasing the apolipoprotein A, reducing the Lp-PLA2, and improving the systolic blood pressure variation, which might help to improve the prognosis in these patients.
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Atrophic glossitis: Etiology, serum autoantibodies, anemia, hematinic deficiencies, hyperhomocysteinemia, and management.
Chiang, CP, Chang, JY, Wang, YP, Wu, YH, Wu, YC, Sun, A
Journal of the Formosan Medical Association = Taiwan yi zhi. 2020;(4):774-780
Abstract
Atrophic glossitis (AG) is characterized by the partial or complete absence of filiform papillae on the dorsal surface of the tongue. AG may reflect the significant deficiencies of some major nutrients including riboflavin, niacin, pyridoxine, vitamin B12, folic acid, iron, zinc, and vitamin E. Moreover, protein-calorie malnutrition, candidiasis, Helicobacter pylori colonization, xerostomia, and diabetes mellitus are also the etiologies of AG. Our previous study found the serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) positivities in 26.7%, 28.4%, and 29.8% of 1064 AG patients, respectively. We also found anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 19.0%, 16.9%, 5.3%, 2.3%, and 11.9% of 1064 AG patients, respectively. Moreover, GPCA-positive AG patients tended to have relatively higher frequencies of hemoglobin, iron, and vitamin B12 deficiencies and hyperhomocysteinemia than GPCA-negative AG patients. Supplementations with vitamin BC capsules plus corresponding deficient hematinics for those AG patients with hematinic deficiencies can achieve complete remission of oral symptoms and AG in some AG patients. Therefore, it is very important to examine the complete blood count, serum hematinic, homocysteine, and autoantibody levels in AG patients before we start to offer treatments for AG patients.
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Rehydration during exercise prevents the increase of homocysteine concentrations.
Maroto-Sánchez, B, Lopez-Torres, O, Valtueña, J, Benito, PJ, Palacios, G, Díaz-Martínez, ÁE, González-Lamuño, D, Zinellu, A, González-Gross, M, Carru, C
Amino acids. 2019;(2):193-204
Abstract
This study aimed to assess the effect of rehydration during and after acute aerobic submaximal exercise on total homocysteine (tHcy) concentrations and related parameters in physically active adult males. Twenty trained males (29.4 ± 7.9 years old) completed four exercise tests: two without rehydration during exercise (NH1 and NH2), one with rehydration during exercise using water (H1) and one with rehydration during exercise using an isotonic sports drink (H2). After finishing the exercise tests, subjects followed a rehydration protocol for 2 h. Serum tHcy, vitamin B12, folate, creatine and creatinine were analysed before, after and at 2, 6 and 24 h after exercise. Data were analysed with and without correcting for haemoconcentration to assess the changes in tHcy related. The methylenetetrahydrofolate reductase (MTHFR) 677TT genotype was also analysed. THcy (uncorrected by haemoconcentration) increased significantly after exercise (P < 0.05) in the NH1 and NH2 tests [mean increase ± SD: 1.55 ± 0.33 (15.18%) and 1.76 ± 0.25 (17.69%) µmol/L, respectively], while no significant differences were found in the H1 and H2 tests [mean increase: 0.65 (6.29%) and 0.90 (8.69%) μmol/L, respectively]. The increase was partly due to haemoconcentration and partly due to the metabolism underlying acute exercise. THcy concentrations recovered to baseline after 24 h in all tests. In conclusion, adequate rehydration during acute aerobic exercise using either water or a sports drink maintains tHcy concentrations at baseline and for up to 2 h after exercise in physically active male adults and prevents further increases when compared to no rehydration.
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Recurrent aphthous stomatitis - Etiology, serum autoantibodies, anemia, hematinic deficiencies, and management.
Chiang, CP, Yu-Fong Chang, J, Wang, YP, Wu, YH, Wu, YC, Sun, A
Journal of the Formosan Medical Association = Taiwan yi zhi. 2019;(9):1279-1289
Abstract
Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases characterized by recurrent and painful ulcerations on the movable or nonkeratinized oral mucosae. Clinically, three types of RAS, namely minor, major, and herpetiform types, can be identified. RAS more commonly affects labial mucosa, buccal mucosa, and tongue. Previous studies indicate that RAS is a multifactorial T cell-mediated immune-dysregulated disease. Factors that modify the immunologic responses in RAS include genetic predisposition, viral and bacterial infections, food allergies, vitamin and microelement deficiencies, systemic diseases, hormonal imbalance, mechanical injuries, and stress. Our previous study found the presence of serum gastric parietal cell antibody, thyroglobulin antibody, and thyroid microsomal antibody in 13.0%, 19.4%, and 19.7% of 355 RAS patients, respectively. We also found anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 20.9%, 20.1%, 4.8%, 2.6%, and 7.7% of 273 RAS patients, respectively. Therefore, it is very important to examine the complete blood count, serum autoantibody, hematinic, and homocysteine levels in RAS patients before we start to offer treatments for RAS. Because RAS is an immunologically-mediated disease, topical and systemic corticosteroid therapies are the main treatments of choice for RAS.
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Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets.
Van Bavel, D, de Moraes, R, Tibirica, E
Fundamental & clinical pharmacology. 2019;(4):428-440
Abstract
The incidence of cardiovascular diseases in vegetarian individuals is lower than that in the general population. Nevertheless, individuals who adhere to vegan diets have a higher prevalence of hyperhomocysteinemia with eventual adverse effects on vascular reactivity. Creatine supplementation (CrS) reduces plasma homocysteine levels and enhances vascular reactivity in the microcirculation. Thus, we investigated the effects of CrS on systemic microcirculation and homocysteine blood levels in strict vegan subjects. Forty-nine strict vegan subjects were allocated to the oral CrS (5 g micronized creatine monohydrate daily for three weeks; n = 31) and placebo (n = 18) groups. Laser speckle contrast imaging coupled with acetylcholine skin iontophoresis was used to evaluate cutaneous microvascular reactivity, and intravital video-microscopy was used to evaluate skin capillary density and reactivity before and after CrS. We demonstrated that CrS reduces the plasma levels of homocysteine and increases those of folic acid. After the CrS period, the homocysteine levels of all of the vegan subjects normalized. CrS also induced increases in baseline skin functional capillary density and endothelium-dependent capillary recruitment in both normo- (N-Hcy) and hyperhomocysteinemic (H-Hcy) individuals. CrS increased endothelium-dependent skin microvascular vasodilation in the H-Hcy vegan subjects but not in the N-Hcy vegan subjects. In conclusion, three weeks of oral CrS was sufficient to increase skin capillary density and recruitment and endothelium-dependent microvascular reactivity. CrS also resulted in plasma increases in folic acid levels and reductions in homocysteine levels among only the H-Hcy individuals.
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[Hyperhomocysteinemia and kidney diseases].
Zhou, YF, Guan, YF
Sheng li xue bao : [Acta physiologica Sinica]. 2018;(6):607-611
Abstract
Homocysteine (Hcy) is an intermediate metabolite of methionine metabolism. Hyperhomocysteinemia (HHcy) is defined as a condition characterized by plasma Hcy level above 16 μmol/L which can result from abnormal Hcy metabolism. HHcy has been confirmed to be related to cardio-cerebrovascular disease, peripheral vascular disorders, neurodegenerative diseases, diabetes, pregnancy-induced hypertension syndrome, liver cirrhosis and kidney diseases. In this review, we summarize the correlation between HHcy and kidney diseases. Elucidating the role of HHcy in kidney diseases may provide a new strategy to prevent and treat kidney diseases.
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[Significance of Homocysteine in Glaucoma].
Jünemann, A, Rejdak, R, Hohberger, B
Klinische Monatsblatter fur Augenheilkunde. 2018;(2):163-174
Abstract
Endothelial dysfunction and vascular dysregulation play a role in the multifactorial pathogenesis of glaucomatous optic nerve atrophy. Hyperhomocysteinemia is a risk factor for endothelial dysfunction and is associated with primary open-angle glaucoma as well as secondary open-angle glaucoma in the pseudoexfoliation syndrome. This paper reviews the literature on the association between homocysteine metabolism and glaucomatous disease and explains the possible role of hyperhomocysteinemia in the pathogenesis and progression of glaucoma. We discuss the role of exogenous modifiable risk factors for the prevention and therapy of glaucoma, as well as modification of these factors by changes in life style, such as weight reduction, changes in nutrition and physical activity. The roles of homocysteine in regulating the extracellular matrix, vasotoxicity, neurodegeneration, and epigenetics are explained. Prevention and therapy of glaucoma by regulation of homocysteine levels are discussed.
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Hyperhomocysteinaemia in children receiving phenytoin and carbamazepine monotherapy: a cross-sectional observational study.
Chandrasekaran, S, Patil, S, Suthar, R, Attri, SV, Sahu, JK, Sankhyan, N, Tageja, M, Singhi, P
Archives of disease in childhood. 2017;(4):346-351
Abstract
OBJECTIVE Long-term therapy with phenytoin and carbamazepine is known to cause hyperhomocysteinaemia. We evaluated the prevalence of hyperhomocysteinaemia in North Indian children receiving phenytoin or carbamazepine monotherapy for >6 months duration and the effect of folic acid supplementation on plasma homocysteine. METHODS In this cross-sectional observational study we enrolled consecutive children aged 2-12 years with epilepsy who had received phenytoin or carbamazepine monotherapy for >6 months. Plasma total homocysteine, folic acid, vitamin B12 and antiepileptic drug concentrations were measured. Healthy age- and sex-matched controls were recruited. Children with homocysteine >10.4 µmol/L received folic acid supplementation for 1 month and homocysteine and folic acid concentrations were measured after 1 month follow-up. RESULTS A total of 112 children receiving antiepileptic monotherapy for >6 months were enrolled. Hyperhomocysteinaemia was present in 54 children (90%) receiving phenytoin, 45 children (90%) receiving carbamazepine therapy and 17 (34%) controls (p<0.05). Mean plasma homocysteine concentrations were significantly higher (18.9±10.2 vs 9.1±3 µmol/L) and serum folic acid concentrations (10.04±8.5 ng/ml vs 12.6±4.8 p<0.001) and vitamin B12 concentrations (365±155 pg/mL vs 474±332 pg/mL, p=0.02) were significantly lower in the study group compared with the control group. Duration of antiepileptic drug therapy correlated significantly with elevated homocysteine and reduced folic acid concentrations (p<0.05). Supplementation with folic acid for 1 month led to a reduction in plasma homocysteine concentrations in the study group (from 20.9±10.3 µmol/L to 14.2±8.2 µmol/L, p<0.05). CONCLUSIONS Phenytoin or carbamazepine monotherapy for >6 months duration is associated with hyperhomocysteinaemia in 90% of North Indian children. Elevated homocysteine concentrations were normalised in these children with folic acid supplementation.