Effect of increased vegetable and fruit consumption on plasma folate and homocysteine concentrations

OBJECTIVE: We assessed the effects of an intervention aimed at increasing the consumption of fruits and vegetables on plasma folate and homocysteine concentrations. METHODS: Seventy-one healthy non-smoking women (mean +/- SD 41 +/- 4 y of age) were randomized to an intervention or a control group. Participants in the intervention group (n = 36) received weekly packets containing fruits and vegetables free of charge and were asked to consume a daily amount of >or=200 g of vegetables and two pieces of fruit (the Dutch recommended intake level) over a period of 1 mo. Control subjects did not receive any intervention. RESULTS: Compared with the control group, reported fruit and vegetable intakes in the intervention group increased by 133 g/d (95% confidence interval [CI] 87-179, P < 0.001) for fruits and juice and 64 g/d (95% CI 37-91, P < 0.001) for vegetables and estimated folate intake from fruits and vegetables increased by 40 microg/d (95% CI 22-58, P < 0.001). However, no effect was observed on plasma folate concentrations (intervention effect 0.3 nmol/L, 95% CI -1.8 to 2.8, P = 0.77) or homocysteine concentrations (intervention effect 0.26 micromol/L, 95% CI -0.34 to 0.87, P = 0.39). CONCLUSION: The results suggest that 4 wk of increased fruit and vegetable consumption to the recommended amounts may be insufficient to change plasma folate and homocysteine concentrations.     

Effect of the methylenetetrahydrofolate reductase 677C-->T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate and homocysteine metabolism. The common MTHFR 677C-->T polymorphism decreases the enzyme's activity. OBJECTIVE: The objective of the study was to assess the effect of the polymorphism on the relations among folate intake, plasma folate concentration, and total plasma homocysteine (tHcy) concentration. DESIGN: The design was a cross-sectional analysis in a random sample (n = 2051) of a Dutch cohort (aged 20-65 y). RESULTS: At a low folate intake (166 micro g/d), folate concentrations differed significantly among the genotypes (7.1, 6.2, and 5.4 nmol/L for the CC, CT, and TT genotypes, respectively; P for all comparisons < 0.05). At a high folate intake (250 microg/d), folate concentrations in CT and CC subjects did not differ significantly (8.3 and 8.6 nmol/L, respectively, but were significantly higher (P = 0.2) than those in TT subjects (7.3 nmol/L; P = 0.04). At a low folate concentration (4.6 nmol/L), TT subjects had a significantly higher (P = 0.0001) tHcy concentration than did CC and CT subjects (20.3 compared with 15.0 and 14.1 micromol/L, respectively), whereas at a high folate concentration (11.9 nmol/L), the tHcy concentration did not differ significantly between genotypes (P > 0.2; <13.1 for all genotypes). The relation between folate intake and tHcy concentration had a pattern similar to that of the relation between plasma folate and tHcy concentrations. CONCLUSIONS: At any folate intake level, TT subjects have lower plasma folate concentrations than do CT and CC subjects. Yet, at high plasma folate concentrations, tHcy concentrations in TT subjects are as low as those in CT and CC subjects.     

Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population

BACKGROUND: Elevated blood concentrations of total homocysteine (tHcy) have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. Previous studies identified suboptimal nutritional status and dietary intake of folate, vitamin B-6, and vitamin B-12 as determinants of elevated tHcy. OBJECTIVE: We identified other nutritional factors associated with tHcy in 260 retired schoolteachers in the Baltimore metropolitan area. DESIGN: We performed observational analyses of baseline and 2-4-mo follow-up data collected in a study designed to test the feasibility of conducting a large-scale clinical trial of vitamin supplements by mail. The study population consisted of 151 women and 109 men with a median age of 64 y. At baseline, each participant completed a food-frequency questionnaire. At follow-up, fasting serum tHcy was measured. RESULTS: In multivariable linear regression and generalized linear models, there was an independent, inverse dose-response relation between dietary protein and In tHcy (P = 0.002) and a positive, significant dose-response relation between coffee consumption and In tHcy (P for trend = 0.01). Other significant predictors of In tHcy were creatinine (positive; P = 0.0001) and prestudy use of supplemental B vitamins (inverse; P = 0.03). In stratified analyses restricted to persons receiving standard multivitamin therapy, the association of 1n tHcy with dietary protein and coffee persisted. CONCLUSIONS: These results support the hypothesis that increased protein intake and decreased coffee consumption may reduce tHcy and potentially prevent atherosclerotic cardiovascular disease and other disease outcomes.     

Impact of voluntary folate fortification on plasma homocysteine and serum folate in Australia from 1995 to 2001: a population based cohort study

STUDY OBJECTIVE: To investigate the effect of the voluntary folate fortification policy in Australia on serum folate and total plasma homocysteine (tHcy) concentrations. DESIGN: Population based cohort study. SETTING: Perth, Western Australia. PARTICIPANTS: Men and women aged 27 to 77 years (n = 468), who were originally randomly selected from the Perth electoral roll. The cohort was surveyed in 1995/96 before widespread introduction of folate fortification of a variety of foods, and followed up on two occasions, firstly in 1998/99 and again in 2001, when a moderate number of folate fortified foods were available. Subjects with abnormal serum creatinine concentrations at baseline were excluded from this analysis. MAIN RESULTS: Repeated measures analysis of variance was used to determine changes in serum folate and tHcy over the three surveys and to assess whether time trends were related to age, sex, MTHFR C677T genotype, or consumption of folate fortified foods. An increase (38%) in mean serum folate (p < 0.0005) and a decrease (21%) in mean tHcy (p < 0.0005) were seen after introduction of the voluntary folate fortification policy in Australia. Serum folate was consistently higher (p = 0.032) and tHcy was consistently lower (p = 0.001) in subjects who consumed at least one folate fortified food compared with subjects who did not consume any folate fortified foods in the previous week. The time related changes in serum folate and tHcy were affected only by intake of folate fortified foods (p < 0.0005) and not by any other measured variables including age, sex, or MTHFR genotype. CONCLUSION: Voluntary fortification of foods with folate in Australia has been followed by a substantial increase in serum folate and decrease in tHcy in the general population.     

Association between depressive symptoms and serum concentrations of homocysteine in men: a population study

BACKGROUND: Results of studies of the association between blood concentrations of homocysteine and depression in general populations and among psychiatric patients are inconsistent. OBJECTIVE: The objective was to study the association between depression and serum concentrations of total homocysteine (tHcy). DESIGN: A cross-sectional study of a sample of 924 men aged 46-64 y was conducted as a part of the Kuopio Ischaemic Heart Disease Risk Factor Study. Those who had a history of psychiatric disorder (6.0%) were excluded. Depressive symptoms were assessed with the 18-item Human Population Laboratory Depression Scale. Those who scored > or =5 at baseline or at the 4-y follow-up were considered to have a tendency toward depression. RESULTS: The participants were ranked according to their blood tHcy concentration and divided into tertiles. Those in the upper tertile for serum tHcy had a more than twofold (odds ratio: 2.30; 95% CI: 1.35, 3.90; P=0.002) higher risk of being depressed than did those in the lowest tertile for serum tHcy. The results remained significant after adjustment for the month of study, history of ischemic heart disease, smoking habits, alcohol consumption, marital status, education, and socioeconomic status in adulthood (odds ratio: 2.23; 95% CI: 1.30, 3.83; P=0.004). CONCLUSION: High serum concentrations of tHcy may be associated with depression in middle-aged men.     

Folate intake,plasma folate and homocysteine status in a random Finnish population

OBJECTIVE: To assess the folate status of Finnish adults using plasma folate and homocysteine as biomarkers and to evaluate dietary and supplementary folate intakes. MATERIALS AND METHODS: Plasma folate, vitamin B(12) and total homocysteine (tHcy) were determined in a random sample of 643 subjects aged 25-74 y living in the Helsinki area. The methylenetetrahydrofolate reductase (MTHFR)-genotypes were analyzed from a subsample (n=394). Dietary intake data by 24 h recall and use of vitamin supplements were collected. RESULTS: Plasma folate was normal (>/=5 nmol/l) in 99% of subjects and optimal (>/=8 nmol/l) in terms of a minimum tHcy in 90%. Mean plasma folate of non-supplement users was 13.7 and 12.9 nmol/l and tHcy 11.3 and 9.2 micro mol/l for men and women, respectively. Elevated tHcy (>14 micro mol/l) was found in 11% of subjects. Homozygote frequency for MTHFR genotype TT was 5.0% and their plasma tHcy was 14.8 micro mol/l compared to the mean of the other subjects, 10.5 micro mol/l, P<0.05. The mean dietary folate intake was 241 micro g/day (29 micro g/MJ of energy) for men and 205 micro g/day (33 micro g/MJ) for women, respectively. The main dietary sources of folate were vegetables 12%, wholemeal ryebread 11%, fruits 10%, and potato 10%. Regular supplement users (n=97) received on average 207 micro g folic acid per day from supplements. CONCLUSIONS: The folate status of Finnish adults seems to be adequate according to energy adjusted folate intake, plasma folate and homocysteine. The MTHFR homozygote frequency was low compared to other countries. Regular use of supplementary folic acid less than 300 micro g increased plasma folate, but supplemental folic acid over 300 micro g was required to lower tHcy values significantly.     

Higher total homocysteine concentrations and lower folate concentrations in premenopausal black women than in premenopausal white women.

BACKGROUND: Premenopausal black women have a greater rate of coronary artery disease (CAD) than do premenopausal white women. Plasma total homocysteine concentrations, a risk factor for CAD, have not been reported in premenopausal black women. OBJECTIVE: The purpose of this study was to compare plasma total homocysteine, folate, and vitamin B-12 concentrations in premenopausal black and white women. DESIGN: Eighty-nine black and 90 white, healthy, premenopausal women living in Portland, OR, were recruited. Dietary histories were obtained by using the Diet Habit Survey, a 40-item eating-behavior questionnaire. Plasma concentrations of total homocysteine, folate, and vitamin B-12 were measured. RESULTS: Black women had higher plasma total homocysteine (8.32 compared with 7.60 micromol/L;P = 0. 013), lower plasma folate (6.62 compared with 9.88 nmol/L;P < 0. 0001), and higher vitamin B-12 (355 compared with 283 pmol/L;P < 0. 001) concentrations than white women. White women had a greater rate of daily multivitamin supplement use (42.4% compared with 24.7%;P = 0.019) and ate more ready-to-eat cereal than did black women. After adjustment for multivitamin use and intake of ready-to-eat cereal, plasma total homocysteine concentrations did not differ significantly, but plasma folate remained significantly lower in the black women. None of the black women but 12.3% of the white women (P = 0.013) were homozygous for the cytosine to thymidine mutation at nucleotide 677 in the methylenetetrahydrofolate reductase gene. CONCLUSIONS: Black women had higher plasma total homocysteine and lower plasma folate concentrations than white women, largely because of lifestyle factors, which may contribute to the greater rate of CAD in premenopausal black than in white women.     

Relation of body mass index to blood folate and total homocysteine concentrations in Japanese adults

Purpose  

Plasma folate concentrations are suggested to be negatively associated with body mass index (BMI, kg/m²), although these findings are controversial. Our objective was to evaluate the association of BMI with blood folate and total homocysteine (tHcy) concentrations.     

Urinary excretion of folate catabolites responds to changes in folate intake more slowly than plasma folate and homocysteine concentrations and lymphocyte DNA methylation in postmenopausal women

Folate turnover involves urinary excretion, fecal excretion, and catabolism that involves cleavage of the C9-N10 bond to yield pterins and para-aminobenzoylglutamate (pABG). Little is known about the relationship between the function of folate pools and their rates of catabolism. We report here an investigation of excretion of urinary pABG and its primary excretory form, para-acetamidobenzoylglutamate (ApABG) in samples collected during a previously published study of postmenopausal women. Ten women (49-63 y) were fed a low folate diet (56 microg/d) supplemented with folic acid to yield total folate intakes of 195 microg/d (d 1-5), 56 microg/d (d 6-41), 111 microg/d (d 42-69), 286 microg/d (d 70-80) and 516 microg/d (d 81-91). This caused changes in plasma folate, plasma homocysteine and global methylation of lymphocyte DNA. For each subject, a 7-d pooled urine sample was collected over d 1-7, 36-42, 64-70 and 85-91. ApABG constituted >85% of total catabolite excretion, and folate intake did not significantly influence ApABG or pABG excretion. The molar ratio of total catabolite excretion/folate intake varied significantly, with ratios of 1.0 +/- 0.17 (d 1-7), 3.0 +/- 0.55 (d 36-42), 1.1 +/- 0.18 (d 64-70) and 0. 33 +/- 0.054 (d 85-91). These observations indicate that the rate of folate catabolite excretion is related mainly to masses of slow-turnover folate pools governed by long-term folate intake. Folate pools functioning in some forms of methyl group metabolism respond to dietary changes in folate intake much more rapidly.     

A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations.

Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocysteine metabolism. Previous studies revealed that a common mutation in MTHFR gene C677T is related to hyperhomocysteinemia and occlusive vascular pathology. In the current study, we determined the prevalence of a newly described mutation in the human MTHFR gene A1298C, and the already known C677T mutation, and related them to plasma total homocysteine and folate concentrations. We studied 377 Jewish subjects, including 190 men and 186 women aged 56.8 +/- 13 y (range 32-95 y). The frequency of the homozygotes for the A1298C and the C677T MTHFR mutations was common in the Jewish Israeli population (0.34 and 0.37, respectively). Subjects homozygous (TT) for the C677T mutation had significantly greater plasma total homocysteine concentrations (P < 0.01) than subjects without the mutation (CC). Homozygotes (CC) for the A1298C mutation did not have elevated plasma total homocysteine concentrations. Our study indicated that subjects with the 677CC/1298CC genotype had significantly lower concentrations (P < 0. 05) than those with a 677CC/1298AA genotype. Neither mutation (the A1298C and the C677T) was associated with established cardiovascular risk factors such as hypertension, elevated total cholesterol or body mass index.     

Total serum homocysteine, folate and vitamin B12 in a Greek school age population

BACKGROUND & AIMS: Moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD) even among children. The purpose of this study is to investigate for the first time the distribution and determinants of total serum homocysteine (tHcy) levels in healthy Greek children. METHODS: tHcy, folate, B12 were measured in 524 children (275 boys and 249 girls) aged 6-15 years old from different socioeconomic status in Northern Greece. RESULTS: The geometric mean tHcy level for boys and girls was 7.8 (3.4-24.2) and 7.5 (3.9-29.0) micromol/L, respectively. Eighty one (15.4%) children had homocysteine levels above the upper reference limits (>10 micromol/L). The geometric mean serum tHcy level was significantly (P<0.001) increasing with age; 6.4 (3.4-11.2) micromol/L was found in the age group of 6-9 yr (group1), 7.2(4.1-22.1) micromol/L in the one of 10-12 yr (group 2) and 8.5 (3.9-29.0) micromol/L in the one of 13-15 yr (group 3). Serum folate levels were found to be statistically significant (P<0.001) between age group 1 and age group 3 [11.8 (4.66-20.00) vs. 7.5 (0.99-20.00)ng/mL) and between age group 2 and 3 [10.0 (1.82-20.0) vs. 7.5 (0.99-20.00)ng/mL]. Vitamin B12 levels were significantly (P<0.001) different in the three age groups [1048 (117-2000), 805 (296-2000), 700 (214-2000)pg/mL] respectively. Age, BMI, waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively correlated with tHcy, whereas serum folate and vitamin B12 were negatively correlated. No association was found between tHcy levels and parental education status. In multiple linear regression analysis only age (Beta: 0.248, 95%, CI: (0.159-0.361), P<0.05) and folate (Beta: 0.347, 95%, CI: [(-0.206)-(-0.118)], P<0.05) were found significantly and independently associated with tHcy. CONCLUSIONS: tHcy levels were increasing with age and boys were found to have slightly higher levels than girls. Age and folate levels were the most significantly and independently determinants associated with tHcy. Children with tHcy levels above the upper reference limits (>10 micromol/L) were found to be correlated with BMI, WC, SBP, serum folate and vitamin B12 levels. These children should be encouraged to include high folate food items in their diet and where necessary folate supplements should be recommended. In addition, more prospective studies are necessary in order to evaluate the relationship of tHcy and CVD risk factors in children of our region.     

Lifestyle factors and plasma homocysteine concentrations in a general population sample.

The authors cross-sectionally investigated the extent to which coffee, tea, and alcohol consumption, physical activity, and smoking were associated with nonfasting total plasma homocysteine concentrations in a random sample of 3,025 Dutch adults aged 20--65 years from a population-based cohort examined in 1993--1996 (n = 19,066). The lifestyle factors most strongly associated with plasma total homocysteine level were smoking (positive), alcohol drinking (negative), and coffee consumption (positive). The smoking effect was most prominent in women, and the alcohol effect was most pronounced in men. Data indicated that independently of other lifestyle factors, age, and intake of folate and B vitamin supplements, a change in lifestyle could result in a 0.1- to 1.7-micromol/liter change in plasma total homocysteine level. The authors conclude that lifestyle changes could result in a public-health-relevant change in plasma total homocysteine concentrations.     

Effects of the intake of craft or industrial beer on serum homocysteine

Abstract

Beer is a source of folate, vitamin B₆ and B₁₂, molecules involved in the pathways of homocysteine (HCY), a risk factor for cardiovascular disease. This research evaluated if a consumption of craft or industrial beer could reduce serum HCY. In a randomised cross-over study, 12 men (28.7?±?6.0?years) and 12 women (29.4?±?7.5?years), healthy, omnivorous, with normal body mass index, non-smoking and not taking oral supplements or contraceptives, followed a free-living diet and received, daily, for 3?weeks, 330?ml of industrial (4.5% of alcohol) or craft beer (9% of alcohol). Anthropometric measures and blood samples were taken at the beginning and at the end of each period. The consumption of industrial beer reduced (p?<?0.05) HCY (7.35 vs. 6.50?µmol/L) and increased folic acid (3.46 vs. 3.94?ng/mL). Craft beer increased gamma-gluamyl transpeptidase (GGT) (16.6 vs. 18.6?U/L) and reduced vitamin B₆ (20.9 vs. 16.9?ng/mL).     

Association of beer consumption with arsenic concentration in urine: a result from a cross-sectional study of the general Japanese population

Objectives

The first aim of this study was to evaluate the association between time spent living near a contaminated area and concentration of arsenic (As) compounds in the urine among study subjects. The second aim is to assess the association between consumption of various foods or beverages and As concentration in urine among them.

Methods

Urine sampling was performed on 177 persons who voluntarily participated in the survey in May 2014. The median value of the sum of inorganic As (iAs) and total As (tAs) compounds was used for us to divide into two groups, such as the high and low iAs and high and low tAs groups. We analyzed data separately in two-age strata of age group A (the subjects <18 years old), and age group B (the subjects ≥18 years old). A multivariate analysis was performed with the logistic regression model to adjust for potential confounding variables.

Results

No link between time spent living near a contaminated area and urinary As concentration was observed in our study. For age group B, frequently drinking beer was significantly associated with risk of being in the high tAs group (p = 0.008). Compared to not drinking beer, odds ratios (95 % confidence intervals) of drinking beer <1 or 2 times per week, and drinking beer ≥3 or 4 times per week were 3.09 (1.32–7.24) and 3.00 (1.02–8.80), respectively, after adjusting for age, sex, and smoking index.

Conclusion

Frequent consumption of beer may be associated with high tAs in age group B

     

Plasma, liver and kidney folate and plasma homocysteine concentrations are poor response variables at very low dietary folate intakes, in a folate depletion/repletion rat model

Folate depletion/repletion rat models are popular protocols for assessing the bioavailability of folate. Much of the early work carried out on folate bioavailability concentrated on foods naturally high in folate. However, foods low in folate often contribute significantly to folate intake because of their high consumption in the general population. Therefore, the assessment of the bioavailability of foods low in folate is essential to properly estimate folate intake. The present study investigated plasma, liver and kidney folate and plasma homocysteine concentrations as appropriate response variables for measuring folate bioavailability in the rat at very low dietary folate intakes. One hundred and one weanling male rats (Wistar strain) were fed a folate-deficient diet containing 1% succinyl sulfathiazole for 28 d. Following depletion, six rats were randomly assigned to each of 16 repletion diets containing folic acid, fortified white bread, unfortified wholemeal bread or unfortified rye bread calculated to provide 6.25, 12.5, 18.75 and 25 micrograms folate/kg of each diet. After a further 28 d, plasma, liver and kidney folate concentrations were determined by microbiological assay. Plasma homocysteine was measured by HPLC as a functional indicator of folate status. Only a weak correlation was found between the response variables measured and dietary folate intake, indicating that this folate depletion/repletion rat model is not suitable for testing the response of rats fed diets containing very low levels of folate.     

Genes, folate and homocysteine in embryonic development

Population-based studies of human pregnancies show that periconceptional folate supplementation has a significant protective effect for embryos during early development, resulting in a significant reduction in developmental defects of the face, the neural tube, and the cono-truncal region of the heart. These results have been supported by experiments with animal models. An obvious quality held in common by these three anatomical regions is that the normal development of each region depends on a set of multi-potent cells that originate in the mid-dorsal region of the neural epithelium. However, the reason for the sensitive dependence of these particular cells on folic acid for normal development has not been obvious, and there is no consensus about the biological basis of the dramatic rescue with periconceptional folate supplementation. There are two principal hypotheses for the impact of folate insufficiency on development; each of these hypotheses has a micronutrient component and a genetic component. In the first hypothesis the effect of low folate is direct, limiting the availability of folic acid to cells within the embryo itself; thus compromising normal function and limiting proliferation. The second hypothetical effect is indirect; low folate disrupts methionine metabolism; homocysteine increases in the maternal serum; homocysteine induces abnormal development by inhibiting the function of N-methyl-D-aspartate (NMDA) receptors in the neural epithelium. There are three general families of genes whose level of expression may need to be considered in the context of these two related hypotheses: folate-receptor genes; genes that regulate methionine-homocysteine metabolism; NMDA-receptor genes.