Prevalence of hyperhomocysteinemia in an elderly population

Clinical chemistry, 2001

Hyperhomocysteinemia is a cardiovascular disease (CVD) risk factor. We determined plasma homocysteine (Hcy) reference values at optimized vitamin status and investigated their influence on the prevalence of hyperhomocysteinemia in healthy adults. Results were compared with those obtained using European Concerted Action Project (ECAP) cutoff values. Healthy adults (n = 101) received folic acid (5 mg/day) and vitamin B(12) (1 mg/day) for 2 weeks and the same dosages of folic acid and vitamin B(12) plus vitamin B(6) (1 mg. kg(-1). day(-1)) during the following 2 weeks. Hcy concentrations, both fasting and 6-h post-methionine load, were determined at baseline and after 4 weeks. Baseline (4 weeks) fasting and 6-h postload Hcy reference values were 4.7-14.6 (4.1-9.3) and 18.8-49.7 (12.9-35.1) micromol/L, respectively. Mean fasting and 6-h postload Hcy decreased after 4 weeks of vitamin supplementation by 3.5 micromol/L (33.5%) and 8.5 micromol/L (26.3%), respectively. The percentages of s...

QJM, 2002

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.

Atherosclerosis, 1999

Moderate hyperhomocysteinemia is an atherogenic risk factor and plays an important role in geriatrics. Here, we have investigated the role of hyperhomocysteinemia in two elderly groups: 104 longeval subjects of 85-102 years, 100 seniors aged 65-75 years, and 75 controls of 19-60 years. Elevated homocysteine levels were found in 58% of longeval subjects in comparison with 32% in seniors. The homocysteine level in serum correlated positively with age as well as serum creatinine, and inversely with serum folate, but there was no correlation with serum B-vitamins. The frequency of vitamin B deficiency in serum of longeval subjects compared to seniors was as follows: vitamin B6 43% vs. 22%, vitamin B12 20% vs. 8%, and folic acid 1% in both groups. Increased serum creatinine levels (> 1.1 mg/dl) were found in 63% of the longeval subjects and in 32% of seniors. The 677-missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, responsible for moderate homocysteine elevation, was found in 35, 37 and 27% of alleles in longeval persons, senior subjects and younger controls, respectively, showing no significant difference in frequency distributions of the MTHFR gene mutation. It can be concluded that hyperhomocysteinemia is very common with increased age. Its importance as an atherogenic risk factor with advanced age has to be clarified.

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

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...

The Journal of nutrition, 2004

The mechanism by which homocysteine (Hcy) causes endothelial dysfunction is probably mediated by oxidative stress. The aim of this study was to evaluate the effect of oxidative stress on endothelial function in young and elderly hyperhomocysteinemic (HHcy) men. A total of 35 HHcy (Hcy > 15 micro mol/L), young (n = 15; 20-40 y) and elderly men (n = 20; > 65 y) and 33 normohomocysteinemic (NHcy; controls) young (n = 14) and elderly (n = 19) men (Hcy < 13 micro mol/L), without classic cardiovascular risk factors were recruited. Serum Hcy, folate, and vitamin B-12, whole-blood glutathione, plasma total antioxidants status, TBARS, and 8-F(2alpha) isoprostanes were determined. Noninvasive ultrasound measurements of endothelium-dependent (EDVR) and -independent dilatation (EIVR) were performed. EDVR, EIVR, and markers of oxidative stress did not differ among the groups. Folate concentrations were higher in elderly than in young men (P < 0.001), independent of Hcy concentrations...

To investigate whether hyperhomocysteinemia is an independent risk factor for atherosclerotic disease in elderly individuals.

Clinical chemistry, 1998

The variability of plasma total homocysteine (tHcy) was examined in 96 individuals over a 1-yr period. Blood tHcy concentrations varied from 7.1 micromol/L in the bottom quintile to 14.5 micromol/L in the top quintile. The mean tHcy was 10.4 micromol/L, the between-person SD was 2.5 micromol/L, and the within-person SD was 0.93 micromol/L. There was little seasonal variation, and the reliability coefficient was 0.88. Mean tHcy concentrations were inversely related to mean plasma folate (r = -0.36) and vitamin B12 (r = -0.35) concentrations. Median tHcy concentrations were approximately 1 micromol/L higher in men than in women and in older (70 to 74 years) than in younger (65 to 69 years) individuals and higher in those with the TT and CT genotypes for the methylenetetrahydrofolate reductase polymorphism than in those with the CC genotype (10.7 and 10.6 vs 9.6 micromol/L). Epidemiological studies based on single tHcy measurements may underestimate the magnitude of any risk associatio...

British Journal of Nutrition, 2010

Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease but lowering tHcy with B-vitamins, including folate, has generally not reduced vascular events in secondary prevention trials. Elevated plasma S-adenosylhomocysteine (AdoHcy) concentration may be a more sensitive indicator of vascular disease than plasma tHcy. However, unlike tHcy, plasma AdoHcy did not correlate with folate concentration in one study indicating that folate supplementation may not lower AdoHcy. Our aim was to determine whether providing B-vitamin supplements to healthy older people with elevated tHcy (. 13 mmol/l) affects plasma AdoHcy and S-adenosylmethionine (AdoMet) concentrations. Healthy older participants (n 276; $65 years) were randomised to receive a daily supplement containing folate (1 mg), vitamin B 12 (500 mg) and vitamin B 6 (10 mg), or placebo, for 2 years. Of these participants, we selected the first fifty participants in each treatment group and measured plasma AdoHcy and AdoMet. Plasma tHcy was 4·4 (95 % CI 3·2, 5·6; P,0·001) mmol/l lower at 2 years in the vitamins group compared with the placebo group. At 2 years, there were no significant differences in plasma AdoMet (þ 4 % (95 % CI 2 2, 11); P¼ 0·19), AdoHcy (21 % (95 % CI 2 10, 8); P¼ 0·61) or the AdoMet:AdoHcy ratio (0·22 (95 % CI 2 0·04, 0·49); P¼0·10) between the two groups. In conclusion, B-vitamin supplementation of older people lowered plasma tHcy but had no effect on plasma AdoMet or AdoHcy concentration. If elevated plasma AdoHcy is detrimental, this may explain why B-vitamins have generally failed to reduce vascular events in clinical trials.