Folate status worsens in recently institutionalized elderly people without evidence of functional deterioration

OBJECTIVE: To follow folate status, hematological and cognitive changes during the first year of institutionalization among elderly subjects. DESIGN: Prospective study. SETTING: Long-stay unit of the Dijon University Geriatric Hospital. SUBJECTS: Twenty women and four men older than 65 years admitted consecutively. MAIN OUTCOME MEASURES: Folate and vitamin B-6 dietary intake was evaluated by a five-day record on admission (day 1 or d 1), at day 45 (d 45), day 90 (d 90), day 135 (d 135), day 180 (d 180), day 360 (d 360). Circulating levels of folate, vitamin B-6, total homocysteine (tHcy), blood counts and cognitive performance were determined in parallel. RESULTS: From d 1 to d 360, mean folate and vitamin B-6 intakes remained below the French RDA and mean folate intakes decreased significantly (delta = 10.2%, p < 0.05). Mean plasma or erythrocyte folate decreased significantly (delta = 33.7%, p <0.05 and delta = -30.2%, p < 0.001, respectively) from d 1 to d 360; no significant change was observed for the other blood parameters. The incidence of folate deficiency increased (8% vs. 37% for plasma folate <6.8 nmol/L and 8% vs. 17% for erythrocyte folate <340 nmol/L) from d I to d 360. Mean plasma pyridoxal 5'-phosphate (PLP) remained <20 nmol/L during the one-year follow-up. There was no difference between genders for plasma tHcy. Although mean plasma tHcy was <14 micromol/L. plasma tHcy was >14 micromol/L in about one-third of the subjects. At each period, 50% or more subjects were anemic (Hct <35% in women and Hct <40% in men), but the anemia was normocytic (MCV <100 fL). Subjects had a moderate dementia at admission, and no change was observed during the study. CONCLUSIONS: Subjects were already vitamin B-6 deficient at admission. Folate status was impaired during the study. Low vitamin intakes were the main cause of vitamin B-6 deficiency and folate status deterioration. Hematology and mental status capacity were not aggravated by folate status deterioration. Plasma tHcy didn't appear to be an earlier predictor of folate deficiency.     

Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete

BACKGROUND: Current data suggest that physiologic doses of vitamin B-6 have no significant homocysteine-lowering effect. It is possible that an effect of vitamin B-6 was missed in previous trials because of a much greater effect of folic acid, vitamin B-12, or both. OBJECTIVE: The aim of this study was to investigate the effect of low-dose vitamin B-6 supplementation on fasting total homocysteine (tHcy) concentrations in healthy elderly persons who were made replete with folate and riboflavin. DESIGN: Twenty-two healthy elderly persons aged 63-80 y were supplemented with a low dose of vitamin B-6 (1.6 mg/d) for 12 wk in a randomized, double-blind, placebo-controlled trial after repletion with folic acid (400 microg/d for 6 wk) and riboflavin (1.6 mg/d for 18 wk); none of the subjects had a vitamin B-12 deficiency. RESULTS: Folic acid supplementation lowered fasting tHcy by 19.6% (P < 0.001). After folic acid supplementation, baseline tHcy concentrations ranged from 6.22 to 23.52 micromol/L and 10 subjects had suboptimal vitamin B-6 status (plasma pyridoxal-P < 20 nmol/L). Two-way analysis of variance showed that the significant improvement in vitamin B-6 status in response to vitamin B-6 supplementation (on the basis of both pyridoxal-P: and the erythrocyte aspartate aminotransferase activation coefficient) was reflected in a significant reduction in plasma tHcy of 7.5%. CONCLUSIONS: Low-dose vitamin B-6 effectively lowers fasting plasma tHcy in healthy subjects who are both folate and riboflavin replete. This suggests that any program aimed at the treatment or prevention of hyperhomocysteinemia should include vitamin B-6 supplementation.     

Homocysteine,cardiovascular disease risk factors,and habitual diet in the French Supplementation with Antioxidant Vitamins and Minerals Study

BACKGROUND: An elevated plasma total homocysteine (tHcy) concentration seems to increase the risk of cardiovascular disease. OBJECTIVE: We evaluated the determinants of tHcy in healthy French adults. DESIGN: tHcy was measured by HPLC and fluorometric detection in 1139 women and 931 men aged 35-60 y. Subjects were participants of the Supplementation with Antioxidant Vitamins and Minerals Study, which investigates the effects of antioxidant supplementation on chronic diseases. Red blood cell folate (RBCF), plasma vitamins B-6 and B-12, and cardiovascular disease risk factors were also measured. The habitual diet was assessed in 616 subjects. Cross-sectional analyses were adjusted for age, smoking, energy intake, and concentration or intake of folate and vitamin B-6, where appropriate. RESULTS: The mean (+/-SD) tHcy concentration was 8.74 +/- 2.71 micro mol/L in women and 10.82 +/- 3.49 micro mol/L in men. In women, tHcy was positively related to age (P = 0.001), apolipoprotein B (P < 0.01), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.02), and coffee and alcohol consumption (both P < 0.01) and inversely related to RBCF (P = 0.11) and plasma vitamin B-12 (P = 0.08) and vitamin B-6 (P = 0.01) intakes. In men, tHcy was positively associated with body mass index (P = 0.03), blood pressure (P < 0.02), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.01), and energy intake (P < 0.01) and inversely associated with physical activity (P = 0.04), RCBF (P = 0.02), plasma vitamin B-12 (P = 0.09), and dietary fiber (P < 0.01), folate (P = 0.03), and vitamin B-6 (P = 0.09) intakes. CONCLUSION: To control tHcy, decreasing coffee and alcohol consumption may be important in women, whereas increasing physical activity, dietary fiber, and folate intake may be important in men.     

Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort

BACKGROUND: Established determinants of fasting total homocysteine (tHcy) concentration include folate and vitamin B-12 status, serum creatinine concentration, and renal function. OBJECTIVE: Our objective was to examine the relation between known and suspected determinants of fasting plasma tHcy in a population-based cohort. DESIGN: We examined the relations between fasting plasma tHcy concentrations and nutritional and other health factors in 1960 men and women, aged 28-82 y, from the fifth examination cycle of the Framingham Offspring Study between 1991 and 1994, before the implementation of folic acid fortification. RESULTS: Geometric mean tHcy was 11% higher in men than in women and 23% higher in persons aged > or = 65 y than in persons aged < 45 y (P < 0.001). tHcy was associated with plasma folate, vitamin B-12, and pyridoxal phosphate (P for trend < 0.001). Dietary folate, vitamin B-6, and riboflavin were associated with tHcy among non-supplement users (P for trend < 0.01). The tHcy concentrations of persons who used vitamin B supplements were 18% lower than those of persons who did not (P < 0.001). tHcy was positively associated with alcohol intake (P for trend = 0.004), caffeine intake (P for trend < 0.001), serum creatinine (P for trend < 0.001), number of cigarettes smoked (P for trend < 0.001), and antihypertensive medication use (P < 0.001). CONCLUSIONS: Our study confirmed, in a population-based setting, the importance of the known determinants of fasting tHcy and suggested that other dietary and lifestyle factors, including vitamin B-6, riboflavin, alcohol, and caffeine intakes as well as smoking and hypertension, influence circulating tHcy concentrations.     

High prevalence of hyperhomocysteinemia in Chinese adults is associated with low folate, vitamin B-12, and vitamin B-6 status

Elevated plasma total homocysteine (tHcy) concentrations are associated with lower folate, vitamin B-12, and vitamin B-6 status and are considered an independent risk factor for cardiovascular disease in developed countries, but data in developing countries are limited. We conducted a cross-sectional study to explore tHcy status and its association with plasma B vitamin status in 2471 Chinese men and women aged 35 to 64 y, living in the urban and rural areas of the northern and the southern regions of China. Blood samples were also collected in 2 seasons (spring and fall). The geometric mean plasma tHcy concentration was significantly higher in the north (adjusted geometric mean, 95% CI; 13.0 micromol/L, 12.6-13.3) than in the south (9.1, 8.9-9.4) after controlling for gender, area (urban and rural), age, and season (spring and fall). Twenty-eight percent of northerners and 7% of southerners had plasma tHcy concentrations>or=16.0 micromol/L, a level used to define hyperhomocysteinemia. Within each region, men had higher plasma tHcy concentrations than women (16.1 vs. 10.6 micromol/L in the north, and 10.7 vs. 7.9 micromol/L in the south) and 40% of the northern men had hyperhomocysteinemia. Generally, individuals living in the urban areas had 30% (95% CI, 1.0-1.6) greater odds of having high tHcy levels (>or=16 micromol/L) than those living in the rural areas. Low plasma concentrations of folate, vitamins B-12 and B-6, older age, being male, and living in urban areas were all independently associated with elevated tHcy, with low folate as the strongest determinant.     

Longitudinal change in plasma total homocysteine during pregnancy and postpartum in Brazilian women and its relation with folate status and other factors

Fasting plasma total homocysteine (tHcy) concentration was determined in a cohort of pregnant Brazilian women (n = 46) supplemented with folic acid from the second trimester of pregnancy. Blood samples were obtained in the first and third trimesters from all women, and 30-40 days postpartum from seventeen women. Plasma tHcy decreased during pregnancy from 10.3 to 8.7 micromol/L, and was 11.6 micromol/L in the postpartum. Plasma and erythrocyte folate increased, consistent with use of the folate supplement, but decreased slightly in the postpartum, whereas the opposite occurred for plasma vitamin B12. tHcy was inversely correlated with plasma and erythrocyte folate in the third trimester (r = -0.585 and -0.460, respectively). This relationship occurred despite the fact that all women had attained what could be considered adequate levels of folate indices. Furthermore, the change (third trimester minus first trimester levels) of tHcy was inversely correlated (p < 0.01) with the changes in plasma (r = -0.573) and erythrocyte folate (r = -0.525). tHcy had no correlation in any of the periods tested with plasma vitamin B12, plasma albumin, hematocrit, hemoglobin, iron indices, dietary intakes of folate, vitamins B12 and B6, and levels of folate supplement.     

Effect of age on plasma homocysteine concentrations in young and elderly subjects considering serum vitamin concentrations and different lifestyle factors

OBJECTIVES: The aim of this study was to investigate whether an increase in total homocysteine (tHcy) concentration with increasing age is due to diminishing serum concentrations of pyridoxal-5-phosphate (PLP), vitamin B-12, and folate. The possible influence of different lifestyle factors on tHcy concentration was considered. METHODS: Plasma tHcy, serum concentrations of pyridoxal-5-phosphate, vitamin B-12, and folate, intake of coffee and tea, alcohol, and methionine, as well as cigarette smoking, were determined in 252 elderly subjects (60-87 years old) of the longitudinal study on nutrition and health status in an aging population in Giessen (GISELA) and 99 young adults (20-34 years old) of the study on health and nutrition of young adults (GEJE). RESULTS: Mean plasma tHcy concentrations were significantly higher in elderly than in young female subjects (9.7 +/- 1.9 micromol/L vs. 9.0 +/- 1.6 micromol/L, p < 0.05), but there was no difference between elderly and young men (10.6 +/- 2.1 micromol/L vs. 10.7 +/- 2.6 micromol/L). No differences in tHcy were observed between young and elderly subjects after adjustment for serum concentrations of PLP, vitamin B-12, and folate. Multiple linear regression analysis revealed a significant influence of age only in elderly, but not in younger subjects. CONCLUSION: Higher tHcy concentrations in the elderly, in comparison to younger women, are due to lower serum concentrations of PLP, vitamin B-12, and folate, whereas within the age group of elderly subjects alone tHcy concentrations increase with age irrespective of serum vitamin concentrations.     

Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study

BACKGROUND: Deficiencies of vitamin B-12, folic acid, and vitamin B-6-as defined by laboratory measures-occur in 10-20% of elderly subjects. The clinical significance remains unresolved. OBJECTIVE: The objective was to explore any association between vitamin status and vitamin treatment and movement and cognitive performance in elderly subjects. DESIGN: Community-dwelling subjects (n = 209) with a median age of 76 y were randomly assigned to daily oral treatment with 0.5 mg cyanocobalamin, 0.8 mg folic acid, and 3 mg vitamin B-6 or placebo (double blind) for 4 mo. Movement and cognitive performance tests were performed before and after treatment. RESULTS: A high plasma total homocysteine (tHcy) concentration (> or =16 micromol/L) was found in 64% of men and in 45% of women, and a high serum methylmalonic acid (MMA) concentration (> or =0.34 micromol/L) was found in 11% of both sexes. Movement time, digit symbol, and block design (adjusted for age, sex, smoking, and creatinine) correlated independently with plasma tHcy (P < 0.01, < 0.05, and < 0.01, respectively); the simultaneity index and block design correlated with serum MMA (P < 0.05 for both). Vitamin therapy significantly decreased plasma tHcy (32%) and serum MMA (14%). No improvements were found in the movement or cognitive tests compared with placebo. Neither vitamin therapy nor changes in plasma tHcy, serum MMA, serum vitamin B-12, plasma folate, or whole-blood folate correlated with changes in movement or cognitive performance. CONCLUSIONS: High plasma tHcy and serum MMA were prevalent and correlated inversely with movement and cognitive performance. Oral B vitamin treatment normalized plasma tHcy and serum MMA concentrations but did not affect movement or cognitive performance. This might have been due to irreversible or vitamin-independent neurocognitive decline or to an insufficient dose or duration of vitamins.     

Plasma homocysteine concentrations in Greek children are influenced by an interaction between the methylenetetrahydrofolate reductase C677T genotype and folate status

Risk factors established at young ages may set the stage for later cardiovascular disease (CVD). Elevated total homocysteine (tHcy) in blood is an emerging risk factor for CVD, yet few studies have been conducted in children, especially in the Mediterranean. We described plasma tHcy concentrations in a group of healthy Greek children and examined its relation with physiologic, metabolic, and genetic variables. Fasting blood samples were collected from 186 students, 11.6 +/- 0.4 years old, and tHcy, folate, vitamin B-12, and routine biochemistry variables in plasma were measured. The methylenetetrahydrolate reductase (MTHFR) C677T genotype was determined and anthropometric and dietary data were obtained. The distribution of tHcy was positively skewed with a median of 7.9 micromol/L (mean: 8.2 +/- 2.3 micromol/L; range: 4.4-22.2 micromol/L). tHcy was inversely related to plasma folate (r = -0.34, P < 0.0001), vitamin B-12 (r = -0.20, P = 0.008), and glucose (r = -0.15, P = 0.045). An interaction between the MTHFR genotype and plasma folate on tHcy was detected (P = 0.047). Specifically, the homozygous mutant TT genotype was associated with higher tHcy only in children with lower plasma folate (< 19.9 nmol/L), (P = 0.012). In our sample of healthy Greek children, plasma tHcy concentrations were higher than values reported in children of Northern European descent and were associated with folate, vitamin B-12, and glucose in plasma. The results also show that, similar to adults, plasma folate concentration is important in determining the contribution of the MTHFR C677T mutation to tHcy concentrations in children.     

A daily intake of approximately 6 microg vitamin B-12 appears to saturate all the vitamin B-12-related variables in Danish postmenopausal women

BACKGROUND: Recommended daily intakes of vitamin B-12 vary between 2 and 6 microg. OBJECTIVE: The objective was to examine the associations between vitamin B-12 intake and markers of vitamin B-12 deficiency. DESIGN: We studied 98 Danish postmenopausal women aged 41-75 y. Serum cobalamin, transcobalamin (TC) saturated with vitamin B-12 (holo-TC), TC saturation (holo-TC/total TC), methylmalonic acid (MMA), and total homocysteine (tHcy) were measured to assess vitamin B-12 status. Dietary intakes of vitamin B-12 were determined from 7-d weighed food records. Gastric pH measurement and the alkali-challenge test were performed with the use of Heidelberg radiotelemetric capsules. RESULTS: The total intake of vitamin B-12 ranged from 1.2 to 23.9 microg/d. All vitamin B-12-related variables, except gastric pH, correlated significantly with total vitamin B-12 intake. Those taking supplements (54%) had higher circulating concentrations of cobalamin and TC saturation and lower concentrations of MMA and tHcy than did those not taking supplements. All subjects were divided into quintiles according to their total vitamin B-12 intake. For all the variables analyzed, the curves appeared to level off at a daily vitamin B-12 intake of approximately 6 microg; the median (and 25th-75th percentiles) for cobalamin was 380 (270-480) pmol/L, for holo-TC was 119 (92-162) pmol/L, for MMA was 0.12 (0.14-0.17) micromol/L, and for tHcy was 9.75 (8.3-11.40) micromol/L (n = 58). CONCLUSION: A daily vitamin B-12 intake of 6 microg appeared to be sufficient to correct all the vitamin B-12-related variables measured in the postmenopausal Danish women in this study.     

Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease.

BACKGROUND: Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-micromol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater. OBJECTIVE: Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease. DESIGN: This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/=100% of the recommended dietary allowances for 23 micronutrients, including folate. RESULTS: Mean folate intakes at 10 wk were 601 +/- 143 microgram/d with the PMP and 270 +/- 107 microgram/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/- 5.8 to 9.3 +/- 4.9 micromol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD. CONCLUSIONS: The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease.     

Folate Status Worsens in Recently Institutionalized Elderly People without Evidence of Functional Deterioration

Objective: To follow folate status, hematological and cognitive changes during the first year of institutionalization among elderly subjects.

Design: Prospective study.

Setting: Long-stay unit of the Dijon University Geriatric Hospital.

Subjects: Twenty women and four men older than 65 years admitted consecutively.

Main outcome measures: Folate and vitamin B-6 dietary intake was evaluated by a five-day record on admission (day 1 or d 1), at day 45 (d 45), day 90 (d 90), day 135 (d 135), day 180 (d 180), day 360 (d 360). Circulating levels of folate, vitamin B-6, total homocysteine (tHcy), blood counts and cognitive performance were determined in parallel.

Results: From d 1 to d 360, mean folate and vitamin B-6 intakes remained below the French RDA and mean folate intakes decreased significantly (Δ = ?10.2%, p <0.05). Mean plasma or erythrocyte folate decreased significantly (Δ = ?33.7%, p <0.05 and Δ = ?30.2%, p <0.001, respectively) from d 1 to d 360; no significant change was observed for the other blood parameters. The incidence of folate deficiency increased (8% vs. 37% for plasma folate <6.8 nmol/L and 8% vs. 17% for erythrocyte folate <340 nmol/L) from d 1 to d 360. Mean plasma pyridoxal 5′-phosphate (PLP) remained <20 nmol/L during the one-year follow-up. There was no difference between genders for plasma tHcy. Although mean plasma tHcy was <14 μmol/L, plasma tHcy was >14 μmol/L in about one-third of the subjects. At each period, 50% or more subjects were anemic (Hct <35% in women and Hct <40% in men), but the anemia was normocytic (MCV <100 fL). Subjects had a moderate dementia at admission, and no change was observed during the study.

Conclusions: Subjects were already vitamin B-6 deficient at admission. Folate status was impaired during the study. Low vitamin intakes were the main cause of vitamin B-6 deficiency and folate status deterioration. Hematology and mental status capacity were not aggravated by folate status deterioration. Plasma tHcy didn’t appear to be an earlier predictor of folate deficiency.     

Total homocysteine and its predictors in Dutch children

BACKGROUND: Vitamin status, methylenentetrahydrofolate reductase (MTHFR) genotype, age, sex, and lifestyle factors are all predictors of total homocysteine (tHcy) concentrations in adults. Limited data are available about the influence of these factors on tHcy in children. OBJECTIVE: The objective was to describe tHcy and its predictors in Dutch children. DESIGN: A sample of 234 white children aged 0-19 y was analyzed cross-sectionally. RESULTS: The geometric mean tHcy concentrations were 5.1 (95% CI: 4.6, 5.6), 4.6 (4.2, 5.1), 6.2 (5.6, 6.9), 7.3 (6.7, 8.0), and 8.7 (7.9, 9.6) micromol/L in the 0-1, 2-5, 6-10, 11-14, and 15-19 y groups, respectively. Plasma folate and vitamin B-12 concentrations decreased markedly with age. The inverse association between tHcy and plasma folate seen at all ages was stronger than that between tHcy and plasma vitamin B-12. A negative association of plasma folate with tHcy was confined to folate concentrations <20 nmol/L. Homozygosity for the MTHFR 677C-->T polymorphism was identified in 8.2% of the children. The homocysteine concentration did not differ significantly between the MTHFR genotypes. CONCLUSIONS: This study provided age-specific data regarding tHcy concentrations and their predictors in the whole range of childhood. The tHcy concentration increased as a function of age in both sexes. Plasma folate was a concentration-dependent predictor of tHcy. The MTHFR 677C-->T polymorphism played a minor role in determining tHcy concentrations in children.     

The association between betaine and choline intakes and the plasma concentrations of homocysteine in women

BACKGROUND: Elevated total homocysteine (tHcy), a risk factor for many chronic diseases, can be remethylated to methionine by folate. Alternatively, tHcy can be metabolized by other 1-carbon nutrients, ie, betaine and its precursor, choline. OBJECTIVE: We aimed to assess the association between the dietary intakes of betaine and choline and the concentration of tHcy. DESIGN: We conducted a cross-sectional analysis in 1477 women by using linear regression models to predict mean fasting tHcy by intakes of of betaine and choline. RESULTS: tHcy was 8% lower in the highest quintile of total betaine + choline intake than in the lowest quintile, even after control for folate intake (P for trend = 0.07). Neither choline nor betaine intake individually was significantly associated with tHcy. Choline from 2 choline-containing compounds, glycerophosphocholine and phosphocholine, was inversely associated with tHcy. These inverse associations were more pronounced in women with folate intake < 400 mug/d than in those with intakes >or=400 microg/d (P for interaction = 0.03 for phosphocholine) and in moderate alcohol drinkers (>or=15 g/d) than in nondrinkers or light drinkers (<15 g/d) (P for interaction = 0.02 for glycerophosphocholine and 0.04 for phosphocholine). The strongest dose response was seen in women with a low-methyl diet (high alcohol and low folate intake) (P for interaction = 0.002 for glycerophosphocholine and 0.001 for phosphocholine). CONCLUSIONS: Total choline + betaine intake was inversely associated with tHcy, as was choline from 2 water-soluble choline-containing compounds. Remethylation of tHcy may be more dependent on the betaine pathway when methyl sources are low as a result of either inadequate folate intake or heavier alcohol consumption.     

B vitamin status and concentrations of homocysteine and methylmalonic acid in elderly German women

BACKGROUND: Prior investigations found that elderly persons are at higher risk than are younger persons for B vitamin deficiency, which leads to elevated plasma total homocysteine (tHcy) concentrations that are associated with an increased risk for certain diseases such as coronary artery disease. To date, published data have shown decreased vitamin status and elevated tHcy among the elderly. OBJECTIVE: We evaluated the dietary intake and the blood status of various B vitamins and tHcy and methylmalonic acid (MMA) concentrations in 178 younger (60-70-y-old) female seniors. DESIGN: Dietary intake was assessed with a 3-d diet record. Thiamine, riboflavin, and vitamin B-6 activity coefficients of erythrocyte transketolase (EC 2.2.1.1), erythrocyte glutathione reductase (EC 1.6.4.2), and erythrocyte alpha-aspartic aminotransferase (EC 2.6.1.1) were used as functional indexes for the status of the 3 vitamins, respectively. Concentrations of serum and red blood cell folate, serum cobalamin and MMA, and plasma tHcy were measured. RESULTS: Indexes of thiamine, pyridoxine, and cobalamin indicated insufficient status in one-third of the women, whereas tHcy and MMA concentrations were elevated in 17.4% and 9.6% of the women, respectively. An association between vitamin intake and vitamin concentration in the blood was found only for folate. The mean tHcy concentration in subjects in the lowest quartile of serum folate concentration was 23% higher than that in subjects in the highest quartile. There was no association between riboflavin and tHcy concentrations. MMA was positively correlated with age and inversely correlated with serum cobalamin concentration. CONCLUSIONS: Even in younger, well-educated, female seniors, the prevalence of low B vitamin status and elevated plasma tHcy concentration is high. Thiamine, pyridoxine, folate, and cobalamin supplementation should be considered.     

Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations

BACKGROUND: Remethylation of homocysteine to methionine can occur through either the folate-dependent methionine synthase pathway or the betaine-dependent betaine-homocysteine methyltransferase pathway. The relevance of betaine as a determinant of fasting total homocysteine (tHcy) is not known, nor is it known how the 2 remethylation pathways are interrelated. OBJECTIVE: The objectives of the study were to examine the relation between plasma betaine concentration and fasting plasma tHcy concentrations and to assess the effect of folic acid supplementation on betaine concentrations in healthy subjects. DESIGN: A double-blind randomized trial of 6 incremental daily doses of folic acid (50-800 microg/d) or placebo was carried out in 308 Dutch men and postmenopausal women (aged 50-75 y). Fasted blood concentrations of tHcy, betaine, choline, dimethylglycine, and folate were measured at baseline and after 12 wk of vitamin supplementation. RESULTS: Concentrations of tHcy were inversely related to the betaine concentration (r = -0.17, P < 0.01), and the association was independent of age, sex, and serum concentrations of folate, creatinine, and cobalamin. Folic acid supplementation increased betaine concentration in a dose-dependent manner (P for trend = 0.018); the maximum increase (15%) was obtained at daily doses of 400-800 microg/d. CONCLUSIONS: The plasma betaine concentration is a significant determinant of fasting tHcy concentrations in healthy humans. Folic acid supplementation increases the betaine concentration, which indicates that the 2 remethylation pathways are interrelated.     

Homocysteine concentrations in adults with trisomy 21: effect of B vitamins and genetic polymorphisms

BACKGROUND: The effects of supplementation with B vitamins and of common polymorphisms in genes involved in homocysteine metabolism on plasma total homocysteine (tHcy) concentrations in trisomy 21 are unknown. OBJECTIVES: We aimed to determine the effects of orally administered folic acid and of folic acid combined with vitamin B-12, vitamin B-6, or both on tHcy in adults with trisomy 21. The study was also intended to analyze the possible influence of gene polymorphisms. DESIGN: One hundred sixty adults with trisomy 21 and 160 healthy, unrelated subjects aged 26 +/- 4 y were included. Plasma tHcy, red blood cell folate, serum folate, and vitamin B-12 were measured. Genotyping for the common methylenetetrahydrofolate reductase (MTHFR) 677C-->T, MTHFR 1298A-->C, cystathionine beta-synthase 844Ins68, methionine synthase 2756A-->C, methionine synthase reductase 66A-->G, and reduced folate carrier 80G-->A polymorphisms was carried out. RESULTS: The mean tHcy concentration (9.8 +/- 0.7 micromol/L) of cases who did not use vitamins was not significantly different from that of controls (9.4 +/- 0.3 micromol/L). Plasma tHcy concentrations (7.6 +/- 0.3 mmol/L) in cases who used folic acid were significantly lower than in cases who did not. Folic acid combined with vitamin B-12 did not significantly change tHcy concentrations compared with those in cases who used only folic acid. Folic acid combined with vitamins B-6 and B-12 significantly lowered tHcy (6.5 +/- 0.5 micromol/L). The difference in tHcy according to MTHFR genotype was not significant. However, tHcy concentrations were slightly higher in TT homozygotes among the controls but not among the cases. CONCLUSION: This study provides information on the relation between several polymorphisms in genes involved in homocysteine and folate metabolism in adults with trisomy 21.     

Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women

BACKGROUND: An elevated total homocysteine (tHcy) concentration is considered to be an independent risk factor for cardiovascular diseases and has also been associated with an increased risk of neural tube defects. OBJECTIVE: The objective of this study was to investigate folate intake, folate status, and the association between folate intake, other dietary and lifestyle factors, and tHcy concentrations in young and older women. DESIGN: tHcy concentrations were measured in 290 young women aged 25-30 y and in 288 older women aged 60-65 y. All participants completed questionnaires about factors including lifestyle, health, and use of vitamin supplements. Red blood cell folate was measured in 204 of the participants. A subgroup of 258 participants completed dietary records. RESULTS: Median tHcy was 7.6 micromol/L (range: 6.5-8.9) in the younger women and 9.4 micromol/L (7.7-11.1) in the older women. Folate intake from diet was 283 (224-348) and 268 (210-326) microg/d, respectively, in the 2 age groups. Folic acid intake from supplements (P: < 0.001 for the younger women and P: = 0.026 for the older women) and total folate intake (P: = 0.024 and P: = 0.079) were inversely associated with log tHcy in multiple linear regression analyses. Smoking status, coffee consumption, systolic blood pressure, and body mass index were positively associated and estrogen replacement therapy and tea consumption were inversely associated with log tHcy in some of the models. CONCLUSIONS: According to the criteria used, between 1% and 36% of the women had suboptimal folate intake. Folic acid is a strong predictor of tHcy concentration; however, several dietary and other lifestyle factors seem to be important as well.     

Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 does not affect the proportion of (n-3) long chain polyunsaturated fatty acids in plasma phosphatidylcholine

There is evidence to suggest that folate, homocysteine, or both affect the (n-3) long chain PUFA composition of tissues; however, this evidence is derived largely from experiments with animals and small observational studies in humans. Results from randomized controlled trials are needed. The objective of this study was to determine whether homocysteine lowering with a B vitamin supplement affects the proportion of (n-3) long-chain PUFA in plasma phosphatidylcholine. We conducted a double-blind, placebo-controlled, randomized clinical trial involving 253 participants, 65 y or older, with plasma homocysteine concentrations of at least 13 micromol/L. Participants in the vitamin group (n = 127) took a daily supplement containing 1000 microg folate, 500 microg vitamin B-12, and 10 mg vitamin B-6 for 2 y. The fatty acid composition of plasma phosphatidylcholine was measured at baseline and at 2 y. Plasma homocysteine concentrations during the course of the study were 4.4 micromol/L lower in the vitamin group than in the placebo group. The proportions of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids in plasma phosphatidylcholine did not differ between the vitamin and placebo groups at 2 y; the mean differences after adjusting for baseline values and sex were -0.03 (99% CI: -0.22, 0.16), 0.03 (99% CI: -0.03, 0.09), and -0.02 (99% CI: -0.27, 0.24) mol%, respectively. Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 had no effect on the proportion of (n-3) long-chain PUFA in plasma phosphatidylcholine.     

Dietary predictors of plasma total homocysteine in the Hordaland Homocysteine Study

Established dietary predictors of plasma total homocysteine (tHcy) include folate, riboflavin, and vitamins B6 and B12, while information is scarce regarding other dietary components. The aim of this study was to examine the relation between a variety of food groups, food items and nutrients, and plasma tHcy in a large population-based study. The study population included 5812 men and women aged 47-49 and 71-74 years who completed a 169-item FFQ. tHcy was examined across quartiles of dietary components by multiple linear regression analyses adjusting for age, sex, energy intake, various risk factors for elevated tHcy, as well as for dietary and plasma B-vitamins. Among 4578 non-users of vitamin supplements, intake of vegetables, fruits, cereals, eggs, fish and milk, as well as chicken and non-processed meats were inversely associated with tHcy level. The estimated mean difference in tHcy per increasing quartile of intake ranged from - 0.11 (95 % CI - 0.21, - 0.01) micromol/l for milk to - 0.32 (95 % CI - 0.42, - 0.22) micromol/l for vegetables. Positive associations were found for sweets and cakes. Whole-grain bread was significantly inversely related to tHcy only after additional adjustment for dietary and plasma B-vitamins. The nutrients folate, vitamin B6, B12, and riboflavin were inversely related to tHcy. Complex carbohydrates were inversely, and fat positively associated with tHcy, also after adjustment for dietary and plasma B-vitamins. In conclusion, food items rich in B-vitamins and with a low content of fat and sugar were related to lower tHcy levels. Eggs, chicken, non-processed meat, fish and milk were inversely associated with tHcy.