Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “folate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2003

Folate status response to controlled folate intake is affected by the methylenetetrahydrofolate reductase 677C-->T polymorphism in young women.

This study was designed to evaluate the effect of the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism on folate and homocysteine response in non-Hispanic women consuming a low folate diet followed by a diet providing the Recommended Dietary Allowance (RDA) for folate. Women (aged 20-30 y old) with either the TT (n = 19) or CC (n = 22) MTHFR 677C-->T genotype participated in a folate depletion-repletion study (7 wk, 115 microg dietary folate equivalents (DFE)/d; 7 wk, 400 microg DFE/d). Overall serum folate decreased (P < 0.0001) during depletion and increased (P < 0.0001) during repletion with lower (P = 0.03) postdepletion serum folate in women with the TT versus CC genotype. Folate status was low (serum folate < 13.6 nmol/L) in more women with the TT (59%) compared with the CC genotype (15%) postdepletion. Red blood cell folate for all subjects decreased during depletion (P < 0.0001) and repletion (P = 0.02) with lower (P = 0.04) red blood cell folate in women with the TT compared with the CC genotype postrepletion. Homocysteine increased (P < 0.0001) for both genotype groups postdepletion and decreased (P = 0.02) postrepletion for the CC genotype group only. Homocysteine concentrations tended to be higher (P = 0.09) in the TT versus CC genotype group postdepletion and postrepletion. These data suggest that the MTHFR 677C-->T polymorphism negatively affects the folate and homocysteine response in women consuming low folate diets followed by repletion with the RDA. These results may be important when evaluating the impact of the MTHFR 677C-->T polymorphism in countries in which low folate diets are chronically consumed.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2005

A long-term controlled folate feeding study in young women supports the validity of the 1.7 multiplier in the dietary folate equivalency equation.

The presence of folic acid in enriched cereal grain products and the higher bioavailability of folic acid than food folate led to the expression of the 1998 folate RDA, 400 microg/d, as dietary folate equivalents (DFE). DFE are defined as: mug natural food folate + 1.7 x microg synthetic folic acid. The 1.7 multiplier was based on assumptions that added folic acid was 85% available and food folate was 50% available. The 85/50 ratio also inferred that the bioavailability of food folate was approximately 60% relative to added folic acid. The objective of this long-term controlled feeding study was to assess the dietary folate equivalency of folic acid. After a 2-wk period of folate restriction, women (n = 42, 18-45 y old) consumed either 400 or 800 microg DFE/d derived from various combinations of food folate and folic acid for 12 wk. Folic acid was converted to DFE using the 1.7 multiplier from the DFE calculation and was consumed with a meal throughout the treatment period. Folate status response to the various treatments was assessed during wk 12-14. Serum folate, RBC folate, and plasma total homocysteine did not differ among the 400 microg DFE/d groups or among the 800 microg DFE/d groups. In contrast, consumption of 800 microg DFE/d led to higher (P </= 0.05) serum and RBC folate than consumption of 400 microg DFE/d. These data support the validity of the 1.7 multiplier in the DFE equation and suggest that food folate bioavailability is approximately 60% that of added folic acid when consumed as part of a mixed diet.

Administration, Oral↗
PubMed2006

Trends in serum folate, RBC folate, and circulating total homocysteine concentrations in the United States: analysis of data from National Health and Nutrition Examination Surveys, 1988-1994, 1999-2000, and 2001-2002.

Folate intakes increased dramatically after folic acid fortification. We investigated the changes in serum folate, RBC folate, and total homocysteine (tHcy) concentrations utilizing data from National Health and Nutrition Examination Surveys (NHANES) 1988-2002. NHANES 1988-2002 were based on a stratified, multistage, probability sampling design conducted among civilian U.S. residents. The current study included 17,144, 17,213, and 11,415 measurements for serum folate, RBC folate, and tHcy, respectively. Overall, geometric mean serum folate concentrations were 149.6 and 129.8% higher in 1999-2000 and 2001-2002, respectively, than in 1988-1994 (P < 0.0001). Sex-, age-, and race-ethnicity-adjusted serum folate was significantly lower in 2001-2002 than in 1999-2000 (10.4%, P < 0.0002). The prevalence of low serum folate decreased from 18.4% in 1988-1994 to 0.8% in 1999-2000 and to 0.2% in 2001-2002 (P < 0.0001). RBC folate increased from 391 nmol/L in 1988-1994 to 618 nmol/L in 1999-2000, and to 611 nmol/L in 2001-2002. Consequently, the prevalence of low RBC folate decreased from 45.8% in 1988-1994 to 7.3% in 1999-2000 and to 7.1% in 2001-2002 (P < 0.0001). Although, RBC folate status improved after folic acid fortification in all race-ethnicities, the prevalence of low RBC folate ( approximately 20.5%) continues to be high in non-Hispanic blacks. Age-, sex-, and race-ethnicity-adjusted tHcy declined from 9.5 micromol/L in 1988-1994 to 7.6 mumol/L in 1999-2000 and to 7.9 micromol/L in 2001-2002. Although folic acid fortification contributed to significant improvement in folate status, serum folate concentrations have declined recently. This may be attributable to lower folic acid intakes.

Adolescent↗
PubMed2001

Folate supplementation in peritoneal dialysis patients with normal erythrocyte folate: effect on plasma homocysteine.

The possible role of folate supplementation in reducing hyperhomocysteinemia in dialysis patients has been reported in several recent papers. However, scant data are available for peritoneal dialysis patients; besides, none of these studies investigated either the role of intraerythrocyte folate concentration or the presence of side effects caused by folate administration. Sixty-six peritoneal dialysis patients with hyperhomocysteinemia (>15 micromol/l) and normal folate status (as assessed by erythrocyte folate level >600 nmol/l) were randomly allocated to receive either oral folate (5 mg/day) or no vitamin supplementation. After 2 months of therapy, patients were requested to answer a questionnaire investigating the occurrence of symptoms possibly related to folate supplementation. Twenty-nine treated patients and 30 untreated controls completed the study. In the treated patients, serum and erythrocyte folate increased significantly (p < 0.0001) (respectively from 10.6 +/- 4.9 to 237 +/- 231 nmol/l and from 1,201 +/- 297 to 2,881 +/- 294 nmol/l) to levels at the uppermost limit of detection by laboratory methods. Serum vitamin B(12) levels did not change. Plasma homocysteine levels decreased from 54 +/- 32 to 23 +/- 14 micromol/l after folate supplementation and remained unchanged in the control group. After 4 months of folate therapy, homocysteine concentration was within the normal range in 5 patients (17%) and below 30 micromol/l in the other 21 (72%). Folate therapy resulted in a decrease in homocysteine of more than 50% in 45% of the patients and decrease of more than 20% in a further 38%. No significant symptoms were reported. Thus, serum and erythrocyte folate increase confirms that normal folate levels are inadequate in dialysis patients, even if serum and erythrocyte levels before folate supplementation cannot predict the effect on homocysteine plasma levels.

Anorexia↗
PubMed1986

Receptor-mediated folate accumulation is regulated by the cellular folate content.

Cultured monkey kidney cells are shown to possess a cell-surface receptor that binds 5-methyltetrahydro[3',5',7,9-3H4]folic acid (5-methyltetrahydro[3H]folic acid) with high affinity (Kd = 3 nM at 4 degrees C). The cell-surface binding capacity for [3H]folic acid or [3H]methotrexate is equivalent to that for 5-methyltetrahydro[3H]folate, but the Kd values are 0.4 and 20 nM, respectively. These nonlabeled folates also inhibit cellular binding and accumulation of 5-methyltetrahydro[3H]folate, whereas specific moieties of folic acid (i.e., p-aminobenzoylglutamic acid, pteroic acid, and glutamic acid) had no effect. Surface-bound folate(s) can be released by incubation of the cells at pH 3.5. At 37 degrees C the bound material is slowly transferred into cells, where it becomes resistant to acid release. Within 4 hr the cells internalize about 3-4 times as much folate as is bound to the surface in the steady state. The amount of receptor activity increases markedly when cells are depleted of folate through growth in folate-depleted medium. Binding of folate was inhibited by an antibody raised against a soluble plasma folate-binding protein, suggesting that the cell-surface receptor and the circulating folate-binding protein are immunologically related. These data indicate that cells possess a high-affinity, high-specificity folate receptor whose expression is regulated by the folate content of the cell. They also suggest that a small molecule such as folate can enter cells by receptor-mediated endocytosis.

Animals↗
PubMed1998

Indium-111-DTPA-folate as a potential folate-receptor-targeted radiopharmaceutical.

UNLABELLED: Indium-111-labeled diethylenetriamine pentaacetic acid (DTPA)-folate was evaluated as a radiopharmaceutical for targeting tumor-associated folate receptors. METHODS: Athymic mice were subcutaneously inoculated with approximately 1.8 x 10(6) folate receptor-positive KB (human nasopharyngeal carcinoma) cells, yielding 0.2- to 0.6-g tumors in 15 days, at which time (111)In-DTPA-folate, (111)In-DTPA or (111)In-citrate was administered by intravenous injection. RESULTS: The (111)In-DTPA-folate conjugate afforded marked tumor-specific (111)In deposition in vivo using this mouse model. The involvement of the folate receptor in mediating tumor uptake of (111)In-DTPA-folate was demonstrated by the blocking of tumor uptake by coadministration of free folic acid (intravenous). The (111)In-DTPA-folate also shows folate receptor-mediated uptake and retention in the kidneys, presumably reflecting radiotracer binding to folate receptors of the proximal tubules. In control experiments, the (111)In-citrate radiopharmaceutical precursor was also shown to afford significant tumor uptake of (111)In, but with much poorer tumor-to-background tissue contrast than that obtained with (111)In-DTPA-folate. Unconjugated (111)In-DTPA showed no tumor affinity. CONCLUSION: Indium-111-DTPA-folate appears suitable as a radiopharmaceutical for targeting tumor-associated folate receptors.

Animals↗
PubMed1980

An inverse relationship of rat liver folate polyglutamate chain length to nutritional folate sufficiency.

The relative concentrations of folylpolyglutamates of differing chain length in rat liver and the uptake of exogenous [3H]folic acid (20 microCi, 20 microgram) into liver folylpolyglutamates were examined in rats maintained on (a) standard and folate-supplemented standard diets and (b) semi-defined folate-sufficient and folate-deficient diets. Folylpolyglutamates extracted from liver were cleaved to p-aminobenzoylpolyglutamates which were separated by ion-exchange chromatography. The relative concentrations and ultimate radiolabeling of longer-chain folylpolyglutamates (six, seven and eight glutamate residues) were greatest in the livers of folate-deficient rats, whereas the intermediate-chain folylpolyglutamates (three, four and five glutamate residues) were the greatest portion of total liver folates of folate-supplemented rats. Thus, the length of the polyglutamate chain added to liver folates is inversely related to the total concentration of liver folates. These data suggest that folylpolyglutamate biosynthesis in the liver may be controlled by the liver folate concentrations. In folate insufficiency such a control mechanism would serve to enhance the affinity of folates for folate-dependent enzymes and to conserve the liver folate concentration.

4-Aminobenzoic Acid↗
PubMed1996

Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects.

BACKGROUND: Recommendations by the UK Department of Health suggest that protection from neural tube defects (NTD) can be achieved through intakes of an extra 400 microgram daily of folate/folic acid as natural food, foods fortified with folic acid, or supplements. The assumption is that all three routes of intervention would have equal effects on folate status. METHODS: We assessed the effectiveness of these suggested routes of intervention in optimising folate status. 62 women were recruited from the University staff and students to take part in a 3-month intervention study. Participants were randomly assigned to one of the following five groups: folic acid supplement (400 microgram/day; I); folic-acid-fortified foods (an additional 400 microgram/day; II); dietary folate (an additional 400 microgram/day; III); dietary advice (IV), and control (V). Responses to intervention were assessed as changes in red-cell folate between pre-intervention and post-intervention values. FINDINGS: 41 women completed the intervention study. Red-cell folate concentrations increased significantly over the 3 months in the groups taking folic acid supplements (group I) or food fortified with folic acid (group II) only (p<0.01 for both groups). By contrast, although aggressive intervention with dietary folate (group III) or dietary advice (group IV) significantly increased intake of food folate (p<0.001 and p<0.05, respectively), there was no significant change in folate status. INTERPRETATION: We have shown that compared with supplements and fortified food, consumption of extra folate as natural food folate is relatively ineffective at increasing folate status. We believe that advice to women to consume folate-rich foods as a means to optimise folate status is misleading.

Adolescent↗
PubMed2002

The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet.

Folate intake is strongly influenced by various methods of cooking that can degrade the natural forms of the vitamin in foods. The aim of the present study was to determine the effect of different cooking methods on folate retention in various foods that contribute to folate intake in the UK diet. Typical purchasing and cooking practices of representative food folate sources were determined from a questionnaire survey of local shoppers (n 100). Total folate was determined by microbiological assay (Lactobacillus casei NCIMB 10463) following thermal extraction and tri-enzyme (alpha-amylase, protease and conjugase) treatment in raw foods and after typical methods of cooking. Boiling for typical time periods resulted in only 49 % retention of folate in spinach (191.8 and 94.4 microg/100 g for raw and boiled spinach respectively; P<0.005), and only 44 % in broccoli (177.1 and 77.0 microg/100 g for raw and boiled broccoli respectively, P<0.0001). Steaming of spinach or broccoli, in contrast, resulted in no significant decrease in folate content, even for the maximum steaming periods of 4.5 min (spinach) and 15.0 min (broccoli). Prolonged grilling of beef for the maximum period of 16.0 min did not result in a significant decrease in folate content (54.3 and 51.5 microg/100 g for raw and grilled beef respectively). Compared with raw values, boiling of whole potatoes (skin and flesh) for 60.0 min did not result in a significant change in folate content (125.1 and 102.8 microg/100 g for raw and boiled potato respectively), nor was there any effect on folate retention whether or not skin was retained during boiling. These current results show that the retention of folate in various foods is highly dependent both on the food in question and the method of cooking. Thus, public health efforts to increase folate intake in order to improve folate status should incorporate practical advice on cooking.

Brassica↗
PubMed2006

Folate absorption from folate-fortified and processed foods using a human ileostomy model.

Data on folate absorption from food from validated human studies using physiological folate doses are still needed to estimate dietary requirements and to formulate recommendations. The aim of the present work was to study the effects from fortified and processed foods on folate absorption in ileostomy volunteers (n 9) using the area under the plasma concentration curve (AUC) and kinetic modelling. Using a standardized single-dose protocol, dairy products fortified with a candidate fortificant (6S)-5-methyltetrahydrofolate ((6S)-5-CH3-H4folate), folic acid-fortified bread and a dessert crème containing natural yeast folate polyglutamates were compared with folate supplements. Absorbed folate was estimated by AUC and a kinetic model, and non-absorbed folate by ileostomal folate excretion. Median apparent absorption from test foods ranged from 55 to 86 %. Added folate-binding proteins (FBP) significantly reduced folate absorption from dairy products, as in the absence of FBP, AUC-dose-corrected ratios were increased and ileal folate excretion decreased. After in vivo gastrointestinal passage of dairy products containing FBP, up to 43 % of the ingested FBP was found in ileostomal effluent. Folate absorption was similar for (6S)-5-CH3-H4folate fortificant from fermented milk and for folic acid from fortified bread. Folic acid, ingested as food fortificant in bread, was significantly less absorbed compared with an isolated supplement. We conclude that all tested foods were suitable matrices for folate fortification. However, dairy products, fortified with the new candidate fortificant (6S)-5-CH3-H4folate, are suitable if no active FBP is present.

Absorption↗
PubMed1990

Impaired milk folate secretion is not corrected by supplemental folate during iron deficiency in rats.

Decreased milk folate secretion in iron-deficient rat dams contributes to the impairment of folate metabolism in nursing pups. The present study was designed to assess whether impaired milk folate secretion secondary to iron deficiency is due to a decrease in the supply of folate to the mammary gland or to an inability of the mammary gland to effectively use folate. Rats were fed diets containing 0.5, 2.0 or 7.0 mg folate/kg and 8 (-Fe) or 250 (+Fe) mg Fe/kg throughout gestation and until d 17 of lactation. Regardless of dietary Fe content, maternal plasma, red blood cell, liver and kidney folate concentrations correlated with dietary folate content (r = 0.75-0.85, p less than 0.0001). With the exception of plasma folate level, which was 46% lower for -Fe than +Fe dams fed 0.5 mg folate/kg, no other differences in indices of folate status were noted between +Fe and -Fe dams. Dietary folate content had a direct impact on milk folate content in +Fe dams but not in -Fe dams. Mammary tissue methionine synthase and folylpolyglutamate synthetase activities were not depressed in Fe deficiency; rather, mean activities were elevated among -Fe dams fed 0.5 mg folate/kg. In conclusion, the reduction in milk folate secretion during Fe deficiency is not due to a decrease in the amount of folate supplied to the mammary gland; rather, the defect causing this reduction is specific to the mammary gland.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1998

Urinary excretion of [2H4]folate by nonpregnant women following a single oral dose of [2H4]folic acid is a functional index of folate nutritional status.

In a 10-wk study with nonpregnant women (21-27 y, n = 5-6 per group), subjects were fed a diet containing approximately 68 nmol/d (30 microg/d) folate from food that was supplemented with folic acid in apple juice to yield a constant intake of 454, 680 or 907 nmol/d (200, 300 or 400 microg/d) to evaluate folate status and long-term in vivo kinetics. Reported here is an additional phase of this protocol conducted to determine the relationship between short-term urinary excretion after a single isotopically labeled dose and various measures of folate nutritional status. It was hypothesized that urinary excretion from a single [glutamate-2H4]folic acid ([2H4]folic acid) dose would increase in proportion to folate nutritional status due to saturable cellular uptake and retention processes along with saturation of renal reabsorption. Each subject was given 1.13 micromol (500 microg) of [2H4]folic acid orally on the morning of d 70 of the study, followed by a complete 24-h urine collection. Urine was analyzed to determine the isotopic enrichment of urinary folate by gas chromatography-mass spectrometry and the concentration of urinary folate by HPLC. Urinary excretion of [2H4]folate was greatest at the 907 nmol/d intake and was positively correlated with serum folate concentration but was not correlated with erythrocyte folate. Excretion of [2H4]folate tended to be greatest when plasma homocysteine concentrations were low (<8 micromol/L), although this relation was not significant. These results suggest that 24-h urinary excretion after a single oral dose of isotopically labeled folate is a functional indicator of folate nutritional status that complements other measures of folate nutriture.

Adult↗
PubMed2003

Methylenetetrahydrofolate reductase 677C-->T variant modulates folate status response to controlled folate intakes in young women.

A common genetic variant in the methylenetetrahydrofolate reductase (MTHFR) gene involving a cytosine to thymidine (C-->T) transition at nucleotide 677 is associated with reduced enzyme activity, altered folate status and potentially higher folate requirements. The objectives of this study were to investigate the effect of the MTHFR 677 T allele on folate status variables in Mexican women (n = 43; 18-45 y) and to assess the adequacy of the 1998 folate U.S. Recommended Dietary Allowance (RDA), 400 micro g/d as dietary folate equivalents (DFE). Subjects (14 CC, 12 CT, 17 TT genotypes) consumed a low folate diet (135 micro g/d DFE) for 7 wk followed by repletion with 400 micro g/d DFE (7 CC, 6 CT, 9 TT) or 800 micro g/d DFE (7 CC, 6 CT, 8 TT) for 7 wk. Throughout repletion with 400 micro g/d DFE, the TT genotype had lower (P </= 0.05) serum folate and higher (P </= 0.05) plasma total homocysteine (tHcy) concentrations than the CC genotype. CT heterozygotes did not differ (P > 0.05) in their response relative to the CC genotype. Throughout repletion with 800 micro g/d DFE, the CT genotype had lower (P </= 0.05) serum folate concentrations and excreted less (P </= 0.05) urinary folate than the CC genotype. However, there were no differences (P > 0.05) in the measured variables between the TT and CC genotypes. Repletion with 400 micro g/d DFE led to normal blood folate and desirable plasma tHcy concentrations, regardless of MTHFR C677T genotype. Collectively, these data demonstrate that the MTHFR C-->T variant modulates folate status response to controlled folate intakes and support the adequacy of the 1998 folate U.S. RDA for all three MTHFR C677T genotypes.

Adult↗
PubMed2005

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.

Amino Acid Substitution↗
PubMed2005

Effect of dietary folic acid supplementation on egg folate content and the performance and folate status of two strains of laying hens.

Enrichment of eggs with folate is possible when dietary folic acid levels are increased. However, development of optimal strategies for the production of folate-enriched eggs requires knowledge as to differences due to strain of bird and a greater understanding of the factors limiting egg folate deposition. To this end, a study was designed to determine the response of two leghorn strains that differ in production performance. Hyline W36 and W98 hens (n = 6 per diet) received a barley-based ration containing 0, 2, 4, 8, 16, 32, 64, or 128 mg/kg of crystalline folic acid for 21 d. Response criteria included production parameters, measures of blood folate status, and egg folate content. Significant (P < 0.05) main effects of folate supplementation were observed for egg folate content and plasma folate, which increased, and homocysteine concentrations, which decreased with supplementation; performance, however, was not affected. The Hyline W98 strain had significantly (P < 0.05) higher total egg and yolk weights and feed consumption when compared with the W36. Significant (P < 0.05) ration x strain interactions were observed for egg and yolk weight, egg folate content, and plasma homocysteine. The higher egg mass producing strain, Hyline W98, benefited from increased folic acid through a reduction in plasma homocysteine concentrations, suggesting that this strain has a higher requirement for folate than the W36 strain. Overall, egg folate content is maximized when crystalline folic acid is supplemented to the diet at 2 mg/kg or higher. Higher levels of egg folate are not achieved due to the saturation of the precursor pool for egg folate deposition.

Animal Feed↗
PubMed2006

Chronic ethanol perturbs testicular folate metabolism and dietary folate deficiency reduces sex hormone levels in the Yucatan micropig.

Although alcoholism causes changes in hepatic folate metabolism that are aggravated by folate deficiency, male reproductive effects have never been studied. We evaluated changes in folate metabolism in the male reproductive system following chronic ethanol consumption and folate deficiency. Twenty-four juvenile micropigs received folate-sufficient (FS) or folate-depleted (FD) diets or the same diets containing 40% of energy as ethanol (FSE or FDE) for 14 wk, and the differences between the groups were determined by ANOVA. Chronic ethanol consumption (FSE and FDE compared with FS and FD groups) reduced testis and epididymis weights, testis sperm concentrations, and total sperm counts and circulating FSH levels. Folate deficiency (FD and FDE compared with FS and FSE groups) reduced circulating testosterone, estradiol and LH levels, and also testicular 17,20-lyase and aromatase activities. There was histological evidence of testicular lesions and incomplete progression of spermatogenesis in all treated groups relative to the FS control, with the FDE group being the most affected. Chronic ethanol consumption increased testis folate concentrations and decreased testis methionine synthase activity, whereas folate deficiency reduced total testis folate levels and increased methionine synthase activity. In all pigs combined, testicular methionine synthase activity was negatively associated with circulating estradiol, LH and FSH, and 17,20-lyase activity after controlling for ethanol, folate deficiency, and their interaction. Thus, while chronic ethanol consumption primarily impairs spermatogenesis, folate deficiency reduces sex hormones, and the two treatments have opposite effects on testicular folate metabolism. Furthermore, methionine synthase may influence the hormonal regulation of spermatogenesis.

Animals↗
PubMed1996

Folate status of gastrointestinal epithelial cells is not predicted by serum and red cell folate values in replete subjects.

Localised folate deficiency has been implicated in colonic carcinogenesis and supplementation has been proposed for certain populations at risk. However, identifying those groups that may benefit is difficult as the relation between blood folate and gut epithelial cell values is unknown. The aim of this study was to define this relation. Epithelial cells mean (SEM) (sigmoid: 5.35 (0.56) x 10(6) cells, caecum: 6.6 (0.71) x 10(6) cells, duodenum: 4.0 (0.62) x 10(6) cells) were isolated from four endoscopic mucosal biopsy specimens (n = 25) by incubation with dithiothreitol (three hours) and EDTA (one hour). Lamina propria contamination was < 1%, with < 6% intraepithelial lymphocytes. Folate assay of isolates showed sigmoid colon folate content to be 20.1 (1.8) pg/micrograms DNA (10.2-46.6). In the same subject, caecal folate concentrations were lower (p < 0.01, n = 11) than sigmoid values, whereas duodenal isolates mirrored those of the sigmoid (19.4 (2.9) v 20.5 (3.2), n = 5). Sigmoid folate values were consistent over one to three weeks (n = 3). In a single case with blood folate deficiency, colonic values were normal. Serum folate and red cell folate correlated poorly with sigmoid epithelial cell folate content (r = 0.41, p = 0.063 and r = 0.17, p > 0.05 respectively). This study reports a modified ion-chelation isolation method for colonic biopsy specimens that yields large numbers of viable epithelial cells. Cell folate values remain constant with time though vary with intestinal region. The inability of serum or red cell folate values to predict those of the sigmoid epithelium suggests that they cannot identify those patients that might benefit from folate supplements.

Adolescent↗
PubMed1995

Growth of ovarian-carcinoma cell lines at physiological folate concentration: effect on folate-binding protein expression in vitro and in vivo.

Ovarian-carcinoma cell lines (OVCAR3, IGROVI, OVCA432, SW626 and SKOV3), grown in standard medium containing supra-physiological (2.3 microM) folate concentration, display different levels of reactivity with the anti-folate-binding-protein (FBP) monoclonal antibody MOv18, which recognizes the alpha-isoform of the protein. Gel-filtration and absorption experiments indicated that on IGROVI cells this molecule accounts for all folic-acid binding at nanomolar concentrations. The aim of the study was to investigate the effect of extracellular folate levels on cells adapted to grow in medium containing physiological folate concentration (20 nM). By the ternary complex assay, all cell lines showed a marked depletion of intracellular reduced folates, compared with those in standard folate medium. The monitoring of FBP by MOv18 showed on IGROVI cells a transient up-regulation of the protein, whereas on the other cell lines, except SKOV3, no changes were detected. These data suggest that in these cells further over-expression of the molecule cannot generally be induced by lowering the extracellular folate concentration. On SKOV3, Scatchard analysis of 125I-MOv18 binding, as well as the evaluation of total folate binding capacity, showed a 2- to 3-fold stable increase of FBP expression after long-term growth in low-folate medium. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated in these cells a 1.5-fold increase in alpha-FBP mRNA. SKOV3 cells, maintained in vitro in medium containing supraphysiological and physiological (i.e., low-folate) concentrations were injected into nude mice. Weight differences, though not statistically significant, were observed in favour of low-folate-derived tumors. Immunohistochemical and immunochemical analysis of the tumor samples showed that in SKOV3 cells the receptor modulation can also be induced by restoring the physiological folate concentration in vivo.

Animals↗