Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia (original) (raw)
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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.
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 speciic 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.
The American Journal of Clinical Nutrition, 2002
Background: Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease and neural tube defects. The polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (FADH 2) (MTHFR) influences the tHcy concentration and the response to tHcy-lowering therapy. Supplementation with folic acid (FA) decreases plasma tHcy, but limited data are available on the effect of 5-methyltetrahydrofolate (MTHF). Objective: We evaluated the tHcy-lowering potential of lowdose FA and of MTHF with respect to the MTHFR genotype. Design: In this randomized, placebo-controlled, double-blind study, 160 women received 400 g FA, the equimolar amount of MTHF (480 g, racemic mixture), or a placebo daily during an 8-wk treatment period. Blood samples were collected at baseline and at 4 and 8 wk. Results: Changes in plasma tHcy concentration depended on the supplemented folate derivative and the MTHFR genotype. Supplementation with FA significantly decreased tHcy concentrations by ≥ 13% in women of all 3 genotypes after both 4 and 8 wk. The greatest decrease was 20% (P < 0.05) in the women with the TT genotype after 4 wk. MTHF supplementation also decreased tHcy, but only the women with the CT genotype had a significant decrease after 4 wk (7%; P < 0.05). The largest nonsignificant reduction (15%) occurred in the women with the TT genotype after 4 wk of MTHF supplementation. Conclusions: The response to tHcy-lowering therapy is influenced by MTHFR genotype. Women with the TT genotype seem to benefit the most from supplementation with either FA or MTHF. In women with the CT or CC genotype, FA is more effective than MTHF in lowering plasma tHcy.
2005
Background: A high plasma concentration of total homocysteine has been linked to a higher risk of cardiovascular disease. Subjects homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C→ →T mutation have depressed folate and elevated homocysteine concentrations. They may have increased folate requirements compared to subjects with CT and CC genotypes. Objective: We investigated whether MTHFR C677T genotypes differ in their associations of 1. folate intake with folate status, and 2. folate status/folate intake with plasma homocysteine concentrations. We also investigated in these three genotypes the effect of one year folic acid supplementation (800 µg/day) on serum folate and plasma homocysteine. Design: In a double blind randomised placebo-controlled trial, 815 volunteers aged 50-70 years (n= 312 CC, 378 CT and 125 TT) with homocysteine above 13 µmol/L at screening, were allocated to daily folic acid (800 µg) or placebo treatment during one year. Results: At baseline, the median folate intake was 194 µg/day and did not differ between genotypes. Subjects with the TT genotype had 13% lower levels of serum folate and 8% higher homocysteine compared with CC subjects. At an intake level above 215 µg/day (upper quartile) subjects with the TT genotype had similar homocysteine compared with subjects with the CC or CT genotypes with folate intakes below 138 µg/day (bottom quartile). This indicates a higher folate requirement of the TT genotype. After one year of folic acid supplementation homocysteine decreased by 35% in the total study population. Subjects with the TT genotype had a 4.3 µmol/L (-40%) decrease of homocysteine compared to placebo, which was significantly greater (p<0.0001) than that of subjects with the CC genotype (-3,2 µmol/L, -32%) or the CT genotype (-3.0 µmol/L, -31%). After one year supplementation, mean homocysteine of subjects with the TT, CT and CC genotypes were 9.2; 9.6 and 9.7 µmol/L respectively.
Nutrition Research, 2009
Serum folate has been shown to correlate well with fasting plasma homocysteine; however, erythrocyte folate concentration is a better index of tissue folate stores and probably could be a more reliable indicator for reflecting long-term supply of the vitamin and homocysteine status. The present study was undertaken to test the hypothesis that serum folate and erythrocyte folate levels had a different degree of correlation to fasting plasma homocysteine in young Taiwanese adults. This study had a cross-sectional design. Healthy young adults were divided into either a hyperhomocysteinemia (HHcy; ≥14.9 μmol/L; n = 13), borderline HHcy (BHcy; fasting homocysteine, 14.9-10.2 μmol/L; n = 52), or normohomocysteinemia (fasting homocysteine, b10.2 μmol/L; n = 65) groups based on fasting homocysteine levels. The concentrations of plasma fasting homocysteine, serum folate, erythrocyte folate, vitamin B 12 , and plasma pyridoxal 5′-phosphate were measured. Fasting homocysteine was only significantly and inversely affected by serum folate (β = −0.21, P b .05) concentration after adjusting for potential confounders. Only serum folate concentration remained to decrease the risk of fasting HHcy (odds ratio, 0.73; confidence interval, 0.56-0.95) after the other B vitamins were additionally adjusted. Serum folate also had the highest area under the receiver operating characteristic (AUC) curve to predict the risk of HHcy (AUC, 0.81) and BHcy (AUC, 0.77). Serum folate is a reliable indicator of fasting hyperhyperhomocysteinemia and BHcy in young adults.
Folate and homocysteine phenotypes: Comparative findings using research and clinical laboratory data
2009
Objectives: A low folate/high homocysteine phenotype is associated with several pathologies, including spina bifida and cardiovascular disease. Folate and total homocysteine (tHcy) measurements are used clinically to assess risk and the need for folic acid supplementation and in research to investigate the metabolic basis of disease. Red blood cell (RBC) folate, the best indicator of long-term folate status, is usually measured as "total" folate. However, different folate derivatives support distinct biochemical functions, suggesting a need to develop more precise methods. This study was designed to evaluate a method based on stable isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS).
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(>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<0.001. Serum folate levels were significantly rose from 4.3 (3-20 ng/mL) to 16.8 (7-20 ng/mL), p<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<0.00...
European Journal of Clinical Nutrition, 1998
Objectives: To assess the long term effects of small increases in dietary folic acid on the concentration of plasma homocysteine, an independent risk factor for occlusive vascular disease, in a general population. Design: A randomized double-blind placebo-controlled intervention study. Subjects: One hundred and nineteen healthy volunteers, whose intake of forti®ed or supplemental folic acid was low, were recruited by letter from the patient register of a large inner-city group general practice. Methods: Volunteers were randomized to receive unforti®ed cereals, or cereals forti®ed with 200 mg of folic acid per portion, with or without other vitamins. Blood samples were taken presupplement and at 4, 8 and 24 weeks on treatment and analysed for plasma homocysteine, cysteine and vitamin B12 and serum and red cell folate. Ninety-four subjects completed the study providing blood samples on all four occasions. Results: There were no signi®cant changes in any measured parameter in those eating unforti®ed cereals. Overall, folic acid forti®cation of cereals led to signi®cant increases (P`0.001) in serum folate (66%), and red cell folate (24%), and a decrease in plasma homocysteine (10%; P`0.001). There were no changes in vitamin B12 or cysteine. The homocysteine decrease persisted until the end of the study and was primarily seen in those who initially had the highest plasma homocysteine or the lowest serum folate. Conclusions: If homocysteine is found to be a causative risk factor in occlusive vascular disease, food forti®cation with physiological levels of folic acid should have a signi®cant impact on the prevalence of the disease in the general population. Sponsorship: We acknowledge, with thanks, ®nancial support from the Kellogg Company of Great Britain.
From 1992-93, we screened 18,043 subjects, aged 40-67 yr, and found 67 cases (0.4%) with total plasma homocysteine (tHcy) Ն 40 mol/liter. Compared to 329 controls, the cases had lower plasma folate and cobalamin levels, lower intake of vitamin supplements, consumed more coffee, and were more frequently smokers. Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase gene was observed in 73.1% of the cases and 10.2% of the controls. Only seven cases with cobalamin deficiency and one with homocystinuria received specific therapeutic instructions. 2 yr after the screening, 58 subjects were reinvestigated. 41 still had tHcy Ͼ 20 mol/liter, and in 37 of these, intervention with low dose folic acid (0.2 mg/d) was started. Notably, 34 of 37 (92%) had homozygosity for the C677T mutation. Plasma tHcy was reduced in all but two after 7 wk, and became normal within 7 mo in 21 of 37 subjects. Most of the remaining subjects obtained a normal tHcy level with 5 mg/d of folic acid. We conclude that most subjects with hyperhomocysteinemia Ն 40 mol/liter in the general population have the C677T mutation combined with low folate status. Daily supplement of low dose folic acid will reduce and often normalize their tHcy level. ( J. Clin. Invest. 1996. 98: 2174-2183.) Key words: homocysteine • methylenetetrahydrofolate reductase • genetics • folic acid • vitamin treatment
Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia
The American journal of clinical nutrition, 1993
We measured the vitamin B-6, vitamin B-12, and folic acid nutritional status in a group of apparently healthy men (n = 44) with moderate hyperhomocysteinemia (plasma homocysteine concentration > 16.3 mumol/L). Compared with control subjects (n = 274) with normal plasma homocysteine (< or = 16.3 mumol/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 vitamin B-6, B-12, and folate status in men with hyperhomocysteinemia was 25.0%, 56.8%, and 59.1%, respectively. In a placebo-controlled follow-up study, a daily vitamin supplement (10 mg pyridoxal, 1.0 mg folic acid, 0.4 mg cyanocobalamin) normalized 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 ef...