Nutritional determinants of plasma total homocysteine distribution in the Canary Islands

OBJECTIVE: We sought to define plasma homocysteine reference values in healthy individuals in the Canary Islands and to determine its relations to folate and vitamin B12 intakes and concentrations. DESIGN: Cross-sectional study. SETTING: Population-based representative sample of 557 participants, aged 18-65 years, from the Canary Islands Nutrition Survey (ENCA). SUBJECTS: All participants completed two 24-h dietary recalls and a general questionnaire collecting socio-demographic and health-related lifestyle information. INTERVENTIONS: Plasma homocysteine and serum vitamin B12 levels were measured by immunoassay, whereas folate levels through an automated ionic capturing method. RESULTS: Median plasma homocysteine was 11.9 micromol/l, higher in men (13.1 micromol/l) than in women (10.9 micromol/l) (P<0.001) and positively associated with age in both sexes (P<0.001). The prevalence of hyperhomocysteinaemia (> or = 15 micromol/l), 21.4%, was also greater in men (32.2%) than in women (13.4%). There were significant negative correlations between plasma homocysteine and serum (r=-0.32, P<0.001) and erythrocyte (r=-0.26, P<0.001) folate, as well as serum vitamin B12 (r=-0.28, P<0.001) concentrations. When divided in quartiles of vitamin intakes or concentrations, men with the lowest vitamin B12 and folate serum values had significantly higher plasma homocysteine concentrations than those in the other three quartiles. In women, hyperhomocysteinaemia was higher in the lowest quartiles of folate intake and serum and erythrocyte folate concentrations. CONCLUSIONS: These data provide further evidence that hyperhomocysteinaemia is a sensitive marker of inadequate folate and vitamin B12 status, allowing for the identification of those with greatest need for nutritional interventions.     

Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study

OBJECTIVE: The essential amino acid L-methionine is a potential compound in the prophylaxis of recurrent or relapsing urinary tract infection due to acidification of urine. As an intermediate of L-methionine metabolism, homocysteine is formed. The objective was to study the metabolism of L-methionine and homocysteine, and to assess whether there are differences between patients with chronic urinary tract infection and healthy control subjects. DESIGN: A randomized placebo-controlled double-blind intervention study with cross-over design. SETTING: Department of Nutritional Physiology, Institute of Nutrition in cooperation with the Department of Internal Medicine III, Friedrich Schiller University of Jena, Germany. SUBJECTS: Eight female patients with chronic urinary tract infection and 12 healthy women (controls). INTERVENTIONS: After a methionine-loading test, the volunteers received 500 mg L-methionine or a placebo three times daily for 4 weeks.Main outcome measures:Serum and urinary concentrations of methionine, homocysteine, cystathionine, cystine, serine, glycine and serum concentrations of vitamin B12, B6 and the state of folate. RESULTS: Homocysteine plasma concentrations increased from 9.4+/-2.7 micromol/l (patients) and 8.9+/-1.8 micromol/l (controls) in the placebo period to 11.2+/-4.1 micromol/l (P=0.031) and 11.0+/-2.3 micromol/l (P=0.000), respectively, during L-methionine supplementation. There were significant increases in serum methionine (53.6+/-22.0 micromol/l; P=0.003; n=20) and cystathionine (0.62+/-0.30 micromol/l; P=0.000; n=20) concentrations compared with the placebo period (33.0+/-12.0 and 0.30+/-0.10 micromol/l; n=20). Simultaneously, renal excretion of methionine and homocysteine was significantly higher during L-methionine intake. CONCLUSIONS: Despite an adequate vitamin status, the supplementation of 1500 mg of L-methionine daily significantly increases homocysteine plasma concentrations by an average of 2.0 micromol/l in patients and in control subjects. An optimal vitamin supplementation, especially with folate, might prevent such an increase.     

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.     

Homocysteine and risk of coronary artery disease: Folate is the important determinant of plasma homocysteine concentration

OBJECTIVES: The purposes of this study were to study the effects of folate and vitamins B6 and B12 on plasma homocysteine concentration and to estimate the risks for coronary artery disease (CAD) according to quartiles of plasma homocysteine concentration. METHODS: The study was designed as a case-reference observational study. Case subjects (CAD group, n = 60) were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery; otherwise, patients were considered for a reference group (n = 60). Risk factors of cardiovascular disease were recorded, including age, sex, blood lipid profile, hypertension, smoking habits, and drinking habits. Plasma homocysteine, folate, pyridoxal 5'-phosphate, and vitamin B12 were measured. RESULTS: CAD subjects had significantly higher mean plasma homocysteine concentrations than did the reference subjects (13.9 +/- 4.9 versus 9.1 +/- 3.3 micromol/L). There were no significant differences between groups with regard to the three B vitamins; however, mean serum folate concentrations for subjects in the highest two quartiles of plasma homocysteine concentration (10.8-13.8 and >/=13.9 micromol/L) were significantly lower than those for subjects in the lowest two quartiles (相似文献   

Serum homocysteine concentration of US adults associated with fortified cereal consumption

BACKGROUND: Elevated serum total homocysteine (tHcy) concentration is implicated in the etiology of cardiovascular disease (CVD). A significant food source of B-vitamins involved in homocysteine metabolism is ready-to-eat cereal (RTEC) in the U.S. OBJECTIVE: To test the hypothesis that tHcy concentration is inversely associated with RTEC intake and blood B-vitamin levels in the U.S. general population. DESIGN: A cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES 1999-2000). Data were stratified according to age and gender. Men and women > or = 19 y (n = 4,218) were classified as RTEC consumers (RTEC-C; n = 824) and RTEC non-consumers (RTEC-NC; n = 3,394) based on 24-hr dietary recall. RESULTS: Forty nine percent of participants showed folate intake with below the estimated average requirements (EARS). Serum folate and red blood cell (RBC) folate concentrations were increased with age in both genders, and significantly higher among RTEC-C than RTEC-NC (p < 0.05). Mean tHcy concentration increased with age, and was significantly lower among both men and women RTEC-C than among RTEC-NC. In multivariate linear regression analyses, RTEC consumption strongly predicted serum folate and tHcy concentrations. CONCLUSION: tHcy concentrations were significantly lower in RTEC-C among the majority of age/gender groups than in RTEC-NC. RTEC consumption may potentially reduce the risk for CVD, mediated through tHcy.     

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.     

Relation between homocysteine concentrations and the consumption of different types of alcoholic beverages: the French Supplementation with Antioxidant Vitamins and Minerals Study

BACKGROUND: Previous studies on the effects of alcohol consumption on total plasma homocysteine (tHcy) concentrations showed contradictory results. The conflicting results may derive in part from confounding by the type of alcoholic beverage consumed. OBJECTIVE: The objective of the study was to evaluate in a predominantly wine-drinking French population whether the relation between alcohol consumption and homocysteine concentrations is dependent on the type of alcoholic beverage consumed. DESIGN: In 1996, a cross-sectional study measuring tHcy and red blood cell folate concentrations was conducted in 1196 middle-aged women and men from the French Supplementation with Antioxidant Vitamins and Minerals Study. Intakes of alcohol, energy, coffee, and B vitamins were assessed by 6 separate 24-h dietary records from the previous year. RESULTS: tHcy concentrations were positively associated with wine intake (P = 0.01) in the women and with beer intake in the men (P = 0.002). No association with the consumption of spirits was observed. The association between beer consumption and tHcy concentrations in the men was modified by the consumption of wine; the association was positive in wine drinkers, whereas an inverse trend was seen in those who drank no wine. CONCLUSION: Wine consumption may increase tHcy concentrations, whereas beer consumption seems to have no effect (or even an inverse effect) on tHcy.     

Preoperative folate and homocysteine status in patients undergoing major surgery

BACKGROUND & AIMS: Patients with folate deficiency and elevated homocysteine (Hcy) levels have increased risk of cerebrovascular and cardiovascular disease. They may also be at increased risk of complications after surgery because nitrous oxide interferes with folate metabolism. The aim of this study was to assess the incidence of folate deficiency and hyperhomocysteinemia in patients presenting for major surgery. We also tested the utility of a brief preoperative medical and dietary questionnaire to identify those with low folate or elevated Hcy levels. METHODS: We enrolled 390 patients and obtained a preoperative fasting blood sample from each of the study participants (folate [n=386], homocysteine [n=387]). RESULTS: Although only one patient had folate deficiency preoperatively (incidence +/-SD folate and Hcy concentrations were 23.7+/-5.2 nmol/l and 9.4+/-4.2 micromol/l, respectively. There was a negative correlation between folate and Hcy, r=-0.27, P<0.001. Multivariate analyses indicated that vegan status and folate supplementation prevented low folate status (P<0.05), while age of the patient, and history of heart failure and anaemia predicted elevated Hcy concentration. CONCLUSIONS: Some factors identified by a brief medical and dietary questionnaire are associated with folate and homocysteine status. Hyperhomocysteinaemia occurs in about 7.5% of surgical patients; however, both low folate status and elevated Hcy concentration are less likely in those taking folate or vitamin B supplements. This has implications for patients undergoing nitrous oxide anaesthesia because of its inhibition of folate metabolism, and should prompt clinicians to consider folate and other nutritional supplementation before elective surgery.     

Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: a 2-y randomized controlled trial

BACKGROUND: In recent prospective studies, higher homocysteine concentrations were shown to be a risk factor for osteoporotic fractures in older persons. Supplements containing folate and vitamins B-12 and B-6 lower homocysteine concentrations. OBJECTIVE: The objective of the study was to determine in healthy older persons whether lowering homocysteine with B vitamins affects plasma biomarkers of bone turnover. DESIGN: Healthy older persons (n = 276; aged >or=65 y) were randomly assigned to receive either a daily supplement containing folate (1 mg), vitamin B-12 (500 microg), and vitamin B-6 (10 mg) or a placebo for 2 y. Of these participants, we selected 135 with baseline homocysteine concentrations >15.0 micromol/L, and we measured serum bone-specific alkaline phosphatase, a marker of bone formation, and bone-derived collagen fragments, a marker of bone resorption, at baseline and 2 y later. RESULTS: At 2 y, plasma homocysteine concentrations were 5.2 mumol/L (95% CI: 3.9, 6.6 micromol/L; P < 0.001) lower in the vitamin than in the placebo group. No significant differences were found in either serum bone-specific alkaline phosphatase (-0.3 microg/L; 95% CI: -2.8, 2.1 microg/L; P = 0.79) or bone-derived collagen fragments (-0.0 microg/L; 95% CI: -0.1, 0.1 microg/L; P = 0.76) between the vitamin and placebo groups, respectively, with 2 y of supplementation. CONCLUSION: Supplementation with folate and vitamins B-6 and B-12 lowered plasma homocysteine but had no beneficial effect on bone turnover at the end of 2 y, as assessed by biomarkers of bone formation and resorption.     

Pro-oxidant activity and methionine metabolism in chronic alcohol abusers: relationship to alcohol withdrawal and folate administration

AIM: The aim of this study was to investigate whether alcohol withdrawal and folate administration could play a role on redox balance and metionine metabolism in heavy drinkers. METHODS: The derivatives of reactive oxygen metabolites (d-ROMs), homocysteine, total thiols, vitamin B12 and folate were evaluated in a selected group of 40 consecutive chronic alcohol abusers by comparison with 44 healthy moderate drinkers, as controls. RESULTS: Before alcohol withdrawal, d-ROMs were significantly higher (p<0.0001) in heavy drinkers than in controls: 368.5 (254.8-718.6) U.CARR vs 245 (200.7-360) U.CARR, respectively, median with range. Plasma homocysteine were significantly higher in alcoholics than in moderate drinkers (p<0.0001): 18 (9.5-82.2) micromol/L vs 9.1 (4.9-19.6) micromol/L, respectively. Heavy drinkers also exhibited higher serum thiols than moderate drinkers (p<0.003): 605.8 (448.2-717.7) micromol/L vs 554.8 (508.3-658.4) micromol/L, respectively. The patients showed lower plasma folate than controls (p<0.0001): 4.1 (1.9-9.7) ng/mL vs 8.8 (5.0-8.4) ng/mL, respectively, but similar vitamin B12 levels: 487 (299-786) pg/mL 621 (243-894) pg/mL. A negative correlation between homocysteine and folate was observed before withdrawal in alcoholics (r=-0.4546, p<0.038). Both serum thiols (549.7 micromol/L, range 402.4-616.6 micromol/L) and homocysteinemia (6.6 micromol/L, range 2.9-18.5 micromol/L) were significantly decreased (p<0.0001 and p<0.022, respectively) after a week of alcohol withdrawal and folate administration. CONCLUSION: Our findings show that both enhanced pro-oxidant activity and a derangement of methionine metabolism can be observed in heavy drinkers before alcohol withdrawal and folate administration. Furthermore, folate seems to be a strong determinant of both plasma homocysteine and thiol concentrations.     

Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh

BACKGROUND: Indian Asian men residing in the United Kingdom have a higher prevalence of hyperhomocysteinemia than do their European counterparts. This has been largely attributed to dietary deficiencies in cobalamin associated with vegetarianism among these Indian Asians. OBJECTIVE: We aimed to ascertain the prevalence of folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh. DESIGN: Plasma concentrations of homocysteine, folate, and cobalamin and urinary concentrations of creatinine were assessed in 1650 adults in Bangladesh. RESULTS: The prevalence of hyperhomocysteinemia (men: >11.4 micromol/L; women: >10.4 micromol/L) was markedly (P < 0.0001) greater among men (63%; x +/- SD: 15.3 +/- 9.5 micromol/L) than among women (26%; 9.5 +/- 4.7 micromol/L). Folate was lower (9.8 +/- 6.5 and 12.3 +/- 7.6 nmol/L, respectively), whereas cobalamin was higher (281 +/- 115 and 256 +/- 118 pmol/L, respectively) (P < 0.0001 for both) among men than among women. Folate explained 15% and cobalamin explained 5% of the variation in homocysteine concentrations. For men, folate (P = 0.005) and cobalamin (P = 0.03) were positively correlated with urinary creatinine. Smoking (P < 0.0003) and betelnut use (P < 0.0002) were independent negative predictors of folate. CONCLUSIONS: Bangladeshi men have a high prevalence of hyperhomocysteinemia, which is more closely associated with folate than with cobalamin, although other factors, eg, smoking and betelnut use, may also contribute to its cause. The positive correlations between urinary creatinine and plasma folate and cobalamin were unanticipated and could suggest that, in marginal nutrition, these vitamins may be limiting for creatine biosynthesis.     

Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y

BACKGROUND: An elevated plasma total homocysteine (tHcy) concentration is associated with an increased risk of cardiovascular diseases. Folate, riboflavin, vitamin B-6, and vitamin B-12 are essential in homocysteine metabolism. OBJECTIVE: The objective was to describe the association between dietary intakes of folate, riboflavin, vitamin B-6, and vitamin B-12 and the nonfasting plasma tHcy concentration. DESIGN: A random sample of 2435 men and women aged 20-65 y from a population-based Dutch cohort examined in 1993-1996 was analyzed cross-sectionally. RESULTS: Univariately, intakes of all B vitamins were inversely related to the plasma tHcy concentration. In multivariate models, only folate intake remained inversely associated with the plasma tHcy concentration. Mean plasma tHcy concentrations (adjusted for intakes of riboflavin, vitamin B-6, vitamin B-12, and methionine and for age, smoking, and alcohol consumption) in men with low (first quintile: 161 microg/d) and high (fifth quintile: 254 microg/d) folate intakes were 15.4 and 13.2 micromol/L, respectively; in women, plasma tHcy concentrations were 13.7 and 12.4 micromol/L at folate intakes of 160 and 262 microg/d, respectively. In men, the difference in the mean plasma tHcy concentration between men with low and high folate intakes was greater in smokers than in nonsmokers (2.8 compared with 1.6 micromol/L) and greater in nondrinkers than in drinkers of >2 alcoholic drinks/d (3.5 compared with 1.4 micromol/L). In women, the association between folate intake and plasma tHcy was not modified by smoking or alcohol consumption. CONCLUSIONS: In this Dutch population, folate was the only B vitamin independently inversely associated with the plasma tHcy concentration. Changing dietary habits may substantially influence the plasma tHcy concentration in the general population.     

Racial differences in prevalence of cobalamin and folate deficiencies in disabled elderly women.

BACKGROUND: Many previous investigations of cobalamin and folate status were performed in white populations. OBJECTIVE: Our objective was to determine whether there are racial differences in the prevalence of cobalamin and folate deficiency. DESIGN: The study was a cross-sectional comparison of baseline serum cobalamin, folate, methylmalonic acid (MMA), total homocysteine (tHcy), and creatinine concentrations, complete blood count, and vitamin supplementation in 550 white and 212 African American subjects from a cohort of physically disabled older women. RESULTS: The mean (+/-SD) serum MMA concentration was significantly higher in whites than in African Americans: 284 +/- 229 compared with 218 +/- 158 nmol/L (P = 0.0001). tHcy concentration was higher in African Americans than in whites: 12.4 +/- 7.0 compared with 10.9 +/- 4.6 micromol/L (P = 0.001). Serum cobalamin was lower in whites (P = 0.0002). Cobalamin deficiency (serum cobalamin <258 pmol/L and MMA >271 nmol/L) was more frequent in the white women (19% compared with 8%; P < 0.0003). Folate deficiency (serum folate <11.4 nmol/L, tHcy >13.9 micromol/L, and MMA <271 nmol/L) was more prevalent in African Americans than in whites (5% compared with 2%; P = 0.01). Multivitamin use was associated with lower tHcy but not with MMA concentrations. Regression models showed that age >85 y, African American race, serum creatinine >90 micromol/L, and high MMA concentration were all significantly correlated with higher tHcy. Creatinine > 90 micromol/L, white race, and folate concentration were positively associated with MMA concentration. CONCLUSIONS: Cobalamin deficiency with elevated serum MMA concentration is more prevalent in elderly white than in African American women and elevated serum tHcy and folate deficiency are more prevalent in elderly African American than in white women.     

The effect of MTHFR(C677T) genotype on plasma homocysteine concentrations in healthy children is influenced by gender

OBJECTIVE: To explore the influence of gender, together with folate status, on the relation between the common methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma total homocysteine (tHcy) concentrations in healthy children. DESIGN: Cross-sectional study by face-to-face interview.Setting and subjects:A total of 186 sixth-grade students participated from twelve randomly selected primary schools in Volos, Greece. METHODS: Fasting tHcy, folate, and vitamin B(12) were measured in plasma. The MTHFR genotypes were determined. Anthropometric and dietary intake data by 24-h recall were collected. RESULTS: Geometric means for plasma tHcy, plasma folate and energy-adjusted dietary folate did not differ between females and males. The homozygous mutant TT genotype was associated with higher tHcy only in children with lower plasma folate concentrations (<19.9 nmol/l, P = 0.012). As a significant gender interaction was observed (P = 0.050), we stratified the lower plasma folate group by gender and found that the association between the genotype and tHcy was restricted to males (P = 0.026). Similar results were obtained when folate status was based on estimated dietary folate. Specifically, only TT males that reported lower dietary folate consumption (<37 microg/MJ/day) had tHcy that was significantly higher than tHcy levels of C-allele carriers (P = 0.001). CONCLUSIONS: Under conditions of lower folate status (as estimated by either plasma concentration or reported dietary consumption), gender modifies the association of the MTHFR(C677T) polymorphism with tHcy concentrations in healthy children. SPONSORSHIP: Kellog Europe.     

Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers

BACKGROUND: An elevated plasma concentration of total homocysteine is considered to be a strong risk factor for cardiovascular disease. Heavy coffee drinking has been related to high homocysteine concentrations in epidemiologic studies and in one experiment in which healthy subjects drank unfiltered, boiled coffee. OBJECTIVE: Our goal was to determine whether daily consumption of paper-filtered coffee raises plasma concentrations of total homocysteine in healthy subjects. DESIGN: Twenty-six volunteers (18-53 y of age) consumed 1 L/d of paper-filtered coffee brewed with 70 g regular ground beans or no coffee for 4 wk each in a randomized, crossover design. RESULTS: The mean (+/-SD) plasma concentration of total homocysteine in fasting blood was 8.1 +/- 1.8 micromol/L after abstention from coffee and 9.6 +/- 2.9 micromol/L after 3-4 wk of coffee drinking, a difference of 1.5 micromol/L (95% CI: 0.9, 2.1 micromol/L) or 18% (P: < 0.001). Coffee increased homocysteine concentrations in 24 of 26 individuals. Circulating concentrations of vitamin B-6, vitamin B-12, and folate were unaffected. CONCLUSION: Drinking large quantities of paper-filtered coffee raises fasting plasma concentrations of total homocysteine in healthy individuals.     

Serum Homocysteine Concentration of US Adults Associated with Fortified Cereal Consumption

Background: Elevated serum total homocysteine (tHcy) concentration is implicated in the etiology of cardiovascular disease (CVD). A significant food source of B-vitamins involved in homocysteine metabolism is ready-to-eat cereal (RTEC) in the U.S.

Objective: To test the hypothesis that tHcy concentration is inversely associated with RTEC intake and blood B-vitamin levels in the U.S. general population.

Design: A cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES 1999–2000). Data were stratified according to age and gender. Men and women ≥ 19 y (n = 4,218) were classified as RTEC consumers (RTEC-C; n = 824) and RTEC non-consumers (RTEC-NC; n = 3,394) based on 24-hr dietary recall.

Results: Forty nine percent of participants showed folate intake with below the estimated average requirements (EARS). Serum folate and red blood cell (RBC) folate concentrations were increased with age in both genders, and significantly higher among RTEC-C than RTEC-NC (p < 0.05). Mean tHcy concentration increased with age, and was significantly lower among both men and women RTEC-C than among RTEC-NC. In multivariate linear regression analyses, RTEC consumption strongly predicted serum folate and tHcy concentrations.

Conclusion: tHcy concentrations were significantly lower in RTEC-C among the majority of age/gender groups than in RTEC-NC. RTEC consumption may potentially reduce the risk for CVD, mediated through tHcy.     

Methylenetetrahydrofolate reductase 677C-->T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial

BACKGROUND: Low folate status and elevated plasma homocysteine are associated with increased risk of neural tube defects and cardiovascular disease. Homocysteine responses to folate may be influenced by genetic variants in folate metabolism. OBJECTIVE: We determined the effect of folate-enhancing dietary interventions on plasma folate and plasma total homocysteine (tHcy) with respect to the methylenetetrahydrofolate reductase 677C-->T genotype. DESIGN: A total of 126 healthy subjects (42 TT, 42 CT, and 42 CC genotypes) completed 3 dietary interventions (4 mo each) in random order: 1) exclusion diet (avoidance of folic acid-fortified foods and ingestion of a placebo daily), 2) folate-rich diet (increased intake of fortified and naturally folate-rich foods to achieve 400 microg folate/d), and 3) supplement (exclusion diet plus a folate supplement of 400 microg/d). RESULTS: Plasma folate was higher (P < or = 0.001) and plasma tHcy lower (P < or = 0.001) after the folate-rich and supplement interventions than after the exclusion diet. Plasma folate was significantly greater after supplementation than after the folate-rich diet, but there was no significant difference in tHcy concentration (P = 0.72). TT homozygotes had higher plasma tHcy (14.5 compared with 8.9 micromol/L, P < or = 0.001) and lower plasma folate (14.8 compared with 19.0 nmol/L, P < or = 0.01) than did subjects with the CC genotype after the exclusion diet. CT heterozygotes had intermediate concentrations. The trend toward higher tHcy in TT homozygotes persisted throughout the study but was less marked with increasing folate intake (TT compared with CC after supplementation, P = 0.097). CONCLUSIONS: A folate-rich diet including folic acid-fortified foods or low-dose supplements effectively increases folate status. TT homozygotes require higher folate intakes than do individuals with the CT or CC genotype to achieve similar tHcy concentrations but are responsive to folate intervention.     

Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women

OBJECTIVE: We investigated the effects of mineral water fortified with folic acid, vitamins B(6), B(12), D and calcium on folate concentrations in serum and erythrocytes, serum vitamin B(12) and plasma homocysteine concentrations in free-living subjects. In addition, we investigated the bioavailability of calcium added to mineral water by measuring urinary calcium excretion and serum alkaline phosphatase activity. DESIGN: Randomized, controlled, double-blinded, parallel design. SETTING: Outpatient dietary intervention with free-living subjects in Eastern Finland. SUBJECTS: Altogether, 66 subjects were recruited for the study. In all, 60 subjects completed the study. INTERVENTIONS: The study began with a 2-week run-in period followed by an 8-week intervention period. During the intervention study, subjects consumed mineral water fortified with folic acid (563 microg/day), vitamins B(6) (1 mg/day), B(12) (7.5 microg/day), cholecalciferol (0.6 microg/day) and calcium (563 mg/day) or placebo mineral water. RESULTS: The fortified mineral water increased serum and erythrocyte folate concentrations by 16.1+/-5.6 nmol/l (P<0.001) and 199+/-76 nmol/l (P<0.001), respectively, and decreased plasma homocysteine concentration by 1.6 micromol/l (P<0.001). Urinary calcium excretion and serum alkaline phosphatase activity for 24 h increased significantly (P<0.001 and P=0.01 respectively) in the intervention group. CONCLUSIONS: Mineral water fortified with folic acid, vitamins B(6), B(12) and D and calcium enhanced folate status and reduced plasma homocysteine concentration in normohomocysteinemic subjects without folate deficiency. Indirect measures of calcium and bone metabolism indicated that the calcium used in the fortification of the mineral water was bioavailable.     

Folate and vitamin B12 in relation to lactation: a 9-month postpartum follow-up study

OBJECTIVE: To investigate the relation between lactation and markers of folate and vitamin B12 (B12) deficiency in women with and without vitamin supplementation. DESIGN: A 9-month follow-up study. Subjects and methods: Blood samples from 91 women, who gave birth to a single healthy child, were collected 3 weeks, 4 and 9 months postpartum and analysed for circulating level of homocysteine (tHcy), methylmalonic acid (MMA), folate and B12. The participants were categorized as exclusively, partly or not breast-feeding dependent on the degree of lactation 4 months postpartum. During follow-up, lifestyle factors were recorded by structured interviews. RESULTS: Among 72 exclusively breast-feeding women, the median (10-90% percentile) tHcy was 5.8 (3.1-8.3) micromol/l 3 weeks postpartum, 6.1 (4.1-10.3) micromol/l 4 months postpartum and 5.3 (3.6-8.7) micromol/I 9 months postpartum. At 9 months postpartum, none of the women breast-fed exclusively. No significant change occurred in the concentration of B12 and folate. Exclusively breast-feeding women without vitamin supplementation had higher median tHcy than supplemented exclusively breast-feeding women 4 and 9 months postpartum (7.0 vs 5.4 micromol/l (P < 0.001) and 5.8 vs 4.5 micromol/l (P = 0.003), respectively). Six women had increased (>15 micromol/l) tHcy; four of these were unsupplemented and exclusively breast-feeding. CONCLUSION: We found no overall indication of depletion of the folate and B12 stores during the lactation period in this population. However, folate-supplemented women had lower tHcy and higher folate levels, suggesting a beneficial effect of supplementation with folate throughout lactation.     

Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans

OBJECTIVE: The aim of this study was to investigate whether milk fortified with folic acid enhances the folate status of humans and whether the presence of folate-binding proteins (FBP) in pasteurised milk affects the bioavailability of folic acid from fortified milk. In untreated and pasteurised milk, folate occurs bound to FBP, while FBP is (partly) denatured in ultra-high-temperature (UHT)-treated milk. The effect of FBP on folate bioavailability is still unclear. DESIGN, SUBJECTS AND SETTING: Healthy, free-living subjects (n=69) aged 18-49 y participated in a 4-week double-blind, placebo-controlled dietary intervention study. INTERVENTION: In addition to a fully controlled diet, the subjects consumed each day 500 ml of pasteurised or UHT milk, either fortified or not with 200 mug folic acid. RESULTS: Consumption of fortified milk increased folate concentrations in serum and in red blood cells (RBC) by 6.6-7.0 nmol/l (P<0.001) and 32-36 nmol/l (P<0.01), respectively. Similarly, plasma homocysteine concentrations were lowered 0.88-0.89 micromol/l (P=0.001) in subjects who consumed fortified milk. The bioavailability of folic acid from pasteurised milk relative to that of folic acid from UHT milk was 74-94% (NS), depending on the parameter used. CONCLUSIONS: Milk fortified to supply an additional 200 microg of folic acid/s substantially increased folate status, and decreased plasma total homocysteine concentrations in young, healthy subjects. Milk is therefore a suitable matrix for fortification to enhance the folate status in humans. No significant effect of endogenous FBP was found on the bioavailability of folic acid from milk.