Determinants and Vitamin Responsiveness of Intermediate Hyperhomocysteinemia ( $ 40 m mol/liter) The Hordaland Homocysteine Study (original) (raw)
Related papers
Journal of Clinical Investigation, 1996
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
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.
Circulation, 1996
From the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (PFJ, AGB, IHR, JS); the NHLBI Family Heart Study, University of Utah Cardiovascular Genetics Research Clinic, Salt Lake City (RRW); the NHLBI Family Heart Study, ...
Hyperhomocysteinemia and the response to vitamin supplementation
The Clinical Investigator, 1993
The long-term vitamin requirements of men (n=22) with moderate hyperhomocysteinemia (plasma total homocysteine concentration > 16.3 gmol/l) were investigated over a period of 48 weeks. An initial 6-week period of vitamin supplementation (1.0 mg folic acid, 10 mg pyridoxine, 0.05 mg cyanocobalamin) reduced plasma homocysteine levels 54.7% (P<0.001). However, 18 weeks after vitamin therapy was discontinued, only seven participants (subgroup A) still had plasma homocysteine levels of 16.3 gmol/1 or lower. The remainder of the participants (subgroup B) required a second 6-week period of vitamin therapy to normalize the elevated plasma homocysteine levels. Substitution of vitamin supplementation by dietary guidelines to increase folate intake from food products failed to maintain normal plasma homocysteine levels in participants from subgroup B. Long-term vitamin supplementation may be required in some individuals to prevent hyperhomocysteinemia.
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.
Vitamin requirements for the treatment of homocysteine in humans
Journal of Nutrition
We have previously shown that a modest vitamin supplement containing folic acid, vitamin B-12 and vitamin B-6 is effective in reducing elevated plasma homocysteine concentrations. The effect of supplementation of the individual vitamins on moderate hyperhomocysteinemia has now been investigated in a placebo-controlled study. One hundred men with hyperhomocysteinemia were randomly assigned to five groups and treated with a daily dose of placebo, folic acid (0.65 mg), vitamin B-12 (0.4 mg), vitamin B-6 (10 mg) or a combination of the three vitamins for 6 wk. Folic acid supplementation reduced plasma homocysteine concentrations by 41.7% (P < 0.001), whereas the daily vitamin B-12 supplement lowered homocysteine concentrations by 14.8% (P < 0.01). The daily pyridoxine dose did not reduce significantly plasma homocysteine concentrations. The combination of the three vitamins reduced circulating homocysteine concentrations by 49.8%, which was not significantly different (P = 0.48) f...
British Journal of Nutrition, 2000
The 677cytosine (c)→thymine(T) mutation identified in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been frequently associated with an elevated plasma homocysteine concentration. The aim of the present study was to determine the impact of this MTHFR common mutation on plasma and erythrocyte folate (RCF) and plasma total homocysteine (tHcy) concentrations in healthy French adults. A cohort of 291 subjects living in the Paris area and participating in the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study were analysed to assess the impact of MTHFR polymorphism 677C→T on folate status and plasma tHcy concentration. The frequency of the mutant homozygote for 677C→T polymorphism (677TT genotype) in the present cohort was 16·8%. There were significant differences in plasma tHcy between 677CC, 677CT and 677TT genotype groups. The RCF concentrations were significantly different between each genotype, the lowest levels being associated with the 677TT gen...