Serum Folate Concentrations Research Articles

Relationship of homocysteine and homocysteine-related vitamins to bone mineral density in Japanese patients with type 2 diabetes.

Aims/Introduction: To estimate nutritional risk factors for osteoporosis in patients with type 2 diabetes, bone mineral density, homocysteine level, and intakes and levels of Hcy-related vitamins including folate, vitamin B6 and vitamin B12 were analyzed in a cross-sectional study. Lumbar spine and femoral neck bone mineral density, serum concentrations of vitamin B6, vitamin B12, and folate and plasma homocysteine levels were measured in 125 Japanese patients with type 2 diabetes. Nutrient intake values were evaluated using a food frequency questionnaire. Homocysteine was inversely correlated with bone mineral density, and with both dietary intake and serum concentration of folate. Intake of green vegetables was correlated with intake and level of folate and homocysteine levels. When the population was analyzed across the quartiles, bone mineral density, serum folate concentration, folate intake and intake of green vegetables were lowest in the highest homocysteine group. In patients with type 2 diabetes, the nutritional status of folate might affect the homocysteine level, a putative risk factor for osteoporosis. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00088.x, 2011).

B vitamin status, dietary intake and length of stay in a sample of elderly rehabilitation patients.

To investigate the relationships between previous diet, biomarkers of selected B vitamins, nutritional status and length of stay. Cross sectional study. Geriatric rehabilitation patients, Sydney, Australia. Fifty two consenting patients with normal serum creatinine levels and no dementia. Serum vitamin B12, plasma vitamin B6, serum and erythrocyte folate, homocysteine and methylmalonic acid (MMA) concentrations; dietary intake using a validated semi-quantitative food frequency questionnaire and nutritional assessment using the Mini Nutritional Assessment (MNA). Length of stay data were collected from medical records after discharge. The age was 80 ± 8 year (mean ± SD), BMI 26.4 ± 6.8 kg/m2 and MNA score 22 ± 3 indicating some risk of malnutrition. Deficiencies of vitamins B6, B12 and folate were found in 30, 22 and 5 subjects respectively. Length of stay was positively correlated with age and MMA (Spearman's correlation 0.4, p<0.01 and 0.28, p<0.05 respectively) and negatively correlated with albumin, vitamin B6 and MNA score (Spearman's correlation -0.35, -0.33 and -0.29, p<0.05). After adjustment for age and sex, ln vitamin B6 and ln MMA concentrations were significant in predicting ln LOS (p=0.006 and p=0.014 respectively). The study indicates a high risk of vitamin B deficiencies in the elderly and suggests that deficiencies of vitamins B6 and B12 are associated with length of stay. This is concerning as B vitamin status is rarely fully assessed.

Serum Homocysteine and Folate Levels are Associated With Late-life Dementia in a Korean Population

ObjectivesWe aimed to determine whether serum levels of homocysteine (Hcy) and its biological determinants, folate and vitamin B12, are related to cognitive decline in elderly people. MethodsThe concentrations of total Hcy, folate, and vitamin B12 were measured in serum samples from 424 cognitively normal controls, 382 mild cognitive impairment patients, and 56 dementia patients from Ansan Geriatric cohort. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery was used to evaluate cognitive functions. ResultsThe dementia patients had higher serum Hcy (dementia, 17.6±6.9μmol/L; control, 12.9±5.0μmol/L; p<0.001) and lower serum folate (dementia, 7.9±4.8ng/mL; control, 10.0±7.1ng/mL; p=0.034) levels compared with controls. There was an inverse relationship between Hcy levels and serum folate or vitamin B12 concentrations. The cognitive status as measured by the (CERAD) score was inversely related to Hcy levels. The adjusted odds ratio of dementia was 5.18 (95% confidence interval: 1.91–14.10; p=0.001) for moderate (30≥Hcy>15) hyperhomocysteinemia compared with normal Hcy levels (≤15μmol/L). In addition, there was weak association between low serum folate (<3.0ng/mL) and the risk for dementia (crude odds ratio=3.68; 95% confidence interval: 1.07–12.69; p=0.039). ConclusionElevated serum Hcy and decreased serum folate concentrations are associated with the risk of dementia in Korean elders.

Betaine reduction of hyperhomocysteinemia and enhancement of 5-hydroxyindoleacetic acid in ethanol-induced hyperhomocysteinemia in rabbits.

Hyperhomocysteinemia is a hypothesis for the association of homocysteine with cerebrovascular diseases, neurodegenerative diseases and depression of mood. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced hyperhomocysteinemia on the monoaminergic system. A total of 32 New Zealand White rabbits were divided into four groups (n=8); the Control group (C). The Ethanol group (E) was administered ethanol at a dosage of 4 g/kg daily. The Betaine group (B) received betaine at a dosage 1.5% (w/w) of the diet daily, and the Betaine and Ethanol group (BE after one hour the rabbits received ethanol at a dosage of 4 g/kg daily. Blood samples were taken in the morning of the day before beginning treatment (0.0 day) and on the 30th, 60th and 90th day of the treatment. Serum folate and vitamin B12 levels were determined using a radioimmunoassay, total plasma homocysteine (tHcy) level was determined by homocysteine EIA kit, and 5- hydroxyindoleacetic acid (5-HIAA) of plasma was measured with HPLC-ECD. There was a significant negative correlation between 5-HIAA and tHcy in the E group (r=-0.473, P=0.02), and compared to the E group the concentrations of 5-HIAA in the B&E group increased considerably (p<0.05). In contrast to the E group, significantly high concentrations of 5-HIAA were observed in the B and C groups. While the serum concentrations of vitamin B12 showed no significant difference in the B&E group on the 90th day compared to the control group, the serum concentrations of folate on the 90th day differed significantly (p<0.05) . However, no significant difference was observed between tHcy and gender. Overall, oral pretreatment with betaine significantly prevented ethanol-induced hyperhomocysteinemia, subsequently increasing 5-HIAA in the plasma as well as vitamin B12 and folate in the serum. Thus, betaine may be recommended as a pretreatment method for depressive patients with alcoholism. Key words: Betaine, hyperhomocysteinemia, 5-HIAA, ethanol, vitamin B12, folate.

Effect of maternal folic acid supplementation on hepatic one-carbon unit associated gene expressions in newborn piglets

Intrauterine growth retardation (IUGR) induces alterations to hepatic gene expressions which might program poor postnatal growth and health status. Maternal folic acid supplementation was administered in gilt diets to test whether hepatic mRNA expressions of some important genes induced by IUGR could be rescued by folic acid supplementation. Thirty-two Yorkshire gilts were allotted to two treatment groups of control (C folic acid 1.3 mg/kg) or folic acid supplementation (FS folic acid 30 mg/kg) after mating, to study the effects of maternal folic acid supplementation on the mRNA expression of methionine adenosyltransferase (MAT), cystathionine-β-synthase (CBS), methylenetetrahydrofolate reductase (MTHFR), DNA methyltransferase1 (DNMT1), peroxisomal proliferator-activated receptor (PPARγ), glucocorticoid receptor (GR), obesity receptor (ob-R) and Acyl-CoA oxidase (AOX) in the liver of IUGR and NBW piglets. Blood and liver samples were collected for determinations of serum folic acid and gene expressions. The total number of born piglets, number of piglets born alive, average birth weight and 21 days average weight were not affected by dietary treatment (P>0.05), and serum folic acid concentration of piglets was greater in FS than C groups (P<0.05). Real-time PCR indicated that gene expression of MAT1A, MAT2A and DNMT1 were lower in IUGR piglets but could be elevated by maternal folic acid supplementation. Transcript expression levels of PPARγ, GR and AOX were higher in IUGR piglets, but were decreased to the level of normal piglets by maternal folic acid supplementation. Our results suggested that maternal folic acid supplementation be an effective way to rescue the gene expressions negatively induced by IUGR.

Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12

We evaluated associations between folate, vitamin B12, and the methylenetetrahydrofolate reductase (MTHFR) gene, and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. This multicenter case-control study enrolled 927 Korean women (440 controls, 165 patients with CIN 1, 167 patients with CIN 2/3, and 155 patients with cervical cancer, aged 20-75years). Patients with cervical cancer had significantly lower median serum folate and vitamin B12 concentrations vs. controls. Higher serum folate was significantly associated with lower cervical cancer risk (p for linear trend=0.0058) with a trend for a lower CIN risk after multivariate adjustment. Low folate and the MTHFR 677 C>T variant were associated with a higher risk for CIN2/3 and cervical cancer vs. wild-type or heterozygous genotypes with high folate [OR, 2.39 (1.18-4.85) and 3.19 (1.43-7.13)]. Low vitamin B12 and the MTHFR 677 C>T variant also were associated with a higher risk for CIN 2/3 and cervical cancers [OR, 2.52 (1.17-5.42) and 2.40 (1-5.73)] vs. wild-type or heterozygous status with high vitamin levels. Serum folate concentration is inversely associated with the risk of cervical cancer, and the MTHFR variant genotype may increase CIN and cervical cancer risk in women with low folate or vitamin B12 status.

Effects of Folic Acid Supplementation on Serum Folate and Plasma Homocysteine Concentrations in Older Adults: A Dose-Response Trial

The authors' objective in this study was to estimate the changes in serum folate and homocysteine concentration that resulted from 6 weeks of supplementation with folic acid. A randomized, double-blind, placebo-controlled, dose-response trial with a parallel-group design was conducted. A total of 133 participants aged 60-90 years (70% female, 19% nonwhite) were assigned to receive 0, 100, 400, 1,000, or 2,000 μg/day of folic acid for 6 weeks. Data were collected in the United States between June and September 1996. At baseline, median serum folate and plasma homocysteine concentrations were 5.7 ng/mL (interquartile range (25th-75th percentiles), 4.1-7.8) and 8.3 μmol/L (interquartile range, 7.1-10.0), respectively. As the folic acid dose increased, serum folate levels increased (P-trend < 0.001). There was no dose-response relation with homocysteine level among all participants. In analyses restricted to persons with the lowest serum folate concentration (<4.5 ng/mL) at baseline, there was a trend (P = 0.06) toward decreased homocysteine levels with increasing folic acid dose. In healthy, older adults with adequate folate status, folic acid supplementation is not beneficial for homocysteine reduction. However, for older adults with low serum folate levels, supplementation will improve folate status and may be beneficial for lowering homocysteine concentrations.

Serum levels of folate, lycopene, β-carotene, retinol and vitamin E and prostate cancer risk

Previous studies relating increased serum levels of folate and fat-soluble vitamins to prostate cancer risk have variously shown null associations or to either decrease or increase the risk of developing prostate cancer. Prospective studies of serum folate levels have been reported to show a null association and increased serum levels to either decrease or increase the risk of subsequently developing prostate cancer. Similarly, serum β-carotene and lycopene levels have either been reported to be inversely correlated or not associated with prostate cancer risk. Using a prospective nested case-control study design, which minimized the possibility of disease effects on serum-vitamin concentrations, we report null associations for serum concentrations of folate, lycopene, β-carotene, vitamin A and vitamin E, and subsequent development of prostate cancer.

Serum Homocysteine and Folate Concentrations Are Associated with Prevalent Age-Related Hearing Loss , ,

Elevated total serum homocysteine (tHcy) concentrations associated with vitamin B-12 or folate deficiencies may adversely affect blood flow to the cochlea, leading to age-related hearing loss (presbycusis). However, only 2 small cross-sectional studies have assessed the link between folate, vitamin B-12, or tHcy and presbycusis. We aimed to determine both the cross-sectional and longitudinal association between serum concentrations of folate, vitamin B-12, or tHcy and risk of age-related hearing loss. The Blue Mountains Hearing Study is a population-based survey of age-related hearing loss (1997–1999 to 2002–2004). Presbycusis was measured in 2956 participants (aged ≥50 y) and was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz >25 dB hearing level (HL). Serum concentrations of folate, vitamin B-12, and tHcy were determined from blood samples. Participants with elevated tHcy (>20 μmol/L) concentrations had a 64% increased likelihood of prevalent hearing loss (>25 dB HL) [multivariate-adjusted odds ratio (OR) 1.64; 95% CI, 1.06–2.53]. Low serum folate levels (<11 nmol/L) increased the odds of prevalent mild hearing loss (>25–40 dB HL), multivariate-adjusted [OR 1.37 (CI 1.04–1.81)]. Serum vitamin B-12, however, was not significantly associated with prevalent hearing loss. Serum folate, vitamin B-12, and tHcy concentrations were also not significantly associated with an increased risk of incident hearing loss. Serum concentrations of tHcy and folate were associated with age-related hearing loss cross-sectionally, but no temporal links were observed, which could be due to insufficient study power. Further, large prospective studies will be required in the future to assess these associations.

Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged ≥60 y in the United States

Unmetabolized serum folic acid (UMFA) has been detected in adults. Previous research indicates that high folic acid intakes may be associated with risk of cancer. The objective was to examine UMFA concentrations in relation to dietary and supplemental folate and status biomarkers in the US population aged > or =60 y. Surplus sera were analyzed with the use of data from the National Health and Nutrition Examination Survey (NHANES) 2001-2002, a cross-sectional, nationally representative survey (n = 1121). UMFA was detected in 38% of the population, with a mean concentration of 4.4 +/- 0.6 nmol/L (median: 1.2+/- 0.2 nmol/L). The group with UMFA (UMFA+) had a significantly higher proportion of folic acid supplement users than did the group without UMFA (60% compared with 41%). UMFA+ men and women also had higher supplemental and total (food + supplements) folic acid intakes than did their counterparts without UMFA. Forty percent of the UMFA+ group was in the highest quartile of total folic acid intake, but total folic acid intake was only moderately related to UMFA concentrations (r(2) = 0.07). Serum folate concentrations were significantly higher in the UMFA+ group and were predictive of UMFA concentrations (r(2) = 0.15). Serum 5-methyltetrahydrofolate and vitamin B-12 concentrations were higher in the UMFA+ group, whereas there was no difference between the 2 UMFA groups in red blood cell folate, serum homocysteine, or methylmalonic acid concentrations. Approximately 40% of older adults in the United States have UMFA that persists after a fast, and the presence of UMFA is not easily explained in NHANES by folic acid intakes alone. Given the possibility that excessive folic acid exposure may relate to cancer risk, monitoring of UMFA may be warranted.

Polymorphism of MTHFR C677T, serum vitamin levels and cognition in subjects with hyperhomocysteinemia in China

Relationships between hyperhomocysteinemia (HHE) and neurodegenerative diseases have been widely studied. However, the impact of serum total homocysteine (tHcy) levels on cognitive function has not been confirmed. C677T polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have impacts on tHcy level; it is suspected to influence cognitive function, but only few investigations have assessed its effects on non-dementia adults and the results have been controversial. Moreover, there is no report about Chinese subjects. In the present study, we determined C677T/MTHFR genotype, serum tHcy concentration and cognition in 182 nondemented subjects aged 55–88 years to probe the associations between MTHFRC677T mutation, increased tHcy levels and decreased cognitive function in a northern city in China. A serum tHcy level ≥ 16 μmol/l was deemed HHE. Cognitive function was assessed by the Mini Mental State Examination (MMSE) and Basic Cognitive Aptitude Tests (BCAT). Results showed that: (i) subjects with the T allele had higher serum tHcy levels than those without, especially in lower folate status; (ii) T allele and CT/TT genotype frequencies in subjects with HHE were higher than in non-HHE subjects (P < 0.05); and (iii) serum tHcy level was inversely related to total BCAT score (P < 0.05) but MTHFR677 C to T polymorphism had no association with it. Our results confirmed that the MTHFR 677 C to T mutation, especially in lower serum folate concentration status, results in the increase of serum tHcy levels which is bad for cognitive function and indicates that higher serum folate level is of benefit in keeping lower serum tHcy level and better cognitive function. The results provide some valuable clues for individualized nutrition intervention of HHE and cognition decline in the middle-aged and the elderly.

Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study

Background/ObjectivesVegans and to a lesser extent vegetarians have low average circulating concentrations of vitamin B12; however, the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear. The objectives were to investigate differences in serum vitamin B12 and folate concentrations between omnivores, vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet.Subjects/MethodsA cross-sectional analysis involving 689 men (226 omnivores, 231 vegetarians and 232 vegans) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort.ResultsMean serum vitamin B12 was highest among omnivores (281, 95% CI: 270-292 pmol/l), intermediate in vegetarians (182, 95% CI: 175-189 pmol/l), and lowest in vegans (122, 95% CI: 117-127 pmol/l). Fifty-two percent of vegans, 7% of vegetarians and one omnivore were classified as vitamin B12 deficient (defined as serum vitamin B12 < 118 pmol/l). There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12. In contrast, folate concentrations were highest among vegans, intermediate in vegetarians, and lowest in omnivores, but only two men (both omnivores) were categorised as folate deficient (defined as serum folate < 6.3 nmol/l).ConclusionVegans have lower vitamin B12 concentrations, but higher folate concentrations, than vegetarians and omnivores. Half of the vegans were categorised as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency.

19-base pair deletion polymorphism of the dihydrofolate reductase (DHFR) gene: maternal risk of Down syndrome and folate metabolism.

Polymorphisms in genes involved in folate metabolism may modulate the maternal risk of Down syndrome (DS). This study evaluated the influence of a 19-base pair (bp) deletion polymorphism in intron-1 of the dihydrofolate reductase (DHFR) gene on the maternal risk of DS, and investigated the association between this polymorphism and variations in the concentrations of serum folate and plasma homocysteine (Hcy) and plasma methylmalonic acid (MMA). Analytical cross-sectional study carried out at Faculdade de Medicina de São José do Rio Preto (Famerp). 105 mothers of individuals with free trisomy of chromosome 21, and 184 control mothers were evaluated. Molecular analysis on the polymorphism was performed using the polymerase chain reaction (PCR) through differences in the sizes of fragments. Folate was quantified by means of chemiluminescence, and Hcy and MMA by means of liquid chromatography and sequential mass spectrometry. There was no difference between the groups in relation to allele and genotype frequencies (P = 0.44; P = 0.69, respectively). The folate, Hcy and MMA concentrations did not differ significantly between the groups, in relation to genotypes (P > 0.05). The 19-bp deletion polymorphism of DHFR gene was not a maternal risk factor for DS and was not related to variations in the concentrations of serum folate and plasma Hcy and MMA in the study population.

Dietary Patterns Are Associated with Hyperhomocysteinemia in an Urban Pakistani Population1–3

Little attention has been given to the association of dietary patterns with plasma homocysteine. Our objective in this study was to identify major dietary patterns and investigate their association with plasma homocysteine. In a cross-sectional survey, 872 healthy adults (355 males, 517 females; aged 18–60 y) were enrolled from an urban population in Karachi. Dietary intake was assessed by a FFQ. We used factor analysis to define major dietary patterns. Fasting concentrations of plasma or serum homocysteine, folate, pyridoxal-phosphate (PLP; coenzyme form of vitamin B-6), and vitamin B-12 were measured. Three major dietary patterns were identified and labeled as “prudent diet,” “high animal-protein diet,” and “high plant-protein diet.” We observed a protective effect of the prudent dietary pattern for the highest quartile of intake compared with the lowest quartile of hyperhomocysteinemia when the model was adjusted for age, gender, household income, BMI, tobacco chewing, and smoking [OR = 0.52 (95% CI = 0.30–0.90); P = 0.01]. The high plant-protein diet pattern was inversely related to hyperhomocysteinemia, with a higher intake being protective. Compared with the 1st quartile, the adjusted OR was 0.42 (95% CI = 0.25–0.69; P = 0.001) for the 4th quartile. The high animal-protein diet was positively associated with hyperhomocysteinemia, with participants in the highest quartile of intake having the greatest increase in risk [OR = 2.10 (95% CI = 1.22–3.60); P = 0.007]. Plasma homocysteine concentrations appeared to be correlated more with circulating folate (r = –0.25; P < 0.001) than with PLP (r = –0.02; P = 0.663) or vitamin B-12 (r = –0.16; P < 0.001). A diet rich in fruits and uncooked vegetables decreased the risk of hyperhomocysteinemia, whereas diets rich in red meat, chicken, and tea with milk were positively associated with hyperhomocysteinemia. J. Nutr. 140: 1261–1266, 2010.

Serological Differences in Folate/Vitamin B12 in Pregnancies Affected by Neural Tube Defects

Laboratory evidence is presented of significant associations between reduced maternal serum folate and vitamin B12 levels and neural tube birth defects (NTD) compared to referents. This was an incident case-control study. Cases of neural tube defects (including anencephaly and open spina bifida) diagnosed in residents within 100 miles of the US-Mexico border from January 1993 to October 2000 were eligible. Most cases were diagnosed in utero upon visits to clinics, obstetrical or genetic expert offices. Cases identified upon hospital admission or at delivery were also eligible. Cases identified after discharge were not. Controls were matched on geographic region, maternal age, race/ethnicity, gestational age, and type of health insurance (including none). Three hundred eighty-two border area residents (107 cases and 275 individually matched controls) provided biological specimens. Median folate concentrations for case mothers were 36% lower than controls (9.8 ng/mL vs. 15 ng/mL). Maternal serum folate concentrations in quartiles above 9.5 ng/mL indicated significantly reduced risk (OR = 0.4, OR = 0.3, and OR = 0.2). Likewise, the risk for NTD decreased (OR = 0.4, OR = 0.3, and OR = 0.2) in quartiles of sera B12 concentrations above 246 pg/mL. Physician attention is invited to significantly lower concentrations of serum folate and vitamin B12 in women with NTD-affected pregnancies. This study assayed sera samples from women while still pregnant or immediately after delivery. The confounding effect of reduced folate and B12 levels with other biological and chemical exposures will be addressed in subsequent communications.

101 INCREASED CANCER CELL PROLIFERATION IN PROSTATE CANCER PATIENTS WITH HIGH LEVELS OF SERUM FOLATE

You have accessJournal of UrologyProstate Cancer: Basic Research I1 Apr 2010101 INCREASED CANCER CELL PROLIFERATION IN PROSTATE CANCER PATIENTS WITH HIGH LEVELS OF SERUM FOLATE Jeffrey Tomaszewski, Jessica Cummings, Anil Parwani, Rajiv Dhir, Joel Mason, Joel Nelson, Dean Bacich, and Denise O'Keefe Jeffrey TomaszewskiJeffrey Tomaszewski Pittsburgh, PA More articles by this author , Jessica CummingsJessica Cummings Pittsburgh, PA More articles by this author , Anil ParwaniAnil Parwani Pittsburgh, PA More articles by this author , Rajiv DhirRajiv Dhir Pittsburgh, PA More articles by this author , Joel MasonJoel Mason Boston, MA More articles by this author , Joel NelsonJoel Nelson Pittsburgh, PA More articles by this author , Dean BacichDean Bacich Pittsburgh, PA More articles by this author , and Denise O'KeefeDenise O'Keefe Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.150AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A recent placebo-controlled prospective clinical trial of folic acid supplementation revealed an increased incidence of prostate cancer in the treatment group. The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from cancer-free organ donors. METHODS Serum and/or prostate tissue folate concentration were measured in 86 patients undergoing radical prostatectomy and from 32 cancer-free organ donors. Expression of Ki67 and PSMA were assessed in a subset of these tissues. RESULTS Mean serum folate concentrations were significantly higher at all age ranges in men with prostate cancer compared to cancer-free organ donors (p<0.002; Figure 1).Fasting serum folate levels were positively correlated with prostate cancer tissue folate content (n= 15; Spearman Correlation r= 0.577, p<0.03). Mean tissue folate levels in prostate cancers were also significantly higher than in cancer-free prostates from age-matched organ donors (p<0.02). Among patients with Gleason Score 7 disease, the mean proliferation index was 6.17 ± 3.2% and 0.86 ± 0.92% in patients in the highest (117±15nM) and lowest (18±9nM) quintiles for serum folate, respectively (p<0.0001; Figure 2). CONCLUSIONS To our knowledge, this is the first report of a positive correlation between serum folate and prostate cancer tissue folate. Increased cancer cell proliferation in men with higher serum folate concentrations is consistent with an increase in prostate cancer incidence observed with folate supplementation. Unexpectedly, more than 25% of the prostate cancer cohort had a serum folate concentration 6-fold greater than considered adequate, suggesting either regular supplement use and/or altered folate metabolism. With widespread dietary folate supplementation the relationship between folate intake and prostate cancer should be better defined. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e41-e42 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeffrey Tomaszewski Pittsburgh, PA More articles by this author Jessica Cummings Pittsburgh, PA More articles by this author Anil Parwani Pittsburgh, PA More articles by this author Rajiv Dhir Pittsburgh, PA More articles by this author Joel Mason Boston, MA More articles by this author Joel Nelson Pittsburgh, PA More articles by this author Dean Bacich Pittsburgh, PA More articles by this author Denise O'Keefe Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Characterization of folate-dependent enzymes and indices of folate status in laying hens supplemented with folic acid or 5-methyltetrahydrofolate

The conversion of folic acid (FA) to the biologically active 5-methyltetrahydrofolate (5-MTHF) is necessary for the deposition of folate in the egg. A study was conducted to compare egg folate concentrations, indices of folate status, and activities of folate-dependent enzymes in response to equimolar intake of either FA or 5-MTHF in laying hens. Forty-eight laying hens, 24 wk of age, from 2 different strains (Shaver White and Shaver Brown) were randomly assigned to receive 1 of 3 (n = 8 per strain) dietary treatments: 1) basal diet with no supplemental folate, 2) basal diet + 10 mg/kg of FA, or 3) basal diet + 11.3 mg/kg of 5-MTHF for 3 wk. A completely randomized design with 3 dietary treatments and 2 laying hen strains in a 3 x 2 factorial arrangement was used. Data were subjected to ANOVA, using the PROC GLM procedure of SAS. Plasma homocysteine, serum, and egg folate concentrations; hepatic serine hydroxymethyltransferase; and methionine synthase activity were affected by dietary folate supplementation but not by its form (FA and 5-MTHF). Relative to control hens, plasma homocysteine was decreased (P < 0.05) by 14.2%, whereas serum and egg folate were increased (P < 0.05) by 78.3 and 61.8%, respectively, in hens consuming either folate compound. Hepatic serine hydroxymethyltransferase and methionine synthase activity were increased and decreased (P < 0.05), respectively, in folate-fed birds compared with control-fed birds. Hepatic dihydrofolate reductase was influenced by both the addition and form of dietary folate, being higher (P < 0.05) in FA-fed birds than in 5-MTHF and control-fed birds. Feed efficiency was improved (P < 0.05) in 5-MTHF-fed birds relative to FA-fed birds. Strain of hen influenced serum folate and plasma homocysteine concentrations but not other indices of folate metabolism. Overall, FA and 5-MTHF have equivalent effects in enhancing egg folate concentrations and improving folate status in laying hens. Also, supplementation and form of folate may modulate the activity of folate-dependent enzymes.

SIGNIFICANT DECREASE IN HOMOCYSTEINE AND ox‐LDL IN HEALTHY HEAVY SMOKERS AFTER NUTRACEUTICAL SUPPLEMENTATION

Nutraceuticals may attenuate some negative effects of cigarette smoking. We evaluated effects of two different encapsulated formulas, consisting primarily of mixed juice powder concentrate (Juice Plus+®), in a randomized placebo controlled, double‐blind study on 101 heavy smokers (&gt;20 cigarettes/d, duration ≥10y, median age 47; 41–57 y, 63 M, mean capsule compliance 85.2%). Smokers were divided into 3 groups: A‐placebo, B‐fruit/vegetable, C‐fruit/vegetable/berry. Serum and erythrocyte folate (s‐fol and ery‐fol, respectively) and total homocysteine (tHcy) concentrations were measured before and after 3‐m supplementation. In 75 (46 M) compliant (&gt;95%) subjects, lipid panel parameters (total Cholesterol, tChol; LDL‐c; oxidized‐LDL, ox‐LDL) were evaluated. Median values were compared (t‐test for paired data); data are reported as mean delta values (± standard deviation). Intervention with both nutraceutical formulations resulted in reduction in ox‐LDL and tHcy compared to placebo.Support: NSA, Collierville, TN A (placebo) B (fruit/veg) C (fruit/veg/berry) tChol (mg/dL) 9.3 (±18.4) −11.6 (±22.9)* −6.3 (±25.5)* LDL‐c (mg/dL) 16.8 (±17.6) −8.1 (±17.9)* −0.8 (±20.5)* ox‐LDL (U/L) −2.3 (±11.3) −13.8 (±12.5)* −11.2 (±12.2)* tHcy (μM) −0.14 (±1.4) −2.38 (±2.3)# −3.20 (±5.2)# s‐fol (nM) 2.8 (±5.5) 13.7 (±9.9)# 16.6 (±9)# ery‐fol (nM) 194 (±178.3) 488.2 (±349)# 646.3 (±362.1)#

Serum folate and homocysteine and depressive symptoms among Japanese men and women

Folate and homocysteine have been implicated to have a role in depression. However, results of epidemiologic studies on this issue have been inconsistent. The objective of this study was to clarify the association between serum folate and homocysteine concentrations and depressive symptoms in Japanese adults. We analyzed cross-sectional data for 530 municipal employees (313 men and 217 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D scale scores of >or=16) with adjustment for potential confounding variables. In total, 113 men (36.1%) and 79 women (36.4%) had depressive symptoms. A higher serum folate was associated with a decreased prevalence of depressive symptoms in men. The multivariate-adjusted odds ratios (95% confidence interval) of depressive symptoms for the lowest to highest quartiles of serum folate were 1.00 (reference), 0.53 (0.27-1.03), 0.33 (0.16-0.68) and 0.51 (0.25-1.03), respectively (trend P=0.03). Furthermore, the data suggested a positive association between serum homocysteine and depressive symptoms in men (trend P=0.06). In women, neither folate nor homocysteine was associated with depressive symptoms. Low serum folate may be related to an increased prevalence of depressive symptoms in Japanese men.

Thrombophilia and abdominal vessel thrombosis in a Greek University hospital: A five year experience

Thrombophilia, either congenital or acquired, has foremost consequences in the abdominal vessels. We review here the cases of patients admitted with abdominal vessel thrombosis over a five-year period. Our data focused on gender and age at diagnosis, site of thrombosis, previous thromboembolic events, underlying conditions, and family history. Investigations included measurement of protein C, protein S, activated PC resistance, and antithrombin, and screening for factor V Leiden, prothrombin G20210A, the C677T variant of the methylenetetrahydrofolate reductase gene, and V617F JAK2 mutation, r lupus anticoagulant, antiphospholipid antibodies and paroxysmal nocturnal hemospherinouria, and also serum folate, vitamin 12, and total homocysteine concentrations. Twenty-nine patients were admitted and 18 of their family members also underwent the same thrombophilia investigations. Eighteen patients (62.1%) presented with portal vein thrombosis (PVT), five patients (17.2%) with mesenteric vein thrombosis (MVT), four patients (13.8%) with splenic vein thrombosis (SVT), and two (6.9%) patients with hepatic vein thrombosis (HVT). There was a high incidence of congenital thrombophilia (37.9%), acquired thrombophilic conditions (27.6%), or both (20.7%). Sixteen of 18 patients with PVT, four of five patients with MVT, all four patients with SVT, and one of two patients with HVT had one or more thrombophilic risk factors. In 13.8% of the patients no underlying condition was identified. We concluded that thrombophilia may have major implications in the pathogenesis of abdominal vessel thrombosis in adult life, and a thorough thrombophilia investigation should be performed in all these patients.