Red Blood Cell Folate Concentrations Research Articles

Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects

To investigate the effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma plasma total homocysteine (tHcy) concentrations in young Japanese male subjects. In a double blind, randomized controlled trial. Subjects were randomly assigned to one of four groups and received a placebo (control group), 800 microg/day folic acid (FA group), 8.4 mg/day riboflavin (R group), or both (FAR group) for 2 weeks. Tokyo, Japan. In total, 32 healthy male volunteers aged 20-29 years. At the end of the 2 week supplementation period, the tHcy concentration decreased significantly in the FA group. Serum folate concentrations had increased between 2.7 and 2.0-fold in the FA and FAR groups, respectively, but the mean within-group changes in serum folate and plasma tHcy concentrations did not differ between these two groups. At the end of the study, alanine amino transferase was decreased in the R and FAR groups, while alanine amino transferase was increased in the FA group. Supplementation with folic acid, 800 microg/day, for 2 weeks, increased the serum and red blood cell folate concentrations and decreased the plasma tHcy concentrations in healthy young male subjects. Riboflavin supplementation may have blunted the effect of folic acid, which resulted in a diminished reduction of tHcy in our subjects.

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.

Low folate status is associated with impaired cognitive function and dementia in the Sacramento Area Latino Study on Aging

Low folate status is associated with poor cognitive function and dementia in the elderly. Since 1998, grain products in the United States have been fortified with folic acid, which has reduced the prevalence of folate deficiency and hyperhomocysteinemia. We investigated whether folate status is associated with cognitive function and dementia in a cohort of elderly Latinos (aged >or= 60 y; n = 1789) exposed to folic acid fortification. Global cognitive function was assessed by the Modified Mini-Mental State Examination (3MSE) and specific cognitive functions by cross-culturally validated neuropsychological tests. Dementia was diagnosed according to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised, and California Alzheimer Disease Diagnostic and Treatment criteria. Red blood cell (RBC) folate was measured by automated chemiluminescence and total plasma homocysteine by HPLC. The prevalence of folate deficiency (RBC folate <or= 160 ng/mL) was <1%. After control for confounding by homocysteine, vitamin B-12, creatinine, demographic variables, and depressive symptom score, RBC folate was directly associated with 3MSE (P = 0.005) and delayed recall (P = 0.007) scores. In addition, adjusted odds ratios for low 3MSE score (<or=78) and dementia diagnosis per unit increase in RBC folate were significantly below unity (P <or= 0.008), which indicated that the relative risks of cognitive impairment and dementia decreased with increasing RBC folate concentration. In contrast, adjusted odds ratios for low 3MSE score and dementia diagnosis per unit increase in homocysteine were not significant. RBC folate is directly associated with cognitive function scores and is inversely associated with dementia in elderly Latinos despite folic acid fortification.

Homocysteine, Vitamin B12, and Folic Acid in Age-Related Macular Degeneration

Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis and thrombosis. The purpose of this study was to evaluate plasma homocysteine, red blood cell folate, plasma folate, and plasma vitamin B12 concentration in patients with exudative age-related macular degeneration (ARMD). The participants of this study included 30 patients aged 60 to 71 years (mean age 66.2+/-3.6) with exudative ARMD. Plasma homocysteine levels were determined by high performance liquid chromatography (HPLC). Red blood cell folate, plasma folate, and plasma vitamin B12 concentration were determined using a standard kit (Dualcount Solid Phase No Boill radioassay kit for B12/folic acid, DPC Diagnostic, USA) by radioassay method. The plasma concentration of Hcy (14.88+/-6.23 micromol/L) in ARMD patients was significantly increased (p<0.0001) compared with the control group (8.72+/-3.34 micromol/L). We found not a significant decrease of the plasma vitamin B12 concentration in the ARMD group (476.88+/-220.91 pg/mL) compared with the control group (527.08+/-208.97 pg/mL). Red blood cell folate (158.44+/-56.30 ng/mL) and plasma folate (6.5+/-3.4 ng/mL) in ARMD patients were also not significantly decreased when compared with the control group (183.86+/-59.33 ng/mL and 7.93+/-5.05 ng/mL). Hyperhomocysteinemia might be one of the risk factors for the exudative form of ARMD.

Association of Low Red Blood Cell Folate Concentrations with Coronary Artery Disease in Iranians: A Matched Case-Control Study

Background: It is not fully established whether the increasing risk of coronary artery disease (CAD) is associated with high plasma homocysteine levels or components of the homocysteine remethylation pathway, e.g. vitamin B₁₂ or 5-methyltetrahydrofolate (5-MTHF) in plasma and red blood cells (RBC). In this study, we tested the hypothesis that 5-MTHF in RBC, which represents the long-term folate status of individuals, may be a more reliable marker of homocysteine remethylation pathway disturbances, and its deficiency may be associated with CAD in Iranians. Methods: Plasma total homocysteine (tHcy), vitamin B₁₂, and plasma and RBC 5-MTHF were measured in 200 angiographically documented patients and 200 controls matched for sex and age. Results: In the plasma, tHcy levels were significantly higher in cases compared to controls (geometric mean 12.9 ± 6.5 vs. 10.6 ± 5.6 µmol/l, p = 0.04). However, RBC 5-MTHF (527.2 ± 185.9 vs. 461.3 ± 117.9 nmol/l, p = 0.007) and vitamin B₁₂ (254.2 ± 132.8 vs. 182.2 ± 110.4 pmol/l, p = 0.04) were significantly higher in controls than patients. RBC 5-MTHF was a strong and independent predictor of plasma tHcy (β = –0.01, p = 0.003, r² = 0.19). Subjects in the lowest quartile of red-cell 5-MTHF had a 2.5-fold increased prevalence of CAD compared to subjects in the highest quartile. The association of CAD in the first quartile with red-cell 5-MTHF remained significant when adjusted for plasma tHcy, vitamin B₁₂, hypertension and hypercholesterolemia (odds ratio, OR 2.3, confidence interval: 1.1–3.9, p = 0.01). However, the association between CAD in the highest quartile and plasma tHcy decreased and became insignificant when adjusted for red-cell 5-MTHF, vitamin B₁₂, hypertension and hypercholesterolemia (OR 1.27, confidence interval: 0.96–1.69, p = 0.11). Conclusion: In this study, the association between CAD and low RBC 5-MTHF was stronger than with plasma 5-MTHF and plasma tHcy levels, indicating that RBC 5-MTHF may be a more stable parameter to study disturbances in the homocysteine remethylation pathway in Iranians.

The Methylenetetrahydrofolate Reductase 677C→T Polymorphism and Dietary Folate Restriction Affect Plasma One-Carbon Metabolites and Red Blood Cell Folate Concentrations and Distribution in Women

Whether folate status and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism interact to affect methionine-cycle metabolite concentrations is uncertain. We evaluated the effects of dietary folate restriction on relations among folate status indices and plasma concentrations of methionine cycle metabolites in women with the MTHFR 677 C/C and T/T genotypes. Healthy, normohomocysteinemic women (n = 18; 20-30 y old) of adequate B vitamin status, and equally divided according to MTHFR 677C-->T genotype (9 C/C and 9 T/T) were recruited. Folate status indices and methionine cycle metabolites were measured in blood samples collected at baseline and after 7 wk of dietary folate restriction (115 microg dietary folate equivalents/d). Significant negative correlations between plasma total homocysteine concentrations and total or 5-methyl folate concentrations (P = 0.041 and 0.023, respectively) in RBCs were found only in T/T subjects. Formylated folates were detected in RBCs of T/T subjects only, and their abundance was predictive of plasma total homocysteine concentration despite no significant alteration by folate restriction. Plasma concentrations of S-adenosylmethionine and S-adenosylhomocysteine were not significantly affected by dietary folate restriction and the MTHFR 677 T/T genotype. In conclusion, plasma total homocysteine concentrations in subjects with the MTHFR 677 T/T genotype were inversely related to 5-methyl folate concentrations and directly related to formylated folate concentrations in RBCs, even though the latter were not significantly affected by moderate folate restriction.

Homocysteine, renal disease and cardiovascular disease in a remote Australian Aboriginal community

Rates of renal and cardiovascular disease are high among Aboriginal Australians living in remote communities. Nutritional problems, in particular low folate levels, are also common. This suggests that increased homocysteine concentrations might be widespread, and a possible contributor to the high rates of cardiovascular disease. To examine homocysteine concentrations, and their relationships to folate levels, and to markers of renal disease and cardiovascular disease in a remote Aboriginal Australian community As part of a cross-sectional survey among adults in one community, homocysteine concentrations, concentrations of the crucial determinants (red blood cell (RBC) folate, vitamin B(12) and the C677T methylene tetrahydrofolate reductase polymorphism) and cardiovascular risk factors were examined. Among 221 people, geometric mean homocysteine concentration was 11.8 micromol/L (range: 11.1-12.5 micromol/L), with 57/221 (26%) values > or =15.0 micromol/L. Higher concentrations were associated with older age, male gender, lower RBC folate and lower vitamin B(12) concentrations and homozygosity for C677T. Homocysteine concentrations were not related to the presence of albuminuria, other than over the overt albuminuria range. Homocysteine concentrations were inversely correlated with calculated glomerular filtration rate (GFR). Carotid intima-media thickness, however, was not related to homocysteine concentration. In multivariate analyses, age, male gender, lower RBC folate concentrations, lower vitamin B(12) concentrations, lower calculated GFR and the C677T polymorphism were all associated with homocysteine concentrations. Homocysteine concentrations were consistent with previous limited reports in Aboriginal communities. Although superficially they are similar to reports from non-Aboriginal settings, the younger age of this cohort and the association of homocysteine concentrations with age suggest that age-specific concentrations are higher among Aboriginal Australians. In addition to dietary determinants, the high prevalence of apparently reduced renal function renal disease appears to be an important determinant of homocysteine concentrations in remote Aboriginal communities. The role of homocysteine concentrations as a potential mediator of the high rates of cardiovascular disease remains to be determined.

A common insertion/deletion polymorphism of the thymidylate synthase (TYMS) gene is a determinant of red blood cell folate and homocysteine concentrations

Substantial evidence suggests that a low folate/high homocysteine phenotype is pathogenic. We analyzed the impact of the thymidylate synthase (TYMS) 3'UTR ins/del polymorphism on folate and homocysteine levels and assessed the relationship between the TYMS 3'UTR ins/del polymorphism and key genetic and lifestyle variables. Among non-smokers only, the TYMS 3'UTR ins/del polymorphism was significantly associated with red blood cell folate (RBC folate; P=0.002) and homocysteine (P=0.03) concentrations. Median RBC folate concentration was much higher for TYMS 3'UTR del/del subjects (434 microg/l) compared with either ins/ins (282 microg/l) or ins/del (298 microg/l) subjects. The median homocysteine concentration for del/del homozygotes was considerably lower compared with either ins/ins homozygotes or ins/del heterozygotes. A possible additive effect for the impact of the TYMS 3'UTR del/del and MTHFR 677CC genotypes on RBC folate concentration was also observed. Our findings suggest that the TYMS 3'UTR del/del genotype is a significant determinant of elevated RBC folate concentration in a non-smoking population of northwestern European adults and that this genotype confers protection against diseases for which a low folate/high homocysteine phenotype appears to be an etiologic component.

P.8.004 Effects of hyperhomocysteinemia on the system of haemostasis under stress

Various dgrees of folate deficiency were produced inrats during gestation and lactation to evaluate maternal folate status effects during both the fetal and neonatal periods. Female rats were fed folate-deficient diets with 1% succinylsulfathiazole for 0, 5 and 9 wk before breeding and until 2 wk postpartum; others were fed a control diet. The most severely deficient group had significantly lower wt gain during gestation, with fetal resorption and no live pups being born. The moderately deficient group, with reduced plasma and red blood cell (RBC) folate concentrations prior to breeding, had impaired gestational wt gain, and, at gestational d 21, their rat fetuses weighed less than controls and had lower folate levels in blood, liver and placenta. The low birthweight pups in this group, at d 14 of age, had poor folate status with depressed brain DNA concentrations. The marginally deficient group produced normal birthweight pups, but growth was impaired at d 14, associated with poor folate status. Milk folate was significantly lower and urinary formiminoglutamic acid (FIGLU) was elevated in folatedeficient dams. These experimental results produced statistically significant correlation coefficients between folate status in rat dams and growth, hematology and folate stauus in their pups, even when folate status was marginal.

The administration of a multivitamin/mineral fortified dairy product improves folate status and reduces plasma homocysteine concentration in women of reproductive age.

Folate deficiency during the periconceptional period is related to the occurrence and recurrence of neural tube defects. The aim of the study was to assess whether the administration of folic acid and other vitamins and minerals as a fortified dairy product (400 microg per day of folic acid) improves the folate status in women of reproductive age. Plasma and red blood cell folate, plasma vitamin E, B12, total plasma homocysteine, plasma lipid profile, and serum ferritin and transferrin levels were investigated in 31 healthy nonpregnant women receiving 500 mL/day of the fortified dairy product for eight weeks. The women showed a significant increase in plasma levels of folate and vitamin B12 concentrations after four and eight weeks of supplementation. Moreover, we observed an increase in red blood cell folate concentration during the period of the study. Simultaneously, total plasma homocysteine levels decreased significantly during the intervention period. The regular consumption of a folic acid and other vitamins (mainly vitamins B6 and B12) and minerals in a fortified dairy product improves folate status and reduces total plasma homocysteine concentration in healthy women of childbearing age.

Concentrations of B vitamins and homocysteine in children with sickle cell anemia.

Elevated concentration of serum homocysteine contributes to thrombosis, a frequent event in patients with sickle cell anemia. We aimed to test whether children with sickle cell anemia have elevated concentrations of serum homocysteine with diminished levels of folate or B vitamins from accelerated blood cell turnover. We conducted a case-control study of children with homozygous sickle cell anemia (n = 17) and unaffected children (n = 11). We measured serum and red blood cell folate, vitamin B6, vitamin B12, and homocysteine concentrations, and assessed micronutrient intake. Children with sickle cell anemia had concentrations of homocysteine slightly higher than those of unaffected children. They had lower vitamin B6 concentrations and comparable concentrations of folate and vitamin B12. Homocysteine concentration was inversely related to vitamin B12 concentration and was not independently associated with levels of vitamin B6 or folate. Despite comparable intake, children with sickle cell anemia had lower concentrations of vitamin B6 than unaffected children. Larger studies are needed to determine if chronically low serum vitamin B6 concentration contributes to hyperhomocysteinemia in this population.

Dietary patterns associated with risk factors for cardiovascular disease in healthy US adults

Certain nutrients are well established as dietary risk factors for cardiovascular disease (CVD), but dietary patterns may be a better predictor of CVD risk. This study tested the hypothesis that the complex dietary behaviors of US adults can be grouped into major dietary patterns that are related to risk factors for CVD. With the use of food-frequency questionnaire data from the third National Health and Nutrition Examination Survey, dietary patterns of healthy US adults (>/or =20 y old; n = 13 130) were identified by factor analysis. Log-transformed biomarker data were associated with major dietary patterns after control for confounding variables in regression analyses. All statistical analyses accounted for the survey design and sample weights. Of 6 dietary patterns identified, 2 patterns emerged as the most predominant: the Western pattern was characterized by high intakes of processed meats, eggs, red meats, and high-fat dairy products, and the American-healthy pattern was characterized by high intakes of green, leafy vegetables; salad dressings; tomatoes; other vegetables (eg, peppers, green beans, corn, and peas); cruciferous vegetables; and tea. The Western pattern was associated (P < 0.05) positively with serum C-peptide, serum insulin, and glycated hemoglobin and inversely with red blood cell folate concentrations after adjustment for confounding variables. The American-healthy pattern had no linear relation with any of the biomarkers examined. The identification of common dietary patterns among free-living persons is promising for characterizing high-risk groups at the US population level. The dietary patterns identified here are similar to those reported in other nonrepresentative samples and are associated with biomarkers of CVD risk, which confirms that dietary pattern analysis can be a valuable method for assessing dietary intakes when predicting CVD risk.

Geographical, Seasonal and Gender Differences in Folate Status among Chinese Adults

Low blood folate concentrations have been associated with cardiovascular disease, neural tube defects and selected cancers, but little is known about folate status in Chinese adults. In a cross-sectional study we measured the plasma and red blood cell folate concentrations in 2422 Chinese men and women aged 35 to 64 y, living in the North and South of China, who provided blood samples either in March or September of 2001. The geometric mean concentrations of plasma and red blood cell folate were lower among Northerners than Southerners (adjusted geometric means, 8.4 and 502, and 16.7 and 811 nmol/L, respectively) controlling for age, gender, season (spring and fall), area (urban and rural), BMI, multivitamin use, alcohol intake and current smoking status. We estimated that approximately 40% of the Northerners and approximately 6% of the Southerners had plasma folate concentrations lower than the 6.8 nmol/L (3 microg/L), and approximately 30% of the Northerners and approximately 4% of the Southerners had red blood cell folate concentrations lower than the 363 nmol/L (160 microg/L), levels used to define folate deficiency. Within each region, men had lower plasma folate concentrations than women (6.9 versus 9.8 nmol/L in the North, and 14.5 versus 19.6 nmol/L in the South). In men, current smokers had a higher risk of folate deficiency compared with nonsmokers [adjusted odds ratios, 1.9 (95% CI, 1.4-2.6) for plasma folate deficiency and 2.5 (95% CI, 1.7-3.6) for red blood cell folate deficiency (P < 0.001)]. Our findings suggest that a large proportion of Chinese adults have a low folate status, especially those living in northern China where 60% of the men are plasma folate deficient in the spring. Further studies are needed to elucidate the factors that influence folate concentrations among middle-aged Chinese and to evaluate possible intervention strategies.

Homocysteine metabolism and B-vitamins in schizophrenic patients: low plasma folate as a possible independent risk factor for schizophrenia

Two apparently unrelated disorders, neural tube defects (NTD) and schizophrenia showed increased risks in birth cohorts exposed to famine during early gestation. NTD is associated with impaired folate metabolism. We investigated whether schizophrenia is also linked with a dysfunctional folate metabolism. In addition to the prevalence of the 677C→T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, we compared plasma and red blood cell (RBC) folate, vitamin B6, vitamin B12, and homocysteine (Hcy) concentrations of 35 schizophrenic patients with those of 104 unrelated controls. Schizophrenic patients had significantly lower plasma folate concentrations after adjustment for Hcy levels, and elevated RBC folate levels compared to controls. Vitamin B6, vitamin B12, and Hcy levels did not differ from control values. Plasma folate levels below the 10th percentile of controls were associated with an approximate 4–7-fold (before and after adjustment of folate levels for Hcy, respectively) risk of having schizophrenia. In addition, a significant dose-response relation between plasma folate concentrations and risk for schizophrenia suggested a protective effect by high plasma folate concentrations. Elevated Hcy levels and, in line with this finding, homozygosity for the 677C→T mutation in the MTHFR gene were not associated with an increased risk for schizophrenia. Evidence is presented suggesting that folate metabolism is disturbed in schizophrenic patients, independently of Hcy.

Consumption of Folic Acid–Fortified Bread Improves Folate Status in Women of Reproductive Age in Chile

Since January 2000 the Chilean Ministry of Health has required the fortification of wheat flour with folic acid (FA) at a concentration of 2.2 mg FA/kg in order to reduce the risk of neural tube defects (NTD) in newborns. This policy was expected to result in a mean additional intake of approximately 400 microg FA/d. We assessed the effectiveness of the FA flour fortification program on bread folate content and on blood folate concentration in women of childbearing age in Santiago, Chile. The prefortification folate status of 751 healthy women of reproductive age was assessed. The folate content of 100 bread samples bought at retail bakeries was measured, average wheat flour consumption was estimated and postfortification FA dietary intake was calculated. The effect of flour fortification on blood folate concentration in this group of women (n = 605) was evaluated in a follow-up study. Blood folate concentrations of the 605 women in the follow-up group increased (P < 0.0001) following fortification. Before fortification the mean serum and red blood cell folate concentrations were 9.7 +/- 4.3 and 290 +/- 102 nmol/L, respectively, compared with 37.2 +/- 9.5 and 707 +/- 179 nmol/L postfortification, respectively. The mean FA content of bread was 2020 +/- 940 micro g/kg. The median FA intake of the group evaluated postfortification was 427 microg/d (95% CI 409-445) based on an estimated intake of 219 g/d (95% CI 201-229) of wheat flour, mainly as bread. Fortification of wheat flour substantially improved folate status in a population of women of reproductive age in Chile. The effect of the FA fortification program on the occurrence of NTD is currently being assessed.

Effect of TCN2 776C>G on vitamin B12 cellular availability in end-stage renal disease patients

Transcobalamin II is a serum protein that transports vitamin B12 from the intestine to the tissues. This complex, holo-transcobalamin II, may reflect vitamin B12 availability in the body. Conflicting data exist with regard to the effect of a polymorphism in the gene coding for transcobalamin II, TCN2 776C>G, on transcobalamin II levels in the general population, which in turn may affect holo-transcobalamin II, vitamin B12, as well as total homocysteine (tHcy) plasma levels. The effect of TCN2 776C>G on vitamin B12 cellular availability in dialysis patients is unknown. We examined the effect of TCN2 776C>G on holo-transcobalamin II, vitamin B12, and tHcy plasma concentrations in 120 dialysis patients. Holo-transcobalamin II levels were normal or supranormal in all patients and showed a linear association with albumin (r = 0.205, P = 0.025) and with vitamin B12 (r = 0.778, P = 0.001), but not with age, creatinine, body mass index, tHcy, ln-tHcy, vitamin B6, plasma folate, and red blood cell folate concentration. TCN2 776C>G showed no effect on holo-transcobalamin II, vitamin B12, and tHcy concentration [one-way analysis of variance (ANOVA), post-hoc Scheffe test]. Multiple linear regression analyses showed that albumin and B12 are independently associated with holo-transcobalamin II, whereas TCN2 776C>G and MTHFR 677C>T had no effect. Independent predictors of ln-tHcy included creatinine, red blood cell folate, and the MTHFR 677TT genotype. There was also an effect of the TCN2 776CC genotype on ln-tHcy levels in this multivariate analysis, however, that deserves cautious interpretation because there was no effect of TCN2 genotypes by ANOVA and Scheffe test [median ln-tHcy concentrations according to TCN2 genotypes (micromol/L): CC, 3.22; CG, 3.30; GG, 3.23]. TCN2 776C>G does not influence holo-transcobalamin II or vitamin B12 levels, and has no major effect on tHcy concentrations of end-stage renal disease patients.

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

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. 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. 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. 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. Wine consumption may increase tHcy concentrations, whereas beer consumption seems to have no effect (or even an inverse effect) on tHcy.

The influence of iron, vitamin B 12, and folate levels on soluble transferrin receptor concentration in pregnant women

Background: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in conditions of increased erythropoiesis. In developing countries like Brazil, pregnant women usually have concurrent iron, vitamin B 12, and folate deficiencies. This study investigated the relationship between serum sTfR concentration and iron, vitamin B 12, and folate status in pregnant women. Methods: The concentration of the sTfR, hematocrit (Hct), hemoglobin (Hb), red blood cell (RBC) and white blood cell (WBC) counts, serum iron (SI), total iron-binding capacity (TIBC), transferrin saturation, serum ferritin, zinc protoporphyrin (ZPP), vitamin B 12, and serum and RBC folate were determined in 40 healthy pregnant women who delivered term babies. Results: sTfR concentration was significantly higher when the women had iron deficiency (serum ferritin <10 μg/l, p<0.01), but there was no significant difference in sTfR concentration according to vitamin B 12, serum, and RBC folate concentrations. Women who had serum ferritin <10 μg/l also had lower vitamin B 12 values ( p<0.01). There was no significant correlation between vitamin B 12 and serum folate with sTfR concentration. According to a regression analysis, sTfR concentration was associated with serum iron, serum ferritin, RBC count, and hemoglobin concentration. Conclusion: Iron was the only micronutrient that influenced the sTfR concentration. Vitamin B 12 and folate concentrations were probably not sufficiently low to have an impact on the sTfR concentration.

Effect of glutamate carboxypeptidase II and reduced folate carrier polymorphisms on folate and total homocysteine concentrations in dialysis patients.

This study was designed to examine the effect of two single nucleotide polymorphisms in the reduced folate carrier 1 (RFC1 80G>A) and the glutamate carboxypeptidase 2 (GCP2 1561C>T) gene on total homocysteine (tHcy) plasma level and folate status in 120 chronic dialysis patients. Red blood cell folate concentration was higher in patients with the GCP2 CT or TT genotype (ANOVA, P = 0.04). Among patient groups with different RFC1 genotypes, red blood cell folate level was not significantly different. A multivariate analysis confirmed that the GCP2 1561C>T genotype (P = 0.011) had a significant influence on the red blood cell folate concentration. Overall, serum folate, creatinine, and the GCP2 polymorphism explained nearly 50% of the variance of red blood cell folate. A linear multivariate regression analysis showed that red blood cell folate (P < 0.001), creatinine (P < 0.001), and the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677T allele (P = 0.013) are independent predictors of tHcy plasma level explaining 49% of the variance of tHcy plasma concentration. GCP2 1561C>T and RFC1 80G>A showed no effect on tHcy and folate plasma level. In conclusion, GCP2 1561C>T, but not RFC1 80G>A, is a predictor of red blood cell folate level in chronic dialysis patients. Both polymorphisms have no major effect on tHcy plasma concentration in end-stage renal disease patients.

Depression and Folate Status in the US Population

Background: Folate deficiency and low folate status have been linked in clinic studies to depression, persistent depressive symptoms, and poor antidepressant response. These relationships have not been demonstrated in general populations. This study examined associations between depression and folate status indicators in an ethnically diverse general US population sample aged 15–39 years. Methods: Healthy subjects whose red blood cell (RBC) folate concentrations had been measured were determined to have no depression (n = 2,526), major depression (n = 301 ), or dysthymia (n = 121) using a diagnostic interview schedule. Serum concentrations of folate and total homocysteine (tHcy) were also measured. Results: After adjustment for sociodemographic factors, serum vitamin B₁₂ concentration, alcohol consumption over the past year and current status as to overweight and use of vitamin/mineral supplements, cigarettes and illegal drugs, subjects who met criteria for a lifetime diagnosis of major depression had folate concentrations in serum and RBCs that were lower than those of subjects who had never been depressed. Subjects who met criteria for dysthymia alone had lower RBC folate concentrations than never-depressed subjects, but the serum folate concentrations of the two groups were comparable. Serum tHcy concentration was not related to lifetime depression diagnoses. Low folate status was found to be most characteristic of recently recovered subjects, and a large proportion of such subjects were folate deficient. Conclusions: Low folate status was detectable in depressed members of the general US population. Folate supplementation may be indicated during the year following a depressive episode.