Hyperhomocysteinemia and the response to vitamin supplementation

We measured the vitamin B-6, vitamin B-l2, and folic acid nutritional status in a group ofapparently healthy men (n = 44) with moderate hyperhomocysteinemia (plasma homocysteine concentration > 16.3 �zmol/L). Compared with control subjects (n = 274) with normal plasma homocysteine (f;; 16.3 �mol/L) concentrations, significantly lower plasma concentrations of pyridoxal-5'-phosphate (P < 0.001), cobalamin (P < 0.001), and folic acid (P = 0.004) were demonstrated in hyperhomocysteinemic men. The prevalence of suboptimal vi- tamin B-6. B-l2, and folate status in men with hyperhomocys- teinemia was 25.0%, 56.8%, and 59.1%, respectively. In a pla- cebo-controlled follow-up study, a daily vitamin supplement (10 mg pyridoxal, 1.0 mg folic acid, 0.4 mg cyanocobalamin) nor- malized elevated plasma homocysteine concentrations within 6 wk. Because hyperhomocysteinemia is implicated as a risk factor for premature occlusive vascular disease, appropriate vitamin therapy may be both e...

Nutrients, 2013

Background/Objectives: To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with "moderate" hyperhomocysteinemia, also taking into account C677T polymorphism of

Hyperhomocysteinemia is a risk factor for atherosclerosis and thrombosis and is inversely related to plasma folate and vitamin B12 levels. We assessed the effects of vitamin supplementation on plasma homocysteine levels in 89 patients with a history of recurrent venous thrombosis and 227 healthy volunteers. Patients and hyperhomocysteinemic (homocysteine level Ͼ16 mol/L) volunteers were randomized to placebo or high-dose multivitamin supplements containing 5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine. A subgroup of volunteers without hyperhomocysteinemia was also randomized into three additional regimens of 5 mg folic acid, 0.5 mg folic acid, or 0.4 mg hydroxycobalamin. Before and after the intervention period, blood samples were taken for measurements of homocysteine, folate, cobalamin, and pyridoxal-5Ј-phosphate levels. Supplementation with high-dose multivitamin preparations normalized plasma homocysteine levels (Յ16 mol/L) in 26 of 30 individuals compared with 7 of 30 in the placebo group. Also in normohomocysteinemic subjects, multivitamin supplementation strongly reduced homocysteine levels (median reduction, 30%; range, Ϫ22% to 55%). In this subgroup the effect of folic acid alone was similar to that of multivitamin: median reduction, 26%; range, Ϫ2% to 52% for 5 mg folic acid and 25%; range, Ϫ54% to 40% for 0.5 mg folic acid. Cobalamin supplementation had only a slight effect on homocysteine lowering (median reduction, 10%; range, Ϫ21% to 41%). Our study shows that combined vitamin supplementation reduces homocysteine levels effectively in patients with venous thrombosis and in healthy volunteers, either with or without hyperhomocysteinemia. Even supplementation with 0.5 mg of folic acid led to a substantial reduction of blood homocysteine levels. (Arterioscler Thromb Vasc Biol. 1998;18:356-361.)

International Journal of Medical Sciences, 2000

A Ab bs st tr ra ac ct t Background & Aims: At least 500 µg of folic acid are required daily to treat hyperhomocysteinemia. To reach this amount by dietary changes alone may be difficult because food has a low folic acid content and bioavailability. No studies have compared the effects of similar amounts of additional folate derived from a combination of folate-rich and fortified foods or folic acid from supplements on plasma total homocysteine (tHcy) concentrations, which was the aim of this study. Methods: Twenty male patients with hyperhomocysteinemia and coronary artery disease were included in a randomized, crossover intervention trial. Patients were treated daily with a combination of foods containing approximately 500 µg of folate or with one 500 µg capsule of synthetic folic acid over two five-week periods separated by a five-week wash-out period. Results: Plasma folate increased markedly (p<0.001) and plasma tHcy decreased (p<0.001) with both therapies. Folate-rich foods decreased tHcy by 8.6% (95% CI: -15.9 to -1.2) and synthetic folic acid capsules by 8% (95% CI: -13.3 to -2.7). Conclusions: This study shows, for the first time in the literature, that a folate-rich diet is as effective as folic acid capsules in decreasing plasma tHcy concentrations and adds further support to the recommendation of those diets to prevent cardiovascular disease.

Asia Pacific Journal of Clinical Nutrition, 2001

The prevalence of subclinical deficiencies of folate and vitamin B 6 in India is high and preliminary investigation showed higher mean plasma total homocysteine level in Indians compared with the values reported for western populations. The present study was carried out in 40 apparently normal men to examine the relationship between plasma total homocysteine level and folate and vitamin B6 status. The mean plasma homocysteine level was high and was inversely related to folate status as judged by red blood cells or plasma folate concentrations. There was no significant relationship between fasting homocysteine level and vitamin B6 status.

Stroke, 2006

Background and Purpose-A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger individuals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels. Methods-We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged Ն75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B 6 , and 400 g of B 12 or placebo. The study groups were balanced regarding age (meanϮSD, 78.9Ϯ2.8 years), B vitamins, and tHcy at baseline. Results-Among the 13% with B 12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 mol/L (95% CI, 3.94 to 9.55 mol/L) compared with 2.88 mol/L (95% CI, 0.07 to 5.69 mol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment and control groups for men with high plasma tHcy compared with the rest of the group was 2.8 mol/L (95% CI, 0.6 to 4.9 mol/L). Baseline vitamin B 12 , serum folate, and tHcy were significantly associated with changes in plasma tHcy at rϭ0.522, and rϭϪ0.903, respectively; Pϭ0.003, Ͻ0.001, and Ͻ0.001, respectively) in the vitamin group. Conclusions-The tHcy-lowering effect of B vitamins was maximal in those who had low B 12 or high tHcy levels.

Nutrients

Hyperhomocysteinemia is recognized as risk factor for cardiovascular and age-associated diseases. Folic acid supplementation efficiently lowers plasma homocysteine (Hcy) levels, but high intake may negatively affect health because of unnatural levels of unmetabolized folic acid in the systemic circulation. Oxoproline (Oxo) provides by glutamic acid production an increase of intracellular folic acid trapping. Aim of this study was to compare the efficacy of three supplementation protocols: (1) traditional therapy (5-methyl-tetrahydrofolate: 15 mg/day); (2) 5 mL/day of Oxo with 300 μg folic acid (oxifolic); (3) 5 mL/day of Oxo alone (magnesio+) in a 90 days randomized trial on thirty-two moderate hyperhomocysteinemic (18.6 ± 2.4 μmol·L−1) patients (age 48 ± 14 years). Thiols: cysteine (Cys), cysteinylglycine (Cys–Gly) and glutathione levels were assessed too. Every supplementation induced significant (p range &lt;0.05–0.0001) reductions of Hcy level and Cys concentration after the thr...

BMC Public Health, 2006

Background: Elevated plasma total homocysteine is an independent risk factor for cardiovascular disease and a sensitive marker of the inadequate vitamin B12 and folate insufficiency. Folate and vitamin B12 have a protective effect on cardiovascular disease. This population based study was conducted to evaluate the plasma total homocysteine, folate, and vitamin B12 in healthy Iranian individuals.

Stroke, 2005

Background and Purpose— A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger individuals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels. Methods— We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged ≥75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B 6 , and 400 μg of B 12 or placebo. The study groups were balanced regarding age (mean±SD, 78.9±2.8 years), B vitamins, and tHcy at baseline. Results— Among the 13% with B 12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 μmol/L (95% CI, 3.94 to 9.55 μmol/L) compared with 2.88 μmol/L (95% CI, 0.07 to 5.69 μmol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment an...

Hippokratia, 2010

Hyperhomocysteimemia is a cardiovascular risk factor even among children. Supplementation of oral folic acid may reduce homocysteine levels to normal. However, data is limited at this point for healthy children and adolescents. Five hundre and twenty four children participated in the study; Twenty six of them were found to be hyperho mocysteinemic(&gt;95(th) percentile for age). Twenty of them received 5 mg of folic acid twice per week for two consecutive months while the other six received a diet rich in dietary folate. Serum homocysteine levels were statistically significantly decreased from 13.1 (10-24.2 micromol/L ) to 7.7 (4.9- 15.2 micromol/L), p&lt;0.001. Serum folate levels were significantly rose from 4.3 (3-20 ng/mL) to 16.8 (7-20 ng/mL), p&lt;0.001. On the contrary, no important changes were observed in the above parameters in children to whom a diet rich in folic acid was recommended. Homocysteine levels were found to be positively associated with age (r=0.314, p&lt;0.00...

South African Journal of Clinical Nutrition, 2014

Hyperhomocysteinaemia is implicated in various diseases, including cardiovascular disease and cancer. Several conditions influence the concentration of homocysteine (Hcy), including demographic, genetic and lifestyle factors. With regard to the latter, dietary components may be manipulated as Hcy can be remethylated to methionine by folate, or metabolised by other one-carbon nutrients, such as betaine and its precursor, choline. This metabolic interplay enables the nutritionist or dietitian to be able to lower Hcy concentrations cost-effectively by tailoring an individual's diet, or by food enrichment and fortification strategies. Evidence supports the safety and benefits of Hcy reduction by simple dietary intervention. B vitamins, and betaine and choline intake lower Hcy, whereas methionine and certain beverages (coffee, tea and alcohol) increase it. Therefore, dietary determinants of Hcy raise the prospect of a simple, inexpensive and safe means of treating and/or preventing diseases contingent on this sulphur-containing protein.

Molecular Medicine Reports, 2013

The role of hyperhomocysteinemia (HHcy) as a cardiovascular risk factor remains a matter of debate, while it correlates with folates, it demonstrates inverse correlation with plasma homocysteine (Hcy) levels and vitamin B12 levels and reduces plasma Hcy levels following supplementation with multivitamins. The purpose of this study was to demonstrate that administering multivitamins at specific doses for 90 days restores normal plasma Hcy levels in women who are homozygous for the thermolabile variant of 5,10 methylenetetrahydrofolate reductase (MTHFR C677T). We enrolled 106 healthy females aged between 30 and 42 years, who were non-smokers, non-vegetarian, normotensive and who had no history of food abuse in the previous months. Only females were enrolled in order to rule out any bias due to the variation in Hcy plasma concentrations between males and females. Patient blood sampling was performed in order to determine plasma Hcy, serum folic acid and vitamin B12 levels. Furthermore, molecular characterization of the C677T polymorphism present in the MTHFR gene, was also performed.

European Journal of Nutrition, 2008

Annals of the New York Academy of …, 1992

A renewed interest in the sulfur-containing amino acid, homocysteine, has emerged over the past few years due to increasingly convincing data that it is associated with, and probably a causative factor of, accelerated occlusive vascular disease.'-' The fact that vitamins Biz, B6, and folate all play important roles as either coenzymes or substrates in the metabolism of h o m o c y~t e i n e~.~ has greatly added to the interest in this amino acid because deficiencies of these three vitamins, or supplementation with them, have been found to have substantial impact on circulating concentrations of homocysteine in selected situations.

QJM, 2002