-
1.
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.
-
2.
Safety of the oral methionine load test: effects on the clinical performance and laboratory tests.
Majluf-Cruz, A, Moreno-Hernández, M, Alvarado-Moreno, JA, Isordia-Salas, I, Guardado-Mendoza, R, Majluf-Cruz, K, Coria-Ramírez, E, Hernández-Juárez, J
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2013;(4):323-30
Abstract
INTRODUCTION Hyperhomocysteinemia is a prothrombotic risk factor. Homocysteine is evaluated during fasting and after an oral methionine load (OML). AIM: To determine the safety of the OML test according to the general performance status and clinical laboratory tests. We studied healthy nonsmoking volunteers and patients with several thrombotic conditions. Before and after receiving an OML, blood samples were obtained to perform several laboratory tests. We also evaluated acute and subacute adverse effects and 30-day associated morbidity and mortality. Of 353 individuals, three were eliminated because they did not tolerate the OML. We studied 175 healthy individuals and 175 patients without age differences. After OML, mild to moderate clinical abnormalities were recorded in 78 subjects (22.1%): nausea (n = 69; 88.5%), dizziness (n = 13; 16.7%) and decreased or increased blood pressure (n = 8; 10.2%). Nausea always disappeared after breakfast in affected individuals. Prevalence of complications was similar in patients and controls. No patient required hospitalization and there was no mortality during the 30-day study period. In conclusion, OML test had no significant undesirable effects on the clinical status or the general laboratory tests of patients and healthy controls. Some mild and moderate symptoms associated with OML tests were observed, and OML test did not negatively affect general laboratory tests. OML test is a safe diagnostic procedure in patients with previous thrombotic events (and with the consequent associated risk factors such as diabetes mellitus or dyslipidemia) and in healthy subjects.
-
3.
Relationship between S-adenosylmethionine, S-adenosylhomocysteine, asymmetric dimethylarginine, and endothelial function in healthy human subjects during experimental hyper- and hypohomocysteinemia.
Doshi, S, McDowell, I, Goodfellow, J, Stabler, S, Boger, R, Allen, R, Newcombe, R, Lewis, M, Moat, S
Metabolism: clinical and experimental. 2005;(3):351-60
Abstract
Experimental hyperhomocysteinemia after an oral methionine or homocysteine load is associated with impaired nitric oxide-dependent vasodilatation in healthy human beings. However, it remains unproven that this effect is mediated by elevations in plasma homocysteine. There is evidence that an increase in plasma homocysteine may increase the formation of asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase. The methyl groups within ADMA are derived from the conversion of S -adenosylmethionine to S -adenosylhomocysteine intermediates in the methionine/homocysteine pathway. No previous study has assessed the role of methylation status, its impact on ADMA formation, and their association with endothelial function in healthy human beings. In a randomized, placebo-controlled, crossover study, 10 healthy subjects (mean age, 29.1 +/- 3.9 years) were administered an oral dose of methionine (0.1 g/kg), l -homocysteine (0.01 g/kg), N-acetylcysteine (NAC) (0.1 g/kg), or placebo. Endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery was impaired after both the methionine and homocysteine load compared with placebo at 4 hours (36 +/- 15, 67 +/- 23 vs 219 +/- 26 microm, respectively, P < .001). N-Acetylcysteine had no effect on flow-mediated dilatation. Plasma total homocysteine was significantly elevated at 4 hours after methionine (23.1 +/- 6.2) and homocysteine (41.5 +/- 8.9) loading, but significantly reduced after NAC 2.4 +/- 0.6 vs 7.1 +/- 2.1 micromol/L in the placebo (P < .001). Plasma S-adenosylmethionine/S-adenosylhomocysteine ratio was significantly (P < .001) increased at 4 hours after methionine (10.9 +/- 0.7) compared with homocysteine (5.4 +/- 0.4), NAC (5.0 +/- 0.3), and placebo (6.0 +/- 0.5). Plasma ADMA concentrations were not altered by any intervention. Our results suggest that endothelial dysfunction due to methionine or homocysteine loading is not associated with an increase in plasma ADMA or a disruption in methylation status.
-
4.
Homocysteine-lowering therapy and carotid intima-media thickness in renal transplant recipients.
Marcucci, R, Zanazzi, M, Bertoni, E, Rosati, A, Fedi, S, Lenti, M, Prisco, D, Castellani, S, Abbate, R, Salvadori, M
Transplantation proceedings. 2005;(6):2491-2
Abstract
The aim of this study was to document, in hyperhomocysteinemic renal transplant recipients, the effect of vitamin supplementation on carotid intima-media thickness (cIMT). Fifty-six hyperhomocysteinemic stable renal transplant recipients were randomly assigned to either vitamin supplementation (group A) or placebo treatment (group B). All patients underwent high-resolution B mode ultrasound to measure IMT of common carotid arteries before and after 6 months of vitamin supplementation. In group A, cIMT significantly decreased after treatment, whereas no significant changes were observed in group B. In conclusion, our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on an early sign of atherosclerosis in a group of renal transplant recipients.
-
5.
Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype.
Williams, C, Kingwell, BA, Burke, K, McPherson, J, Dart, AM
The American journal of clinical nutrition. 2005;(1):26-31
Abstract
BACKGROUND Folic acid reduces plasma homocysteine and may be an important therapy for preventing cardiovascular disease. A key mechanism may be the reduction of arterial stiffness. OBJECTIVE The effect of folic acid supplementation on blood pressure and large artery stiffness was examined in relation to methylenetetrahydrofolate reductase (MTHFR) genotype. DESIGN Forty-one asymptomatic men with normal or high-normal ambulatory blood pressure (systolic: >130 to <145 mm Hg; diastolic: >80 to <90 mm Hg) participated. The study had a randomized, placebo-controlled, double-blind, crossover design that incorporated 3-wk treatments with 5 mg folic acid/d or matching placebo; each treatment was separated by a 4-wk washout phase. RESULTS Folic acid reduced brachial pulse pressure by 4.7 +/- 1.6 mm Hg (P < 0.05) without changing mean arterial pressure. Systemic arterial compliance increased by 0.15 +/- 0.03 mL/mm Hg (P < 0.05) after folic acid treatment but did not change after placebo treatment. These responses did not significantly correlate with either homocysteine or folate plasma concentrations. MTHFR genotype CC homozygotes (without the 677C-->T polymorphism) with normal blood pressure had a larger reduction in homocysteine concentrations in response to folic acid than did T allele carriers. Blood pressure and arterial stiffness responses were independent of MTHFR genotype. CONCLUSION Folic acid is a safe and effective supplement that targets large artery stiffness and may prevent isolated systolic hypertension.
-
6.
Impairment of coronary circulation by acute hyperhomocysteinaemia and reversal by antioxidant vitamins.
Coppola, A, Astarita, C, Liguori, E, Fontana, D, Oliviero, M, Esposito, K, Coppola, L, Giugliano, D
Journal of internal medicine. 2004;(5):398-405
-
-
Free full text
-
Abstract
OBJECTIVE To evaluate the effect of acute hyperhomocysteinaemia with and without antioxidant vitamins pretreatment on coronary circulation and circulating chemokine levels. DESIGN Observer-blinded, randomized crossover study. SETTING This study was conducted at a university hospital and at a general hospital in Italy. SUBJECTS Sixteen healthy hospital staff volunteers (nine men, seven women), aged 26-40 years. INTERVENTIONS Subjects were given each three loads in random order at 1-week intervals: oral methionine, 100 mg kg(-1) in fruit juice; the same methionine load immediately following ingestion of antioxidant vitamin E, 800 IU, and ascorbic acid, 1000 mg; and methionine-free fruit juice (placebo). MAIN OUTCOME MEASURES Coronary flow velocity reserve (CFVR), assessed by noninvasive transthoracic Doppler echocardiography, blood pressure, heart rate, lipid and glucose, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) parameters evaluated at baseline and 4 h following ingestion of the loads. RESULTS The oral methionine load increased plasma homocysteine from 12.8 +/- 1.8 to 33.3 +/- 3.4 micromol L(-1) at 4 h (P < 0.001). A similar increase was observed with same load plus vitamins (P < 0.001) but not with placebo (P = 0.14). Circulating MCP-1 and IL-8 levels rose after the methionine load (P < 0.001), but not after placebo or methionine plus vitamins. The methionine load significantly reduced CFVR (decrease, 26 +/- 8.2%; P < 0.001). The methionine load with ingestion of vitamins partially prevented the impairment of CFVR (decrease, 11 +/- 4%; P < 0.001). CONCLUSION Our data suggest that acute hyperhomocysteinaemia reduces CFVR and increases plasma MCP-1 and IL-8 levels in healthy subjects. Pretreatment with antioxidant vitamin E and ascorbic acid prevents the effects of hyperhomocysteinaemia, suggesting an oxidative mechanism.
-
7.
Atrophic gastritis as a cause of hyperhomocysteinaemia.
Santarelli, L, Gabrielli, M, Cremonini, F, Santoliquido, A, Candelli, M, Nista, EC, Pola, P, Gasbarrini, G, Gasbarrini, A
Alimentary pharmacology & therapeutics. 2004;(1):107-11
-
-
Free full text
-
Abstract
BACKGROUND Hyperhomocysteinaemia is an independent risk factor for atherosclerosis. It is often related to low levels of vitamin B12 and/or folate, enzymatic co-factors of methionine metabolism. Atrophic gastritis, often caused by Helicobacter pylori infection, may impair vitamin absorption. AIM: To assess whether the presence of atrophic gastritis is associated with hyperhomocysteinaemia via deficiency of its vitamin co-factors. METHODS Thirty-one patients with atrophic gastritis were recruited. The control group consisted of 28 patients with non-atrophic gastritis, matched with patients for sex, age and body mass index. The presence and degree of gastric atrophy were assessed by histology. H. pylori infection was assessed by histology/serology. Blood samples were collected for the measurement of homocysteine, vitamin B12 and folates. RESULTS Multiple logistic regression analysis showed that atrophic gastritis (odds ratio, 5.3; 95% confidence interval, 1.23-25.26; chi2=5.2; P=0.01) and low vitamin B12 (odds ratio, 3.7; 95% confidence interval, 1.03-22.08; chi2=3.6; P<0.05) were both predictors of hyperhomocysteinaemia. None of the other variables considered in the analysis, including H. pylori status, showed a significant association with hyperhomocysteinaemia. CONCLUSIONS The present study suggests that atrophic gastritis, rather than H. pylori infection per se, may be a contributing factor to hyperhomocysteinaemia, possibly via vitamin B12 malabsorption.
-
8.
Folic acid does not improve endothelial function in healthy hyperhomocysteinaemic subjects.
Woodman, RJ, Celermajer, DE, Thompson, PL, Hung, J
Clinical science (London, England : 1979). 2004;(4):353-8
Abstract
Folic acid supplementation lowers total plasma homocysteine (tHcy) and improves endothelial function in individuals with coronary artery disease (CAD) and in those with additional CAD risk factors. In the present study, we assessed whether endothelial function is impaired in healthy subjects with hyperhomocysteinaemia but without other CAD risk factors and whether folic acid supplementation improves endothelial function in these subjects. Flow-mediated dilatation (FMD) of the brachial artery was performed on 26 healthy subjects, age 49 +/- 2 years (mean +/- S.E.M.), with high tHcy (15.6 +/- 1.5 micromol/l) and 16 healthy age-matched subjects with low tHcy (7.9 +/- 0.6 micromol/l; P < 0.001). Subjects with high tHcy were then randomized to receive 5 mg/day of folic acid or placebo for 8 weeks in a double-blind cross-over trial with a 4-week washout. FMD was not associated with tHcy and was not different between high and low tHcy groups (7.0 +/- 0.6% compared with 6.6 +/- 1.2%, P = 0.76). Treatment with folic acid decreased tHcy by 34% in hyperhomocysteinaemic subjects ( P = 0.02 compared with placebo), but had no effect on FMD (+ 0.5 +/- 0.6% compared with -0.7 +/- 0.5%; P = 0.17 compared with placebo). In healthy subjects with hyperhomocysteinaemia, but without additional cardiovascular risk, endothelial function is unimpaired and folic acid supplementation has no additional effect.
-
9.
Effect of homocysteine-lowering vitamin treatment on electrocardiography stress tests in a randomized, placebo-controlled trial: comparison between ST-segment changes and Athen QRS-score.
Vermeulen, EG, van Engeland, MI, Visser, FC, Stehouwer, CD, Twisk, JW, van Campen, CM, Rauwerda, JA
International journal of cardiology. 2004;(2-3):323-4
-
10.
The 5,10-methylenetetrahydrofolate reductase C677T polymorphism interacts with smoking to increase homocysteine.
Brown, KS, Kluijtmans, LA, Young, IS, Murray, L, McMaster, D, Woodside, JV, Yarnell, JW, Boreham, CA, McNulty, H, Strain, JJ, et al
Atherosclerosis. 2004;(2):315-22
Abstract
Elevated homocysteine is a risk marker for several human pathologies. Risk factors for elevated homocysteine include low folate and homozygosity for the T allele of the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. Because nitric oxide may inhibit folate catabolism and endothelial nitric oxide synthase activity is reduced in smokers, we postulated that smoking status might modify the impact of the MTHFR C677T polymorphism on homocysteine (tHcy) concentrations. We tested this hypothesis in a healthy young adult population for which MTHFR C677T genotypes and tHcy concentrations were previously reported. The MTHFR 677TT genotype was significantly associated with elevated tHcy concentrations in smokers (P = 0.001) but not in non-smokers (P = 0.36). Among smokers, the MTHFR 677TT genotype was significantly associated with high tHcy in heavy smokers (P = 0.003) but not light smokers (P = 0.09), in men (P = 0.003) but not women (P = 0.11), and in subjects from the lowest serum folate quartile (P = 0.49) but not from folate quartiles 2-4 (P = 0.49). After adjustment for nutritional variables, interactions between MTHFR C677T genotype and NOS3 G894T genotype, and between MTHFR genotype, smoking status and gender were statistically significant. We propose that hyperhomocysteinemia in MTHFR 677TT homozygote smokers is the consequence of mild intracellular folate deficiency caused by a smoking-related reduction of NOS3 activity that is exacerbated when serum folate is low.